152 research outputs found

    Concept design of a fast sail assisted feeder container ship

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    A fast sail assisted feeder container ship concept has been developed for the 2020 container market in the South East Asian and Caribbean regions.The design presented has met the requirements of an initial economic study, with a cargo capacity of 1270 twenty-foot equivalent unit containers, meeting the predictions of container throughput derived from historical data. In determining suitable vessel dimensions, account has also been taken for port and berthing restrictions, and considering hydrodynamic performance. The vessel has been designed for a maximum speed of 25 knots, allowing it to meet the demand for trade whilst reducing the number of ships operating on the routes considered.The design development of the fast feeder concept has involved rigorous analyses in a number of areas to improve the robustness of the final design. Model testing has been key to the development of the concept, by increasing confidence in the final result. This is due to the fact that other analysis techniques are not always appropriate or accurate. Two hull forms have been developed to meet requirements whilst utilising different propulsor combinations. This has enabled evaluation of efficiency gains resulting from different hydrodynamic phenomena for each design. This includes an evaluation of the hydrodynamic performance when utilising the sail system. This has been done using a combination of model test results and data from regression analysis. The final propulsor chosen is a contra-rotating podded drive arrangement. Wind tunnel testing has been used to maximise the performance of a Multi-wing sail system by investigating the effects of wing spacing, stagger and sail-container interactions. This has led to an increase in lift coefficient of 32% from initial predictions. The savings in power requirement due to the sail system are lower than initially predicted. However, another benefit of their installation, motion damping, has been identified. Whilst this has not been fully investigated, additional fuel savings are possible as well as improved seakeeping performance.The design is shown to be environmentally sustainable when compared to existing vessels operating on the proposed routes. This is largely due to the use of low-carbon and zero-sulphur fuel (liquefied natural gas) and improvements in efficiency regarding operation. This especially relates to cargo handling and scheduling. Green house gas emissions have been predicted to fall by 42% and 40% in the two regions should the design be adopted. These savings are also due to the use of the Multi-wing sail system, which contributes to reductions in power requirement of up to 6% when the vessel operates at its lower speed of 15 knots. It is demonstrated that the fast feeder is also economically feasible, with predicted daily cost savings of 27% and 33% in the South East Asian and Caribbean regions respectively. Thus the fast feeder container ship concept is a viable solution for the future of container transhipment. <br/

    Concept design of a fast sail assisted feeder container ship

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    An environmentally sustainable fast sail-assisted feeder-container ship concept, with a maximum speed of 25 knots, has been developed for the 2020 South East Asian and Caribbean container markets. The use of low-carbon and zero-sulphur fuel (liquefied natural gas) and improvements in operational efficiency (cargo handling and scheduling) mean predicted Green house gas emissions should fall by 42% and 40% in the two selected operational regions. The adoption of a Multi-wing sail system reduces power requirement by up to 6% at the lower ship speed of 15 knots. The predicted daily cost savings are respectively 27% and 33% in South East Asian and the Caribbean regions.Two hull forms with a cargo capacity of 1270TEU utilising different propulsion combinations were initially developed to meet operational requirements. Analysis &amp; tank testing of different hydrodynamic phenomena has enabled identification of efficiency gains for each design. The final propulsion chosen is a contra-rotating podded drive arrangement. Wind tunnel testing improved Multi-wing sail performance by investigating wing spacing, wing stagger and sail-container interactions. The associated lift coefficient was increased by 32%. Whilst savings in sail-assisted power requirement are lower than initially predicted an unexpected identified benefit was motion damping.The fast feeder-container ship is a proposed as a viable future method of container transhipment

    The impact of multiple sclerosis on the identity of mothers in Italy

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    Purpose: This paper reports on one of the themes that emerged from the analysis of the study, regarding the perceived influence of multiple sclerosis (MS) on the identity of mothers in the socio-cultural context of Italy. Method: In-depth interviews were conducted with 16 women at various stages of MS, with follow up interviews with seven of the women. Phenomenology guided the methodology and the analysis was conducted using interpretative phenomenological analysis. Results: Through the research the value of motherhood to the women who participated emerged. The findings illustrated how many strove to maintain controlof their MS, which led to some making comparisons of themselves and other mothers and feeling different. Some women described how they adjusted their roles and found strength in being mothers but others spoke of their feelings of loss. Most women described living in the moment, appreciating the present and living each day as it came. Another significant experience was fear of stigma, both realized in the form of “pity” from others, and the perceived and actual associated stigma for their families. This contributed to why some women were reluctant to disclose their condition. The mothers who took part in this study differed in how they perceived their disabled identity. Conclusion: Although this study was conducted in the socio-cultural setting of Italy, the findings have implications for professionals working with disabled mothers and women with MS in Italy and beyond; including recognizing the value associated with fully identifying oneself as a mother, rather than solely focusing on doingmothering tasks. • Implications for Rehabilitation • Professionals need to be mindful of the value of motherhood for women with multiple sclerosis. • Professionals should support women who feel like they are battling with maintaining control of their multiple sclerosis, who may be adjusting their identity as mothers; recognizing that they may be influenced by the stage of their multiple sclerosis and whether they were diagnosed before or after having their children. • Women can have feelings of loss related to their ability to fully participate in their children’s lives and professionals should work with women to help them identify the value of their mothering role not only in physically participating in activities but also in being emotionally and physically present as a mother

