133 research outputs found

    Sensing and interferometry, including design and characterisation of special optical fibres

    Get PDF
    This thesis presents my work in the area of optical fibre sensing, and optical fibre design and characterisation along with the interferometric and signal processing techniques that were developed along the way

    MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

    Get PDF
    Contains fulltext : 170912.pdf (publisher's version ) (Open Access)BACKGROUND: To investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome. METHODS: In 97 patients with ovarian cancer, MMP-14 and CD44 expression as determined by immunohistochemistry was investigated in relation to EMT-like changes. To determine this, immunohistochemical staining of E-cadherin and vimentin was performed. RESULTS: Patients with expression of both MMP-14 and CD44 in their tumors had a poor prognosis despite complete debulking. Serous histology in advanced-stage tumors (FIGO IIB-IV) correlated with CD44 (rho .286, p < 0.01). Also, CD44 correlated with percentage vimentin expression (rho .217, p < 0.05). In logistic regression analysis with complete debulking as the outcome parameter, CD44 expression was found to be significant (OR 3,571 (95 % Confidence Interval 1,112-11,468) p = 0.032), though this was not the case for MMP-14 and EMT parameters. CONCLUSION: The subgroup of patients with double expression of MMP-14 and CD44 had a poor prognosis despite complete debulking. Serous subtype in advanced-stage patients and CD44 expression were found to be correlated with vimentin expression, and CD44 expression was found to be significantly correlated with complete debulking. However, a significant correlation between EMT and clinical parameters was not found

    Ocean Colour Remote Sensing of Flood Plumes in the Great Barrier Reef

    Get PDF
    The objective of the research reported in this thesis was to develop a technique to monitor the dynamics of sediments and nutrients entering the coastal ocean with river plumes associated with high intensity low frequency events (e.g. floods), using ocean colour remote sensing. To achieve this objective, an inverse bio-optical model was developed, based on analytical and empirical relationships between concentrations of optically significant substances and remote sensing of water-leaving radiance. The model determines concentrations of water-colouring substances such as chlorophyll, suspended sediments, and coloured dissolved organic matter, as well as the values of optical parameters using water-leaving radiances derived from the Sea-viewing Wide Field-of-view Sensor (SeaWiFS). To solve atmospheric correction in coastal waters, the aerosol type over clear waters is transferred to adjacent turbid water pixels. The vicinity of the Herbert River, central Great Barrier Reef zone, Australia, was used as a case study for the application of the algorithm developed. The satellite ocean colour technique was successfully validated using sea-truth measurements of water-colouring constituents acquired in the area during various seasons throughout 2002-2004. A high correlation between chlorophyll and dissolved organic matter was found in the coastal waters of the region, and when the bio-optical model was constrained to make chlorophyll a function of dissolved organic matter, the relationship between in situ and satellite-derived data was substantially improved. With reliable retrieval of the major water-colouring constituents, the technique was subsequently applied to study fluxes of particulate and dissolved organic and inorganic matter following a flood event in the Herbert River during the austral summer of 1999. Extensive field observations covering a seasonal flood in the Herbert River in February 2004 revealed high sediment and nutrient exports from the river to the adjacent coastal waters during the flood event. Due to rapid settling, the bulk of the sediment-rich influx was deposited close inshore, while the majority of nutrients exported from the river were consumed by phytoplankton in a relatively small area of the coastal ocean. With the help of ocean colour remote sensing, it was demonstrated that river-borne sediments and nutrients discharged by a typical flood in the Herbert River are mostly precipitated or consumed within the first 20 km from the coast and therefore are unlikely to reach and possibly affect the midshelf coral reefs of this section of the Great Barrier Reef lagoon

    Peroxisome proliferator-activated receptory agonist mediated inhibition of heparanase expression reduces proteinuria

