Οι ολοένα αυξανόμενες ενεργειακές απαιτήσεις των σημερινών κοινωνιών και το γεγονός ότι οι ηλεκτρικές συσκευές και εξοπλισμός έχουν γίνει αναπόσπαστο κομμάτι της καθημερινότητάς μας, έχει οδηγήσει στην αναγωγή του ηλεκτρισμού σε κοινωνικό αγαθό. Παρόλα αυτά, η υπερβολική του χρήση έχει προκαλέσει έντονες ανησυχίες στο κοινό, όσον αφορά τα ηλεκτρομαγνητικά πεδία που εκπέμπονται λόγω του εναλλασσόμενου ρεύματος. Η παρούσα εργασία αποσκοπεί να ξεδιαλύνει το «θολό τοπίο» γύρω από τις επιδράσεις των χαμηλόσυχνων ηλεκτρομαγνητικών πεδίων (δηλαδή τα εκπεμπόμενα πεδία από τις εγκαταστάσεις ηλεκτρικής ενέργειας και τις ηλεκτρικές συσκευές) στην ανθρώπινη υγεία κι έτσι να συνεισφέρει ως ένα βαθμό στην άρση των ανησυχιών του κοινού και των επιπτώσεων που αυτές συνεπάγονται. Ειδικότερα, η εργασία μπορεί να συνοψιστεί ως εξής: Στο Κεφάλαιο 1 γίνεται μια θεωρητική αναφορά στις βασικές έννοιες της ηλεκτρομαγνητικής ακτινοβολίας. Προσδιορίζονται οι επιβλαβείς ακτινοβολίες για την υγεία καθώς επίσης και οι ιδιότητες των χαμηλόσυχνων ηλεκτρομαγνητικών πεδίων. Ακόμη, παρουσιάζονται οι κανονισμοί προστασίας και τα όρια έκθεσης σε ηλεκτρομαγνητικά πεδία, τόσο στην Ευρώπη, όσο και στην Ελλάδα. Στο Κεφάλαιο 2 παρουσιάζονται αναλυτικά οι διαφορετικές πηγές χαμηλόσυχνων ηλεκτρομαγνητικών πεδίων και γίνεται σύγκριση των πεδιακών εντάσεων στο περιβάλλον τους. Στο Κεφάλαιο 3 γίνεται λόγος για τη βιολογική επίδραση των ηλεκτρομαγνητικών πεδίων. Παρουσιάζονται οι επιδράσεις τους στην ανθρώπινη υγεία και οι δράσεις που λαμβάνουν χώρα τόσο για τη μελέτη αυτών των επιδράσεων, όσο και για την προστασία του κοινού. Στο Κεφάλαιο 4 γίνεται ανασκόπηση του προτύπου λήψης μετρήσεων που ακολουθήθηκε. Εξετάζεται το πρότυπο ΙΕC 61786 για μέτρηση χαμηλόσυχνων ηλεκτρομαγνητικών πεδίων και αναφέρονται κάποια χαρακτηριστικά του προτύπου EN 50413 για μέτρηση ηλεκτρομαγνητικών πεδίων όλων των συχνοτήτων. Στο Κεφάλαιο 5 περιγράφεται ο σκοπός και ο εξοπλισμός των μετρήσεων. Παρατίθενται τα αποτελέσματα των μετρήσεων συνοδευόμενα με διαγράμματα και σχόλια επί της μεταβολής της μαγνητικής επαγωγής στο περιβάλλον σχολικών συγκροτημάτων. Τέλος συνοψίζονται τα συμπεράσματα που εξάγονται με βάση όσα εξετάστηκαν στην παρούσα εργασία. Σύμφωνα με αυτά δεν πρέπει να υπάρχει κανένας λόγος ανησυχίας για την επίδραση των χαμηλόσυχνων ηλεκτρομαγνητικών πεδίων στην ανθρώπινη υγεία, καθώς τηρούνται όλοι οι κανονισμοί, οι οποίοι εμπεριέχουν μεγάλους συντελεστές ασφαλείας. / The ever-increasing energy demands of today's society and the fact that electrical appliances and equipment have become an integral part of our daily lives has led to the deduction of electricity into social good. However, its excessive use has caused great concern to the public, regarding to electromagnetic fields’ emissions because of the AC current. This essay aims to unravel the "misty area" around the effects of low frequency electromagnetic fields (i.e. fields emitted from power systems and electrical appliances) to human health and thus contribute to some extent to the disentanglement of public preoccupations and the consequences arising therefrom. In particular, this essay can be summarized as follows: In Chapter 1 there is a theoretical report in the basic concepts of electromagnetic radiation. Harmful radiation as well as the properties of low frequency electromagnetic fields is identified. Moreover, protection regulations and limits on exposure to electromagnetic fields are presented, both in Europe and in Greece. In Chapter 2 different sources of low frequency electromagnetic fields are presented and the fields’ intensities in their environment are compared. Chapter 3 talks about the biological effects of electromagnetic fields. It also presents the effects on human health and the actions that take place for the study of these effects, and for the public’s protection. Chapter 4 gives an overview of the pattern of taking measurements that was followed. The IEC 61786 standard for measuring low frequency electromagnetic fields is examined and some features of the standard EN 50413 for measuring electromagnetic fields of all frequencies are presented. Chapter 5 describes the measurements’ purpose and equipment. The measurements’ results are given, which are accompanied by charts and comments about the change of the magnetic induction around school buildings. Finally, the conclusions based on this essay’s data are summed up, according to which, there should be no reason for public concern about the effect of low frequency electromagnetic fields on human health, since compliance with all special regulations, which contain large safety factors, is being performed.

