PhD theses and post-doctoral training

It is widely accepted by the scientific community that our planet is experiencing a gradual climate change trend with a systematic rise in temperature, which is more pronounced during the last 50 years (Intergovernmental Panel on Climate Change – IPCC, 2018). In addition, in some regions, such as the Arctic or the Mediterranean, the degree of change in the associated processes is higher than the average increase of temperature.
There is an urgent need to intensify the research to investigate all factors that exacerbate or mitigate the effects on the earth-atmosphere energy balance. In particular, there is a limited understanding of the effect of aerosols on the characteristics and properties of clouds (indirect effect) and on their ability to absorb radiation (direct effect), an ability that changes with their ageing. These uncertainties affect both the future climate projections and the estimates of the contribution of various pollutants and other factors to the increase in global temperature and changes of other climatic parameters.
The topic of the PhD thesis is the understanding of the processes that configure, directly and indirectly the aerosols’ optical properties and feedback mechanisms on the local and regional atmospheric system of the Mediterranean. This will be accomplished with a targeted study of the optical properties of aged particles, through time series of observations in characteristic Mediterranean environments along with a comparative study of the background environment, including that of the free troposphere (ACTRIS/GAW Helmos station) and the urban background in Athens (ACTRIS/GAW Athens-Democritus station). Specific phenomena that will be examined among others are the nucleation and modelling to understand the particle condensation to cloud condensation nuclei and their direct effect in radiation transfer (scattering-absorption of radiation), including phenomena such as the wildfires in the Eastern Mediterranean and dust transport from Africa.
The study of the effect of aerosols on the climate for the above cases will be also carried out using advanced radiative transfer models. In parallel, advanced statistical models will be used to identify and extract patterns related to the study of the aerosols’ characteristics and their interaction with the climate over the Mediterranean. The complexity associated with the above interactions requires the use of both linear and non-linear models to derive properties that highlight the role of aerosols in the observed climate change the area of study.

The present Ph.D. study titled “Study on the relation of radioactive pollution and satellite observations of marine parameters and comparative analysis on a Geographic Information System”, aims at the creation of an innovative tool dedicated to the remote control of the conservative pollutants in the marine environment, by integration of in situ measurements, satellite observations and GIS for routine and emergency radiological inventory at first, but also extrapolated to other diluted pollutants too. The case study which will be investigated during this project is in the Aegean Sea, Eastern Mediterranean. Therefore, a program has been developed to explore the relations of Sea Surface Temperature, Sea Surface Salinity, Ocean Colour (OC) parameters (Chlorophyll-A concentration, Particulate Inorganic Carbon concentration, Particulate Organic Carbon concentration, Instantaneous and Daily Photosynthetically Available Radiation) and Biogeochemical parameters (Nitrates concentration, Phosphates Concentration, pH) with 137Cs activity concentrations in the Aegean Sea and analyze them to a GIS platform, as a first step for the development of this tool. SMOS, MODIS, VIIRS and CMEMS time series data are acquired processed and correlated with real time measurements of 137Cs activity concentrations from the Aegean Sea aspiring to result to a conjoint modelscheme for remote survey recording and forecasting pollutant inventory. Furthermore, additional environmental and radiological parameters and models (e.g. ecological and biological half-lives, relative biological effectiveness) will be used to the inter-relations among the study variables and biota in a GIS platform for integration to the impact level. Therefore, the innovative tool will be used for the remote detecting of: a) the inventory of radioactive pollution for a cost efficient monitoring in the marine environment to assess the radiological status, b) the impact assessment of possible radiological events and incidents, c) the estimation of the effects on the ecological pyramid (food chain) of radioactive pollution for dose estimations to both humans and ecosystems on the basis of “the one health concept” (potential capacity) whereas could be used: for the application of scenarios for forecast under accidental releases and furthermore and to investigate the application for other conservative pollutants (e.g. potential capacity heavy/trace metals). Moreover, it may be a reliable tool for support to the decision makers for early application of countermeasures in case of radiological events.

3 member supervising committee:

• Dr. G. Kitis Professor AUTH (School of Physics, Department of Nuclear and Elementary Particle Physics)
• Dr. H. Florou Collaborative Researcher NCSR”D” (Former Head of Research ERL/INRASTES/NCSR”D”)
• Dr. O. Sykioti Senior Researcher NOA (IAASARS)

The radiological characterization of activated components of nuclear reactor – as a result of neutron activation – which always appeared with surface contamination, is essential for the decision-making process on their management during decommissioning. The need of decontamination, the appropriate method selected before the dismantling / cutting process, as well as the cutting techniques to be followed in order to reduce the production of secondary radioactive waste and limit the doses to personnel, must be based on accurate radiological characterization of the radionuclides inside the material and also those which are settled as surface contamination.

A major issue most countries are facing is how to manage effectively the large volume of metallic radioactive waste from decommissioning. A prerequisite for their management is the accurate and precise radiological characterization.

In metallic radioactive wastes from nuclear reactors, there are probably radionuclides inside the materials as result of the neutron activation. At the same time radionuclides are deposited on the surface of the materials which are products of neutron activation or fission. It is important to decide in which cases the decontamination will work as well as to select the appropriate decontamination technique (s).

This thesis concerns the development of a technique for radiological characterization and segregation of metallic Radioactive Waste in different management routes, in order to decide which ones is worth to be decontaminated as well as to select the appropriate decontamination techniques (e.g. sandblasting techniques, chemical decontamination, melting).

The technique will be a combination of a non-destructive gamma spectrometry method and Monte Carlo simulations using the MCNPX code as well as sampling. The radionuclides in radioactive waste can be: either (a) gamma emitters which can easily be detected by a gamma spectrometry system; or (b) alpha or beta emitters without emitting gamma rays (difficult to detect radionuclides) and therefore can only be determined by sampling and costly radiochemical analyses. The samples are taken for determination of scaling factor (the ratio of difficult to detect radionuclides to key radionuclides which are gamma emitters). The total activity is determined by non-destructive measurement, based on gamma spectrometry as well as by the use of the scaling factors.

