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A continuum mechanics model is established for hydrogen storage in single- and multi-wall carbon nanotubes (CNTs) and the bundle of single-wall CNTs. The model accounts for the deformation of CNTs, and van der Waals interactions a...
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A continuum mechanics model is established for hydrogen storage in single- and multi-wall carbon nanotubes (CNTs) and the bundle of single-wall CNTs. The model accounts for the deformation of CNTs, and van der Waals interactions among hydrogen molecules and between hydrogen and carbon atoms. The analytical expressions of hydrogen storage (number of hydrogen molecules per unit volume) in CNTs are obtained, and are validated by atomistic simulations. CNTs are categorized as tiny, small, medium and large CNTs; tiny CNTs cannot achieve the goals of hydrogen storage (62 kg/m~3 and 6.5 wt% of hydrogen set by the US Department of Energy) without fracture; small CNTs are strained during hydrogen storage; medium CNTs can achieve the above goals without the strain and do not self collapse; and large CNTs may self collapse upon the release of hydrogen.
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Modulation of the vascular smooth-muscle-cell (vSMC) phenotype from a quiescent 'contractile' phenotype to a proliferative 'synthetic' phenotype has been implicated in vascular injury repair, as well as pathogenesis of vascular pr...
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Modulation of the vascular smooth-muscle-cell (vSMC) phenotype from a quiescent 'contractile' phenotype to a proliferative 'synthetic' phenotype has been implicated in vascular injury repair, as well as pathogenesis of vascular proliferative diseases. Both bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFbeta)-signalling pathways promote a contractile phenotype, while the platelet-derived growth factor-BB (PDGF-BB)-signalling pathway promotes a switch to the synthetic phenotype. Here we show that PDGF-BB induces microRNA-24 (miR-24), which in turn leads to downregulation of Tribbles-like protein-3 (Trb3). Repression of Trb3 coincides with reduced expression of Smad proteins and decrease in BMP and TGFbeta signalling, promoting a synthetic phenotype in vSMCs. Inhibition of miR-24 by antisense oligonuclotides abrogates the downregulation of Trb3 as well as pro-synthetic activity of the PDGF-signalling pathway. Thus, this study provides a molecular basis for the antagonism between the PDGF and TGFbeta pathways, and its effect on the control of the vSMC phenotype.
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This paper presents a new approach for solving accurate approximate analytical higher-order solutions for strong nonlinear Duffing oscillators with cubic-quintic nonlinear restoring force. The system is conservative and with odd n...
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This paper presents a new approach for solving accurate approximate analytical higher-order solutions for strong nonlinear Duffing oscillators with cubic-quintic nonlinear restoring force. The system is conservative and with odd non-linearity. The new approach couples Newton's method with harmonic balancing. Unlike the classical harmonic balance method, accurate analytical approximate solutions are possible because linearization of the governing differential equation by Newton's method is conducted prior to harmonic balancing. The approach yields simple linear algebraic equations instead of nonlinear algebraic equations without analytical solution. Using the approach, accurate higher-order approximate analytical expressions for period and periodic solution are established. These approximate solutions are valid for small as well as large amplitudes of oscillation. In addition, it is not restricted to the presence of a small parameter such as in the classical perturbation method. Illustrative examples are presented to verify accuracy and explicitness of the approximate solutions. The effect of strong quintic nonlinearity on accuracy as compared to cubic nonlinearity is also discussed.
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A comprehensive numerical study of the equivalent thermal conductivity of a multi-holed clay brick with the size of 240 × 115 × 90 (in mm) has been conducted, and 50 kinds of combination of holes and arrangements are examined. T...
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A comprehensive numerical study of the equivalent thermal conductivity of a multi-holed clay brick with the size of 240 × 115 × 90 (in mm) has been conducted, and 50 kinds of combination of holes and arrangements are examined. The indoor-outdoor temperature difference varies from 50 ℃ to 20 ℃. The effects of following factors are studied in details: the hole surface radiation, the width-wise and length-wise hole numbers, and the indoor-outdoor temperature difference. The major findings are as follows: (1) the radiation between hole surfaces has some effect on the equivalent thermal conductivity, thus it should be taken into account; (2) the hole number and arrangement affect the thermal conductivity in a rather complicated manner. Analysis shows that depending on the relative importance of natural convection, surface radiation and heat conduction through the clay solid, the thermal conductivity may decrease with the hole number or increase with the hole number and (3) among the 50 kinds of combination, the optimum configuration is found which has five length-wise holes, four width-wise holes and all the holes are from bottom to top in the depth direction of a brick. Its equivalent thermal conductivity is 0.419 W/(m K), which is only 53.1% of solid clay of which it is made, showing great energy-saving possibility if it is adopted in the construction of building wall.
Detailed discussion of the simulated results is conducted and flow field and temperature distributions are also provided for some typical configurations.
