548 research outputs found
Investigation of the Antiasthmatic Properties of Ethanol Extract of Callophyllis japonica in Mice
Purpose: To determine whether an ethanol extract from Callophyllis japonica (C. japonica) could attenuate indices of airway inflammation in a murine model of ovalbumin (OVA)-induced asthma.Methods: The free radical scavenging activity of the C. japonica ethanol extracts (CJE) were investigated using an electron spin resonance (ESR) system. To make develop animal model of asthma, mice were sensitized and challenged with OVA.Results: CJE exhibited considerable scavenging activity of 71.08 ± 0.73, 79.11 ± 6.04%, 75.95 ± 7.01%, and 48.56 ± 5.96% of DPPH, alkyl, superoxide, and hydroxyl radicals, respectively. The successive intraperitoneal administration of CJE reduced the number of eosinophils in bronchoalveolar lavage (BAL) fluid, development of airway hyperresponsiveness (AHR), an increase in pulmonary Th2 cytokines, and allergen-specific immunoglobulin E (IgE).Conclusion: Administration of CJE markedly alleviates all indices of airway inflammation. This study provides evidence that CJE plays a critical role in the amelioration of the pathogenetic process of allergic asthma in mice.Keywords: Asthma, Phenolic contents, Free radical scavenging, Airway hyper-responsiveness, Cytokines, Immunoglobulin
Strong and Tunable Nonlinear Optomechanical Coupling in a Low-Loss System
A major goal in optomechanics is to observe and control quantum behavior in a
system consisting of a mechanical resonator coupled to an optical cavity. Work
towards this goal has focused on increasing the strength of the coupling
between the mechanical and optical degrees of freedom; however, the form of
this coupling is crucial in determining which phenomena can be observed in such
a system. Here we demonstrate that avoided crossings in the spectrum of an
optical cavity containing a flexible dielectric membrane allow us to realize
several different forms of the optomechanical coupling. These include cavity
detunings that are (to lowest order) linear, quadratic, or quartic in the
membrane's displacement, and a cavity finesse that is linear in (or independent
of) the membrane's displacement. All these couplings are realized in a single
device with extremely low optical loss and can be tuned over a wide range in
situ; in particular, we find that the quadratic coupling can be increased three
orders of magnitude beyond previous devices. As a result of these advances, the
device presented here should be capable of demonstrating the quantization of
the membrane's mechanical energy.Comment: 12 pages, 4 figures, 1 tabl
Cloud computing and validation of expandable in silico livers
<p>Abstract</p> <p>Background</p> <p>In Silico Livers (ISLs) are works in progress. They are used to challenge multilevel, multi-attribute, mechanistic hypotheses about the hepatic disposition of xenobiotics coupled with hepatic responses. To enhance ISL-to-liver mappings, we added discrete time metabolism, biliary elimination, and bolus dosing features to a previously validated ISL and initiated re-validated experiments that required scaling experiments to use more simulated lobules than previously, more than could be achieved using the local cluster technology. Rather than dramatically increasing the size of our local cluster we undertook the re-validation experiments using the Amazon EC2 cloud platform. So doing required demonstrating the efficacy of scaling a simulation to use more cluster nodes and assessing the scientific equivalence of local cluster validation experiments with those executed using the cloud platform.</p> <p>Results</p> <p>The local cluster technology was duplicated in the Amazon EC2 cloud platform. Synthetic modeling protocols were followed to identify a successful parameterization. Experiment sample sizes (number of simulated lobules) on both platforms were 49, 70, 84, and 152 (cloud only). Experimental indistinguishability was demonstrated for ISL outflow profiles of diltiazem using both platforms for experiments consisting of 84 or more samples. The process was analogous to demonstration of results equivalency from two different wet-labs.</p> <p>Conclusions</p> <p>The results provide additional evidence that disposition simulations using ISLs can cover the behavior space of liver experiments in distinct experimental contexts (there is in silico-to-wet-lab phenotype similarity). The scientific value of experimenting with multiscale biomedical models has been limited to research groups with access to computer clusters. The availability of cloud technology coupled with the evidence of scientific equivalency has lowered the barrier and will greatly facilitate model sharing as well as provide straightforward tools for scaling simulations to encompass greater detail with no extra investment in hardware.</p
On dynamic network entropy in cancer
The cellular phenotype is described by a complex network of molecular
interactions. Elucidating network properties that distinguish disease from the
healthy cellular state is therefore of critical importance for gaining
systems-level insights into disease mechanisms and ultimately for developing
improved therapies. By integrating gene expression data with a protein
interaction network to induce a stochastic dynamics on the network, we here
