203 research outputs found

    A robust Logistics-Electric framework for optimal power management of electrified ports under uncertain vessel arrival time

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    \ua9 2024Maritime transport is responsible for producing a considerable amount of environmental pollution due to the reliance of ports and ships on the carbon-based energy sources. With the increasing trend towards port electrification to reduce carbon emissions, the operation of ports will be increasingly relying on the electricity network. This interconnection creates multiple challenges due to the complexity of power flow in the port network, uncertainty of vessel arrival time and fluctuation of power generation of renewable energy sources. These uncertainties can lead to an overload in electricity networks and delays in cargo-handling activities, resulting in increased vessel handling times and environmental emissions. This paper presents a joint logistics-electric framework for optimal operation and power management of electrified ports, considering multiple uncertainties in the arrival time of vessels, network demand, and renewable power generation. An optimal power flow method is developed for a real-life port, with consideration for multiple port logistic assets such as cargo handling equipment, reefers, and renewable energy sources. The proposed model ensures feasible port operation for all uncertainty realisations defined by robust optimisation, while minimising operational costs. Simulation results demonstrate that the probability of a network constraint violation can be as high as 70% for an electrified major UK port if the uncertainty in the port operation is neglected, presenting an unacceptable risk of disruption to port activities. Furthermore, such uncertainty can cause 150% increase in emissions if the ships use their auxiliary engine instead of using shore power. The numerical study shows that such challenges can be handled by a 0.3% increase in the robustness in face of uncertainty, while the cost increase in the worst case does not exceed 4.7%. This shows the effectiveness of the proposed method enhancing robustness against uncertainty at the minimum cost

    NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts

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    Cancer stem cells (CSCs) are thought to be critical for the engraftment and long-term growth of many tumors, including glioblastoma (GBM). The cells are at least partially spared by traditional chemotherapies and radiation therapies, and finding new treatments that can target CSCs may be critical for improving patient survival. It has been shown that the NOTCH signaling pathway regulates normal stem cells in the brain, and that GBMs contain stem-like cells with higher NOTCH activity. We therefore used low-passage and established GBM-derived neurosphere cultures to examine the overall requirement for NOTCH activity, and also examined the effects on tumor cells expressing stem cell markers. NOTCH blockade by gamma-secretase inhibitors (GSIs) reduced neurosphere growth and clonogenicity in vitro, whereas expression of an active form of NOTCH2 increased tumor growth. The putative CSC markers CD133, NESTIN, BMI1, and OLIG2 were reduced following NOTCH blockade. When equal numbers of viable cells pretreated with either vehicle (dimethyl sulfoxide) or GSI were injected subcutaneously into nude mice, the former always formed tumors, whereas the latter did not. In vivo delivery of GSI by implantation of drug-impregnated polymer beads also effectively blocked tumor growth, and significantly prolonged survival, albeit in a relatively small cohort of animals. We found that NOTCH pathway inhibition appears to deplete stem-like cancer cells through reduced proliferation and increased apoptosis associated with decreased AKT and STAT3 phosphorylation. In summary, we demonstrate that NOTCH pathway blockade depletes stem-like cells in GBMs, suggesting that GSIs may be useful as chemotherapeutic reagents to target CSCs in malignant gliomas

    Influence of surface geometry on the culture of human cell lines: a comparative study using flat, round-bottom and v-shaped 96 well plates

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    © 2017 Shafaie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.In vitro cell based models have been invaluable tools for studying cell behaviour and for investigating drug disposition, toxicity and potential adverse effects of administered drugs. Within this drug discovery pipeline, the ability to assess and prioritise candidate compounds as soon as possible offers a distinct advantage. However, the ability to apply this approach to a cell culture study is limited by the need to provide an accurate, in vitro-like, microenvironment in conjunction with a low cost and high-throughput screening (HTS) methodology. Although the geometry and/or alignment of cells has been reported to have a profound influence on cell growth and differentiation, only a handful of studies have directly compared the growth of a single cell line on different shaped multiwell plates the most commonly used substrate for HTS, in vitro, studies. Herein, the impact of various surface geometries (flat, round and v-shaped 96 well plates), as well as fixed volume growth media and fixed growth surface area have been investigated on the characteristics of three commonly used human cell lines in biopharmaceutical research and development, namely ARPE-19 (retinal epithelial), A549 (alveolar epithelial) and Malme-3M (dermal fibroblastic) cells. The effect of the surface curvature on cells was characterised using a combination of a metabolic activity assay (CellTiter AQ/MTS), LDH release profiles (CytoTox ONE) and absolute cell counts (Guava ViaCount), respectively. In addition, cell differentiation and expression of specific marker proteins were determined using flow cytometry. These in vitro results confirmed that surface topography had a significant effect (p < 0.05) on cell activity and morphology. However, although specific marker proteins were expressed on day 1 and 5 of the experiment, no significant differences were seen between the different plate geometries (p < 0.05) at the later time point. Accordingly, these results highlight the impact of substrate geometry on the culture of a cell line and the influence it has on the cells' correct growth and differentiation characteristics. As such, these results provide important implications in many aspects of cell biology the development of a HTS, in vitro, cell based systems to further investigate different aspects of toxicity testing and drug delivery.Peer reviewedFinal Published versio

    BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors

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    <p>Abstract</p> <p>Background</p> <p>The prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare.</p> <p>Methods</p> <p>We performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m<sup>2 </sup>BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model.</p> <p>Results</p> <p>The median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off).</p> <p>Conclusion</p> <p>In summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.</p

    Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

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    We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)

    Fungal Planet description sheets: 785– 867

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    Novel species of fungi described in this study include those from various countries as follows: Angola, Gnomoniopsis angolensis and Pseudopithomyces angolensis on unknown host plants. Australia, Dothiora corymbiae on Corymbia citriodora, Neoeucasphaeria eucalypti (incl. Neoeucasphaeria gen. nov.)on Eucalyptus sp., Fumagopsis stellae on Eucalyptus sp., Fusculina eucalyptorum (incl. Fusculinaceae fam. nov.) on Eucalyptus socialis, Harknessia corymbiicola on Corymbia maculata, Neocelosporium eucalypti (incl. Neocelosporium gen. nov., Neocelosporiaceae fam. nov. and Neocelosporiales ord. nov.) on Eucalyptus cyanophylla, Neophaeomoniella corymbiae on Corymbia citriodora, Neophaeomoniella eucalyptigena on Eucalyptus pilularis, Pseudoplagiostoma corymbiicola on Corymbia citriodora, Teratosphaeria gracilis on Eucalyptus gracilis, Zasmidium corymbiae on Corymbia citriodora. Brazil, Calonectria hemileiae on pustules of Hemileia vastatrix formed on leaves of Coffea arabica, Calvatia caatinguensis on soil, Cercospora solani-betacei on Solanum betaceum, Clathrus natalensis on soil, Diaporthe poincianellae on Poincianella pyramidalis, Geastrum piquiriunense on soil, Geosmithia carolliae on wing of Carollia perspicillata, Henningsia resupinata on wood, Penicillium guaibinense from soil, Periconia caespitosa from leaf litter, Pseudocercospora styracina on Styrax sp., Simplicillium filiforme as endophyte from Citrullus lanatus, Thozetella pindobacuensis on leaf litter, Xenosonderhenia coussapoae on Coussapoa floccosa. Canary Islands (Spain), Orbilia amarilla on Euphorbia canariensis. Cape Verde Islands, Xylodon jacobaeus on Eucalyptus camaldulensis. Chile, Colletotrichum arboricola on Fuchsia magellanica. Costa Rica, Lasiosphaeria miniovina ontreebranch. Ecuador, Ganoderma chocoense ontreetrunk. France, Neofitzroyomyces nerii (incl. Neofitzroyomyces gen. nov.) on Nerium oleander. Ghana, Castanediella tereticornis on Eucalyptus tereticornis, Falcocladium africanum on Eucalyptus brassiana, Rachicladosporium corymbiae on Corymbia citriodora. Hungary, Entoloma silvae-frondosae in Carpinus betulus-Pinus sylvestris mixedforest. Iran, Pseudopyricularia persiana on Cyperus sp. Italy, Inocybe roseascens onsoilinmixedforest. Laos, Ophiocordyceps houaynhangensis on Coleoptera larva. Malaysia, Monilochaetes melastomae on Melastoma sp. Mexico, Absidia terrestris fromsoil. Netherlands, Acaulium pannemaniae, Conioscypha boutwelliae, Fusicolla septimanifiniscientiae, Gibellulopsis simonii, Lasionectria hilhorstii, Lectera nordwiniana, Leptodiscella rintelii, Parasarocladium debruynii and Sarocladium dejongiae (incl. Sarocladiaceae fam. nov.) fromsoil. New Zealand, Gnomoniopsis rosae on Rosa sp. and Neodevriesia metrosideri on Metrosideros sp. Puerto Rico, Neodevriesia coccolobae on Coccoloba uvifera, Neodevriesia tabebuiae and Alfaria tabebuiae on Tabebuia chrysantha . Russia, Amanita paludosa on bogged soil in mixed deciduous forest, Entoloma tiliae in forest of Tilia Ă— europaea, Kwoniella endophytica on Pyrus communis. South Africa, Coniella diospyri on Diospyros mespiliformis, Neomelanconiella combreti (incl. Neomelanconiellaceae fam. nov. and Neomelanconiella gen. nov.)on Combretum sp., Polyphialoseptoria natalensis on unidentified plant host, Pseudorobillarda bolusanthi on Bolusanthus speciosus, Thelonectria pelargonii on Pelargonium sp. Spain, Vermiculariopsiella lauracearum and Anungitopsis lauri on Laurus novocanariensis, Geosmithia xerotolerans from a darkened wall of a house, Pseudopenidiella gallaica on leaf litter. Thailand, Corynespora thailandica on wood, Lareunionomyces loeiensis on leaf litter, Neocochlearomyces chromolaenae (incl. Neocochlearomyces gen. nov.) on Chromolaena odorata, Neomyrmecridium septatum (incl. Neomyrmecridium gen. nov .), Pararamichloridium caricicola on Carex sp., Xenodactylaria thailandica (incl. Xenodactylariaceae fam. nov. and Xenodactylaria gen. nov.), Neomyrmecridium asiaticum and Cymostachys thailandica fromunidentifiedvine. USA, Carolinigaster