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Hybrid Theranostic Platforms for Cancer Nanomedical TreatmentJulfakyan, Khachatur 10 1900 (has links)
Cancer is a leading case of mortality worldwide. Governments spent multibillion expenses on treatment and palliative care of diseased people. Despite these generous funding and intensive research with aim to find a cure or efficient treatment for cancer, until now there is a lack in selective cancer management strategies. Conventional treatment strategies for cancer, such as surgery, cytotoxic chemotherapy, radiation therapy, hormone therapy don’t have selectivity toward cancer – the property of discrimination of healthy organs and tissues from the diseased site. Chemotherapy is very challenging as the difference between effective and lethal doses is very minuscule in most cases. Moreover, devastating side effects dramatically changes the quality of life for cancer patients. To address these issues two main strategies are intensively utilized in chemistry: (I) the design and synthesis of novel anticancer organic compounds with higher selectivity and low toxicity profiles and the second, design and preparation of biocompatible nanocarriers for imaging and anticancer compound selective delivery nanomedicine. The following dissertation combines the above two strategies as bellows: First project is related to the design and synthetic route development toward novel nature-inspired group of heterocyclic compounds – iso-Phidianidines. The second project focused on design, preparation and evaluation of hybrid theranostics (therapeutic and diagnostic in a single entity).
Chapter 1 is a general background review of the major topics that will be discussed in this dissertation.
The first efficient and high-yielding synthetic route toward iso-phidianidines, containing regioisomeric form of 1,2,4-oxadiazole linked to the indole via methylene bridge is reported in Chapter 2. In vitro test of the synthesized library of iso-phidianidines revealed micromolar range of cytotoxicity toward human cervical cancer cell line. Structure activity relationship revealed the importance of presence of monosubsituted amine in 3 position of oxadiazole to maintain activity. Moreover, gradual increase of activity was detected in increasing of the length of the diamine. Polyamine (spermidine) side chain demonstrated strongest anticancer activity, identified as lead compound and may be studied further as a good candidate for cervical cancer treatment. Finally, the remaining high activity of amino-terminated iso-phidianidines demonstrated that presence of guanidine group in termini is not necessary for high cytotoxicity.
The second part of this dissertation (Chapter 3) discusses the rational design, wet protocol synthesis and complete characterization of the novel hybrid material – polydopamine coated iron-cobalt nanocubes (PDFCs). This material was loaded with anticancer model drug doxorubicin in one step procedure (PDFC-DOX) and the resulting drug-delivery vehicle was found to be successfully internalized by cervical cancer cells. The cytotoxicity test demonstrated inhibition of 50% of the cells at the concentration of 30μg/ml for PDFC-DOX. Moreover, the release was highly attenuated and pH-sensitive in acidic range. PDFC was also modified with fluorescein leading to green fluorescent nanoparticles PDFC-FITC, which demonstrated excellent intracellular molecular imaging property. PDFCs with one of the highest magnetic saturation among the materials used in biomedicine (226 emu/g based on core) showed the absence of any cytotoxicity in vitro and excellent MRI contrasting property (r2=186.44 mMs-1, higher than commercial contrast agents Ferridex® and Clio®), both in vitro and in vivo on mice. They were cleared out from the mice bodies in month without affecting their health. Due to the high density of core (8.3 g/cm3) they demonstrated ability to be contrast materials also for X-Ray CT diagnostic modality, increasing the tumor detection and visualization probability in combination with MRI. In addition to it’s diagnostic and drug-delivery modalities, PDFC was evaluated also for microwave-induced cytotoxicity as a novel concept in cancer treatment. As low as 10 μg/ml concentration of PDFCs in human cervical cancer cells caused extensive death above 73% upon exposure to 2,45 GHz of microwaves for one minute. Laser irradiation (808 nm, 15 minutes) of cancer cells with internalized PDFCs caused cell death above 60%. The specific absorption rate of PDFCs at 470 MHz frequency and 20 mT of the alternating magnetic field power was 180 W/g, which is nearly 100 W higher than for commercial nanoparticles (Ferridex®).
