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Η HDL ως καινοτόμος φαρμακολογικός στόχος : διδάγματα από μελέτες έκθεσης πειραματόζωων σε χαμηλή θερμοκρασίαΞεπαπαδάκη, Ευστρατία 05 February 2015 (has links)
Πρόσφατα δεδομένα σε πειραματικά μοντέλα ζώων αλλά και σε ασθενείς καταδεικνύουν την σημαντικότητα της «ποιότητας» της λιποπρωτεΐνης υψηλής πυκνότητας (HDL), σε σχέση με την ποσότητά της, στην προστασία από τη στεφανιαία νόσο. Τα κύρια χαρακτηριστικά της HDL τα οποία καθορίζουν την «ποιότητά» της, είναι η ανάστροφη μεταφορά χοληστερόλης, οι αντιοξειδωτικές και αντιφλεγμονώδεις ιδιότητές της καθώς επίσης και η ικανότητά της να προάγει την παραγωγή ΝΟ στο αρτηριακό επιθήλιο και να ρυθμίζει την ομοιόσταση της γλυκόζης αίματος.
Στην συγκεκριμένη ερευνητική εργασία μελετάμε την επίδραση που έχει η ενεργοποίηση του φαιού λιπώδους ιστού, μέσω της έκθεσης φυσιολογικών πειραματικών μοντέλων μυών, σε περιβάλλον χαμηλής θερμοκρασίας, στο λιπιδαιμικό προφίλ, καθώς και στην λειτουργικότητα της HDL.
Είναι γνωστό είναι ότι η ενεργοποίηση του φαιού λιπώδους ιστού, λόγω έκθεσης πειραματόζωων σε περιβάλλον χαμηλής θερμοκρασίας, οδηγεί σε θερμογένεση, κάθαρση των τριγλυκεριδίων από το αίμα παχύσαρκων ποντικών, μείωση του βάρους τους, έλεγχο του καταβολισμού των λιποπρωτεϊνών και ομαλοποίηση της ανοχής τους στην γλυκόζη. Έτσι θελήσαμε να επεκτείνουμε την μελέτη μας, στον ενδεχόμενο ρόλο του εγκλιματισμού των πειραματόζωων μετά από μακρόχρονη έκθεσή τους στο ψύχος στους παραπάνω παράγοντες.
Για την επίτευξη των πειραματικών μας στόχων δημιουργήθηκαν τρεις ομάδες C57BL/6 μυών εκ των οποίων η μια εκτέθηκε σε περιβάλλον χαμηλής θερμοκρασίας για 2 εβδομάδες (βραχύχρονη έκθεση στο ψύχος), η άλλη ομάδα για 12 εβδομάδες (μακρόχρονη έκθεση στο ψύχος), ενώ η τρίτη αποτέλεσε την ομάδα ελέγχου.
Στις δύο ομάδες μυών έγιναν κινητικές μελέτες έκκρισης και κάθαρσης τριγλυκεριδίων. Επίσης απομονώθηκαν από το πλάσμα του αίματος, τα λιποπρωτεϊνικά κλάσματα στα οποία έγιναν αναλύσεις για τον έλεγχο της ποσότητας και της ποιότητας της HDL.
Τα αποτελέσματά μας καταδεικνύουν την επαγωγή θερμογένεσης από τον φαιό λιπώδη ιστό και στις δύο πειραματικές ομάδες, με αυτή να είναι πιο έντονη κατά την βραχύχρονη έκθεση στο ψύχος. Παρόλο που η κατανάλωση τροφής στις ομάδες που εκτέθηκαν στο ψύχος αυξήθηκε, το σωματικό τους βάρος παρέμεινε το ίδιο, μιας και η περίσσεια διατροφικών λιπιδίων χρησιμοποιούνταν από τον φαιό λιπώδη ιστό για την παραγωγή θερμότητας παρά για αποθήκευσή τους στον λευκό λιπώδη ιστό. Η εντερική απορρόφηση τριγλυκεριδίων αυξήθηκε σε σχέση με την ομάδα ελέγχου καθώς πιθανά ο οργανισμός χρειαζόταν τα λιπίδια για θερμογένεση, ενώ η ηπατική έκκριση τριγλυκεριδίων μειώθηκε. Η ολική χοληστερόλη των λιποπρωτεϊνικών κλασμάτων, στις πειραματικές ομάδες, έτεινε να βρίσκεται συγκεντρωμένη στα πιο ώριμα κλάσματα, ιδιαίτερα έπειτα από μακρόχρονη έκθεση στο πειραματικό περιβάλλον. Επιπλέον η HDL την 12η εβδομάδα, παρουσίασε καλύτερη αντιοξειδωτική δράση καθώς και διατήρησε αμιγή την ικανότητα να επιτελεί εκροή χοληστερόλης από τα κύτταρα.