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ABSTRACT Background: Dexlansoprazole MR is a novel Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to prolong the plasma concentration-time profile of dexlansoprazole and extend duratio...
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ABSTRACT Background: Dexlansoprazole MR is a novel Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to prolong the plasma concentration-time profile of dexlansoprazole and extend duration of acid suppression with once-daily (QD) dosing. Objectives: To assess the pharmacokinetics and pharmacodynamics of dexlansoprazole at different doses of dexlansoprazole MR and delineate the exposure-response relationship following oral administration of dexlansoprazole MR. Methods: Dexlansoprazole MR was evaluated in two prospective randomized studies in healthy subjects. In study 1 (n = 40), subjects received dexlansoprazole MR 60, 90, and 120 mg and lansoprazole 30 mg QD. In study 2 (n = 45), subjects received dexlansoprazole MR 30 and 60 mg and lansoprazole 15 mg QD. Data from these trials were pooled and analyzed to describe the relationship between intragastric pH and dexlansoprazole systemic exposure. Results: Data from 83 subjects were analyzed. The dexlansoprazole plasma concentration-time profile following administration of dexlansoprazole MR was characterized by two distinct peaks and a prolonged drug exposure during the 24-h dosing interval. Approximate dose proportionality was observed for mean peak plasma concentration and area under the plasma-concentration time curve after administration of dexlansoprazole MR. In each study, doses of dexlansoprazole MR generally produced greater gastric acid suppression than lansoprazole. Based on the exposure-response analysis using combined data from these two trials, the predicted mean 24-h intragastric pH values were 4.06 and 4.35 for the dexlansoprazole MR 30- and 90-mg doses, respectively. The percent of time pH > 4 over 24 h values were 59.2% and 66.7% for dexlansoprazole MR 30 and 90 mg, respectively. No appreciable additional gain in the pharmacodynamic response was predicted for dexlansoprazole MR 120 mg. Despite combining data from two studies to evaluate a broader dose range, this analysis provided a reasonable estimate of the pharmacodynamic parameters and a good characterization of the dexlansoprazole MR exposure-response relationship. Conclusions: Dexlansoprazole MR, a proton pump inhibitor that uses Dual Delayed Release technology, produced a pharmacokinetic profile with a plasma concentration-time curve characterized by two distinct peaks and an extended duration of pharmacologically active dexlansoprazole concentration in plasma. Exposure-response analysis indicated a progressive increase in the pharmacodynamic response as dexlansoprazole MR doses increased from 30 to 90 mg.
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Glycogen synthase kinase 3beta (GSK-3beta) is a ubiquitous serine/threonine protein kinase involved in a number of signaling pathways. Previous studies have demonstrated a role for GSK-3beta in the synaptic plasticity underlying d...
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Glycogen synthase kinase 3beta (GSK-3beta) is a ubiquitous serine/threonine protein kinase involved in a number of signaling pathways. Previous studies have demonstrated a role for GSK-3beta in the synaptic plasticity underlying dopamine-associated behaviors and diseases. Drug sensitization is produced by repeated exposure to the drug and is thought to reflect neuroadaptations that contribute to addiction. However, the role of GSK-3beta in cocaine-induced behavior sensitization has not been examined. The present study investigated the effects of chronic cocaine exposure on GSK-3beta activity in the nucleus accumbens (NAc) and determined whether changes in GSK-3beta activity in the NAc are associated with cocaine-induced locomotor sensitization. We also explored whether blockade of GSK-3beta activity in the NAc inhibits the initiation and expression of cocaine-induced locomotor sensitization in rats using systemic or brain region-specific administration of the GSK-3beta inhibitors lithium chloride (LiCl) and SB216763. GSK-3beta activity in the NAc core, but not NAc shell, increased after chronic cocaine (10 mg/kg, i.p.) administration. The initiation and expression of cocaine-induced locomotor sensitization was attenuated by systemic administration of LiCl (100 mg/kg, i.p.) or direct infusion of SB216763 (1 ng/side) into the NAc core, but not NAc shell. Collectively, these results indicate that GSK-3beta activity in the NAc core, but not NAc shell, mediates the initiation and expression of cocaine-induced locomotor sensitization, suggesting that GSK-3beta may be a potential target for the treatment of cocaine addiction.
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Some forms of seizure activity can be stopped by gap junctional (GJ) blockade. Here, we found that GJ blockers attenuate hippocampal seizure activity induced by a novel seizuregenic protocol using Co(2+). We hypothesized that this...
