Using OSM for real-time redeployment of VNFs based on network status

Στην παρούσα διπλωματική εργασία θα εξετάσουμε την Εικονικοποίηση δικτυακών λειτουργιών (Network Functions Virtualisation - NFV) ως την κατάλληλη αρχιτεκτονική για την υλοποίηση ενός δικτύου κατάλληλου για το Διαδίκτυο των Πραγμάτων (Internet of Things - IoT), το οποίο πρέπει να είναι ευέλικτο και επεκτάσιμο. Πιο συγκεκριμένα, θα επικεντρωθούμε στην αποτελεσματική αξιοποίηση του Open Source MANO (OSM) στην υλοποίηση μιας εφαρμογής που παρακολουθεί την κατάσταση του δικτύου των Εικονικοποιημένων δικτυακών λειτουργιών (Virtual Network Functions – VNFs) και σε περίπτωση κακής κατάστασης του δικτύου (π.χ. συμφόρηση του δικτύου) αναλαμβάνει τη μετακίνηση των επηρεαζόμενων VNFs σε κάποιον άλλο Διαχειριστή Εικονικής Υποδομής (Virtual Infrastructure Manager – VIM), για να αποτραπεί η πτώση στην απόδοση των ενεργών υπηρεσιών.In this thesis we will be examining the Network Functions Virtualisation (NFV) framework as a suitable framework for implementing a network appropriate for Internet of Things (IoT), which needs to be flexible and scalable. More precisely, we will be focusing on how Open Source MANO (OSM) can be efficiently utilized in a solution that monitors the network status of Virtual Network Functions (VNFs) and in case of bad network status (e.g. network congestion) triggers the redeployment of affected VNFs to some other Virtual Infrastructure Manager (VIM) to prevent the underperformance of running services

A Small Animal Optical Tomographic Imaging System with Omni-Directional, Non-Contact, Angular-Resolved Fluorescence Measurement Capabilities

The overall goal of this thesis is to develop a new non-contact, whole-body, fluorescence molecular tomography system for small animal imaging. Over the past decade, small animal in vivo imaging has led to a better understanding of many human diseases and improved our ability to develop and test new drugs and medical compounds. Among various imaging modalities, optical imaging techniques have emerged as important tools. In particular, fluorescence and bioluminescence imaging systems have opened new ways for visualizing many molecular pathways inside living animals including gene expression and protein functions. While substantial progress has been made in available prototype and commercial optical imaging systems, there still exist areas for further improvement in the outcome of existing instrumentations. Currently, most small animal optical imaging systems rely on 2D planar imaging that provides limited ability to accurately locate lesions deep inside an animal. Furthermore, most existing tomographic imaging systems use a diffusion model of light propagation, which is of limited accuracy. While more accurate models using the equation of radiative transfer have become available, they have not been widely applied to small animal imaging yet. To overcome the limitations of existing optical small animal imaging systems, a novel imaging system that makes use of the latest hardware and software advances in the field was developed. At the heart of the system is a new double-conical-mirror-based imaging head that enables a single fixed position camera to capture multi-directional views simultaneously. Therefore, the imaging head provides 360-degree measurement data from an entire animal surface in one step. Another benefit provided by this design is the substantial reduction of multiple back-reflections between the animal and mirror surfaces. These back reflections are common in existing mirror-based imaging heads and tend to degrade the quality of raw measurement data. Furthermore, the conical-mirror design offers the capability to measure angular-resolved data from the animal surface. To make full use of this capability, a novel equation of radiative transfer-based ray-transfer operator was introduced to map the spatial and angular information of emitted light on the animal surface to the captured image data. As a result, more data points are involved into the image reconstructions, which leads to a higher image resolution. The performance of the imaging system was evaluated through numerical simulations, experiments using a well-defined tissue phantom, and live-animal studies. Finally, the double reflection mirror scheme presented in this dissertation can be cost-effectively employed with all camera-based imaging systems. The shapes and sizes of mirrors can be varied to accommodate imaging of other objects such as larger animals or human body parts, such as the breast, head, or feet