The presence of NORM (Naturally Occurring Radioactive Materials) has been recognized since early 1930s in petroleum reservoirs, in oil and gas production and in processing facilities. The origin of NORM waste in the oil industry is due to the formation of both sulphate and carbonate precipitates inside tubulars and other production equipment during oil production.

NORM waste is usually very low-level radioactive waste, which may be sometimes exempted from the radiation regulations, although they present an increased radiation dose rate. There is a widespread need for NORM waste to be characterized and treated properly because of their impact to the human health and environment. The successful characterization of NORM waste will significantly reduce their management costs.

The main objective of this PhD thesis is the development of a fast and cost-effective method for segregation and in situ characterization of NORM waste originating from Oil Industry by using a 1.5×1.5 in. scintillation detector LaBr3(Ce).

The last decade LaBr3(Ce) scintillation detectors have become commercially available and are very promising due to their high light yield (> 65000 photons/MeV) that results in a better energy resolution compared to NaI(Tl) detectors (< 3% FWHM at 137Cs), their decay time of 35 ns and their material density (5.29 g/cm3). Also, there is no need for cooling comparing to HPGe detectors. Thus, LaBr3(Ce) detectors could be a suitable choice for in-situ measurements of NORM.

The method development is based on a combination of experimental gamma spectrometry and computational Monte Carlo techniques for laboratory and in situ measurements.

LaBr3(Ce) scintillator was fully characterized in the laboratory environment (FWHM, energy and efficiency calibration) by using reference point sources and multi-nuclide volume sources made of epoxy material of different densities. Simulated and experimentally calculated efficiencies were compared to determine the accurate dimensions of the LaBr3(Ce) detector crystal.

Optimal NORM radionuclides and the corresponding emitting peak energies for the gamma spectrometry measurements were selected from uranium and thorium radioactive series. The activities of other radionuclides in the series, in radioactive equilibrium with the determined ones can be estimated. Also, the radionuclides not possible to be determined by gamma spectrometry or radioactive equilibrium, can be identified and sent for sampling and radiochemical analyses, if needed.

The method is being developed for Drilling the following NORM waste storage packages: (1) Metallic/plastic drum, (2) Plastic Big Bags FIBC – Flexible Intermediate Bulk Container and (3) IBC – Intermediate Bulk Container. The NORM waste characterization material is Oil Based Drilling Mud – OBM, which is a fluid used to drill boreholes into earth and used while drilling oil and natural gas wells and on exploration rigs.

Uncertainty analysis regarding the density inhomogeneities because of the material moisture will be carried out and a sampling procedure to segregate the NORM packages in groups of different origin will be developed.

Diagnosing various types of cancer at an early stage is vital to their effective treatment and is a major challenge for the scientific community. One of the approaches followed to achieve this goal is the determination of various biomarkers in biological fluids and mainly in blood serum. In particular, for the diagnosis of gynecological cancer and especially of ovarian cancer, the determination in serum of the following three biomarkers has been proposed: cancer antigen 125 (Ca-125), human epidermal secretory protein 4 (HE4), and survivin or BIRC5 (baculoviral inhibitor of apoptosis repeat-containing 5). The combined determination of these three biomarkers is expected to help both in the initial diagnosis of ovarian cancer and in the categorization of ovarian tumors, contributing significantly to the overall survival and prevention of the disease recurrence. Simultaneous determination of cancer markers in a human serum sample with low cost, high sensitivity and reliability can be achieved by appropriate biosensors and more specifically immunosensors. Optical immunosensors offer higher detection sensitivity than other types of sensors and, in addition, allow for the simultaneous detection of multiple analyzers and are subject to less interference from the sample matrix compared to other types of sensors allowing real-time detection of analytes in human serum. The project will develop optical immunosensors for the detection of the three cancer markers, Ca-125, HE4, and survivin based on the principle of Surface-Enhanced Raman Scattering (SERS) . The use of SERS substrates as solid carriers for the immunochemical assay of the three cancer markers is expected to increase the detection sensitivity relative to standard immunochemical techniques. The work to be carried out in the project includes: the development of non-competitive enzyme-linked immunoassays in microtiter wells for the three targeted biomarkers, development of sensors on SERS substrates for each one of the three biomarkers separately, and finally the development of sensors on SERS substrates for the simultaneous determination of the three biomarkers in a single run. The work is carried out in the context of the execution of the project BioNanoDiagnostiki (Τ2ΕΔΚ-03746) and is the subject of the doctoral thesis of Mrs. Georgia Gkeka. The experimental part of the work will take place at the Laboratory of Immunoassays-Immunosensors of IPRETEA in collaboration with the Department of Microelectronics of the Institute of Nanoscience & Nanotechnology of NCSR “Demokritos” and the Chemistry Department of the University of Athens (Prof. A. Economou).

