A proteo-liposome system for the analysis of the intracellular interactome of membrane proteins using amyloid precursor protein as a model

Transmembrane proteins play crucial roles in many important physiological processes. The intracellular domain of membrane proteins is key for their function by interacting with a wide variety of cytosolic proteins. It is therefore important to examine this interaction. A recently developed method to study these interactions, based on the use of liposomes as a model membrane, involves the covalent coupling of the cytoplasmic domains of membrane proteins to the liposome membrane. This allows for the analysis of interaction partners requiring both protein and membrane lipid binding. This thesis further establishes the liposome recruitment system and utilises it to examine the intracellular interactome of the amyloid precursor protein (APP), most well-known for its proteolytic cleavage that results in the production and accumulation of amyloid beta fragments, the main constituent of amyloid plaques in Alzheimer’s disease pathology. Despite this, the physiological function of APP remains largely unclear. Through the use of the proteo-liposome recruitment system two novel interactions of APP’s intracellular domain (AICD) are examined with a view to gaining a greater insight into APP’s physiological function. One of these novel interactions is between AICD and the mTOR complex, a serine/threonine protein kinase that integrates signals from nutrients and growth factors. The kinase domain of mTOR directly binds to AICD and the N-terminal amino acids of AICD are crucial for this interaction. The second novel interaction is between AICD and the endosomal PIKfyve complex, a lipid kinase involved in the production of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) from phosphatidylinositol-3-phosphate, which has a role in controlling ensdosome dynamics. The scaffold protein Vac14 of the PIKfyve complex binds directly to AICD and the C-terminus of AICD is important for its interaction with the PIKfyve complex. Using a recently developed intracellular PI(3,5)P2 probe it is shown that APP controls the formation of PI(3,5)P2 positive vesicular structures and that the PIKfyve complex is involved in the trafficking and degradation of APP. Both of these novel APP interactors have important implications of both APP function and Alzheimer’s disease. The proteo-liposome recruitment method is further validated through its use to examine the recruitment and assembly of the AP-2/clathrin coat from purified components to two membrane proteins containing different sorting motifs. Taken together this thesis highlights the proteo-liposome recruitment system as a valuable tool for the study of membrane proteins intracellular interactome. It allows for the mimicking of the protein in its native configuration therefore identifying weaker interactions that are not detected by more conventional methods and also detecting interactions that are mediated by membrane phospholipids.

Asymptotic Analysis of a Schrödinger-Poisson System with Quantum Wells and Macroscopic Nonlinearities in Dimension 1

2000 Mathematics Subject Classification: 35Q02, 35Q05, 35Q10, 35B40.

Fiber-optic liquid level monitoring system using microstructured polymer fiber Bragg grating array sensors:performance analysis

A highly sensitive liquid level monitoring system based on microstructured polymer optical fiber Bragg grating (mPOFBG) array sensors is reported for the first time. The configuration is based on five mPOFBGs inscribed in the same fiber in the 850 nm spectral region, showing the potential to interrogate liquid level by measuring the strain induced in each mPOFBG embedded in a silicone rubber (SR) diaphragm, which deforms due to hydrostatic pressure variations. The sensor exhibits a highly linear response over the sensing range, a good repeatability, and a high resolution. The sensitivity of the sensor is found to be 98 pm/cm of water, enhanced by more than a factor of 9 when compared to an equivalent sensor based on a silica fiber around 1550 nm. The temperature sensitivity is studied and a multi-sensor arrangement proposed, which has the potential to provide level readings independent of temperature and the liquid density.

Analysis of carrier phase extraction methods in 112-Gbit/s NRZ-PDM-QPSK coherent transmission system

We present a comparative analysis on three carrier phase extraction approaches, including a one-tap normalized least mean square method, a block-average method, and a Viterbi-Viterbi method, in coherent transmission system considering equalization enhanced phase noise. © OSA 2012.

Analysis of Wiener-Hammerstein equalizer for downlink LTE system

We propose a Wiener-Hammerstein (W-H) channel estimation algorithm for Long-Term Evolution (LTE) systems. The LTE standard provides known data as pilot symbols and exploits them through coherent detection to improve system performance. These drivers are placed in a hybrid way to cover up both time and frequency domain. Our aim is to adapt the W-H equalizer (W-H/E) to LTE standard for compensation of both linear and nonlinear effects induced by power amplifiers and multipath channels. We evaluate the performance of the W-H/E for a Downlink LTE system in terms of BLER, EVM and Throughput versus SNR. Afterwards, we compare the results with a traditional Least-Mean Square (LMS) equalizer. It is shown that W-H/E can significantly reduce both linear and nonlinear distortions compared to LMS and improve LTE Downlink system performance.

