367 research outputs found
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Structural Analysis on the Riveted Hull of the Paddle Steamer Medway Queen
This paper presents modelling and Finite Element Analysis (FEA) simulation studies on the reconstruction of the historic Medway Queen riveted steel ship. The objective of this study is to assess the longitudinal stress in the hull plates of the Medway Queen (MQ) under various sea and load conditions. Detailed stress analysis in the localised riveted joint regions on the hull is also undertaken. A detailed three-dimensional (3D) digitised model is generated and the used to obtain the cross sectional steel profiles of the ship and their section properties. Finite element analysis with structural elements is used to assess shear stress and bending moments of the ship structure. The model predictions for longitudinal stresses in hull plates are combined with stress assessments for the individual rivet joints in different, judged to be most critical, locations along the ship’s length. The structural beam model is used to simulate the ship’s stress behaviour under hogging and sagging conditions with two different wave heights. Four sets of live loads are also added to the to the simulation cases. From the longitudinal bending moment and shear force of all sixteen simulations cases, twenty extreme locations are identified and average stress on rivets of joints closed to these locations are predicted. Stress values predicted are below the maximum permissible value of 100Nmm-2 specified by British standards BS153 and BS449. In addition, hull plate test samples with various thicknesses of plates connected with various diameter rivet joints are experimentally tested to assess independently the rivet joint strength and validate the failure criteria adopted in the modelling methodology. The test results have agreed favourably with the limits detailed in the standard
Synergistic and antagonistic interactions of binary mixtures of polycyclic aromatic hydrocarbons in the upregulation of CYP1 activity and mRNA levels in precision-cut rat liver slices
The current studies investigate whether synergistic or antagonistic interactions in the upregulation of CYP1 activity occur in binary mixtures of polycyclic aromatic hydrocarbons (PAHs) involving benzo[a]pyrene and five other structurally diverse PAHs of varying carcinogenic activity. Precision-cut rat liver slices were incubated with benzo[a]pyrene alone or in combination with a range of concentrations of a second PAH, and ethoxyresorufin O-deethylase, CYP1A1 and CYP1B1 mRNA levels determined. Concurrent incubation of benzo[a]pyrene with either dibenzo[a,h]anthracene or fluoranthene in liver slices led to a synergistic interaction, at least at low concentrations, in that ethoxyresorufin O-deethylase activity was statistically higher than the added effects when the slices were incubated with the individual compounds. In contrast, benzo[b]fluoranthene and, at high doses only, dibenzo[a,l]pyrene gave rise to antagonism, whereas 1-methylphenanthrene had no effect at all concentrations studied. When CYP1A1 mRNA levels were monitored, benzo[b]fluoranthene gave rise to an antagonistic response when incubated with benzo[a]pyrene, whereas all other compounds displayed synergism, with 1-methylphenathrene being the least effective. A similar picture emerged when CYP1B1 mRNA levels were determined, though the effects were less pronounced. In conclusion, it has been demonstrated that the benzo[a]pyrene-mediated upregulation of CYP1, at the mRNA and activity levels, is synergistically and antagonistically modulated by other PAHs
Design of a DNA-Encoded Human Papilloma Virus-Like Particle Displaying a Vascular Endothelial Growth Factor Antagonistic Peptide for Characterization in Mammalian Cells
Cancer immunotherapy has evolved as an effective platform for the treatment of a variety of cancer types by enhancing and/or modulating the functionality of the immune system to target cancer cells and consequently mitigate tumour growth. Within the last decade, self-assembled viral-derived protein complexes, known as virus-like particles (VLPs), have been extensively studied for their application toward cancer immunotherapy. These structural viral-mimicking particles possess the capability to engender potent immune responses, and in doing so, combat the immunosuppressive tumour microenvironment. VLP-based vaccines have been commercialized, however, VLPs encoded as a genetic sequence, such as a DNA-VLP strategy, for delivery and subsequent in vivo formation, has not been licensed to date. This would enable transcription and translation of the introduced genetic