MULTI – MODALITY MOLECULAR IMAGING OF ADOPTIVE IMMUNE CELL THERAPY IN BREAST CANCER

Cancer treatment by adoptive immune cell therapy (AIT) is a form of immunotherapy that relies on the in vitro activation and/or expansion of immune cells. In this approach, immune cells, particularly CD8+ T lymphocytes, can potentially be harvested from a tumor-bearing patient, then activated and/or expanded in vitro in the presence of cytokines and other growth factors, and then transferred back into the same patient to induce tumor regression. AIT allows the in vitro generation and activation of T-lymphocytes away from the immunosuppressive tumor microenvironment, thereby providing optimum conditions for potent anti-tumor activity. The overall objective of this study is to: a) develop multi-modality (optical- and radionuclide-based) molecular imaging approaches to study the overall kinetics of labeled adoptively transferred T- lymphocytes in vivo, b) to non-invasively image and assess in-vivo, targeting and retention of adoptively transferred labeled T-lymphocytes at the tumor site. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in vitro with Bryostatin/ Ionomycin for 18 hours, and were grown in either Interleukin-2 (IL-2) or combination of Interleukin-7 and Interleukin-15 (IL-7/IL-15) for 13 days, (cells grown in IL-2 called IL2 cells, and cells grown in IL7/15 called IL7/15 cells). In order to validate the methodology and to offer future clinical translation, both direct and indirect cell labeling methods were expanded and employed. The first method was based on direct in vitro cell labeling by lipophilic near-infrared (NIR) fluorescent probe, 1,1- dioctadecyltetramethyl indotricarbocyanine iodide, (DiR), followed by intravenous (i.v.) injection into BALB/C mice for multi-spectral fluorescence imaging (MSFI). The second method was based on indirect labeling of T- lymphocytes through transduction of a reporter gene (cell cytoplasm labeling Herpes Simplex Virus type 1- thymidine kinase (HSV-1 tk). The product of this reporter gene is an enzyme (HSV-1TK) which phosphorylates a radio labeled substrate 2-fluoro-2-deoxy-1 β- D- arabinofuranosyl-5-iodouracil ([124I]-FIAU) for Positron Emission tomography (PET) imaging. ATP based cell viability assay, flow cytometry and interferon-γ (IFN-γ) ELISA were used to investigate if there are any changes in cell viability, proliferation and function respectively, before and after direct and indirect labeling. The results showed that cell viability, proliferation, and function of labeled 4T1 specific T-lymphocytes were not affected by labeling for direct labeling methods at DiR concentration of 320µg/ml. For the indirect labeling method, the viability and proliferation results showed that cell viability decreases as multiplicity of infectious (MOI) increases. In particular, at MOI of 10 almost all cells die 3 days post transduction. At MOI of 5, cells viability was ≤ 30% and at MOI of 2 was ≤ 60%. Cell viability was 80% at MOI of 1. The results of optical imaging were as follows: when the recipient mice with established 4T1 tumors were injected with DiR labeled 4T1 specific T-lymphocytes, the 4T1 specific T-lymphocytes (IL2 cells) infused into tumor-bearing mice showed high tumor retention, which peaked 3 or 6 days post infusion depending on the tumor size and persisted at the tumor site for 3 weeks. In contrast, IL7/15 cells showed lower signal at the tumor site and this peaked on day 8. On the other case when 4T1 tumor cells were implanted 1-week post-infusion of labeled T-lymphocytes. IL2 T-lymphocytes moved out of lymphoid compartments to the site of subsequent 4T1 inoculation within two hours and peaked on day 3 and the signal persisted for 2 more weeks. In contrast with infusion of IL7/15 cells, the signal was barely detected and did not show a similar trafficking pattern as with IL2 cells. The results of the indirect labeling method, PET reporter gene (PRG) system (HSV-1tk / [124I ] FIAU ) showed that both IL2 and IL7/15 cells were successfully transduced as verified ex vivo by real time PCR and western blot. T Cells transduction efficiency was assessed from cell uptake study in comparison to stable transduced Jurkat cells which have transduction efficiency of 100 %. Both IL2 and IL7/15 cells showed lower transduction efficiency (≤ 30%) compared to Jurkat cells. Consequently, PET imaging did not show a detectable signal of transduced T cells in vivo. Biodistribution study was carried out on day 3 post [124I]-FIAU injections. Results were consistent with the optical imaging results, except for IL7/15 cells. Transduced and untransduced IL2 and IL7/15 cells were labeled with DiR and injected ( i.v.) into Balb / C mice and then imaged by both imaging modalities (MSFI and PET) at the same time. MSFI images of transduced IL2 cell showed detectable signal starting from 2 hours, peaked at 72 hours and persisted up to 2 weeks, while IL7/15 cells were detectable at the tumor site starting at 24 hours, peaked at 72 hours and persisted up to 2 weeks. By the end of this study animals were dissected and tissue activities were counted using gamma counting and expressed as % Injected dose/gram of tissue (%ID/gm). Transduced IL2 and IL7/15 cells showed higher %ID/gm than other organs at lungs, liver, spleen, tumor, lymph nodes and bone/bone marrow. IL7/15 cells compared to IL2 cells showed higher %ID/gm at same organs. Neither IL2 nor IL7/15 untransduced DiR labeled cells showed any activity at tumor site, and their activities at other organs was very low compared to transduced cells. To investigate whether labeled T-lymphocytes will localize at tumor metastases or not, and to study the difference in their migration patterns to the tumor site versus tumor metastases, 4T1 tumor cells were successfully transduced with HSV-1tk as confirmed by RT-PCR , western blot and cell uptake study. Transduced 4T1 cells were implanted in the right flank or in the mammary fat pad of the mouse. Serial PET imaging was carried out in the third and fourth week post tumor implantation to know when the tumor will metastasizes. PET imaging showed only signal at the tumor site and no metastasis were detected