Food quality and safety assessment is of major importance to both the food industry, the food producers and the consumers. For some foods, such as milk, it is necessary to test both the material and the processed products against harmful substances as quickly as possible. Such tests include the detection of aflatoxin M1 (AFM1), as well as of several pathogenic bacteria including Salmonella spp., Escherichia Coli O157: H7, Staphylococcus aureus, Bacillus cereus and Listeria monocytogenes. AFM1 is one of the most carcinogenic and toxic aflatoxins produced by fungi and therefore the European Union has set very strict maximum allowable limits for AFM1 in food. Simiral limits have been set regarding microorganisms in food for which in many cases the presence is completely prohibited due to the seriousness of the problems they might cause to human health. The detection of various harmful substances in food is carried out by analytical methods that are characterized by high sensitivity and accuracy, however they are quite time consuming, require expensive equipment and cannot be used for field analysis. For this reason, the use of immunosensors, and in particular optical immunosensors, has been explored as alternative that could replace existing methodologies. Optical immunosensors are divided into two categories, those that require the use of labels to detect the substance to be determined and the label-free ones. In the latter category are included those based on Mach-Zehnder interferometry. In this context, the project aims to develop optical immune sensors for the detection of harmful species (e.g., mycotoxins, bacteria) in food. More specifically, an immersible photonic chip is developed in which two interferometers are realized, one working and one reference interferometer. The sensor arm of the reference interferometer will be coated with an inert protein, while the sensor arm of the working interferometer will be modified with the toxin or microorganism whose detection in milk is targeted, following a competitive immunoassay. The chip integrates the complete Mach-Zehnder interferometers photonic circuit but the optical coupling and signal recording is done via a double optical fiber that connects the chip input with a white light source and its output with a digital spectral analyzer. For analysis, the chip will be immersed in a solution containing the sample and specific antibodies against each analyte without the need for microfluidic cells. The work is carried out in the context of the execution of the FOODSENS project (Τ2ΕΔΚ-01934) and is the subject of the doctoral thesis of Mrs. Dimitra Kourti. The experimental part of the work is carried out at the Immunoassays-Immunosensors Laboratory of IPRETEA in collaboration with the Department of Microelectronics of the Institute of Nanoscience & Nanotechnology of NCSR “Demokritos” and the Department of Chemistry of the University of Athens (Prof. A. Economou).

Mycotoxins are chemical compounds produced by various families of fungi and belong to a class of substances whose concentration must be determined in several categories of food due to their negative effects on human health as these compounds present, each to varying degrees, hepatotoxic, immunosuppressive, mutagenic and/or carcinogenic effects. In order to ensure the good quality of food, continuous control is required at all stages of their production and processing to verify absence of mycotoxins. However, due to the large volume of samples, it is practically impossible to analyze them in a short period. Therefore, there is a need for methods and devices capable of accurately identifying groups of harmful substances outside the laboratory. Biosensors are detection devices that can meet these needs as they enable the simultaneous identification of multiple analytes in a sample and at the same time, they can be integrated into small size devices. In this context, the aim of the project is to develop an optical biosensor for the simultaneous identification of three mycotoxins, namely Aflatoxin B1, Fumonisin B1 and Deoxynivalenol in cereal samples. The choice of the three mycotoxins was due to the fact that they are one most commonly encountered in cereals as well as due to their high toxicity. Simultaneous determination of the targeted mycotoxins is pursued through the development of an immunosensor based on White Light Reflectance Spectroscopy using silicon chips with multiple reactive areas made of silicon dioxide layer with different thickness. Each of these regions is activated by a protein conjugate of a different mycotoxin. The reflection spectrum received from all regions during the immune responses is analyzed by appropriate processing into the individual spectra allowing the reactions that take place in each region to be monitored separately without the need for moving optical components. The experimental part of the thesis is performed in the Immunoassays/Immunosensors Lab of INRASTES in collaboration with the Chemistry Department of the University of Athens (Prof. A. Economou).

Sepsis, one of the leading causes of death worldwide, occurs when a local microbial infection spreads into blood circulation triggering a vigorous inflammatory response. This response can result in multiple organ failure, which is usually fatal. Thus, early diagnosis is the only way to increase the survival rate. The aim of this project is the development of a multi-analyte optical label-free biosensor based on White Light Reflectance Spectroscopy (WLRS) for sepsis diagnosis through the rapid and accurate determination of a panel of three markers related to sepsis in blood serum samples. The targeted markers are C-reactive protein, procalcitonin and inteleukin-6. The simultaneous determination of these markers is essential to early sepsis diagnosis. In combination with the overall clinical picture of the patient could help to manage successfully the treatment. The main objectives of the project are the development of: a) label-free assays for the three targeted analytes that will be characterized by high accuracy and dynamic range covering not only the pathological serum concentrations but also the concentration range of healthy individuals, b) sensors capable for the simultaneous determination of the three analytes in the same sample by appropriate structuring and biofunctionalization of the biosensor surface, and c) a prototype instrument and accompanying software for the acquisition and processing of the signals obtained from the different assays and presentation to the final user in a concise and easy to interpret format. The project is realized in the frame of the PhD thesis of Mrs. Dimitra Tsounidi, who is the recipient of a Stavros Niarchos Foundation Industrial Fellowship in collaboration and with co-founding from the company ThetaMetrisis S.A. The experimental part of the thesis is performed in the Immunoassays/Immunosensors Lab of INRASTES in collaboration with the Chemistry Department of the University of Patras (Prof. Th. Christopoulos).

Quinazolines are anticancer agents that are clinically used for the targeted treatment of tumors where the ErbB receptors are overexpressed or bear specific mutations. These agents can also act as radiosensitizers. The purpose of this Ph.D. project is the evaluation of new anticancer quinazolines derivatives as radiosensitizers. These will belong to the following categories:

1. Derivatives that inhibit the tyrosine kinase domain and have inhibitory action in specific mutations of EGFR: deletions of exon 19 (del 746-750) or/and the exon 21 (L858R) (1^st generation)
2. Derivatives that have broader activity to overcome EGFR resistant mutations to the 1^st generation and inhibit all ErbB family signaling (2^nd generation).
3. Derivatives that have high specificity for the T790 mutation of EGFR, which is the most common mechanism of resistance to the therapy using the first two generation quinazolines (3^rd generation).