sequence into viral structural proteins, assembly of the expressed proteins to form VLPs, and successive immune response stimulation, characterizing this type of treatment modality as both an immunotherapeutic and gene therapeutic. Delivery of VLPs encoded as a genetic sequence, opposed to conventional VLP delivery, enables viral structural protein expression and assembly into VLPs directly within cancer and immune cells, promoting enhanced cell-mediated immune responses, which can contribute to a greater extent towards tumour eradication. Here, we are seeking to apply this concept toward the design of a DNA-VLP gene cassette to produce human papillomavirus (HPV) 16 VLPs as a gene therapy-based cancer immunotherapeutic. The DNA-VLP gene cassettes were designed to encode the major capsid protein of HPV16, known as L1, along with an inserted peptide. This peptide, known as VGB, is characterized as an anti-angiogenic molecule that has previously demonstrated active reduction of cancer cell proliferation and tumour growth. Transfection of the designed DNA-VLP gene cassettes was conducted within mammalian cells, which successfully encoded the HPV16 L1 protein, in addition to possible in vitro assembly of VGB-displaying HPV16 L1 VLPs. This was validated via western blot analysis, enzyme-linked immunosorbent assay experimentation, and visualization using transmission electron microscopy. Potential display of the VGB peptide within surface exposed regions of the VLPs was observed by increased binding towards VGB’s targeted receptor, VEGFR. The prospective for cell lysis contributed by the accumulation of VLPs within mammalian cells was not validated, as decreased cell growth and viability subsequent to transfection were not observed. Overall, the characterization of VGB-displaying HPV16 L1 VLPs encoded within the designed DNA-VLP gene cassettes, promotes further investigation to employ this as a potential gene therapy-based cancer immunotherapeutic for future clinical applications
Sicherung der gentechnikfreien Produktion. Eintrittswege gentechnisch veränderter Organismen, Gegenmassnahmen und Empfehlungen.
Die Bioproduktion verwendet weder gentechnisch veränderte Organismen (GVO) noch deren Folgeprodukte. Infolge der weltweiten Verbreitung und Anwendung von GVOs in der konven¬tionellen Landwirtschaft und Lebensmittelherstellung besteht aber zunehmend die Gefahr unerwünschter Verunreinigungen von Bioprodukten mit GVO-Erzeugnissen. Die vorliegende Studie zeigt die relevanten Kontaminationspfade auf, stellt die bisherigen gesetzlichen Vor¬schriften und die Regelungen der Bioorganisationen dar und diskutiert Massnahmen zur Vermeidung der Verunreinigungen. Die folgenden Strategien stehen dabei im Vorder¬grund: strikte räumliche Trennung und lückenlose Warenflussdokumentation, Ausschluss von kritischen Stoffen, Verwendung von Lebens- und Futtermittelkomponenten ausschliess¬lich in zertifizierter Bioqualität sowie Sicherheitsabstände zwischen GVO- und Biofeldern
Lentil (Lens culinaris Medikus): A Whole Food Rich in Prebiotic Carbohydrates to Combat Global Obesity
Lentil (Lens culinaris Medik.) is a cool season food legume that is high in protein (20–30%) and in a range of micronutrients (e.g., minerals, carotenoids, folates) but very low in phytic acid. Recent research indicates that lentil contains a wide array of low-molecular weight carbohydrates (LMWC) or prebiotic carbohydrates, such as mono- and disaccharides, raffinose-family oligosaccharides (RFO), fructooligosaccharides (FOS), and sugar alcohols, and high-molecular weight resistant starches. Lentil provides more than 13 g of prebiotic carbohydrates per 100 g serving, and this level increases almost two-fold upon cooking, cooling, and reheating. In addition, prebiotic carbohydrate levels vary with lentil genotype and growing location/country. Intestinal microbiome and prebiotic studies suggest a prebiotic-rich, low-calorie diet can reduce the prevalence of obesity and related non-communicable diseases. Lentil thus represents a whole food source of prebiotics that can play a role in efforts to reduce obesity and non-communicable diseases. This chapter provides an overview of the current obesity-related health issues, holistic approaches to reduce obesity, worldwide lentil production, and the promise of pulses, mainly lentil, to be a whole food solution to combat global obesity. In addition, lentil’s superior LMWC profile and the genetic potential for further enrichment of prebiotic carbohydrates are briefly discussed
A multiphysics modeling and experimental analysis of pressure contacts in power electronics applications