Τα ευρήματά μας οδηγούν σε δύο ενδιαφέρουσες ανακαλύψεις: 1) Η βραχεία έκθεση στο ψύχος έχει μεγαλύτερη επίδραση στη θερμογένεση και την παραγωγή ATP, απ’ ότι η μακρά έκθεση. 2) Η μακρά έκθεση στο ψύχος οδηγεί σε πιο λειτουργική HDL σε σχέση με την ομάδα βραχείας έκθεσης.
Κατά συνέπεια τα αποτελέσματα μας αυτά, καταδεικνύουν εγκλιματισμό των πειραματόζωων στο ψύχος, ο οποίος συνοδεύεται από ποιοτικότερη και πιο λειτουργική HDL. / Recent data indicate the significance of “HDL quality” in atherosclerosis, rather than HDL cholesterol levels in plasma, suggesting that composition as well as functionality of HDL particle, imparts the atheroprotective property of HDL. The main atheroprotective property of HDL is cholesterol efflux in addition to anti-inflammatory and antioxidant properties. HDL has also the ability to promote NO production in the arterial lining and to regulate blood glucose levels.
In this study we intend to examine whether brown adipose tissue activation, through low environmental temperature, affects lipid profile and functionality of HDL in C57BL/6 mice.
Previous studies have shown that BAT is activated in animals which have been exposed to low temperature environment, resulting in thermogenesis, blood triglycerides clearance, weight reduction, control of lipoproteins catabolism and normalization of glucose tolerance.
Thus we intended to study the possible role of acclimatization after long-term exposure to cold temperature regarding the above factors. Therefore we formed three groups of C57BL/6 mice, one of which was exposed to 4oC environment for 2 weeks (short-term exposure), the other one for 12 weeks (long-term exposure) and the last one at 28oC environment (control group).
Kinetic studies of triglyceride secretion and clearance where performed, to all groups of animals. Analyses regarding HDL quantity and quality, where performed in lipoprotein fractions isolated from plasma.
Our data demonstrate the induction of thermogenesis in BAT in both experimental groups, which appeared to be more intense during the short-term exposure. Although food consumption, in groups exposed to cold, was increased, body weight did not change, as BAT used the excess dietary lipids in order to produce heat rather than storing them in white adipose tissue. Intestinal absorption of triglycerides was increased compared to the control group, possibly because lipids are needed due thermogenesis. Total cholesterol in HDL fractions, tended to be concentrated in more mature fragments, especially after long-term exposure. In addition HDL, during long-term exposure, showed to have more effective antioxidant potential and cholesterol efflux, compared to the group exposed to cold temperature for 2 weeks.
Our observations lead to two interesting findings: 1) Short-term exposure to cold has greater effect on thermogenesis and ATP production rather than long-term exposure. 2) After long-term exposure to cold, HDL appears to be more functional compared to the short-term exposure group.
Therefore our results indicate acclimation of the animals to low temperature environment, followed by a qualitative HDL.
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Framework For Design: The Study Of Parametrics For Contextually Responsive High Rise DesignCaron, Nicholas 24 November 2011 (has links)
The following thesis investigates parametric thinking and evolutionary solving principles in the creation of a framework for residential high rise design. Site specific parameters such as site access (pedestrian and vehicular), views, acknowledgement of neighbours, or climatic, such as natural day lighting and ventilation, should be used to inform the design. Parametric software is used as a tool to generate designs dynamically. With the help of an evolutionary solver component, the design potential is augmented by generating multiple iterations which are analyzed for their success or failure in an effort to provide an appropriate response within the context of the site. The framework is tested on a site located at the corner of Duplex Avenue and Eglinton Avenue West in Toronto, Canada.
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High cell density culivation of Methylosinus trichosporium OB3bAdegbola, OLUFEMI 04 September 2008 (has links)
Methylosinus trichosporium OB3b is a wild type, obligate methanotroph that grows only on one-carbon compounds and, in the absence of copper, produces high levels of soluble methane monooxygenase (sMMO) to metabolize methane to methanol. SMMO has gained a great deal of attention in the bioremediation and chemical industries because of its low substrate specificity and its ability to oxidize chlorinated hydrocarbons. Much literature exists on cultivating this organism on methane, however no one has achieved dry cell weight densities exceeding 18 g/L. Biomass growth is limited due to mass transfer of methane to cells. This study investigated the growth of M. trichosporium on the water soluble carbon source, methanol while retaining sMMO activity.