This dissertation develops surface integral equations using constraint-based Helmholtz decompositions for electromagnetic modeling. This new approach is applied to the electric field integral equation (EFIE), and it incorporates a Helmholtz decomposition (HD) of the current. For this reason, the new formulation is referred to as the EFIE-hd. The HD of the current is accomplished herein via appropriate surface integral constraints, and leads to a stable linear system. This strategy provides accurate solutions for the electric and magnetic fields at both high and low frequencies, it allows for the use of a locally corrected Nyström (LCN) discretization method for the resulting formulation, it is compatible with the local global solution framework, and it can be used with non-conformal meshes. To address large-scale and complex electromagnetic problems, an overlapped localizing local-global (OL-LOGOS) factorization is used to factorize the system matrix obtained from an LCN discretization of the augmented EFIE (AEFIE). The OL-LOGOS algorithm provides good asymptotic performance and error control when used with the AEFIE. This application is used to demonstrate the importance of using a well-conditioned formulation to obtain efficient performance from the factorization algorithm.

Underwater acoustic pressure transducers measure pressure fluctuations, a scalar parameter of the acoustic field. Acoustic vector sensors contain an omnidirectional pressure transducer (omni) and also bi- or tri-axial sensing elements that respond to either the particle velocity or pressure gradient of the acoustic field; which are vector quantities. The amplitude of the signal output of each directional channel of a vector sensor is proportional to the orientation relative to the direction of acoustic pressure propagation. The ratio of the signal amplitudes between two directional channels and the cross-spectra between the vector sensor omni and directional channels enable one to estimate the bearing to the source from a single point measurement. In order to accurately estimate the bearing across the usable frequency band of the vector sensor, the complex sensitivities of the omni and directional channels must be known. Since there is no standard directional reference transducer for a comparative calibration, the calibration must be performed in an acoustic field with a known relationship between the acoustic pressure and the acoustic particle velocity. Free-field calibrations are advantageous because this relationship is known for both planar and spherical wave fronts. However, reflections from waveguide boundaries present a practical limitation for free-field calibrations, especially at low frequencies. An alternative approach is to perform calibration measurements in a standing-wave field, where the relationship between pressure and particle velocity is also known. The calibration facility described in this thesis is composed of a laboratory-based, vertically-oriented, water-filled, elastic-walled waveguide with a piston velocity source at the bottom end and a pressure release boundary condition at the air/water interface at the top end. Some of the challenges of calibrating vector sensors in such an apparatus are discussed, including designing the waveguide to mitigate dispersion, mechanically isolating the apparatus from floor vibrations, understanding the impact of waveguide structural resonances on the acoustic field, and developing the calibration algorithms. Data from waveguide characterization experiments and calibration measurements are presented along with engineering drawings and calibration software. / text

To preserve multi-centennial length variability in annual tree-ring chronologies, the Regional Curve Standardization (RCS) method calculates anomalies from a regionally common, non-climatic age-trend function. The influence of various factors on the estimation of the regional curve (RC) and resulting RCS- chronology is discussed. These factors are: the method of calculating anomalies from the age-trend function, estimation of the true pith offset, the number of series used, species composition, and site characteristics. By applying RCS to a collection of millennium-length tree-ring data sets, the potential and limitations of the RCS method are investigated. RCS is found to be reasonably robust with respect to tested factors, suggesting the method is a suitable tool for preserving low-frequency variance in long tree-ring chronologies.