This paper details a modeling and experimental assessment of the packaging process for a silicon carbide Schottky diode using pressure contacts. The work detailed in this paper is original, as it applies a combined electrothermomechanical modeling analysis to this packaging method supported by experimental validation. A key design objective for this packaging process is to identify suitable contact pad materials, heatsinks, and process variables such as clamping force to meet electrical, thermal, and reliability specifications. Molybdenum and aluminum graphite (ALG) have been identified as two suitable materials for the contact pads. Clamping forces ranging from 300 to 500 N and electric current ranging from 10 to 30 A have been investigated in terms of the resulting electrical and thermal contact resistances, temperatures, and stresses induced across the package. The performance of two heatsink designs with heat dissipation rates of 12893 and 4991 W/m2k has also been investigated. Both the modeling and initial experimental results detailed in this paper show that ALG provides better performance in terms of generating a lower average chip temperature. Both temperature and stress in the diode are predicted as a function of clamping force and load current. This will aid the packaging engineer to identify suitable process parameters to meet junction temperature requirements at different applied load currents
Visualization of coronary arteries in paediatric patients using whole-heart coronary magnetic resonance angiography: comparison of image-navigation and the standard approach for respiratory motion compensation
Aims: To investigate the use of respiratory motion compensation using image-based navigation (iNAV) with
constant respiratory efficiency using single end-expiratory thresholding (CRUISE) for coronary magnetic resonance
angiography (CMRA), and compare it to the conventional diaphragmatic navigator (dNAV) in paediatric patients
with congenital or suspected heart disease.
Methods: iNAV allowed direct tracking of the respiratory heart motion and was generated using balanced steady
state free precession startup echoes. Respiratory gating was achieved using CRUISE with a fixed 50% efficiency.
Whole-heart CMRA was acquired with 1.3mm isotropic resolution. For comparison, CMRA with identical imaging
parameters were acquired using dNAV. Scan time, visualization of coronary artery origins and mid-course, imaging
quality and sharpness was compared between the two sequences.
Results: Forty patients (13 females; median weight: 44 kg; median age: 12.6, range: 3 months–17 years) were
enrolled. 25 scans were performed in awake patients. A contrast agent was used in 22 patients. The scan time was
significantly reduced using iNAV for awake patients (iNAV 7:48 ± 1:26 vs dNAV 9:48 ± 3:11, P = 0.01) but not for
patients under general anaesthesia (iNAV = 6:55 ± 1:50 versus dNAV = 6:32 ± 2:16; P = 0.32). In 98% of the cases,
iNAV image quality had an equal or higher score than dNAV. The visual score analysis showed a clear difference,
favouring iNAV (P = 0.002). The right coronary artery and the left anterior descending vessel sharpness was
significantly improved (iNAV: 56.8% ± 10.1% vs dNAV: 53.7% ± 9.9%, P < 0.002 and iNAV: 55.8% ± 8.6% vs dNAV:
53% ± 9.2%, P = 0.001, respectively). Conclusion: iNAV allows for a higher success-rate and clearer depiction of the mid-course of coronary arteries in
paediatric patients. Its acquisition time is shorter in awake patients and image quality score is equal or superior to
the conventional method in most cases.Medical Engineering at King’s College London WT 088641/Z/09/ZBHF Centre of Excellence RE/08/0
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A numerical procedure for the optimization of IGBT module packaging
A numerical solution procedure for optimizing the thermal-mechanical reliability of an IGBT module has been described in this paper. The procedure is robust and it can handle both discrete and continuous decision variables in the design of IGBT packaging. An example has been given to demonstrate its application. The objective functions in this example are the accumulated plastic work density in solder joints of a simplified IGBT module that is subject to cyclic temperature cycling and the maximum junction temperature when the model is subject to a constant thermal loading. The thickness of the chip mount-down solder, thickness of the substrate solder joint, and the location of the chip are used as continuous decision variables. The material selection for the baseplate is treated as a discrete variable. The objective function values are calculated using Finite Element Analysis method
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