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SIGTRAN : Signaling over IP -- a step closer to an all-IP networkImmonen, Mia January 2005 (has links)
The mass popularization of telecommunication services in recent years have resulted in a heavily loaded signaling network. The Signaling System number 7 (SS7) is used in fixed and wireless networks and is needed for call control and services such as caller ID, roaming, and for sending SMS. The traditional SS7 networks are expensive to lease and to expand, hence a new suite of protocols have been designed to carry signaling messages over IP. This suite contains a transport protocol called Stream Control Transmission Protocol (SCTP) and various user adaptation layer protocols such as M2PA, M2UA, M3UA, and SUA. To transport the highly loss and delay sensitive signaling messages over IP, it is mandatory that the transport protocol meets the high performance requirements of SS7. Not before the IP-solution has been tested in detail, will it replace significant parts of the national telephone network. In this thesis, the failover duration in the case of link failure was tested using the feature of SCTP called multi-homing. The results suggest that carrying SS7 signaling traffic over IP is possible, since the failover duration does not exceed the required limit. / Under de senaste åren har telekommunikationstjänster blivit allt mer populära, vilket har lett till ett tungt belastat signaleringsnätverk. The Signaling System number 7 (SS7) används i fasta och trådlösa nätverk och behövs för att kontrollera telefonsamtal och för tjänster såsom caller ID, roaming och för att skicka SMS. De traditionella SS7- nätverken är dyra att hyra och att expandera, varför en ny grupp av protokoll har designats för att bära signaleringsmeddelanden över IP. De nya protokollen innehåller ett transportprotokoll som heter Stream Transmission Control Protocol (SCTP) och flera adaptionslagerprotokoll, bl.a. M2PA, M2UA, M3UA och SUA. För att transportera de förlust- och förseningskänsliga signaleringsmeddelandena över IP, måste transportprotokollet möta de höga krav som SS7 har. Inte förrän IP-lösningen har testats ingående, kommer den att ersätta betydelsefulla delar av det nationella telefonnätet. I detta examensarbete har failovertiden mätts då en nätverkslänk mellan två noder har utsatts för ett avbrott. Resultaten pekar på att det är möjligt att bära SS7-trafik över IP eftersom failovertidskraven inte överstigs.
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Accelerated Corrosion Test with Operation Simulation of All-Aluminum Microchannel Heat ExchangersVaughan, Haydn 05 1900 (has links)
The HVAC&R industry is looking to transition from copper-aluminum heat exchangers to all-aluminum microchannel technology. The want for the transition stemmed from seeing the performance improvement of all-aluminum microchannel radiators in the automotive industry. Applications differ between the two industries; therefore, applying this technology for HVAC&R use must be validated. Research towards operating modes of an all-aluminum heat exchanger in a defined corrosive environment will provide the industry with a better understanding of heat exchanger design and heat exchanger material selection. The worth in this is preventing overdesign and producing more efficient heat exchangers. Furthermore, ASHRAE members and the corrosion community will find value in a defined corrosion system and corrosion test procedure. The information gained through past research has progressed assessment of material performance; however, the methods improperly simulate and expedite natural weathering. The most common method being used is the ASTM (American Society of Testing Materials) Sea Water Acetic Acid Test. The research discussed in this paper was focused on improving a standard corrosion system by implementing system modifications to simulate heat exchanger operation while performing a modified wet-dry cyclic test (e.g. ASTM G85 Annex 5). The goal is to produce results that are more representative of natural corrosion behavior and its forms. Current results were gathered from five of ten samples that underwent initial testing. Finally, possible improvements towards the chamber system and the test method, including the salt solution, are discussed.
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Monetary policy and the stock market in South Africa: how do South African equity prices respond to expected and unexpected changes in the repo rate?Ramatlo, Tshegofatso 28 January 2020 (has links)
This analyses the impact of unexpected changes in monetary policy on the South African equity market over the period 2005 -2018. In an attempt to understand this relationship, two main views have emerged. The wealth effect suggests that monetary policy changes have an indirect effect on the stock market, via changes in the value of private portfolios. On the other hand, it has been argued that the stock market is an independent source of macroeconomic volatility to which policy makers may wish to consider. This paper applies an event study approach to examine the stock market reaction to monetary policy. Furthermore, to understand the economic sources underpinning that reaction a Vector autoregressive model is estimated. The results suggest that on average, a surprise rate hike of 100 basis points causes short term JSE All Share index total returns to decline by 2.71%. We also find that the stock market reacts positively (negatively) to expansionary (contractionary) unexpected monetary policy actions due to revised market expectations about future dividends, excess premiums and the discount rate. The findings are crucial for central bank policy makers and JSE stock market investors.