For the purpose of this study, the new produced quinazolines derivatives are evaluated for their anti-cancer activity and for their ability of radiosensitizing. The most promising radiosensitizers of this study will be compared with the current quinazolines that are used nowadays in clinical routine. The ultimate goal is to propose new promising anticancer agents that can also act as radiosensitizers.

The extensive use of low doses of ionizing radiation (≤100 mSv) for diagnostic and therapeutic purposes increases concern on the radiation safety of both patients and physicians. Ionizing radiation exposures have almost doubled in the last decade, mainly due to the rise in medical diagnostic and therapeutic interventions, which are responsible for approximately 40% of the cumulative effective dose of radiation to the population. Despite the wide use of low-ionizing-radiation doses and the recent evidence that cancer risk may increase even at lower doses (between 50-100 mSv)  the effects of such exposures in patients exposed to cardiac images and interventional cardiology procedures remain unclear.

According to epidemiologic literature, the impact of low doses are hampered by limited statistical power at radiation levels of less than 100 mSv, even for very large studies. Alternatively, the investigation of the radiation-induced effects after exposure to low doses could be carried out with radiobiological data. The present study’s objective is to determine the biological effects of low doses in patients exposed to ionizing radiation during interventional cardiology procedures by using several biomarkers and the correlation of these doses with the potential development of cancer.

The 1^st  objective involves the use of molecular and cytogenetic biomarkers to investigate the biological effects delivered to patients after their exposure to cardiovascular procedures at Onassis Cardiac Surgery Centre. Blood samples (6-7 ml) from  patients who undergo ordinary interventional cardiology procedures, such as Coronary Angiography, Percutaneous Transluminal Coronary Angioplasty, and ablation are collected directly before, and immediately after the end of the procedure and incubated in heparin-containing vials for each time interval. The induction and repair of DSBs is visualized and quantified by using the highly sensitive epigenetic biomarker γ-H2AX, a phosphorylated histone H2A variant. Chromosomal aberrations and micronuclei are both crucial predictors of the degree of radiation damage. The frequency of dicentric chromosomes and micronuclei is detected and is compared to the baseline.

Furthermore, the 2^nd objective involves the potentiation of the unrepaired DSBs to induce asymmetric cell divisions and chromosomal instability, is tested by using the methodology of CB-iFISH that combines cytokinesis block mediated cell culturing with interphase Fluorescence in situ Hybridization (CB-iFISH) in human lymphocytes that are irradiated in vitro with low ionizing radiation doses. This combined methodology enables the visualization of centromeric regions in the micronuclei as well as the monitoring of the chemically-induced asymmetric cell divisions. The evaluation of the potential ability of the unrepaired radiation-induced DSBs to induce chromosomal instability and asymmetric cell division, will contribute in the research of radiobiology and radioprotection.

Radiation Therapy (RT) is often used in conjunction with other therapies such as chemotherapy or tumour removal surgery as an integral part of both curative and palliative treatments for cancer. While RT is one of the most effective single modalities in cancer therapy, it can have significant side effects both during and after treatment, which can impact both the quality and the duration of life. Although rapid technological advances have led to a more precise delivery of radiation dose and to a decreased risk of side effects, there is still a significant need for personalized treatment to be achieved through the development of predictive tools that may guide therapy decisions. Project’s objectives are the prediction of individual radiosensitivity in clinical practice, the investigation of the potential of combining radiation therapy with G2/M cell cycle checkpoint abrogators in vitro, as well as, the evaluation of the efficiency of advanced radiotherapy techniques such as VMAT and IMRT, using phantoms in conjunction with cytogenetic techniques.

Dual-modality contrast agents (DMCA), such as radiolabeled magnetic nanoparticles, are promising candidates for a number of diagnostic applications, since they combine the advantages of two different imaging modalities, namely single photon emission computed tomography (SPECT) or positron emission tomography (PET) with magnetic resonance imaging (MRI). The benefit of such a combination relates to the interpretation of the obtained imaging information in a more efficient and accurate way so that underlying diseases are reliably diagnosed at early stages.

The objective of the project focuses on a novel DMCA and refers to synthesis, basic characterization (crystallographic, morphologic etc.), thorough evaluation of the physical properties (radioactivity, magnetization etc.) and eventually both in vitro and in vivo evaluation on donated human blood and animal models. The DMCA consists of magnetic nanoparticles, mainly iron oxides (i.e. magnetite Fe₃O₄ and/or maghemite Fe₂O₃), radiolabeled with gamma-emitting (i.e. Technetium-99m) and/or positron-emitting (i.e. Gallium-68) isotopes. The DMCA is evaluated extensively all the way up to (i) in vitro biocompatibility experiments conducted on donated human blood, (ii) in vivo biodistribution experiments on animal models and (iii) imaging applications in animal models by means of SPECT/MRI and PET/MRI standard modalities.

For the realization of the project, the following experimental techniques are used:
Wet chemistry methods: for the preparation of the DMCA
X-Ray Diffraction (XRD): to crystallographically characterize the starting materials and the DMCA
Superconducting Quantum Interference Device (SQUID): to study the magnetic properties of starting materials and the DMCA.
Atomic Force Microscopy (AFM): to study the morphology of the DMCA and to obtain reliable quantitative information on their geometric characteristics at the nanoscopic level.
Optical Microscopy (OM): to study the morphology of the DMCA and to obtain reliable quantitative information on their geometric characteristics at the microscopic level to check the possible existence of agglomerates.
Standard MRI unit employed in clinical practice.
Experimental small-animal SPECT camera.
Experimental small-animal PET camera.
All ex vivo biodistribution studies on animal models are conducted at the animal experimentation facilities of the Radiochemical Studies laboratory, I.P.R.E.T.E.A, NCSR “Demokritos”, in compliance with European and national legislation. These studies have been further approved by the Ethics Committee of the NCSR “Demokritos” and animal care and procedures followed are in accordance with institutional guidelines and licenses issued by the Department of Agriculture and Veterinary Policies of the Prefecture of Attiki.