bonitoi (incl. Carolinigaster gen. nov.)fromsoil, Penicillium fortuitum from house dust, Phaeotheca shathenatiana (incl. Phaeothecaceae fam. nov.) from twig and cone litter, Pythium wohlseniorum from stream water, Superstratomyces tardicrescens from human eye, Talaromyces iowaense from officeair. Vietnam, Fistulinella olivaceoalba onsoil. Morphological and culture characteristics along with DNA barcodes are provided Novel species of fungi described in this study include those from various countries as follows: Angola, Gnomoniopsis angolensis and Pseudopithomyces angolensis on unknown host plants. Australia, Dothiora corymbiae on Corymbia citriodora, Neoeucasphaeria eucalypti (incl. Neoeucasphaeria gen. nov.)on Eucalyptus sp., Fumagopsis stellae on Eucalyptus sp., Fusculina eucalyptorum (incl. Fusculinaceae fam. nov.) on Eucalyptus socialis, Harknessia corymbiicola on Corymbia maculata, Neocelosporium eucalypti (incl. Neocelosporium gen. nov., Neocelosporiaceae fam. nov. and Neocelosporiales ord. nov.) on Eucalyptus cyanophylla, Neophaeomoniella corymbiae on Corymbia citriodora, Neophaeomoniella eucalyptigena on Eucalyptus pilularis, Pseudoplagiostoma corymbiicola on Corymbia citriodora, Teratosphaeria gracilis on Eucalyptus gracilis, Zasmidium corymbiae on Corymbia citriodora. Brazil, Calonectria hemileiae on pustules of Hemileia vastatrix formed on leaves of Coffea arabica, Calvatia caatinguensis on soil, Cercospora solani-betacei on Solanum betaceum, Clathrus natalensis on soil, Diaporthe poincianellae on Poincianella pyramidalis, Geastrum piquiriunense on soil, Geosmithia carolliae on wing of Carollia perspicillata, Henningsia resupinata on wood, Penicillium guaibinense from soil, Periconia caespitosa from leaf litter, Pseudocercospora styracina on Styrax sp., Simplicillium filiforme as endophyte from Citrullus lanatus, Thozetella pindobacuensis on leaf litter, Xenosonderhenia coussapoae on Coussapoa floccosa. Canary Islands (Spain), Orbilia amarilla on Euphorbia canariensis. Cape Verde Islands, Xylodon jacobaeus on Eucalyptus camaldulensis. Chile, Colletotrichum arboricola on Fuchsia magellanica. Costa Rica, Lasiosphaeria miniovina ontreebranch. Ecuador, Ganoderma chocoense ontreetrunk. France, Neofitzroyomyces nerii (incl. Neofitzroyomyces gen. nov.) on Nerium oleander. Ghana, Castanediella tereticornis on Eucalyptus tereticornis, Falcocladium africanum on Eucalyptus brassiana, Rachicladosporium corymbiae on Corymbia citriodora. Hungary, Entoloma silvae-frondosae in Carpinus betulus-Pinus sylvestris mixedforest. Iran, Pseudopyricularia persiana on Cyperus sp. Italy, Inocybe roseascens onsoilinmixedforest. Laos, Ophiocordyceps houaynhangensis on Coleoptera larva. Malaysia, Monilochaetes melastomae on Melastoma sp. Mexico, Absidia terrestris fromsoil. Netherlands, Acaulium pannemaniae, Conioscypha boutwelliae, Fusicolla septimanifiniscientiae, Gibellulopsis simonii, Lasionectria hilhorstii, Lectera nordwiniana, Leptodiscella rintelii, Parasarocladium debruynii and Sarocladium dejongiae (incl. Sarocladiaceae fam. nov.) fromsoil. New Zealand, Gnomoniopsis rosae on Rosa sp. and Neodevriesia metrosideri on Metrosideros sp. Puerto Rico, Neodevriesia coccolobae on Coccoloba uvifera, Neodevriesia tabebuiae and Alfaria tabebuiae on Tabebuia chrysantha. Russia, Amanita paludosa on bogged soil in mixed deciduous forest, Entoloma tiliae in forest of Tilia Ă— europaea, Kwoniella endophytica on Pyrus communis. South Africa, Coniella diospyri on Diospyros mespiliformis, Neomelanconiella combreti (incl. Neomelanconiellaceae fam. nov. and Neomelanconiella gen. nov.)on Combretum sp., Polyphialoseptoria natalensis on unidentified plant host, Pseudorobillarda bolusanthi on Bolusanthus speciosus, Thelonectria pelargonii on Pelargonium sp. Spain, Vermiculariopsiella lauracearum and Anungitopsis lauri on Laurus novocanariensis, Geosmithia xerotolerans from a darkened wall of a house, Pseudopenidiella gallaica on leaf litter. Thailand, Corynespora thailandica on wood, Lareunionomyces loeiensis on leaf litter, Neocochlearomyces chromolaenae (incl. Neocochlearomyces gen. nov.) on Chromolaena odorata, Neomyrmecridium septatum (incl. Neomyrmecridium gen. nov .), Pararamichloridium caricicola on Carex sp., Xenodactylaria thailandica (incl. Xenodactylariaceae fam. nov. and Xenodactylaria gen. nov.), Neomyrmecridium asiaticum and Cymostachys thailandica fromunidentifiedvine. USA, Carolinigaster bonitoi (incl. Carolinigaster gen. nov.)fromsoil, Penicillium fortuitum from house dust, Phaeotheca shathenatiana (incl. Phaeothecaceae fam. nov.) from twig and cone litter, Pythium wohlseniorum from stream water, Superstratomyces tardicrescens from human eye, Talaromyces iowaense from officeair. Vietnam, Fistulinella olivaceoalba onsoil. Morphological and culture characteristics along with DNA barcodes are provided