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All-Sky Measurements of the Mesospheric "Frontal Events" From Bear Lake Observatory, UtahSeo, Seon-Hee 01 May 1998 (has links)
Studies of internal gravity waves in the earth's upper atmosphere are of considerable interest. These waves play a very important role in the dynamics of the mesosphere and lower thermosphere (ML T) region where they can transfer large amounts of energy and momentum from the lower atmosphere via wave saturation and dissipation. In particular, small-scale short-period (50ms"1) . Another unusual characteristic of "frontal events" is an apparent reversal in contrast of the wave structures as imaged in the hydroxyl (OH) emission (peak altitude- 87 km) when compared with the oxygen (OJ) "green line" (557.7 nm) emission (peak altitude -96 km) that can sometimes occur. In one isolated case, observed from Haleakala, Hawaii, the bright wave crests in the OH emission appeared to propagated through a dark structureless sky, whereas in the OI emission the same waves appeared to propagate into a bright sky, leaving an apparently depleted emission in its wake. Recent theoretical studies based on noble measurements have shown that frontal events may be due to a "bore-like" intrusion that raises the OJ (557. 7 nm) layer by a few km and at the same time depresses the OH layer by a similar amount. However, studies of fronts and bores in the ML T region are exceptionally rare. I have discovered and analyzed 16 frontal events from image data recorded at Bear Lake Observatory, Utah ( 41.6°N, 111.6°W), over the past four years. I have investigated some of their properties such as their horizontal wavelengths, horizontal phase speeds, observed periods, and their directions of motion. In addition, I have made comparative measurements of their relative intensities in the OH and OI emissions. These studies provide the first "extensive" data set on such events detailing their morphology and dynamics and should provide important information necessary for a deeper understanding of their occurrence frequency and properties.
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Fabrication and characterization of thin-film microbatteries based on self-organized titania nanotubes / Fabrication et caractérisation de microbatteries à couche mince à base de nanotubes de titaneSalian, Girish Dayanand 26 September 2018 (has links)
Un nanotube de dioxyde de titane autoporteur (TiO2 nts) est exploré en tant qu’électrode négative potentielle pour les microbatteries Li-ion 3D. Différentes modifications chimiques du TiO2 ont été explorées et étudiées, comme le TiO2 allié au Nb, le TiO2 revêtu d'ALD-Al2O3, le titanate de lithium-TiO2 et le TiO2 sulfuré. Le dépôt d'électrolyte polymère à base de PEO (oxyde d'éthylène) (PMMA-PEG) portant le sel de LiTFSI dans du TiO2 a été obtenu par la réaction d'électropolymérisation sur l'anode TiO2 et la cathode Lithum nickel oxyde de manganèse (LNMO). L'objectif principal ici était d'exploiter la surface active des électrodes par électrodéposition et d'améliorer ainsi l'interface électrode-électrolyte. Une telle micro-batterie contenant des électrodes revêtues de polymère révèle que les valeurs de capacité obtenues à différents taux de C sont doublées lorsque les électrodes sont complètement remplies par l'électrolyte polymère par rapport à la micro-batterie à électrodes brutes. Les excellentes performances électrochimiques sont attribuées aux interfaces électrode-électrolyte améliorées dans les deux électrodes / Self-supported titanium dioxide nanotube (TiO2 nts) is explored as a potential negative electrode for 3D Li-ion microbatteries. Different chemical modifications on the TiO2 nts have been explored and studied like Nb-alloyed TiO2 nts, ALD-Al2O3 coated TiO2 nts, Lithium titanate-TiO2 nts and sulphurized TiO2 nts. The deposition of PEO (polyethylene oxide) based polymer electrolyte (PMMA-PEG) carrying LiTFSI salt into TiO2 nts has been achieved by the electropolymerization reaction on the TiO2 nts anode and the Lithum nickel manganese oxide (LNMO) cathode. The main aim here was to exploit the active surface area of the electrodes using electrodeposition and there by enhance the electrode-electrolyte interface. Such a microbattery containing polymer-coated electrodes reveal that the capacity values obtained at different C-rates are doubled when the electrodes are completely filled by the polymer electrolyte compared with the microbattery with the raw electrodes. The excellent electrochemical performance is attributed to the improved electrode-electrolyte interfaces in both the electrodes
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Mississippi State University EcoCAR Extended Range Electric Vehicle Thermal System Design, Integration, Optimization, and ValidationBarr, Michael Lynn 13 December 2014 (has links)
A continued increase in government regulations for fuel economy and emissions has driven automakers and suppliers to take a large interest in hybridizing vehicles to help them achieve the new requirements. This increased vehicle electrification has resulted in unconventional vehicle cooling requirements. Electrified vehicle batteries and motors operate under different temperature regimes and cooling loads change drastically with driving styles and conditions. A variable-load cooling system was designed, implemented and tested on the Mississippi State University EcoCAR extended-range electric vehicle (E-REV). This system, utilizing variable flow pumps and variable speed fans, was shown to successfully cool the electronic components under the worst-case design conditions, while providing low energy consumption under normal conditions. When compared to a baseline system utilizing no variable duty cycle components, the variable cooling power system reduced energy consumption during testing both on-road at MSU’s facility and on-road at General Motors proving grounds in Michigan.
