645 research outputs found
Coagulation kinetics beyond mean field theory using an optimised Poisson representation
Binary particle coagulation can be modelled as the repeated random process of
the combination of two particles to form a third. The kinetics can be
represented by population rate equations based on a mean field assumption,
according to which the rate of aggregation is taken to be proportional to the
product of the mean populations of the two participants. This can be a poor
approximation when the mean populations are small. However, using the Poisson
representation it is possible to derive a set of rate equations that go beyond
mean field theory, describing pseudo-populations that are continuous, noisy and
complex, but where averaging over the noise and initial conditions gives the
mean of the physical population. Such an approach is explored for the simple
case of a size-independent rate of coagulation between particles. Analytical
results are compared with numerical computations and with results derived by
other means. In the numerical work we encounter instabilities that can be
eliminated using a suitable 'gauge' transformation of the problem [P. D.
Drummond, Eur. Phys. J. B38, 617 (2004)] which we show to be equivalent to the
application of the Cameron-Martin-Girsanov formula describing a shift in a
probability measure. The cost of such a procedure is to introduce additional
statistical noise into the numerical results, but we identify an optimised
gauge transformation where this difficulty is minimal for the main properties
of interest. For more complicated systems, such an approach is likely to be
computationally cheaper than Monte Carlo simulation
Weyl's Lagrangian in teleparallel form
The main result of the paper is a new representation for the Weyl Lagrangian
(massless Dirac Lagrangian). As the dynamical variable we use the coframe, i.e.
an orthonormal tetrad of covector fields. We write down a simple Lagrangian -
wedge product of axial torsion with a lightlike element of the coframe - and
show that this gives the Weyl Lagrangian up to a nonlinear change of dynamical
variable. The advantage of our approach is that it does not require the use of
spinors, Pauli matrices or covariant differentiation. The only geometric
concepts we use are those of a metric, differential form, wedge product and
exterior derivative. Our result assigns a variational meaning to the tetrad
representation of the Weyl equation suggested by J. B. Griffiths and R. A.
Newing
Dark spinors with torsion in cosmology
We solve one of the open problems in Einstein-Cartan theory, namely we find a
natural matter source whose spin angular momentum tensor is compatible with the
cosmological principle. We analyze the resulting evolution equations and find
that an epoch of accelerated expansion is an attractor. The torsion field
quickly decays in that period. Our results are interpreted in the context of
the standard model of cosmology.Comment: 7 pages, 3 figures; reference added, minor improvement
Novi derivati 9-aminoakridina kao inhibitori botulinum neurotoksina i P. falciparum parazita malarije
Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials.. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50 % is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to the antimalarial activity, the adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI gt 326), indicating that an adamantyl group is a better carrier than a steroidal motif for this indication.Sintetisani su derivati steroidnih i adamantil-akridina i ispitana je njihova inhibitorna aktivnost prema botulinum neurotoksinima (BoNT) i parazitu malarije. Steroidni akridini pokazuju dobru inhibiciju prema kratkom nizu (LCs) BoNT/A i BoNT/B. Ostvarena inhibicija BoNT/B LC od oko 50% je najviša postignuta vrednost akridinskih derivata prema ovom serotipu. Adamantil-akridinski derivati su pokazali najveću antimalarijsku aktivnost (IC50 u opsegu 6-9 nM, SI gt 326), pokazujući da je adamantil-grupa bolji nosač farmakofore u poređenju sa steroidnim, prema ovoj indikaciji.
Performance of cages as large animal-exclusion devices in the deep sea
Sedimentary, deep-sea communities include megafaunal animals (e.g., sea cucumbers, brittle stars, crabs) and demersal fishes, collectively termed the large, motile epifauna (LME). Individuals of the LME are common, and their biomass approximates that of the macrofauna. Based on analogies with shallow-water animals, they are likely to be sources of mortality for the infauna and to create spatial and temporal heterogeneity in the community. Given present theories of deep-sea community organization, such effects could be important. Unfortunately, this hypothesis has not been tested because of the difficulty of conducting experiments in the deep sea and because tools for manipulating the LME have not been developed. We studied the suitability of exclusion cages for this purpose at 780 m depth in San Diego Trough. We placed 16 cages of two mesh sizes for 4.5 months over regions of the seafloor that appeared free of LME. Time-lapse photographs of a cage and a control plot coupled with observations of all cages at the end of the experiment indicated that small (1.27-cm × 1.27-cm square)-mesh cages were effective at excluding LME. Further, the cages were essentially free of cage artifacts that have been reported in shallow-water studies. Large, mobile and disruptive animals (e.g., fishes, crabs) did not establish long-term residence adjacent to or on the cages. Bio-fouling slightly reduced the open surface area of the cage mesh, potentially reducing flow through the cage, but the composition of surface sediments in terms of organic C and N, phytoplankton-derived pigments, and grain size was indistinguishable between cages and control areas. Activities of excess 234Th were significantly higher (average = 37%) inside of small-mesh cages, which might suggest enhanced particulate deposition inside cages. However, this measurement was an artifact of experimental manipulation. Particles that accumulated on the cage during the experiment were dislodged and settled to the seafloor when the cage was opened just prior to sampling. These particles would have been highly enriched in 234Th, and their inclusion in core samples artificially inflated the calculated sediment accumulation rates inside cages. Therefore, the cages performed well; they excluded the targeted LME without causing artifacts and thus should be useful for experimental study of a group of animals that may have substantial impact on the structure and organization of deep-sea communities
Supplementary data for article: Opsenica, I.; Tot, M.; Gomba, L.; Nuss, J. E.; Sciotti, R. J.; Bavari, S.; Burnett, J. C.; Šolaja, B. A. 4-Amino-7-Chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity. Journal of Medicinal Chemistry 2013, 56 (14), 5860–5871. https://doi.org/10.1021/jm4006077
Supporting information for: [https://doi.org/10.1021/jm4006077]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1381
A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype A Has a Very Different Conformation than SNAP-25 Substrate
SummaryBotulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (Ki = 41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the “proton shuttle” E224. This mechanism of inhibition is aided by residue contacts in the conserved S1′ pocket of the substrate binding cleft and by the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2′ residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes or thermolysin
Light scattering from ultracold atomic gases in optical lattices at finite temperature
We study light scattering from atoms in optical lattices at finite
temperature. We examine the light scattered by fermions in the noninteracting
regime and by bosons in the superfluid and Mott insulating regimes. We extend
previous theoretical studies to include the full band structure of the optical
lattice. We find that light scattering that excites atoms out of the lowest
band leads to an increase in light scattering away from the classical
diffraction peaks and is largely temperature independent. This additional light
scattering leads to lower efficiency of temperature measurements based on
photon counting.Comment: 10 pages, 6 figure
Targeting Ovarian Cancer and Endothelium with an Allosteric PTP4A3 Phosphatase Inhibitor
Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, selective, reversible, and noncompetitive PTP4A inhibitor, JMS-053, markedly enhanced microvascular barrier function after exposure of endothelial cells to vascular endothelial growth factor or lipopolysaccharide. JMS-053 also blocked the concomitant increase in RhoA activation and loss of Rac1. In human ovarian cancer cells, JMS-053 impeded migration, disrupted spheroid growth, and decreased RhoA activity. Importantly, JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer. These data demonstrate that PTP4A phosphatases can be targeted in both endothelial and ovarian cancer cells, and confirm that RhoA signaling cascades are regulated by the PTP4A family
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