Methanol was found to completely inhibit growth at 40 g/L. For online methanol measurements during fed-batch cultivation, an in situ probe was constructed from autoclavable materials and equipped with a Figaro TGS822 vapor sensor. The probe was designed to prevent the sensor coming in contact with water aerosols which affect its performance. The probe was an essential component of a feedback methanol control system. The cumulative CO2 production (CCP) strategy was used to feed methanol in fed-batch experiments.
In an initial bioreactor study, growth nutrients were fed in excess. The yields of biomass to nutrients were determined and the growth medium modified accordingly. A biomass density of 19 g/L (growth rate of 0.013-0.065 h-1) was achieved with sMMO activity of 300 to 500 [µmol naphthol][g of biomass]-1[h]-1. The subsequent bioreactor study involved feeding of nutrients based on their yields in relation to methanol, a biomass density of 62 g/L (growth rate of 0.034- 0.08 h-1) was achieved.
The inoculum cultures utilized in the bioreactor studies were maintained on Noble agar plates containing nitrogen minimal salts medium and methane. After 6 months of subsequent plate transfers, M. trichosporium lost the ability to produce high levels of sMMO. The enzyme activity in methanol grown cells was recovered by subculturing in liquid NMS medium with methane as the sole carbon source, the activity increased from 8 to 600 [µmol naphthol][g of biomass]-1[h]-1. It is recommended that further studies be carried out on stimulating sMMO activity during cultivation on methanol. / Thesis (Master, Chemical Engineering) -- Queen's University, 2008-08-21 15:14:42.475
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Effect of stearate/stearic acid coating on filled high density polyethylene propertiesPetiraksakul, Pinsupha January 2000 (has links)
High density polyethylene (HDPE) is a widely used plastic but it is also a combustible material. One way of reducing flammability is to add fillers, such as magnesium hydroxide (Mg(OH)2). However, this has a deleterious effect on the mechanical properties of composites. It has been found that one possible method of restoring mechanical properties is to modifY the filler particles with coating agents, such as stearic acid. In the present work, this idea was taken a stage further with the use of various metal stearates (e.g. magnesium stearate, calcium stearate, and zinc stearate) for modifying filler. The fillers examined were magnesium hydroxide and calcium carbonate. A filler loading of 40% w/w was used in all samples. Samples were moulded into a variety of shapes for mechanical testing. Such tests included, tensile, flexural, and impact testing. To obtain deeper understanding of the effect of the coating agents on the fillers, a variety of fundamental tests were carried out. These included Diffuse Reflectance FTIR (DRIFT), Thermal Analysis using a DSC cell, Xray Diffraction (XRD), contact angle measurement. Unfilled HDPE, uncoated filled-HDPE, and coated filled-HDPE were compared using uncoated filled-HDPE as a base line. Uncoated filled-HDPE is more brittle than unfilled HPDE. Surface modification of filler improves the toughness properties. Comparing coated filled-compounds, stearic acid and zinc stearate caused a small improvement, magnesium stearate improved the properties significantly with calcium carbonate while calcium stearate gave the best results for coating magnesium hydroxide. One monolayer coating gave the best compound properties compared to other degrees of coating. Although, tensile/flexural strength was not greatly affected elongation at yield, extension at maximum load, and impact properties increased significantly. DSC was used to observe the disappearance and conversion of coating agents as coating proceeded. X-ray diffraction showed the effect of injection moulding on the orientation of the filler and polymer. During coating of the filler particles, XRD and DSC were used to follow incorporation of stearate particles to produce the monolayer coverage. Surface free energy results showed that surface modification of filler resulted in the reduction of hydrophilicity of filler leading to tougher composites compared with uncoated filled-compounds.
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Regulation of lipoprotein transport in the metabolic syndrome : impact of statin therapy /Ooi, Esther M. M. January 2007 (has links)
Thesis (Ph.D.)--University of Western Australia, 2007.
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Effect of acute exercise on postprandial lipemia and HDL cholesterol subfractions /Zhang, Qiang, January 1997 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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Effect of acute exercise on postprandial lipemia and HDL cholesterol subfractionsZhang, Qiang, January 1997 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.
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Einfluss der Ernährung und von Genussmitteln auf Risikofaktoren für das Auftreten von ischämischem Herzinfarkt und SchlaganfallEckoldt, Joachim, January 2005 (has links)
Hohenheim, Univ., Diss., 2005.
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Hormonal regulation of ATP binding cassette transportersTaher, Mohammed Ahmed A. January 2004 (has links) (PDF)
Regensburg, Univ., Diss., 2004.