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Ligament Model Fidelity in Finite Element Analysis of the Human Lumbar SpineHortin, Mitchell Scott 01 May 2015 (has links) (PDF)
The purpose of this project is to quantify the effects of increasing spinal ligament fidelity on the mechanics of the human lumbar spine using finite element analysis (FEA). In support of this goal, a material characterization study was completed to provide anisotropic, nonlinear material parameters for the human anterior longitudinal ligament. (ALL). Cadaveric samples of the human ALL were tested using a punch test technique. Multi- axial force-deformation data were gathered and fit to a commonly used transversely isotropic material model using an FEA system identification routine. The resulting material parameters produced a curve that correlated well with the experimental curve (R2≥0.98). Recently published material data on several major spinal ligaments have been incorporated into an existing finite element model of the human lumbar spine. This data includes the results from the above mentioned material characterization, similar material characterizations of the supraspinous (SSL) and interspinous (ISL) ligaments, localized material properties of the SSL and pre-strain data for the ISL, SSL and ALL. These results have been incorporated both separately and compositely into the finite element model and each configuration has been simulated in spinal flexion, extension, axial rotation and lateral bending. Results suggest that the effects of increased ligament model fidelity on bone strain energy were moderate and the effects on disc pressure were slight, and do not justify a change in modeling strategy for most clinical applications. There were significant effects on the ligament stresses of the ligaments that were directly modified, suggesting that these phenomenon should be included in FE models where ligament stresses are the desired metric.
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PCR-Based Test for Differentiating Varieties of <i>Gaeumannomyces graminis</i>, The Take-All PathogensRachdawong, Sansanalak 11 April 1999 (has links)
Take-all is the most devastating root disease of wheat worldwide. The causal agent is <I>Gaeumannomyces</I> <I>graminis</I> (Sacc.) Arx & Olivier. Based on morphological characteristics and host ranges, three varieties of <I>G</I>. <I>graminis</I> have been recognized. <I>G</I>. <I>graminis</I> var. <I>tritici</I> Walker (Ggt) is the major causal agent of take-all of wheat and barley and the most economically important take-all pathogen. <I>G</I>. <I>graminis</I> var. <I>avenae</I> (Turner) Dennis (Gga) attack oats and causes take-all patch of turf grasses while <I>G</I>. <I>graminis</I> var. <I>graminis</I> (Ggg) is pathogenic on turf grasses but is non-pathogenic on wheat. Conventional diagnosis of take-all pathogens is based on field symptoms such as blackened roots, stunted growth, and white-heads and morphological characteristics such as hyphopodia type, size of perithecia, asci, and ascospores. These procedures are time-consuming, laborious, and often inconclusive. The objective of this study was to develop a rapid, simple, and specific method for differentiation of <I>G</I>. <I>graminis</I> varieties using PCR and molecular-based technology. Exploitation of genes associated with pathogenicity of <I>G</I>. <I>graminis</I> as markers for the test was proposed. Metabolic activities of <I>G</I>. <I>graminis</I> associated with pathogenesis were investigated, namely, the abilities to produce avenacinase and to oxidize manganese. Avenacinase, an avenacin detoxifying enzyme, was associated with Gga pathogenicity for oats but this enzyme is not important in Ggt pathogenicity for wheat. Manganese oxidation was also correlated with Ggt virulence. In this study, avenacinase-like genes were discovered in Ggt and Ggg and manganese oxidation was confirmed for Ggt, Gga, and Ggg. All isolates of Ggt except isolate ATCC 28230 were manganese oxidizers. Ggg and Gga isolates could oxidize manganese but their precipitation patterns were not as intense or closely correlated with mycelial growth as for Ggt. Pathogenicity assays on oats for Ggt, Gga, and Ggg isolates confirmed that Ggt isolates could not cause disease on oats aside from occasional slight root damage. Root weight was reduced for oat seedlings inoculated with Gga isolates. Comparison of partial sequences of avenacinase-like genes from Ggt and Ggg showed strong homology to that of Gga (94.8% identity to Ggt and 94.6% identity to Ggg). However, the Ggt gene was more closely related to that