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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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With increasing data rate and power density, high-performance memories have started to require dynamic thermal management (DTM), following the trend of processor and hard drive. There are also lack of a memory thermal model and si...
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With increasing data rate and power density, high-performance memories have started to require dynamic thermal management (DTM), following the trend of processor and hard drive. There are also lack of a memory thermal model and simulation tools to facilitate the research of memory DTM. This study investigates the approach of coordinating processor, which is the source of memory access requests, and memory to improve system performance and/or power efficiency during memory thermal emergency. Two such schemes, namely adaptive core gating (DTM-ACG) and coordinated DVFS (DTM-CDVFS), are proposed and evaluated on a real server platform. DTM-ACG gates processor cores and DTM-CDVFS scales down the frequency and voltage level of processor cores according to memory thermal emergency level. Their combination, namely DTM-COMB, is also evaluated. The experimental results show that the two schemes, while successfully controlling memory activities and handling thermal emergencies, improve performance significantly under the given thermal envelope. The measurement results from an Intel SR1500AL server testbed show that on average, DTM-ACG and DTM-CDVFS improve performance by 6.7 and 15.3 percent, respectively, over a prior memory bandwidth throttling scheme. DTM-CDVFS also reduces the processor power rate by 15.5 percent and system (including processor and memory) energy by 22.7 percent. Additionally, we propose a DRAM thermal model and validate it with measurement on the instrumented server platform. We find that our proposed model faithfully catches the dynamic DRAM temperature changes; the average difference between the modeled and measured temperature is less than $(1^{circ}{rm C})$.
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Web portal services have become an important medium to deliver digital content and service, such as news, advertisements, and so on, to Web users in a timely fashion. To attract more users to various content modules on the Web por...
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Web portal services have become an important medium to deliver digital content and service, such as news, advertisements, and so on, to Web users in a timely fashion. To attract more users to various content modules on the Web portal, it is necessary to design a recommender system that can effectively achieve online content optimization by automatically estimating content items' attractiveness and relevance to users' interests. User interaction plays a vital role in building effective content optimization, as both implicit user feedbacks and explicit user ratings on the recommended items form the basis for designing and learning recommendation models. However, user actions on real-world Web portal services are likely to represent many implicit signals about users' interests and content attractiveness, which need more accurate interpretation to be fully leveraged in the recommendation models. To address this challenge, we investigate a couple of critical aspects of the online learning framework for personalized content optimization on Web portal services, and, in this paper, we propose deeper user action interpretation to enhance those critical aspects. In particular, we first propose an approach to leverage historical user activity to build behavior-driven user segmentation; then, we introduce an approach for interpreting users' actions from the factors of both user engagement and position bias to achieve unbiased estimation of content attractiveness. Our experiments on the large-scale data from a commercial Web recommender system demonstrate that recommendation models with our user action interpretation can reach significant improvement in terms of online content optimization over the baseline method. The effectiveness of our user action interpretation is also proved by the online test results on real user traffic.
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A type of disruption/delay tolerant networks, known as pigeon networks, utilizes controllable special purpose vehicles called pigeons to convey messages among segregated areas. This paper aims to provide optimization methods for t...
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A type of disruption/delay tolerant networks, known as pigeon networks, utilizes controllable special purpose vehicles called pigeons to convey messages among segregated areas. This paper aims to provide optimization methods for the challenging problem that how a pigeon should design its route to minimize the average delay of messages. For small scale networks, we construct an exact optimization algorithm that shows significant reduction in delay over the existing heuristic algorithms. For large scale networks, we present both the lower bound and upper bound of the average delay, and devise partitioning-based optimization algorithms that perform close to the lower bound. Both theoretical analysis and numerical results show that the delay could be reduced by as much as 50% compared to the existing algorithm.
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A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St-MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) back...
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A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St-MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) backbones and poly(ethylene glycol) (PEG) side chains are synthesized as a type of non-viral gene vector. The copolymers self-assemble into spherical micelles in the aqueous media and turbidity and cytotoxicity measurements show that those micelles have excellent dispersive stability and low cytotoxicity. The interactions between the copolymers and calf-thymus DNA are studied by fluorescence spectroscopy and viscosity. The former discloses electrostatic interaction, hydrophobic interaction, and hydrogen bonding in the copolymer/DNA system, whereas the latter indicates that these graft copolymers can bind DNA via the electrostatic and classical intercalation modes. The DNA-binding capacity determined by the gel retardation assay and UV-visible spectrophotometry shows that the copolymers have good binding capacity to DNA and a high charge density or HFMA content in the copolymers bode well for DNA-binding. Transmission electron microscopy, photon correlation spectroscopy, and zeta potential data reveal that stable colloidal complexes (particles) can form easily between the copolymer micelles and DNA. Our results suggest that the copolymers are a promising non-viral vector in a gene delivery system.