Eficiencia portuaria y modelos de gobernanza

Programa Oficial de Doutoramento en Análise Económica e Estratexia Empresarial. 5033V01[Resumen] El transporte marítimo está fuertemente influenciado por la evolución de la economía y el comercio mundial. La actividad industrial, la producción económica, el comercio de mercancías y el transporte marítimo, crecen a diferentes velocidades, pero, en definitiva, todos estos factores dependen de la evolución de la economía mundial. Por otra parte, el desempeño logístico es uno de los factores claves en el comercio internacional, ya que, las economías con un mayor nivel de desarrollo logístico crecen más rápido, y por tanto son más competitividad y eficientes. El interés del tema radica en que permite evaluar la conveniencia de llevar a cabo nuevas inversiones en infraestructuras e instalaciones portuarias que mejoren las condiciones de vida de la población y que acrecienten la eficiencia de los puertos. En esta tesis doctoral se estiman dos modelos. En el primero, se estudian los efectos sobre el PIB per cápita de cambios en el transporte marítimo contenerizado y en un conjunto de variables socio-económicas de los países analizados utilizando datos panel y realizando las estimaciones pertinentes (efectos fijos y errores estándar corregidos para panel). Este estudio revela que el movimiento de mercancía contenerizada presenta un impacto positivo en el crecimiento del PIB per cápita (en Poder de Paridad Adquisitivo expresado en dólares constantes de 2011). El segundo modelo utilizado es un análisis de frontera estocástica, en el que se analiza los efectos provocados por la existencia de grúas pórtico y grúas móviles como factores determinantes de ineficiencia portuaria y se calcula la eficiencia técnica de cada puerto. Además, se introduce dentro de la función frontera variables como la frecuencia de escalas o los sistemas de gobernanza. Lo novedoso del análisis llevado a cabo en esta tesis se diferencia de los trabajos realizados hasta la fecha en el área geográfica que se selecciona, en la elección del periodo temporal, en centrar el estudio en la mercancía contenerizada, en la especificación de los tipo de grúas utilizadas y, por último, en la introducción de los tratados y la gobernanza portuaria.[Resumo] O transporte marítimo está fortemente influenciado pola evolución da economía e o comercio mundial. A actividade industrial, a producción económica, o comercio de mercadorías e o transporte marítimo, crecen a diferentes velocidades, pero, en definitiva todos estes factores dependen da evolución da economía mundial. Por outra banda, o desempeño loxístico é un dos factores claves no comercio internacional, xa que, as economías con un maior nivel de desenvolvemento loxístico crecen máis rápido, e por tanto son máis competitivas e eficientes. O interese do tema radica en que permite avaliar a conveniencia de levar a cabo novos investimentos en infraestructuras e instalacións portuarias que melloren as condicións de vida da poboación e que acrecenten a eficiencia dos portos. Nesta tese de doutoramento estimanse dous modelos. No primeiro, estúdanse os efectos sobre o PIB per cápita de cambios no transporte marítimo contenerizado e nun conxunto de variables socio-económicas dos países analizados utilizando datos panel e realizando as estimacións pertinentes (efectos fixos e erros estándar correxidos para panel). Este estudo revela que o movemento de mercadoría conteneriza presenta un impacto positivo no crecemento do PIB per cápita (en Poder de Paridade Adquisitivo expresado en dólares constantes de 2011). O segundo modelo empregado é unha análise de fronteira esotcástica, na que se analizan os efectos provocados pola existencia de guindastres pórtico e mobeis como factores determinantes de ineficiencia portuaria, e calculase a eficiencia técnica de cada porto. Ademáis, introdúcese dentro da función fronteira variables como a frecuencia de escalas ou os sistemas de gobernanza. O novedoso da análise levada a cabo nesta tese de doutoramento diferénciase dos traballos realizados até a data, na área xeográfica seleccionada, na elección do período temporal, en centrar o estudo na mercadoría contenerizada, na especificación dos tipos de guindastres utilizados e, por último, na introducción dos tratados e da gobernanza portuaria.[Abstract] Maritime transport is strongly influenced by the evolution of the economy and world trade. Industrial activity, economic production, merchandise trade and maritime transport grow at different speeds, but all these factors ultimately depend on the evolution of the world economy. On the other hand, logistics performance is one of the key factors in international trade, since economies with a higher level of logistics development grow faster, and therefore are more competitive and efficient. The interest of the subject is that it allows evaluating the convenience of carrying out new investments in infrastructures and port facilities that improve the living conditions of the population and the efficiency of ports. In this doctoral thesis, two models are estimated. The first studies the effects on GDP per capita of changes in containerized maritime transport and a set of socio-economic variables of the countries analyzed using panel data and making the suitable estimates (fixed effects and panel corrected standard errors). This study reveals that the movement of containerized goods has a positive impact on GDP growth per capita (in Purchasing Parity Power expressed in constant 2011 dollars). The second model used a stochastic frontier analysis, in which the effects caused by the existence of gantry cranes and mobile cranes as determinants of port inefficiency are analyzed and the technical efficiency of each port is calculated. In addition, variables such as the frequency of scales or governance systems are introduced within the boundary function. The originality of the analysis carried out in this thesis differs from the work carried out to date, in the geographical area selected, in the choice of the temporary period, in focusing the study on containerized goods, in the specification of the type of cranes used and, finally, in the introduction of trade agreements and port governance