of Ggg (99.2% identity) than to Gga. DNA restriction endonuclease polymorphisms of the genes supported DNA sequencing information and revealed that there were variations within the genes among Ggt, Gga, and Ggg. Variety-specific electrophoretic patterns were obtained when the genes were digested with <I>Hae</I>III. Ggt, Gga, and Ggg upstream (5') variety-specific primers and a downstream (3') universal primer were designed from the avenacinase and avenacinase-like DNA sequences. PCR amplification with Ggt-, Gga-, and Ggg-specific primers generated fragments of 870, 617, and 1,086 bp, respectively. Each 5'-specific primer showed high specificity for its own DNA template in mixed populations of DNA templates. The optimized PCR procedure was sensitive to DNA template concentration as low as 100 pg. Genomic DNA of sixteen Ggt isolates, seven Gga isolates, and five Ggg isolates were tested. Although all Ggt isolates were originally isolated from wheat, seven isolates produced Ggg-specific fragments. This result corresponded well with <I>Hae</I>III DNA polymorphisms, pathogenicity assay, and manganese oxidizing ability. All but one Gga isolates produced the variety-specific fragment. Ggt- and Gga- specific products were generated from Gga isolate RB-W. Although Ggg-specific fragments were produced from all Ggg isolates, non-specific products were also observed from isolates that were not from wheat origin suggesting some genetic variations due to host ranges. Additionally, no non-specific amplification was obtained from any closely related fungi such as <I>Gaeumannomyces</I> <I>cylindrosporus</I> or <I>Phialophora</I> spp. The test developed in this study is the first test capable of identification of Ggt, Gga, and Ggg in a single PCR tube with a basic PCR protocol. The test is rapid and specific. Interpretation of results is simple and conclusive based on differences in size of each variety-specific fragment. / Ph. D.
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Dynamic Modeling of a Supersonic Tailless Aircraft with All-moving Wingtip Control EffectorsWhite, Brady Alexander 19 December 2007 (has links)
A six degree-of-freedom model for a tailless supersonic aircraft (TSA) concept was developed using MATLAB and Simulink. Aerodynamic data was provided through the computational fluid dynamics analysis of Techsburg, Inc. A three degree-of-freedom model of the configuration's longitudinal dynamics was completed first. Elevator control power was derived from the dynamic response requirements for pitch chosen by Techsburg. The propulsion model utilized General Electric F-414-400-like turbofan engines because an engine deck was readily available. Work on the six degree-of-freedom dynamic model began with determining the necessary rolling and yawing moment coefficients necessary to meet the rest of the chosen dynamic response requirements. These coefficients were then used to find the corresponding all-moving tip deflections. The CFD data showed that even at small all-moving tip deflections the rolling moment coefficient produced was much greater than the amount of yawing moment coefficient produced. This result showed that an additional roll effector was needed to counteract excess rolling moment at any given all-moving tip deflection and trim the aircraft. An angle of attack and pitch rate feedback controller was used to improve the longitudinal dynamics of the aircraft. Because this configuration lacked a vertical tail, a lateral-directional stability augmentation system was vital to its success. The lateral-directional dynamics were improved to Level 1 flying qualities through use of a modified roll/yaw damper. The modified controller fed yaw rate back to both the all-moving tips and roll effector. The six degree-of-freedom model was augmented with actuator dynamics for the elevator, roll effector, and all-moving tips. The actuators were modeled as first order lags. The all-moving tip actuator time constant was varied to determine the effect of actuator bandwidth on the lateral-directional flying qualities. After the actuator dynamics were successfully implemented, the six degree-of-freedom model was trimmed for both standard cruise and engine-out situations. The eccentuator concept from the DARPA Smart Wing program was selected as a possible conceptual design for the all-moving tip actuation system. The success of the TSA six degree-of-freedom dynamic model proved that morphing all-moving tips were capable of serving as effective control surfaces for a supersonic tailless aircraft. / Master of Science
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