Better queue management in a busy public hospital of a developing country without appointment system::an application using data envelopment analysis

Queuing is a key efficiency criterion in any service industry, including Healthcare. Almost all queue management studies are dedicated to improving an existing Appointment System. In developing countries such as Pakistan, there are no Appointment Systems for outpatients, resulting in excessive wait times. Additionally, excessive overloading, limited resources and cumbersome procedures lead to over-whelming queues. Despite numerous Healthcare applications, Data Envelopment Analysis (DEA) has not been applied for queue assessment. The current study aims to extend DEA modelling and demonstrate its usefulness by evaluating the queue system of a busy public hospital in a developing country, Pakistan, where all outpatients are walk-in; along with construction of a dynamic framework dedicated towards the implementation of the model. The inadequate allocation of doctors/personnel was observed as the most critical issue for long queues. Hence, the Queuing-DEA model has been developed such that it determines the ‘required’ number of doctors/personnel. The results indicated that given extensive wait times or length of queue, or both, led to high target values for doctors/personnel. Hence, this crucial information allows the administrators to ensure optimal staff utilization and controlling the queue pre-emptively, minimizing wait times. The dynamic framework constructed, specifically targets practical implementation of the Queuing-DEA model in resource-poor public hospitals of developing countries such as Pakistan; to continuously monitor rapidly changing queue situation and display latest required personnel. Consequently, the wait times of subsequent patients can be minimized, along with dynamic staff scheduling in the absence of appointments. This dynamic framework has been designed in Excel, requiring minimal training and work for users and automatic update features, with complex technical aspects running in the background. The proposed model and the dynamic framework has the potential to be applied in similar public hospitals, even in other developing countries, where appointment systems for outpatients are non-existent.

Temporal analysis of land use and transportation investments with geographic information system

Land use and transportation interaction has been a research topic for several decades. There have been efforts to identify impacts of transportation on land use from several different perspectives. One focus has been the role of transportation improvements in encouraging new land developments or relocation of activities due to improved accessibility. The impacts studied have included property values and increased development. Another focus has been on the changes in travel behavior due to better mobility and accessibility. Most studies to date have been conducted in metropolitan level, thus unable to account for interactions spatially and temporally at smaller geographic scales. ^ In this study, a framework for studying the temporal interactions between transportation and land use was proposed and applied to three selected corridor areas in Miami-Dade County, Florida. The framework consists of two parts: one is developing of temporal data and the other is applying time series analysis to this temporal data to identify their dynamic interactions. Temporal GIS databases were constructed and used to compile building permit data and transportation improvement projects. Two types of time series analysis approaches were utilized: univariate models and multivariate models. Time series analysis is designed to describe the dynamic consequences of time series by developing models and forecasting the future of the system based on historical trends. Model estimation results from the selected corridors were then compared. ^ It was found that the time series models predicted residential development better than commercial development. It was also found that results from three study corridors varied in terms of the magnitude of impacts, length of lags, significance of the variables, and the model structure. Long-run effect or cumulated impact of transportation improvement on land developments was also measured with time series techniques. The study offered evidence that congestion negatively impacted development and transportation investments encouraged land development. ^

Numerical heat transfer analysis of carbon-based foams for use in thermal protection system

The applicability of carbon-based foams as an insulating or active cooling material in thermal protection systems (TPSs) of space vehicles is considered using a computer modeling. This study focuses on numerical investigation of the performance of carbon foams for use in TPSs of space vehicles. Two kinds of carbon foams are considered in this study. For active cooling, the carbon foam that has a thermal conductivity of 100 W/m-k is used and for the insulation, the carbon foam having a thermal conductivity of 0.225 W/m-k is used. A 3D geometry is employed to simulate coolant flow and heat transfer through carbon foam model. Gambit has been used to model the 3D geometry and the numerical simulation is carried out in FLUENT. Numerical results from this thesis suggests that the use of CFOAM and HTC carbon foams in TPS's may effectively protect the aluminum structure of the space shuttle during reentry of the space vehicle.