Cancer theranostics is a relatively new term that encompasses both diagnosis and treatment. The hindrances of conventional diagnostic and therapeutic agents are plenty, compromising not only the therapeutic process but even the life of the patient. Therefore, the need for more evolved, cancer-specific and effective theranostic tools is imperative. The development of an effective diagnostic but at the same time therapeutic nanosystem would be a major breakthrough in cancer theragnosis.

The aim of this project is to develop a novel theranostic agent with improved properties that will actively target tumor sites. In particular, the proposed radiolabeled functionalized nanocrystal clusters (Co-CNCs) of magnetic nanoparticles (MNPs) will be capable of dual-modality Positron Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) attributed to the presence of the radioisotope Gallium-68 (⁶⁸Ga) and the MNPs, respectively. Furthermore, the presence of a chemotherapeutic agent is anticipated to induce a strong antineoplasmatic effect while the addition of a pharmacophore enables us to achieve targeted delivery and improved selectivity of the nanostructure. A triple therapeutic effect will be achieved, after targeted delivery of the functionalized MNPs, attributed to the simultaneous presence of the chemotherapeutic agent, the therapeutic radioisotope Lutetium-177 (¹⁷⁷Lu) and the application of magnetic hyperthermia (MH)

With the main goal of early diagnosis of various cancers, Radiopharmaceutical Science is directly linked to the best possible prognosis and the therapeutic approach that will be chosen afterwards.

The objective of this dissertation is the synthesis, characterization, and comparative evaluation of multimodal ^99mTc and ⁶⁸Ga imaging complexes, which carry as a pharmacophore moiety mannosylated dextrans of different molecular weight.

The radiolabeled mannosylated dextrans have been extensively studied for use in sentinel lymph node detection (SLND) and cancer diagnosis, and consist of a dextran backbone, several mannose moieties for the recognition from mannose receptors in sentinel lymph node macrophages as well as a chelating agent, necessary for binding to the radioactive metal.

The sentinel lymph node theory assumes that the first lymph node to receive lymph and metastatic cells from the primary site of the tumor is also the first site of the lymphogenic spread of the disease, that there are no skip metastases and that the absence of metastatic disease in the sentinel lymph node implies the absence of metastases in the entire lymphatic pathway. Thus, with the administration of these complexes, it is possible to in vivo visualize and localize the sentinel lymph node in a non-invasive manner.

Objective of the project is the development of radiolabeled tyrosine kinase inhibitors that could be potentially used as radiopharmaceutical drugs for epidermal growth factor receptor family (Erb B) and specifically EGFR.

EGFR is overexpressed in a variety of tumors and involved in several signaling pathways regulating various cellular functions associated with carcinogenesis, metastasis, uncontrollable cell proliferation and resistance to some therapeutic methods. The EGFR inhibitors’ radiolabeling is among interesting issues of Radiopharmaceutical Chemistry, contributing to a valid diagnosis of tumors overexpressing EGFR and its metastases, used to monitor the patient’s response to the proposed treatment and to determine the appropriate treatment.

Following this perspective, the dissertation aims to develop radiolabeled EGFR inhibitors with radioisotopes used in Νuclear Μedicine for diagnosis and treatment. The inhibitors are either analogues of 4-anilinoquinazoline core or other structures used in Pharmaceutical Chemistry. The new analogues are evaluated as potential radiopharmaceuticals by in vitro studies, stability and lipophilicity studies as well as in vivo pharmacokinetic and / or imaging studies on experimental animals.

Urban areas of high population density are important research areas for the exposure of the public to pathogenic environmental factors, namely atmospheric pollutants. To assess the risks and impacts of air pollution and to design control policies, it is necessary to accurately quantify the daily exposure of citizens. The object of the present study is to assess urban population exposure to air pollutants by measuring each subject’s exposure, combining location, activity and air pollution data in various microenvironments that each volunteer moves, using new, low-cost static and portable sensors. The experimental process has been a combination of personal and static monitoring sensors of high-technology, as well as, low cost. The PhD thesis aims to create a high spatial and temporal analysis sampling methodology in order to, accurately, estimate population exposure to air pollution through personal exposure, by setting a network of technologically upgraded, low cost, portable and static, real-time, exposure monitoring sensors, combined with qualitative data to be obtained through questionnaires. The development of a predictive computational model based on direct, real-time, exposure measurements, which will assess the risk to human health as a result of changing conditions, such as socio-economic parameters, health parameters, etc. is the main research outcome of this dissertation. The above mentioned model / tool, will comprise a decision support system for policy makers to develop strategies to improve air quality. This will be due to the fact that they will have valid procedures for  assessing the exposure of citizens to gaseous pollution and its health effects. The long-term perspective of the dissertation’s results is the promotion of this research methodology to be used in studies of integrated population exposure assessment, in large urban centers.

The aim of the present research is to study the presence and environmental fate of short chain chlorinated alkanes (SCCPs), which is a new category of persistent organic pollutants (POPs), in the urban environment. These compounds are widely used industrially as additives in the processing of metals, as plasticizers, in rubber, in paints and more, while their production has increased the last years. During their production and use they are released into the environment and distributed in the various environmental compartments. Research shows that SCCPs are toxic compounds and have long-term carcinogenic effects. In addition, SCCPs meet the criteria for their designation as POPs, for the possibility of causing adverse effects on organisms, their accumulation in them and their transport over long distances. As a result of this behavior SCCPs are detected in the atmosphere, aquatic environment and organisms, even in remote areas such as the Arctic and Antarctic. In addition, research shows that SCCPs are toxic compounds and have long-term carcinogenic effects. Their danger has led the EU to include them in priority water pollutants. Also, these compounds are characterized as harmful to the marine environment. Moreover, the Environmental Protection Agency (EPA) classifies them as toxic compounds for aquatic organisms. The number of surveys on the levels and environmental fate of SCCPs in Europe is limited. As far as Greece is concerned, there is no evidence for these associations. In the context of this study, SCCPs will be identified in the atmosphere of Athens, in order to determine the environmental concentrations, to investigate the possible sources of pollution and to evaluate the exposure to these pollutants.