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Diagnosing User-Visible Performance Problems in Production High-Density Wi-Fi NetworksMickulicz, Nathan D. 01 May 2018 (has links)
Large-scale, high-density Wi-Fi networks use hundreds of access points to serve thousands of closelypacked users within a large physical space (hundreds of thousands of square feet or more, such as in a stadium or arena). Because of their scale, these are complex and dynamic systems comprised of several layers and multiple components within each layer, and faults may be present in any one of these components. The problems that manifest from these faults are usually not network-wide and may be localized to a certain physical areas of the network. This makes these problems challenging to detect and diagnose; in most cases, only a small number of devices tend to be impacted by any given problem. However, many such problems may occur simultaneously in different areas of the network. Adding to the complexity is the dynamic nature of such networks, where the physical positions of radios (in end-user devices), human bodies, and other objects in the space are constantly changing, thereby creating a continually-changing RF environment. Taken together, these properties make problem diagnosis in large-scale, high-density Wi-Fi networks challenging. There are many existing techniques for diagnosing problems in Wi-Fi networks. Many of these approaches rely on data from only a single perspective of the network to diagnose problems, for example, either the client, the infrastructure (access points), or external Wi-Fi sensors that passively monitor the network. In addition, many of these approaches require the invasive modification of the network’s components in order to collect data, through techniques such as the installation of specialized software on clients, modifying the firmware on access points, or even physically installing specialized devices in the RF environment of the Wi-Fi network. Finally, many approaches rely on offline analysis of the collected instrumentation, in which case diagnosis cannot be done in real time (minutes or less). Many others require network connectivity for real-time diagnosis, in which case the device must be able to communicate using the Wi-Fi infrastructure (that may be experiencing a problem). As a result, many of these approaches are difficult to deploy in production networks (due to the high financial cost or maintenance effort required), and those that are deployed often fail to detect and diagnose problems that are localized to a small number of devices (10 or less) or problems that are only present for a short time (minutes or less). This dissertation takes a unique approach that contrasts with existing approaches in three key ways. First, we combine the Wi-Fi performance data from multiple layers of the Wi-Fi network and attempt to diagnose problems at all of these layers, rather than focusing on a single layer alone, and we introduce a fault model that includes faults that can occur across all layers of the system. Second, we require no invasive modification of the Wi-Fi network or its components in order collect data and perform problem diagnosis and mitigation. Third, we present an infrastructure-free approach to problem diagnosis that relies on Bluetooth communication with other devices nearby (peers) to perform diagnosis based on multiple perspectives of the Wi-Fi network. With this approach, our diagnosis algorithm is able to collect data from multiple network perspectives without relying on Wi-Fi infrastructure, which may be slow or unavailable. Our approach begins with the construction of an instrumentation and data-collection system to obtain Wi-Fi performance metrics from both the client and infrastructure perspectives of the network. We then build upon our instrumentation to determine when user-visible problems occur. We define a user-visible problem as a Wi-Fi-network-performance problem that causes users to disengage from using the network. Once we have detected a user-visible problem, we then proceed to diagnose the root cause of the problem as one of the faults in our fault model using an approach based on decision trees. Finally, based on the diagnosed fault, we apply an automated mitigation-strategy, which forces the device to associate with a different access point that will likely provide better performance. To validate our approach and demonstrate its real-world impact, we have conducted a number of studies to collect data in support of our approach from both a laboratory testbed and real-world production Wi-Fi networks. We used our instrumentation and data-collection system to obtain data from over 25 real-world, large-scale, high-density Wi-Fi networks located within collegiate and professional stadiums. Our diagnostic system was deployed in a real-world mobile video-streaming application used over the Wi-Fi networks in these stadiums. Using this data, we determined the thresholds for when a Wi-Fi performance problem becomes user visible, based on our study of when users disengage from using the video-streaming application in the face of buffering. In addition to obtaining real-world data, we have studied this phenomenon in a testbed for fault injection and diagnosis that has been deployed both in a lab environment and in an arena to collect data on the behavior of large-scale, high-density Wi-Fi networks and understand how best to diagnose problems. Using this testbed, we evaluated the performance of our problem-diagnosis approach in terms of its precision and recall on injected faults. We also evaluated the performance of our mitigation strategy on our testbed by injecting faults and verifying that the selected mitigation strategy successfully mitigated the problem caused by that fault. We found that our approach diagnoses the correct root cause of faults with high precision and recall (often above 90%) and can mitigate problems via alternative access-point selection in 100% of our test cases. While we have studied our approach in certain test environments and for video-streaming applications, we believe that our approach can be applied to any Wi-Fi network and many other applications outside of video streaming. Our work in this dissertation could be extended through the automated discovery of the parameters for our diagnosis and mitigation algorithms that provide the best performance in other Wi-Fi networks, along with further studies of how Wi-Fi performance problems manifest in other types of applications and under what conditions users disengage with those applications due to problems.
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