We use a simulation model to generate tree-ring like data with systematic growth forcings and subject it to two methods of standardization: Regional Curve Standardization (RCS) and Negative Exponential Curve Standardization (NECS). The coherency between very low frequency forcings (hundreds of years) and the chronologies was higher when RCS was used to detrend the component series. There was no difference between standardization methods at decadal or annual time scales. We found that the detectability of systematic forcings was heavily dependent on amplitude and wavelength of the input signal as well as the number of trees simulated. These results imply that for very long tree-ring chronologies where the analyst is interested in low-frequency variability, RCS is a better method for detrending series if the requirements for that method can be met. However, in the majority of situations NECS is an acceptable detrending method. Most critically, we found that multi-centennial signals can be recovered using both methods.

Genome wide association studies (GWAS) and their subsequent meta-analysis have identified a large number of susceptibility variants for Type 2 diabetes (T2D) risk. However, the familial aggregation seen in this disease is not yet fully explained. The sibling relative risk (λ_s) due to all known variants is ~1.104 which is well below the epidemiological estimates of λ_s of ~3.0. There has therefore been great interest in the potential role of variants that would have been largely invisible to the initial wave of GWAS and linkage approaches. Low frequency (minor allele frequency 1-5%), incompletely penetrant (odds ratio 2-4) variants (LFIP), are one such group of potential susceptibility variants. The overall objective of this project (designed and implemented in 2007-2010) was to evaluate the contribution of LFIP variants to the inherited susceptibility to T2D. I tested the specific hypothesis that genes already-implicated in diabetes pathogenesis (due to an established role in monogenic or multifactorial disease) also harbour LFIP variants, and that those variants may contribute appreciably to the prediction of disease risk. Mutations in exons only encoding isoform-A of HNF1A have been demonstrated to lead to a later age of diagnosis of HNF1A-MODY. This region was therefore felt to be auspicious for harbouring LFIP variants impacting on T2D risk. I have demonstrated that such variants impacting on T2D risk are unlikely to be present in this region by use of Sanger sequencing in a sample enriched for young onset, familial T2D. The role in T2D risk of candidate LFIP variants across 5 genes (HNF1A, HNF4A, PDX1, KCNJ15 and LARS2), was evaluated by large scale association studies. For one variant, T130I of HNF4A, a modest association (p=5x10^-4) with T2D was seen in UK samples and the strength of association was marginally improved by incorporation of all previous studies of this variant in T2D in a meta-analysis (p=2.1x10^-5). This study demonstrated the difficulties encountered in confirming the association of low frequency variants to complex diseases, especially for those with modest effect sizes. At the time of project design and inception “next-generation” sequencing platforms were in their infancy and the study design I planned (that of pooled, targeted sequencing) had not been widely applied. It was therefore necessary to design and optimise protocols for sample preparation for sequencing on this platform. I used the Genome Analyzer II platform to sequence ten genes previously implicated in T2D or monogenic diabetes pathogenesis in pooled DNA samples. This approach yielded in excess of 2900 variants, a large portion being novel. As part of this project I have highlighted heuristics that can be used in the follow-up of potential susceptibility variants discovered using high throughput sequencing. I have also established protocols and pathways for sample preparation that can be utilised across several next generation sequencing platforms for future studies in the host institution and beyond.