The main purpose of Ms. Ioanna Koromilas’ phD dissertation is to propose a general risk model for assessing a passenger ship’s fire safety level at the design stage. It will be based on the principles of quantitative risk assessment (QRA), as set out in the alternative design requirements of the International Maritime Organization (IMO). This method will support the design of passenger ships, whilst allowing its future application to other ship types. The proposed model will be able to determine the safety level of a ship by enhancing the decision-making process for the evaluation of various alternative designs. More specifically, both the conceptual and mathematical framework for calculating fire risk will be developed, as well as will be employed advanced fire and evacuation simulation tools (including Fire Dynamics Simulator and PathFinder). The mathematical model will be used to demonstrate the method on a cruise ship.

Ms Koromila’s phD is conducted at the School of Naval Architecture and Marine Engineering of the National Technical University of Athens and is supervised by Professor K. Spyrou, Dr Zoe Nivolianitou, and Professor G. Athanasoulis.

Some of the most important challenges in the field of Monte-Carlo (MC) reactor analysis are the integration of thermal-hydraulic feedback, the extension of the method to the study of transient phenomena, and the convergence acceleration of the MC algorithm for the analysis of reactor criticality. This thesis tries to meet these three challenges by suggesting algorithms that can cope with the encountered issues.

As a first step, this work investigates the insertion of Thermal-Hydraulic (T-H) feedback to static Monte-Carlo. Initially, a “serial” coupling scheme, that corresponds to the sequential execution of the involved solvers, is developed to provide reference results. Then, this work suggests the use of an approximate Newton coupling algorithm. The motivation for this approach is the interest in an algorithm that can maintain the distinct treatment of the involved fields of physics within a tight coupling context. This work investigates the behaviour of the proposed method when the open-source MC neutronics code OpenMC is coupled with the T-H code COBRA-EN. The performance and the accuracy of the proposed coupling scheme are evaluated and compared with those of the traditional serial iterative scheme. The results show a significant numerical improvement leading to more accurate results.

Secondly, this thesis investigates the development of a Monte-Carlo dynamic module in OpenMC for the analysis of transient phenomena. A straightforward physical treatment of a transient problem requires the assessment of the temporal evolution of the simulated neutrons, which is no present in static Monte-Carlo; however, this is not adequate. To properly analyze transient phenomena, the simulation of delayed neutrons and other necessary extensions and modifications are needed. The selected method has been recently proposed in the literature and is here inserted in OpenMC following the code’s features. Hence, an extra challenge that this work meets is the desire for an optimum embodiment in OpenMC, minimizing the necessary modifications and maximizing the advantage resulting from its existing capabilities. Moreover, the addition of dynamic T-H feedback is investigated. The key points of the developed module, as well as the results of the analysis of various numerical experiments, are presented and discussed. The results confirm the successful development of the dynamic Monte-Carlo module, pointing out its capability to effectively analyze various reactor core transients.

Finally, a new convergence acceleration method of the Monte-Carlo classical Source Iteration (SI) is presented. Whereas the classical SI guarantees the convergence to the fundamental eigenmode, very often the convergence is slow. In this thesis, an alternative version of the traditional Monte-Carlo SI algorithm is formulated, developed, and analyzed to accelerate the Monte-Carlo criticality analysis numerically. More specifically, the Jacobian-Free Newton Krylov method is adopted in the Monte-Carlo k-eigenvalue context to accelerate the convergence. The method is evaluated in three test cases showing better performance than the traditional Coarse-Mesh Finite-Difference acceleration technique.

The necessity for precise simulations of a nuclear reactor especially in case of complex core and fuel configurations has imposed the increasing use of Monte Carlο neutronics codes. Besides, a demand of additional stochastic codes’ inherent capabilities has emerged regarding mainly the simulation of the temporal variations in the core isotopic composition as well as the incorporation of the Thermal Hydraulic feedback. In addition to the above, the design of innovative nuclear reactor concepts such as the Accelerator Driven Systems (ADSs, a promising alternative for an improved management of highly active nuclear waste), imposed extra requirements of simulation capabilities. More specifically, the combination of an accelerator and a nuclear reactor in the ADS requires the simulation of both subsystems for an integrated system analysis. Therefore a need arises for more advanced simulation tools, able to cover the broad neutrons energy spectrum involved in these systems. In the frame of this thesis, ANET, a new stochastic code was further developed aiming to satisfy the following issues: a) the reliability in simulating certain reactor parameters important to safety, i.e. the reactor criticality as well as the neutron flux and fission rates, b) the internal “on-the-fly” core inventory evolution and fuel depletion calculation and c) the improvement of the ADSs simulation. The ANET reliability in analyzing typical configurations was tested using various installations and international benchmarks along with parallel simulations by different codes. The results obtained by the ANET code verify its ability to successfully simulate important parameters of critical and subcritical systems. Also, the application of the enhanced ANET for dynamic reactor core analysis is very promising since it indicates the code capability to inherently provide a reasonable prediction for the core inventory evolution. Lastly, the inherent ANET capability of analyzing ADSs was demonstrated by the satisfactory code performance in the analysis of a prototype accelerator driven system fulfilling thus the requirements of an advanced stochastic neutronics code with scope of application at both conventional and innovative nuclear fission reactors.

