1,100 research outputs found
In silico identification of potential inhibitors for human aurora kinase b
Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer
In silico identification of potential inhibitors for human aurora kinase b
Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer
Fast Structuring of Radio Networks for Multi-Message Communications
We introduce collision free layerings as a powerful way to structure radio
networks. These layerings can replace hard-to-compute BFS-trees in many
contexts while having an efficient randomized distributed construction. We
demonstrate their versatility by using them to provide near optimal distributed
algorithms for several multi-message communication primitives.
Designing efficient communication primitives for radio networks has a rich
history that began 25 years ago when Bar-Yehuda et al. introduced fast
randomized algorithms for broadcasting and for constructing BFS-trees. Their
BFS-tree construction time was rounds, where is the network
diameter and is the number of nodes. Since then, the complexity of a
broadcast has been resolved to be rounds. On the other hand, BFS-trees have been used as a crucial building
block for many communication primitives and their construction time remained a
bottleneck for these primitives.
We introduce collision free layerings that can be used in place of BFS-trees
and we give a randomized construction of these layerings that runs in nearly
broadcast time, that is, w.h.p. in rounds for any constant . We then use these
layerings to obtain: (1) A randomized algorithm for gathering messages
running w.h.p. in rounds. (2) A randomized -message
broadcast algorithm running w.h.p. in rounds. These
algorithms are optimal up to the small difference in the additive
poly-logarithmic term between and . Moreover, they imply the
first optimal round randomized gossip algorithm
Development of Mucoadhesive Nanoparticulate System of Ebastine for Nasal Drug Delivery
Purpose: To prepare and evaluate mucoadhesive nanoparticulate system of ebastine for nasal drug delivery.Methods: The nanoparticles were prepared by ionic gelation method using drug-chitosan weight ratios 1:1, 1:2 and 1:3, and incorporating 0.5 or 0.7 % w/v sodium tripolyphosphate (STPP) and poloxamer 407. The mucoadhesive nanoparticles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning colorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) and evaluated for drug loading, entrapment efficiency, in vitro mucoadhesion, in vitro drug release and ex-vivo permeation.Results: FTIR and DSC studies indicate that no chemical interaction occurred between the drug and polymer. Nanoparticle size ranged from 169 to 500 nm. Drug loading and entrapment efficiency increased with increase in chitosan concentration and decreased with increase in poloxamer 407 concentration. The highest drug loading obtained for the nanoparticles was 19.5 %. With increase in polymer (chitosan) concentration (1:1 to 1:3), production yield was unchanged (73.2 to 74.4 % (F6)). Mucoadhesion increased with increase in the concentration of chitosan. In vitro drug release from all the formulations was biphasic, being characterized by a slight âburstâ followed by slow release. At the end of 8 h F6 (1:3) showed drug release of only 86.9 %, indicating sustained release. Ex-vivo permeation of pure ebastine was more rapid than from F6, thus indicating the capability of chitosan to control drug permeation rate through sheep nasal mucosa.Conclusion: The results indicate that a mucoadhesive nanoparticulate system can be used effectively for the nasal delivery of the antihistamine, ebastine.Keywords: Chitosan, Ebastine, Mucoadhesive, Nanoparticles, Ionotropic gelation, Permeation, Drug release, Poloxame
Self-stabilizing algorithms for Connected Vertex Cover and Clique decomposition problems
In many wireless networks, there is no fixed physical backbone nor
centralized network management. The nodes of such a network have to
self-organize in order to maintain a virtual backbone used to route messages.