Wireless sensors are an emerging technology that has the potential to revolutionize the monitoring of simple and complex physical systems. One of the biggest challenges with wireless sensors technology is power management and hence cost. A wireless sensor system incapable of managing its power consumption either by maintaining long battery life and/or harvesting from its surroundings, is simply not cost effective. Prolonging or eliminating the battery entirely would reduce the cost of battery replacement and maintenance. A viable family of materials for this purpose is piezoelectric materials because of their inherent ability to convert vibrations into electrical energy. Currently, a wide variety of piezoelectric materials are available and the appropriate choice for harvesting energy depends on their characteristics and properties. In addition to the material choice, energy harvesting circuitry is needed to efficiently convert and filter the signal from the piezoelectric device into a form that can be used by a load (battery). This thesis addresses the theoretical and experimental use of a type of pre-stressed PZT-5A Unimorph called a Thunder® to actively convert mechanical vibrations into useable power. Two types of devices of Thunder diaphragms are used: (1) a composite made of stainless steel, plain polyimide, a piezoelectric layer, plain polyimide, and copper; (2) and a second composite made with the same materials except that micro nickel inclusions are suspended into the polyimide layer. The first type produced a maximum average power of 2,585μW (~2.6mW) with a power density of 1411μW/cm2 (~1.4mW). The maximum total energy was 541,114μJ (~0.54J). The second type produced a maximum average power of 3,800μW (~3.8mW) with a power density of 2,073μW/cm2 (~2mW/cm2). The maximum total energy produced 1,187,939μJ (~1.19J). Based on these energy calculations, it was found that a plain polyimide diaphragm could theoretically charge a 1000mA-hr battery in a range from 3.32 hours to 32.32 hours depending on the energy harvesting circuit while nickel polyimide diaphragm could charge it in a range from 3.38 hours to 20.01 hours. These results show that THUNDER can effectively generate power from a steady sinusoidal source at frequencies below 10 Hz for the charging of batteries or for directly powering a device.

Analisa-se no presente trabalho o problema das medidas de relaxação dielétrica a U.B.F. (Ultra Baixa Frequência). Propõe-se um modelo de ponte para tais medidas capaz de varrer o intervalo 10-3 Hz-10Hz, baseada na medida de fase conforme a discussão original de Van Turnhout e colaboradores. Analisa-se também os principais problemas experimentais com tal equipamento de U.B.F. e descreve-se a sua construção e funcionamento. Analisa-se também o modelo teórico de correlação entre medidas de U.B.F. e descarga de eletreto com correntes termo-estimulado. Em particular calculamos uma correção para a expressão integral dado por Van Turnhout e colaboradores que leva em conta a influência da energia de ativação na correlação entre as duas técnicas. Tal conversão é significante para valores da energia de ativação menor que 0,5eV e que ocorrem experimentalmente com frequência / In the present work we investigate the problem of U.L.F. (Ultra Low Frequency) dielectric relaxation. An experimental model is proposed for a bridge covering the range of 10-3Hz-10Hz, based on phase shift measurements originally proposed by Van Turhout and collaborators. We also analyze the main experimental problems with such U.L. F. measurements and describe its construction and performance. We have also investigated the theoretical correlation between U.L.F. dielectric relaxation and electret thermal stimulated currents. We calculate in particular, a correction for the integral expression given by Turnhout and collaborators that takes into account the value of the activation energy in the relation between the two techniques. The correction is important for values of the activation energy below 0,5eV, which occur frequently in dielectric relaxation processes