This project aims to develop novel tools for energy disaggregation and monitoring of device health status. These tools will perform analysis of complex energy load time-series using real-time pattern recognition/matchmaking and hardware accelerated algorithms, and will transmit the recognised events to a main server.

During its first 20 months, the project has successfully achieved the milestones set in the proposal. Following the initial training of the Fellow -also involving the review of cutting edge methodologies and current trends-, a prototype was developed for High frequency sampling of energy data. Deployment of the prototype to a commercial building has so far provided over 1Tb of energy consumption and ground truth data.

Publications:

1. Kotsilitis S., Marcoulaki E., Kalligeros E., Mousmoulas Y., 2018. Energy efficiency and predictive maintenance applications using smart energy measuring devices. In S. Haugen, A. Barros, C. van Gulijk, T. Kongsvik & J.E. Vinnem (eds.) “Safety and Reliability – Safe Societies in a Changing World”, CRC Press, ISBN 978-0-8153-8682, pp. 987-994, https://www.taylorfrancis.com/books/9781351174657

2. Kotsilitis S., Marcoulaki E., Kalligeros E. & Mousmoulas Y., 2018. Distributed edge computing paradigm with dedicated devices for energy efficiency and predictive maintenance applications. In “Industrial Internet of Things and Smart Manufacturing”, Springer Series on Lecture Notes on Data Engineering and Communications Technologies (NDECT), in press (ISBN: 978-1-912532-06-3)

3. Kotsilitis S., Marcoulaki E., Kalligeros E., 2019. High Frequency Energy Disaggregation Sampling and Analysis towards Predictive Maintenance Applications. In M. Beer & E. Zio (eds.) “Proceedings of the 29th European Safety and Reliability Conference”, Research Publishing, Singapore, pp. 1214-1222, ISBN: 978-981-11-2724-3; https://doi.org/10.3850/978-981-11-2724-3.

Hellenic Seawaters, with the Aegean Archipelago consisting their center, form one of the most important maritime links of the Mediterranean Sea. At the same time, they are also characterized by an extremely rich and unique marine environment with a large coastline, thousands of islands and intense activity of ships. The coexistence of so many important countries around the Mediterranean along with the geomorphology of their coasts has resulted in increased maritime traffic through specific routes in the Aegean Sea.

These routes represent a unique example of an area where a serious marine accident with high environmental impact may happen. Hence, the need to reduce the possibility of maritime accidents in the Aegean is of vital importance, as a possible accident would affect all the social, economic, environmental and cultural sectors of Greece and the wider region of the Eastern Mediterranean basin. There is therefore a pressing need to identify ships with a potentially high accident risk crossing the Aegean Sea by developing a suitable model and highlighting areas with increased environmental risk in the area.

The current PhD thesis stems from the above-mentioned need and its goal is the monitoring and reduction of ecological risk in Greek national waters and especially in the Aegean Sea, due to a marine accident. The probability of a vessel accident occurrence is due to internal (vessel) parameters (age and kind of the vessel etc), and external (dynamical) parameters (weather etc). The former present a static character because they cannot change during the travel of a vessel. Instead the latter have a dynamic character because they continuously change. Another important aspect of the current research is the development of a consequences model which will refer to the estimated cleanup cost after a certain accident occurs. The model developed is based on Bayesian Networks and Fuzzy Logic.

Thermonuclear fusion offers the possibility of a safe, abundant, clean and sustainable source of energy using small amounts of fuel (hydrogen isotopes). High temperatures as well as high fluxes of neutrons and other highly energetic particles during the operation of a magnetic confinement plasma device (Tokamak) make imperative the use of materials that are resistant to high temperatures and radiation. Tungsten (W) is a candidate plasma facing material for the interior walls of a fusion reactor due to its high melting point, high thermal conductivity, low tritium retention and heat stress resistance. However, tungsten suffers from brittle behavior at low temperatures due to the relatively high ductile to brittle transition temperature (DBTT) which ranges between 400 and 700 K, limiting its exploitation.

The objective of Vasileios Chatzikos’ PhD is to study the transmutation products of tungsten as well as the created open volume defects as a function of the irradiation temperature, the neutron irradiation dose and the tungsten microstructure. The experimental methods used to achieve this investigation are gamma-spectroscopy and positron annihilation lifetime spectroscopy (PALS).
Three types of tungsten are under investigation a) single crystal tungsten W (100), b) cold rolled tungsten sheet and c) double forged tungsten in the form of a square bar (ITER grade). These materials have been irradiated at the BR2 research reactor in Belgium, at four temperatures (600, 800, 900 and 1200 C) and at irradiation doses corresponding to 0.1, 0.18, 0.5 and 0.75 displacements per atom (dpa).

The experimental results of gamma-spectroscopy measurements on tungsten samples lead to the identification and determination of the radioactive isotopes of Tungsten, Rhenium and Tantalum concentrations as a function of the neutron irradiation dose. Through the comparison of the experimental values with theoretical calculations, using MCNP neutron transport code and FISPACT-II radionuclide inventory code, the quantification of the transmutation products in the irradiated tungsten is achieved.
Employing Positron Annihilation Lifetime Spectroscopy (PALS) spectroscopy technique the evolution of the open volume defects type (vacancies, dislocations and vacancy clusters) and their relative concentrations is determined as a function of irradiation temperature and dose. Moreover, the evolution of the open volume defects will be assessed in correlation with the transmutation products.

Understanding the radiation effects of energetic ions and neutrons on steel has considerable scientific interest and additionally important technological impact related to energy production by fusion. These two aspects are interrelated, as a basic understanding of the phenomena will promote the development of radiation resistant materials, necessary for the implementation of the international plans for a fusion reactor in the next twenty years.

Ferritic–martensitic steels based on Fe–Cr alloys are candidate materials for the structural components of fusion power plants. These materials will be exposed to extremely high neutron fluxes and elevated temperatures.