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Little is known of how the Toll-like receptor (TLR) system can modulate the function of non-parenchymal liver cells (NPC) as a major component of the innate and adaptive immune system of the liver. To investigate the diversificati...
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Little is known of how the Toll-like receptor (TLR) system can modulate the function of non-parenchymal liver cells (NPC) as a major component of the innate and adaptive immune system of the liver. To investigate the diversification of TLR signalling pathways in NPC, we isolated Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC) from wild-type C57BL/6 mice and examined their responses to TLR1 to TLR9 agonists. The data show that KC respond to all TLR ligands by producing tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), to TLR3 and TLR4 ligands only by producing interferon-beta (IFN-beta), to TLR1 and TLR8 ligands by significantly up-regulating major histocompatibility complex (MHC) class II and costimulatory molecules, and to TLR1, -2, -4 and -6 ligands by inducing high levels of T-cell proliferation and IFN-gamma production in the mixed lymphocyte reaction (MLR). Similarly, LSEC respond to TLR1 to -4, -6, -8 and -9 ligands by producing TNF-alpha, to TLR3 and -4 ligands by producing IL-6, and to TLR3 ligands by producing IFN-beta. Interestingly, despite significant up-regulation of MHC class II and co-stimulatory molecules in response to TLR8 ligands, LSEC stimulated by TLR1, -2 or -6 could stimulate allogeneic T cells as assessed by MLR. By contrast, myeloid dendritic cells, used as positive control for classical antigen-presenting cells, respond to TLR1, -2, -4 and -9 ligands by both up-regulation of CD40 and activation of allogeneic T cells. In conclusion, NPC display a restricted TLR-mediated activation profile when compared with 'classical' antigen-presenting cells which may, at least in part, explain their tolerogenic function in the liver.
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OBJECTIVE: Polycythemia vera (PV) is characterized by erythrocytosis associated with the presence of the activating JAK2(V617F) mutation in a variable proportion of hematopoietic cells. JAK2(V617F) is detected in other myeloprolif...
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OBJECTIVE: Polycythemia vera (PV) is characterized by erythrocytosis associated with the presence of the activating JAK2(V617F) mutation in a variable proportion of hematopoietic cells. JAK2(V617F) is detected in other myeloproliferative neoplasms, does not appear to be the PV-initiating event, and its specific role in deregulated erythropoiesis in PV is incompletely understood. We investigated the pathogenesis of PV to characterize abnormal proliferation and apoptosis responses and aberrant oncogenic pathway activation in primary PV erythroid precursors. MATERIALS AND METHODS: Peripheral blood CD34(+) cells isolated from PV patients and healthy controls were grown in liquid culture to expand a population of primary erythroblasts for experiments designed to analyze cellular proliferation, apoptosis, JAK2(V617F) mutation status, cytokine-dependent protein phosphorylation and gene expression profiling using Affymetrix microarrays. RESULTS: The survival and proliferation of PV erythroblasts were growth factor-dependent under strict serum-free conditions requiring both erythropoietin (EPO) and stem cell factor. PV erythroblasts exhibited EPO hypersensitivity and enhanced cellular proliferation associated with increased EPO-mediated extracellular signal-regulated kinases 1 and 2 phosphorylation. EPO-induced AKT phosphorylation was observed in PV but not normal erythroblasts, an effect associated with apoptosis resistance in PV erythroblasts. Analysis of gene expression and oncogenic pathway activation signatures revealed increased RAS (p<0.01) and phosphoinositide-3 kinase (p<0.05) pathway activation in PV erythroblasts. CONCLUSION: Deregulated erythropoiesis in PV involves EPO hypersensitivity and apoptosis resistance of erythroid precursor cells associated with abnormally increased activation of RAS-ERK and phosphoinositide-3 kinase-AKT pathways. These data suggest that investigation of the mechanisms of abnormal RAS and phosphoinositide-3 kinase pathway activation in erythroblasts may contribute to our understanding of the molecular pathogenesis of PV.
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CDDO-Me, a synthetic triterpenoid derived from oleanolic acid, is a promising anticancer agent that has shown strong activity against a wide variety of cancer types in vitro and in vivo. We have previously shown that CDDO-Me induc...