Moreover, any node of the network can be a priori at the origin of a malicious
attack. Thus, in one hand the backbone must be fault-tolerant and in other hand
it can be useful to monitor all network communications to identify an attack as
soon as possible. We are interested in the minimum \emph{Connected Vertex
Cover} problem, a generalization of the classical minimum Vertex Cover problem,
which allows to obtain a connected backbone. Recently, Delbot et
al.~\cite{DelbotLP13} proposed a new centralized algorithm with a constant
approximation ratio of for this problem. In this paper, we propose a
distributed and self-stabilizing version of their algorithm with the same
approximation guarantee. To the best knowledge of the authors, it is the first
distributed and fault-tolerant algorithm for this problem. The approach
followed to solve the considered problem is based on the construction of a
connected minimal clique partition. Therefore, we also design the first
distributed self-stabilizing algorithm for this problem, which is of
independent interest
Class of self-limiting growth models in the presence of nonlinear diffusion
The source term in a reaction-diffusion system, in general, does not involve
explicit time dependence. A class of self-limiting growth models dealing with
animal and tumor growth and bacterial population in a culture, on the other
hand are described by kinetics with explicit functions of time. We analyze a
reaction-diffusion system to study the propagation of spatial front for these
models.Comment: RevTex, 13 pages, 5 figures. To appear in Physical Review
Species identification of Australian marsupials using collagen fingerprinting
The study of faunal remains from archaeological sites is often complicated by the presence of large numbers of highly fragmented, morphologically unidentifiable bones. In Australia, this is the combined result of harsh preservation conditions and frequent scavenging by marsupial carnivores. The collagen fingerprinting method known as zooarchaeology by mass spectrometry (ZooMS) offers a means to address these challenges and improve identification rates of fragmented bones. Here, we present novel ZooMS peptide markers for 24 extant marsupial and monotreme species that allow for genus-level distinctions between these species. We demonstrate the utility of these new peptide markers by using them to taxonomically identify bone fragments from a nineteenth-century colonial-era pearlshell fishery at Bandicoot Bay, Barrow Island. The suite of peptide biomarkers presented in this study, which focus on a range of ecologically and culturally important species, have the potential to significantly amplify the zooarchaeological and paleontological record of Australia.1. Introduction 2. Material and methods 2.1. Materials 2.1.1. Modern reference specimens 2.1.2. Archaeological specimens 2.2. Collagen extraction 2.3. Matrix-assisted laser desorption/ionizationâtandem time of flight mass spectrometry 2.4. Liquid chromatography with tandem mass spectrometry 2.5. Identification and confirmation of biomarkers 3. Results 3.1. Novel ZooMS peptide markers 3.2. Marsupial versus monotreme ZooMS markers 3.3. Marsupial ZooMS markers 3.4. Using ZooMS to identify macropods 3.5. Collagen fingerprinting of archaeological specimens 4. Discussion 4.1. ZooMS insights at Bandicoot Bay 4.2. Comparison to published markers 4.3. Challenges and future prospect
Probing the Inner Jet of the Quasar PKS 1510-089 with Multi-waveband Monitoring during Strong Gamma-ray Activity
We present results from monitoring the multi-waveband flux, linear
polarization, and parsec-scale structure of the quasar PKS 1510-089,
concentrating on eight major gamma-ray flares that occurred during the interval
2009.0-2009.5. The gamma-ray peaks were essentially simultaneous with maxima at
optical wavelengths, although the flux ratio of the two wavebands varied by an
order of magnitude. The optical polarization vector rotated by 720 degrees
during a 5-day period encompassing six of these flares. This culminated in a
very bright, roughly 1 day, optical and gamma-ray flare as a bright knot of
emission passed through the highest-intensity, stationary feature (the "core")
seen in 43 GHz Very Long Baseline Array images. The knot continued to propagate
down the jet at an apparent speed of 22c and emit strongly at gamma-ray
energies as a months-long X-ray/radio outburst intensified. We interpret these
events as the result of the knot following a spiral path through a mainly
toroidal magnetic field pattern in the acceleration and collimation zone of the
jet, after which it passes through a standing shock in the 43 GHz core and then
continues downstream. In this picture, the rapid gamma-ray flares result from
scattering of infrared seed photons from a relatively slow sheath of the jet as
well as from optical synchrotron radiation in the faster spine. The 2006-2009.7
radio and X-ray flux variations are correlated at very high significance; we
conclude that the X-rays are mainly from inverse Compton scattering of infrared
seed photons by 20-40 MeV electrons.Comment: 10 pages of text + 5 figures, to be published in Astrophysical
Journal Letters in 201
Partially Annealed Disorder and Collapse of Like-Charged Macroions
Charged systems with partially annealed charge disorder are investigated
using field-theoretic and replica methods. Charge disorder is assumed to be
confined to macroion surfaces surrounded by a cloud of mobile neutralizing
counterions in an aqueous solvent. A general formalism is developed by assuming
that the disorder is partially annealed (with purely annealed and purely
quenched disorder included as special cases), i.e., we assume in general that
the disorder undergoes a slow dynamics relative to fast-relaxing counterions
making it possible thus to study the stationary-state properties of the system
using methods similar to those available in equilibrium statistical mechanics.
By focusing on the specific case of two planar surfaces of equal mean surface
charge and disorder variance, it is shown that partial annealing of the
quenched disorder leads to renormalization of the mean surface charge density
and thus a reduction of the inter-plate repulsion on the mean-field or
weak-coupling level. In the strong-coupling limit, charge disorder induces a
long-range attraction resulting in a continuous disorder-driven collapse
transition for the two surfaces as the disorder variance exceeds a threshold
value. Disorder annealing further enhances the attraction and, in the limit of
low screening, leads to a global attractive instability in the system.Comment: 21 pages, 2 figure
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