Self – ion irradiation can simulate the neutron – induced radiation damage in materials, because the dominant damage arises from Primary Knock-on Atoms (PKA) in which the neutron energy is transferred.

Decomposition occurring in FeCr alloys during thermal aging is typically occurring between 773 and 813 K, temperatures at which the thermal diffusion is adequate to drive it. Under irradiation, short-range ordering or decomposition can be observed at even lower temperatures, because the point defect supersaturation accelerates diffusion processes i.e. radiation induced segregation (RIS). RIS is the process by which the composition of an alloy is altered due to preferential participation of certain species with the vacancy and/or interstitial flux to sinks.

Τhe objective of the PhD thesis is the study of the effect of iron ion irradiation on the properties of Fe-Cr films as a function of Cr content, irradiation dose and temperature, damage rate and iron ion energy. The focus will be on the determination of the global equilibrium conditions which are reflected by the solute Cr content in the matrix after irradiation. Also the observed phenomena will be related to the mechanical behavior of the FeCr films under irradiation.

High temperatures, as well as high fluxes of neutrons and other highly energetic particles during the operation of a magnetic confinement plasma device (Tokamak) make imperative the use of materials that are resistant to high temperatures and radiation. Tungsten is a candidate plasma facing material for the interior walls of a fusion reactor due to its high melting point, high thermal conductivity, low tritium retention and heat stress resistance. However, tungsten suffers from brittle behavior at low temperatures due to the relatively high ductile to brittle transition temperature, limiting its exploitation.

The objective of Dimitris Papadakis’ PhD is the study of the annealing effects of fission neutron irradiated tungsten materials.

Selected neutron irradiated tungsten materials will be annealed in the temperature range of 600 – 1500 C with the aim of studying the restoration of the properties of tungsten to the pre-irradiated state. Neutron irradiation causes damage in a material, resulting in the creation of defects. With the use of Positron Annihilation Lifetime Spectroscopy the type and percentage of open volume defects will be determined. Additionally, optical and electron microscopy (SEM), as well as X-ray diffraction (XRD) will be used to determine the changes in the structure of the materials during annealing and irradiation.

Annealing at very high temperatures results in structural changes of the tungsten material through diffusion and the interaction of various defects in the crystalline lattice, or even through the mechanism of recrystallization. These structural changes lead into the change of the mechanical and electrical properties of the materials. Through various techniques of characterization of mechanical properties (Macro-Nano Indentation, Impulse Excitation) and electrical properties (DC Resistivity), structural changes will be correlated with changes in the physical properties of the material.

The PhD thesis will be defended at the Physics Department of UoA.

Objective of the project is the study of the interactions between radiation defects and solute atoms in ferritic steels based on the binary Fe‑Cr system. The experimental results will be compared with theoretical prediction in order to validate theoretical models.

Ferritic steels are considered the main choice as structural materials for the future fusion power plants. The impurities solute atoms such as carbon (C) and nitrogen (N) are main components in steels that define their mechanical and thermal properties and play also an important role to the configuration of their microstructure. During the ion irradiation the interaction of energetic particles with matter can cause atomic displacements leading to several types of defects such as vacancies and interstitial atoms. After their creation defects can diffuse and interact with solute impurities resulting to changes in microstructure and therefore to macroscopic properties.

In order to study the radiation defects, samples of ferritic alloys are irradiated by protons at NCSR “Demokritos” TANDEM accelerator at the facility IR2 [link: infrastructure/IR2]. The irradiations are performed at cryogenic temperature so the defects are immobile into the sample. Subsequently, through a post-irradiation thermal annealing process of the samples the defects can diffuse and their evolution is observed by in-situ electrical resistivity measurements. Information about the interactions between radiation defects and impurities can be revealed by comparing the resistivity recovery spectrum of samples with different impurity concentration.

Interaction between plasma and plasma facing materials is an issue of great importance for the safe operation of the fusion devices. Beryllium (Be) is a candidate material to be used in the main chamber of ITER and the future fusion devices based on magnetically confined plasma. Beryllium due to its low atomic number prevents the dilution of plasma and presents low fuel retention which is crucial for the life time of the wall and the conservation of the fuel. Moreover, beryllium is an oxygen getter which reduces oxygen impurities inside the vessel.

The objective of Pavlos Tsavalas’ PhD is the investigation of plasma facing material from the JET tokamak main chamber after the interaction with the plasma in order to assess material erosion, fuel retention and material deposition from other areas of the tokamak. In order to achieve this investigation, the following methods have been used:

1. Ιon beam analysis with deuteron (2H) and helium (3He) to detect, quantify and assess the depth profile of the light elements (deuterium, beryllium, carbon, nitrogen and oxygen) and the micro-beam to depict the mapping of the same elements on the surface.
2. Differential cross sections measurements of deuteron reaction on beryllium which are necessary for the quantitative results of the ion beam analysis.
3. X-Ray fluorescence to assess the relative concentration of the heavier elements (chromium, iron, nickel, molybdenum and tungsten) in the whole volume of the samples.
4. Scanning electron microscopy with energy dispersive spectroscopy of X-rays to investigate the mapping of the heavier elements and the morphology of the surface.
5. X-Ray diffraction to assess any compound formation in the samples.

The PhD thesis will be defended in at the School of Applied Mathematical and Physical Sciences of National Technical University of Athens.

Mr. Achilleas Krikas will develop an in-silico trial that will allow the deep analysis of vascular diseases and will be sought to be compared with existing in-vitro and in-vivo experiments so as to assure its validity. The modeling tool will incorporate several computation modules that will be able to simulate and analyze the pathway of the particles. More, specifically, the main focus will lie on the dispersion of particles in blood, the adhesion of particles on endothelium and diffusion of particles within the arterial wall.