No presente trabalho descreve-se: a determinação da permitividade dielétrica complexa através de medidas de fase; a aplicação de técnicas de correlação e análise em séries de Fourier, para a determinação da fase, amplitude, qualidade e deformação do sinal atrasado; os circuitos eletrônicos do medidor de fase e do oscilador de U.B.F. programável; a programação desenvolvida em FORTRAN IV e MACRO-ASSEMBLER para o computador PDP 11/45, utilizado para operar o medidor de fase e o oscilador de U.B.F. / In the present work we describe: the determination of the complex dielectric permittivity by phase shift measurements; the application of correlation and Fourier series analyses to determine the phase shift, amplitude, quality and deformation of the shifted signal; the designed electronic hardware of the phase meter and programmb1e ultra-low frequency oscillator; the developed software written in FORTRAN IV and MACRO- ASSEMBLER for PDP 11/45, to operate the phase meter

O câncer de pele é uma doença com grande incidência mundial. O tratamento tópico do câncer de pele é uma estratégia desejada uma vez que pode diminuir os efeitos adversos graves causados pelo tratamento cirúrgico e quimioterapia sistêmica. No entanto, os tratamentos tópicos atuais são limitados pela baixa efetividade das formulações em carrear o fármaco até as camadas mais profundas da pele. Desta forma, o ultrassom de baixa frequência (LFU) apresenta-se como um método atrativo, mas ainda pouco estudado, para aumentar a permeabilidade da pele. Portanto, o objetivo desse trabalho foi estudar modificações na composição dos meios de acoplamento do LFU visando aumentar as regiões de transporte localizadas (LTRs) da pele e a permeabilidade do quimioterápico doxorrubicina (DOX) para o tratamento tópico do câncer de pele. Para isso, um hidrogel de Poloxamer (nanogel) enriquecido com nanopartículas lipídicas sólidas (NLS) contendo DOX foi preparado e caracterizado; diferentes meios de acoplamento, dentre eles os tradicionais, contendo tensoativo, e os inovadores, contendo as NLS ou hidrogéis com diferentes potenciais zeta e viscosidades semelhantes, foram avaliados associados ao LFU para verificar sua influência na formação das LTRs e penetração cutânea de dois fármacos, calceína e DOX; a penetração cutânea da DOX livre e encapsulada em NLS foi quantificada nas diferentes camadas da pele pré-tratada com LFU; e, finalmente, o pré-tratamento mais promissor, LFU associado ao nanogel, seguido da aplicação passiva da DOX incorporada no nanogel foi avaliada in vivo em tumores cutâneos induzidos em camundongos imunossuprimidos. As NLS apresentaram tamanho e PdI de aproximadamente 200 nm e 0,3 respectivamente, com alto potencial zeta catiônico e pH de 3. A incorporação das NLS no nanogel não alterou o tamanho e PdI, no entanto, diminuiu o potencial zeta da formulação e elevou o pH para 5,5. Verificou-se por difração de raios X a baixo ângulo que as NLS continham fases cristalinas lamelares, enquanto o nanogel, fases cristalinas cúbicas, que foram mantidas quando as formulações foram associadas. O uso das NLS e dos hidrogéis, incluindo o nanogel, como meio de acoplamento do LFU modificou consideravelmente a distribuição e número de LTRs na pele em relação aos meios tradicionais. Tanto o número de LTRs quanto a sua distribuição parecem estar relacionados à tensão interfacial e a viscosidade do meio hidrofílico, sendo que a maior viscosidade dos géis gerou maior área de LTRs. O uso do nanogel originou LTRs em 50% da área da pele tratada, área esta 24 vezes maior do que a área de LTRs formada quando o meio de acoplamento convencional, com lauril sulfato de sódio, foi utilizado. Observou-se que a influência das LTRs na penetração de fármacos aniônicos (calceína) e catiônicos (DOX) depende do potencial zeta do hidrogel usado como meio de acoplamento e da dissociação do fármaco. Desta forma, a permeação cutânea da calceína foi menor quando gel aniônico foi utilizado como meio de acoplamento e o inverso ocorreu para a DOX. A penetração da DOX através do estrato córneo da pele pré-tratada com LFU/nanogel aumentou mais de 4 vezes, mas a encapsulação da DOX nas NLS dificultou a passagem da DOX para as camadas mais profundas da pele após o pré-tratamento da mesma com LFU, sugerindo um recuperação da pele desestruturada pelas partículas lipídicas administradas após o pré-tratamento. Nos estudos in vivo, o pré-tratamento da pele com LFU/nanogel seguido da aplicação diárias do nanogel contendo DOX resultou em diminuição de 6 vezes do volume do tumor após 21 dias de tratamento e apenas 5 aplicações do LFU/nanogel. No entanto, a diminuição do volume do tumor só ocorreu quando a sonda do LFU foi posicionada a 10 mm da superfície do tumor. O posicionamento da sonda a uma distância mais próxima do tumor (5 mm) não diminuiu o tamanho do tumor. Conclui-se que a aplicação de LFU com hidrogéis como meio de acoplamento é uma