    Get PDF
    Background Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor y (PPARy) agonists can ameliorate proteinuria. Since a recent study showed that PPARy regulates HPSE expression in liver cancer cells, we hypothesized that PPARy agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.Methods Regulation of HPSE by PPARy was assessed in the adriamycin nephropathy rat model, and cultured glomerular endothelial cells and podocytes. Analyses included immunofluorescence staining, real-time PCR, heparanase activity assay and transendothelial albumin passage assay. Direct binding of PPARy to the HPSE promoter was evaluated by the luciferase reporter assay and chromatin immunoprecipitation assay. Furthermore, HPSE activity was assessed in 38 type 2 diabetes mellitus (T2DM) patients before and after 16/24 weeks treatment with the PPARy agonist pioglitazone.Findings Adriamycin-exposed rats developed proteinuria, an increased cortical HPSE and decreased heparan sulfate (HS) expression, which was ameliorated by treatment with pioglitazone. In line, the PPARy antagonist GW9662 increased cortical HPSE and decreased HS expression, accompanied with proteinuria in healthy rats, as previously shown. In vitro, GW9662 induced HPSE expression in both endothelial cells and podocytes, and increased trans -endothelial albumin passage in a HPSE-dependent manner. Pioglitazone normalized HPSE expression in adriamycin-injured human endothelial cells and mouse podocytes, and adriamycin-induced transendothelial albumin passage was reduced as well. Importantly, we demonstrated a regulatory effect of PPARy on HPSE promoter activity and direct PPARy binding to the HPSE promoter region. Plasma HPSE activity of T2DM patients treated with pioglitazone for 16/24 weeks was related to their hemoglobin A1c and showed a moderate, near significant correlation with plasma creatinine levels.Interpretation PPARy-mediated regulation of HPSE expression appears an additional mechanism explaining the anti-proteinuric and renoprotective effects of thiazolidinediones in clinical practice.Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Radiolog

    Characterization of anticoagulant heparinoids by immunoprofiling

    Get PDF
    Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III, resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs (extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics, such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural and biological characteristics

    Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

    Get PDF
    Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

    DESA1002 'Nine Quarter City' - <Nik Zulhazmi Bin Nik Fuaad>

    No full text
    My individual block is located in Jerusalem. At the beginning of the semester I decided to design a motorcycle workshop which would provide necessary services to nearby Jerusalem people. It is also essential as motorcycle is one of the main transportation in Jerusalem. My design in the first place consists of several boxes which were dull and uninteresting. My tutor however advised me to ‘think outside the box’ and try to loosen up and play around with the design. Well, thanks to her, my mind has now opened to a whole lot of new ideas. From there I begin to work continuously with that design and developed several functions for the building. Apart from the motorcycle workshop, there is also a cafĂ©, a place to dine in which is located on the ground floor adjacent to the workshop but separated by a courtyard. On the second floor there is a multi-purpose hall which is owned by the public and can be used for different kinds of functions and programs. There are also several apartment houses on the 2nd floor as well as on the whole 3rd floor which offer permanent and temporary accommodations. The building uses white limestone as a cladding materials and there’s an extensive usage of glasses which allows inhabitants on the outside to recognize the different functions of the building. However, the usage is minimal on the apartment houses in order to protect the privacy of the occupants. In addititon, there are also public toilets located on the 2nd floor and verandah for the apartment residents located on the 2nd and 3rd floor. The 3rd floor verandah provides large open space which can be used as a place for private parties, playground or a scenic place to hang out and enjoy the picturesque panorama of Jerusalem. Nevertheless in the end the design kind of failed in terms of bringing forward the main function which is the motorcycle workshop and emerged more as a multi-functional edifice. I realized that I should have developed the motorcycle workshop more and present a more vibrant motorcycle workshop which is what it had been in the first place

    HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection

    Get PDF
    Contains fulltext : 174418.pdf (publisher's version ) (Open Access)The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry. Finally, a cytokine array profile generated during HSV-1 infection in DRG explant indicated an enhanced expression of chemokines (LIX, TIMP-2, and M-CSF)-known regulators of HS. Taken together, these results highlight the significance of HS during HSV-1 entry in DRG explant. Further investigation is needed to understand which isoforms of 3-O-sulfotransferase (3-OST)-generated HS contributed during HSV-1 infection and associated cell damage
    • 

    corecore