    FIB patterning of stainless steel for the development of nano-structured stent surfaces for cardiovascular applications

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    Stent implantation is a percutaneous interventional procedure that mitigates vessel stenosis, providing mechanical support within the artery and as such a very valuable tool in the fight against coronary artery disease. However, stenting causes physical damage to the arterial wall. It is well accepted that a valuable route to reduce in-stent re-stenosis can be based on promoting cell response to nano-structured stainless steel (SS) surfaces such as by patterning nano-pits in SS. In this regard patterning by focused ion beam (FIB) milling offers several advantages for flexible prototyping. On the other hand FIB patterning of polycrystalline metals is greatly influenced by channelling effects and redeposition. Correlative microscopy methods present an opportunity to study such effects comprehensively and derive structure–property understanding that is important for developing improved patterning. In this chapter we present a FIB patterning protocol for nano-structuring features (concaves) ordered in rectangular arrays on pre-polished 316L stainless steel surfaces. An investigation based on correlative microscopy approach of the size, shape and depth of the developed arrays in relation to the crystal orientation of the underlying SS domains is presented. The correlative microscopy protocol is based on cross-correlation of top-view scanning electron microscopy, electron backscattering diffraction, atomic force microscopy and cross-sectional (serial) sectioning. Various FIB tests were performed, aiming at improved productivity by preserving nano-size accuracy of the patterned process. The optimal FIB patterning conditions for achieving reasonably high throughput (patterned rate of about 0.03 mm2/h) and nano-size accuracy in dimensions and shapes of the features are discussed as well
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