    False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

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    Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT

    Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells

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    Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen tensions ranging from 1% to 21% O2, representative of ischemic or healthy tissues and standard culture conditions. Compared to HMVECs, hECFCs (1) exhibited significantly greater proliferation in both ischemic conditions and ambient air; (2) demonstrated increased migration compared to HMVECs when exposed to chemotactic gradients in reduced oxygen; and (3) exhibited comparable or superior proangiogenic potential in reduced oxygen conditions when assessed using a vessel-forming assay. These data demonstrate that the angiogenic potential of both endothelial populations is influenced by the local oxygen microenvironment. However, hECFCs exhibit a robust angiogenic potential in oxygen conditions representative of physiologic, ischemic, or ambient air conditions, and these findings suggest that hECFCs may be a superior cell source for use in cell-based approaches for the neovascularization of ischemic or engineered tissues

    Maternal Undernutrition and Long-term Effects on Hepatic Function

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    Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which illustrate how the placidity of the developing liver can be exploited to prevent the onset of long-term metabolic disease

    Collateral circulation: Past and present

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    Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors

    Construction of a large scale integrated map of macrophage pathogen recognition and effector systems

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    <p>Abstract</p> <p>Background</p> <p>In an effort to better understand the molecular networks that underpin macrophage activation we have been assembling a map of relevant pathways. Manual curation of the published literature was carried out in order to define the components of these pathways and the interactions between them. This information has been assembled into a large integrated directional network and represented graphically using the modified Edinburgh Pathway Notation (mEPN) scheme.</p> <p>Results</p> <p>The diagram includes detailed views of the toll-like receptor (TLR) pathways, other pathogen recognition systems, NF-kappa-B, apoptosis, interferon signalling, MAP-kinase cascades, MHC antigen presentation and proteasome assembly, as well as selected views of the transcriptional networks they regulate. The integrated pathway includes a total of 496 unique proteins, the complexes formed between them and the processes in which they are involved. This produces a network of 2,170 nodes connected by 2,553 edges.</p> <p>Conclusions</p> <p>The pathway diagram is a navigable visual aid for displaying a consensus view of the pathway information available for these systems. It is also a valuable resource for computational modelling and aid in the interpretation of functional genomics data. We envisage that this work will be of value to those interested in macrophage biology and also contribute to the ongoing Systems Biology community effort to develop a standard notation scheme for the graphical representation of biological pathways.</p

    The ubiquitin proteasome system in neuropathology

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    The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis. The UPS facilitates the turnover of proteins in several settings. It targets oxidized, mutant or misfolded proteins for general proteolytic destruction, and allows for the tightly controlled and specific destruction of proteins involved in development and differentiation, cell cycle progression, circadian rhythms, apoptosis, and other biological processes. In neuropathology, alteration of the UPS, or mutations in UPS target proteins may result in signaling abnormalities leading to the initiation or progression of tumors such as astrocytomas, hemangioblastomas, craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of the UPS may also contribute to tumor progression by perturbation of DNA replication and mitotic control mechanisms, leading to genomic instability. In neurodegenerative diseases caused by the expression of mutant proteins, the cellular accumulation of these proteins may overload the UPS, indirectly contributing to the disease process, e.g., sporadic Parkinsonism and prion diseases. In other cases, mutation of UPS components may directly cause pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and muscle and nerve diseases, e.g., inclusion body myopathy and giant axon neuropathy. This paper describes the basic biochemical mechanisms comprising the UPS and reviews both its theoretical and proven involvement in neuropathological diseases. The potential for the UPS as a target of pharmacological therapy is also discussed

    The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli

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    Background: Escherichia coli is a model prokaryote, an important pathogen, and a key organism for industrial biotechnology. E. coli W (ATCC 9637), one of four strains designated as safe for laboratory purposes, has not been sequenced. E. coli W is a fast-growing strain and is the only safe strain that can utilize sucrose as a carbon source. Lifecycle analysis has demonstrated that sucrose from sugarcane is a preferred carbon source for industrial bioprocesses
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