alternativa simples e efetiva para aumentar a penetração de fármacos na pele. Esta penetração pode ser modulada em função do potencial zeta do meio de acoplamento e da posição da sonda do ultrassom em relação à superfície do tumor. Desta forma, o tratamento tópico do câncer de pele usando LFU/nanogel como pré-tratamento é uma estratégia promissora para o tratamento tópico do câncer de pele. / Skin cancer is a disease with high worldwide incidence. Topical treatment of skin cancer is a desired strategy since it can reduce the serious adverse effects caused by surgery and systemic chemotherapy. However, current topical treatments are limited by low effectiveness of the formulations delivery drug to the deeper layers of the skin. Thus, the low frequency ultrasound (LFU) presents itself as an attractive method, but still little studied, to increase skin permeability. Therefore, the objective of this work was to study changes in the LFU coupling medium composition to increase the transport localized region (LTRs) in the skin and the permeability of chemotherapeutic doxorubicin (DOX) for the topical skin cancer treatment. For this, a Poloxamer hydrogel (nanogel) supplemented with solid lipid nanoparticles (SLN) containing DOX was prepared and characterized; different coupling medium, including traditional, containing surfactant, and innovative, containing the NLS or hydrogels with different viscosities and zeta potential similar, were evaluated associated with the LFU to verify its influence in LTRs formation and skin penetration of two drugs, calcein and DOX; skin penetration of free and encapsulated DOX was quantified in the different layers of the LFU pretreated skin; and finally, the most promising pretreatment, LFU associated with nanogel, followed by the passive application of DOX incorporated into the nanogel was evaluated in vivo, in skin tumors induced in immunosuppressed mice. The NLS showed size and PDI of approximately 200 nm and 0.3, respectively, with high cationic zeta potential and pH 3 value. The incorporation of the NLS into the nanogel did not change the size and PDI, however, decreased the zeta potential of the formulation and increased pH value to 5.5. It was found by low angle X-ray diffraction that NLS-containing lamellar crystalline phase while the nanogel, cubic crystalline phases, which were maintained when the formulations were associated. The use of NLS and hydrogels, including nanogel, as coupling medium of LFU substantially modify the distribution and number of the LTRs in the skin compared to traditional medium. Both, LTRs number and distribution may be related to the interfacial tension and viscosity of the hydrophilic medium, hydrogel with higher viscosity produced greater LTRs area. The use of nanogel as coupling medium resulted in LTRs formation in 50% of treated skin area, this area is 24 times larger than the LTR area LTRs formed when conventional coupling medium sodium lauryl sulfate was used. It was observed that the influence of the LTRs in the penetration of anionic drugs (calcein) and cationic (DOX) depends on the zeta potential of the hydrogel used as coupling medium and drug. Thus, the permeation of calcein was lower when anionic gel was used as the coupling medium and the opposite occurred for DOX. DOX penetration through the stratum corneum of the skin pretreated with LFU / nanogel increased more than 4 times but the encapsulation of DOX in the NLS difficult the passage of DOX to the deeper layers of the skin after pre-treatment with LFU, suggesting the recovery of the skin by lipid particles administered after pretreatment. In the in vivo study, pretreatment of the skin with LFU / nanogel followed by the daily application of nanogel containing DOX resulted in a 6-fold decrease in tumor volume after 21 days of treatment with only 5 applications LFU / nanogel. However, the reduction of tumor volume occurred only when the LFU probe was positioned 10 mm from the tumor surface. The positioning of the probe at distance closer tumor (5 mm) has not decreased tumor size. It is concluded that the application of coupling medium hydrogels with LFU is a simple and effective alternative to enhance drug penetration into the skin. This penetration can be adjusted depending on the zeta potential of the coupling means and ultrasound probe position on the tumor surface. Therefore, topical treatment of skin cancer using LFU / nanogel as pre-treatment is a promising strategy for the topical treatment of skin cancer.