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Some forms of seizure activity can be stopped by gap junctional (GJ) blockade. Here, we found that GJ blockers attenuate hippocampal seizure activity induced by a novel seizuregenic protocol using Co(2+). We hypothesized that this activity may occur because of the altered expression of connexin (Cx) and/or pannexin (Panx) mRNAs and protein. We found a 1.5-, 1.4-, and 2-fold increase in Panx1, Panx2, and Cx43 mRNAs, respectively. Significant post-translational modifications of the proteins Cx43 and Panx1 were also observed after the Co(2+) treatment. No changes were observed in the presence of tetrodotoxin, indicating that seizure activity is required for these alterations in expression, rather than the Co(2+) treatment itself. Further analysis of the QPCR data showed that the Cx and Panx transcriptome becomes remarkably re-organized. Pannexin (Panxs 1 and 2) and glial connexin mRNA became highly correlated to one another; suggesting that these genes formed a transcriptomic network of coordinated gene expression, perhaps facilitating seizure induction. These data show that seizure activity up-regulates the expression of both glial and neuronal GJ mRNAs and protein while inducing a high degree of coordinate expression of the GJ transcriptome.
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Ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) are the two most important routes for degradation of aggregated/misfolded proteins. Additionally, ALP is so far the only known route to clear entire organelles...
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Ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) are the two most important routes for degradation of aggregated/misfolded proteins. Additionally, ALP is so far the only known route to clear entire organelles, such as mitochondria. We proposed that enhancement of ALP may be beneficial for some neurodegenerative disorders, such as Parkinson's disease (PD), in which the accumulation of aggregated/misfolded proteins and the dysfunction of mitochondria are the two major pathogenesis. Mitochondrial complex I inhibitor rotenone, which causes dysfunction mitochondria and UPS, has been considered as one of the neurotoxins related to PD. In this study, rotenone-exposed human neuronal SH-SY5Y cells were used as an in vitro model for us to determine whether autophagy enhancer rapamycin could protect against rotenone-induced injury and its underlying mechanisms. The observed results showed that rapamycin alleviated rotenone-induced apoptosis, whose effects were partially blocked when autophagy related gene 5 (Atg5) was suppressed by Atg5 small interference RNA (siRNA) transfection. Additionally, the results showed that rapamycin pretreatment diminished rotenone-induced accumulation of high molecular weight ubiquitinated bands, and reduced rotenone-induced increase of cytochrome c in cytosolic fraction and decreased mitochondrial marker cytochrome oxidase subunit IV (COX IV) in mitochondrial fraction. The changes in cytochrome c and COX IV indicated that the decreased translocation of cytochrome c from mitochondria to cytosol was probably due to the turn over of entire injured mitochondria. The results that lysosome and mitochondria were colocolized within the cells pretreated with rapamycin and that the mitochondria could be found within autophagy double membrane structures further supported that the damaged mitochondria might be cleared through autophagy, which process has been termed as "mitophagy." Our studies suggested that autophagy enhancer rapamycin is neuroprotective against rotenone-induced apoptosis through autophagy enhancement. We concluded that pharmacologically induction of autophagy by rapamycin may represent a useful therapeutic strategy as disease-modifiers in PD.
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Abstract The nitrones of alpha-phenyl-tert-butyl nitrone (PBN) and 4-hydroxyl-PBN (4-OH-PBN) that have anti-cancer activity in models of liver cancer and glioblastomas were tested in the ApcMin/+ mouse model. Mice were administere...
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Abstract The nitrones of alpha-phenyl-tert-butyl nitrone (PBN) and 4-hydroxyl-PBN (4-OH-PBN) that have anti-cancer activity in models of liver cancer and glioblastomas were tested in the ApcMin/+ mouse model. Mice were administered PBN and 4-OH-PBN in drinking water and intestinal tumour size and number assessed after 3-4 months. Throughout the experiment, contrast-enhanced magnetic resonance imaging (MRI) was used to monitor colon tumours. MRI data showed a time-dependent significant increase in total colonic signal intensity in sham-treated mice, but a significant decrease for PBN-treated mice and slight decrease for 4-OHPBN treated mice, probably due to the limited water solubility of 4-OH-PBN. Final pathological and percentage survival data agreed with the MRI data. PBN had little effect on oxaliplatin-mediated killing of HCT116 colon cancer cells and caused only a slight decrease in the amount of active fraction caspase 3 in oxaliplatin-treated cells. PBN has significant anti-cancer activity in this model of intestinal neoplasia.
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Resveratrol is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Sulforaphane belongs to the family of isothiocyanates and is highly enriched in cruciferous ve...
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Resveratrol is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Sulforaphane belongs to the family of isothiocyanates and is highly enriched in cruciferous vegetables. Our previous study showed that resveratrol, when used at high concentrations, inhibited cell proliferation, caused the cell cycle arrest and induced apoptotic cell death in glioma cells. In the current study, we tested the effect of combination treatment with resveratrol and sulforaphane, when both were used at low concentrations, on cell proliferation, migration and death in human U251 glioma cells. Our study shows that combination treatment with resveratrol and sulforaphane inhibits cell proliferation and migration, reduces cell viability, induces lactate dehydrogenase release, decreases pro-survival Akt phosphorylation and increases caspase-3 activation. The use of combination of bioactive food components, such as resveratrol and sulforaphane, may be a viable approach for the treatment of glioma.
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