demonstrate that cancer cells are characterised by an increase in the dynamic
network entropy, compared to cells of normal physiology. Using a fundamental
relation between the macroscopic resilience of a dynamical system and the
uncertainty (entropy) in the underlying microscopic processes, we argue that
cancer cells will be more robust to random gene perturbations. In addition, we
formally demonstrate that gene expression differences between normal and cancer
tissue are anticorrelated with local dynamic entropy changes, thus providing a
systemic link between gene expression changes at the nodes and their local
network dynamics. In particular, we also find that genes which drive
cell-proliferation in cancer cells and which often encode oncogenes are
associated with reductions in the dynamic network entropy. In summary, our
results support the view that the observed increased robustness of cancer cells
to perturbation and therapy may be due to an increase in the dynamic network
entropy that allows cells to adapt to the new cellular stresses. Conversely,
genes that exhibit local flux entropy decreases in cancer may render cancer
cells more susceptible to targeted intervention and may therefore represent
promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte
Gas nitriding and subsequent oxidation of Ti-6Al-4V alloys
Ti-6Al-4V alloys consisting of α-Ti grains and intergranular β-Ti islands were nitrided at 850°C for 1 to 12 h under a nitrogen pressure of 1 Pa. With increasing nitriding time, the Ti-N compound layer became thicker, and the α-Ti diffusion zone containing dissolved nitrogen became wider. In the Ti-N compound layer, the initially formed Ti2N became TiN as the nitriding progressed. The nitride layers were oxidized to rutile-TiO2 after oxidation at 700°C for 10 h in air
Structure and mechanism of human DNA polymerase η
The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites
Fabrication of Highly Ordered Polymeric Nanodot and Nanowire Arrays Templated by Supramolecular Assembly Block Copolymer Nanoporous Thin Films
Realizing the vast technological potential of patternable block copolymers requires both the precise controlling of the orientation and long-range ordering, which is still a challenging topic so far. Recently, we have demonstrated that ordered nanoporous thin film can be fabricated from a simple supramolecular assembly approach. Here we will extend this approach and provide a general route to fabricate large areas of highly ordered polymeric nanodot and nanowire arrays. We revealed that under a mixture solvent annealing atmosphere, a near-defect-free nanoporous thin film over large areas can be achieved. Under the direction of interpolymer hydrogen bonding and capillary action of nanopores, this ordered porous nanotemplate can be properly filled with phenolic resin precursor, followed by curation and pyrolysis at middle temperature to remove the nanotemplate, a perfect ordered polymer nanodot arrays replication was obtained. The orientation of the supramolecular assembly thin films can be readily re-aligned parallel to the substrate upon exposure to chloroform vapor, so this facile nanotemplate replica method can be further extend to generate large areas of polymeric nanowire arrays. Thus, we achieved a successful sub-30 nm patterns nanotemplates transfer methodology for fabricating polymeric nanopattern arrays with highly ordered structure and tunable morphologies
Identification of Methanoculleus spp. as active methanogens during anoxic incubations of swine manure storage tank samples
Methane emissions represent a major environmental concern associated with manure management in the livestock industry. A more thorough understanding of how microbial communities function in manure storage tanks is a prerequisite for mitigating methane emissions. Identifying the microorganisms that are metabolically active is an important first step. Methanogenic archaea are major contributors to methanogenesis in stored swine manure, and we investigated active methanogenic populations by DNA stable isotope probing (DNA-SIP). Following a preincubation of manure samples under anoxic conditions to induce substrate starvation, [U-¹³C] acetate was added as a labeled substrate. Fingerprint analysis of density-fractionated DNA, using length-heterogeneity analysis of PCR-amplified mcrA genes (encoding the alpha subunit of methyl coenzyme M reductase), showed that the incorporation of ¹³C into DNA was detectable at in situ acetate concentrations (~7g/liter). Fingerprints of DNA retrieved from heavy fractions of the ¹³C treatment were primarily enriched in a 483-bp amplicon and, to a lesser extent, in a 481-bp amplicon. Analyses based on clone libraries of the mcrA and 16S rRNA genes revealed that both of these heavy DNA amplicons corresponded to Methanoculleus spp. Our results demonstrate that uncultivated methanogenic archaea related to Methanoculleus spp. were major contributors to acetate-C assimilation during the anoxic incubation of swine manure storage tank samples. Carbon assimilation and dissimilation rate estimations suggested that Methanoculleus spp. were also major contributors to methane emissions and that the hydrogenotrophic pathway predominated during methanogenesis
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