X-ray diffraction analysis, binocular component analysis and radiocarbon dating of sediment cores from the NW Iberian shelf system

Based on a well-established stratigraphic framework and 47 AMS-14C dated sediment cores, the distribution of facies types on the NW Iberian margin is analysed in response to the last deglacial sea-level rise, thus providing a case study on the sedimentary evolution of a high-energy, low-accumulation shelf system. Altogether, four main types of sedimentary facies are defined. (1) A gravel-dominated facies occurs mostly as time-transgressive ravinement beds, which initially developed as shoreface and storm deposits in shallow waters on the outer shelf during the last sea-level lowstand; (2) A widespread, time-transgressive mixed siliceous/biogenic-carbonaceous sand facies indicates areas of moderate hydrodynamic regimes, high contribution of reworked shelf material, and fluvial supply to the shelf; (3) A glaucony-containing sand facies in a stationary position on the outer shelf formed mostly during the last-glacial sea-level rise by reworking of older deposits as well as authigenic mineral formation; and (4) A mud facies is mostly restricted to confined Holocene fine-grained depocentres, which are located in mid-shelf position. The observed spatial and temporal distribution of these facies types on the high-energy, low-accumulation NW Iberian shelf was essentially controlled by the local interplay of sediment supply, shelf morphology, and strength of the hydrodynamic system. These patterns are in contrast to high-accumulation systems where extensive sediment supply is the dominant factor on the facies distribution. This study emphasises the importance of large-scale erosion and material recycling on the sedimentary buildup during the deglacial drowning of the shelf. The presence of a homogenous and up to 15-m thick transgressive cover above a lag horizon contradicts the common assumption of sparse and laterally confined sediment accumulation on high-energy shelf systems during deglacial sea-level rise. In contrast to this extensive sand cover, laterally very confined and maximal 4-m thin mud depocentres developed during the Holocene sea-level highstand. This restricted formation of fine-grained depocentres was related to the combination of: (1) frequently occurring high-energy hydrodynamic conditions; (2) low overall terrigenous input by the adjacent rivers; and (3) the large distance of the Galicia Mud Belt to its main sediment supplier.

Solitons in Exciton-Polariton System: Reduced Modelling, Analysis, and Numerical Studies

In this dissertation, we study the behavior of exciton-polariton quasiparticles in semiconductor microcavities, under the sourceless and lossless conditions.

First, we simplify the original model by removing the photon dispersion term, thus effectively turn the PDEs system to an ODEs system,

and investigate the behavior of the resulting system, including the equilibrium points and the wave functions of the excitons and the photons.

Second, we add the dispersion term for the excitons to the original model and prove that the band of the discontinuous solitons now become dark solitons.

Third, we employ the Strang-splitting method to our sytem of PDEs and prove the first-order and second-order error bounds in the $H^1$ norm and the $L_2$ norm, respectively.

Using this numerical result, we analyze the stability of the steady state bright soliton solution. This solution revolves around the $x$-axis as time progresses

and the perturbed soliton also rotates around the $x$-axis and tracks closely in terms of amplitude but lags behind the exact one. Our numerical result shows orbital

stability but no $L_2$ stability.

Numerical Analysis on a Dual-Loop Waste Heat Recovery System Coupled with an ORC for Vehicle Applications

The internal combustion (IC) engines exploits only about 30% of the chemical energy ejected through combustion, whereas the remaining part is rejected by means of cooling system and exhausted gas. Nowadays, a major global concern is finding sustainable solutions for better fuel economy which in turn results in a decrease of carbon dioxide (CO2) emissions. The Waste Heat Recovery (WHR) is one of the most promising techniques to increase the overall efficiency of a vehicle system, allowing the recovery of the heat rejected by the exhaust and cooling systems. In this context, Organic Rankine Cycles (ORCs) are widely recognized as a potential technology to exploit the heat rejected by engines to produce electricity. The aim of the present paper is to investigate a WHR system, designed to collect both coolant and exhausted gas heats, coupled with an ORC cycle for vehicle applications. In particular, a coolant heat exchanger (CLT) allows the heat exchange between the water coolant and the ORC working fluid, whereas the exhausted gas heat is recovered by using a secondary circuit with diathermic oil. By using an in-house numerical model, a wide range of working conditions and ORC design parameters are investigated. In particular, the analyses are focused on the regenerator location inside the ORC circuits. Five organic fluids, working in both subcritical and supercritical conditions, have been selected in order to detect the most suitable configuration in terms of energy and exergy efficiencies.

Simulation and analysis of an emergency lowering system for crane applications

An emergency lowering system for use in safety critical crane applications is discussed. The system is used to safely lower the payload of a crane in case of an electric blackout. The system is based on a backup power source, which is used to operate the crane while the regular supply is not available. The system enables both horizontal and vertical movements of the crane. Two different configurations for building the system are described, one with an uninterruptible power source (UPS) or a diesel generator connected in parallel to the crane’s power supply and one with a customized energy storage connected to the intermediate DC-link in the crane. In order to be able to size the backup power source, the power required during emergency lowering needs to be understood. A simulation model is used to study and optimize the power used during emergency lowering. The simulation model and optimizations are verified in a test hoist. Simulation results are presented with non-optimized and optimized controls for two example applications: a paper roll crane and a steel mill ladle crane. The optimizations are found to significantly reduce the required power for the crane movements during emergency lowering.