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CDDO-Me, a synthetic triterpenoid derived from oleanolic acid, is a promising anticancer agent that has shown strong activity against a wide variety of cancer types in vitro and in vivo. We have previously shown that CDDO-Me induces apoptosis in prostate cancer cells irrespective of their hormonal status. To further understand the proapoptotic mechanism of CDDO-Me, we investigated the role of reactive oxygen species (ROS) in mediating the apoptosis inducing activity of CDDO-Me in LNCaP and PC-3 prostate cancer cell lines. Here, we show that CDDO-Me induces ROS generation from both nonmitochondrial and mitochondrial sources, which is associated with the induction of apoptosis as characterized by increased annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c. In addition, CDDO-Me inhibited cell survival Akt, NF-kappaB and mTOR signaling proteins. The inhibition of ROS generation by N-acetylcysteine (NAC) or by overexpression of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase-1 (SOD-1) prevented CDDO-Me-induced apoptosis. Pretreatment with NAC blocked annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c by CDDO-Me. NAC also prevented the inhibition of constitutively active Akt, NF-kappaB and mTOR by CDDO-Me. Together, these data indicate that ROS plays an essential role in the induction of apoptosis by CDDO-Me in prostate cancer cells.
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Mutation in the tubby gene causes adult-onset obesity, progressive retinal, and cochlear degeneration with unknown mechanism. In contrast, mutations in tubby-like protein 1 (Tulp1), whose C-terminus is highly homologous to tubby, ...
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Mutation in the tubby gene causes adult-onset obesity, progressive retinal, and cochlear degeneration with unknown mechanism. In contrast, mutations in tubby-like protein 1 (Tulp1), whose C-terminus is highly homologous to tubby, only lead to retinal degeneration. We speculate that their diverse N-terminus may define their distinct disease profile. To elucidate the binding partners of tubby, we used tubby N-terminus (tubby-N) as bait to identify unknown binding proteins with open-reading-frame (ORF) phage display. T7 phage display was engineered with three improvements: high-quality ORF phage display cDNA library, specific phage elution by protease cleavage, and dual phage display for sensitive high throughput screening. The new system is capable of identifying unknown bait-binding proteins in as fast as approximately 4-7 days. While phage display with conventional cDNA libraries identifies high percentage of out-of-frame unnatural short peptides, all 28 tubby-N-binding clones identified by ORF phage display were ORFs. They encode 16 proteins, including 8 nuclear proteins. Fourteen proteins were analyzed by yeast two-hybrid assay and protein pull-down assay with ten of them independently verified. Comparative binding analyses revealed several proteins binding to both tubby and Tulp1 as well as one tubby-specific binding protein. These data suggest that tubby-N is capable of interacting with multiple nuclear and cytoplasmic protein binding partners. These results demonstrated that the newly-engineered ORF phage display is a powerful technology to identify unknown protein-protein interactions.
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Iron-induced oxidative stress is thought to play a crucial role in the pathogenesis of Parkinson's disease (PD). Based on our previous in vivo experiments showing that down-regulation of the iron transporters ferroportin 1 (FP1) a...
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Iron-induced oxidative stress is thought to play a crucial role in the pathogenesis of Parkinson's disease (PD). Based on our previous in vivo experiments showing that down-regulation of the iron transporters ferroportin 1 (FP1) and hephaestin (HP) might account for the nigral iron accumulation in 6-hydroxydopamine (6-OHDA)-lesioned animal models, in this study we investigated whether FP1 and HP were involved in cellular iron accumulation and the underlying mechanisms in a cell model of PD. The findings showed that 6-OHDA induced FP1 and HP down-regulation, followed by decreased iron efflux and iron accumulation in primary ventral mesencephalic neurons and MES23.5 dopaminergic cells. Silencing of FP1 but not HP led to increased iron levels and aggravated reactive oxygen species generation in MES23.5 cells. Under iron-overloaded conditions, FP1 showed dose-dependent up-regulation, whereas HP showed no response, indicating their down-regulation was not due to the increased intracellular iron content. In 6-OHDA-treated cells, both iron-regulatory protein (IRP) 1 and IRP2 were up-regulated, and silencing of IRPs in MES23.5 cells dramatically blocked 6-OHDA-induced FP1 down-regulation and reversed HP down-regulation. These results suggest that FP1 but not HP contributes to 6-OHDA-induced intracellular iron accumulation, and down-regulation of FP1 and HP by 6-OHDA is IRPs-dependent.
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