<p> The object of this work was to evaluate the Supernova ninicomputer as a process simulation tool. To accomplish this obje c tive the GEMCS ste2dy-state simulation system wa.s programmed for the Supernova. This system was programmed to run in five different modes, BASIC , two modes which require that al.L progra1ns are written in Assembly Language, and two modes in which programs may be called from the disk. Of these latter two modes, one requires all programs to be written in Assembly Language; the other mode allows programs to be written in Assembly Language or FORTRAN IV. </p> <p> Two case studies which had previously been run on the CDC 6400 were run on the Supernova to test and evaluate f our of the modes in which GEMCS was proerammed for the Supernova. </p> <p> The studies have also provided an a ssessment of the hardware and softws.re facilities of the Supernova and the results of thjs assessment were documented. In addition the opera tion of the various strategies used to impl ement GEMCS have provided an indication of the feasibility of the impl ementation of the dynamic system simulation program, DYNSYS. </p> / Thesis / Doctor of Philosophy (PhD)

[pt] As fluorquinolonas constituem uma importante classe de agentes antimicrobianos sintéticos utilizados clinicamente por mais de 30 anos. Além da atividade antibacteriana, algumas fluorquinolonas, assim como seus complexos metálicos, mostraram ter atividade citotóxica, sendo, portanto, promissores como agentes antitumorais. Neste trabalho, obtivemos complexos de Au(III), Cu(II) e Bi(III) com as seguintes fluorquinolonas: norfloxacina, levofloxacina e esparfloxacina. Esses novos complexos foram caracterizados por diversas técnicas, tais como: análise elementar, condutimetria, espectroscopia na região do infravermelho, ressonância paramagnética eletrônica (RPE), ressonância magnética nuclear (RMN) de 1H e 13C, espectroscopia UV-Vis, fluorescência estacionária e resolvida no tempo. Atividades biológicas foram realizadas para todos os complexos. Usualmente, as fluorquinolonas coordenam-se aos íons metálicos de modo bidentado, através da carbonila do ácido carboxílico e da carbonila cetônica. Esta coordenação foi confirmada para os complexos de Cu(II), entretanto, para os complexos de Au(III) e Bi(III), os resultados de infravermelho e do RMN de 1H e 13C mostraram que a coordenação foi feita através dos nitrogênios do anel piperazina, uma coordenação não encontrada usualmente para as fluorquinolonas. Os complexos de Au(III) mostraram ser ativos frente às linhagens tumorais A20 (Linfoma murino), B16-F10 (Melanoma murino) e K562 (Leucemia mielóide humana). Os complexos de Cu(II) mostraram significativa atividade antiparasitária, enquanto os complexos de Bi(III), mostraram atividade antibacteriana. / [en] The fluoroquinolones are an important class of synthetic antimicrobial agents clinically used for over 30 years. In addition to antibacterial activity, some fluoroquinolones, as well as their metal complexes, presented cytotoxic activity and are therefore promising as antitumor agents. In order to obtain new complexes of Au (III) and other metal ions that have biological activity, this work had the objective to synthesize new complexes using ligands of the group of fluoroquinolones. These new complexes were characterized by various techniques such as elemental analysis, conductometry, infrared spectroscopy, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR) of 1H and 13C NMR, UV-Vis, stead state and time-resolved fluorimetry studies. Biological activities were analized for all complexes. Usually, the fluoroquinolones coordinate to the metal ions as bidentate through the carbonyl and carboxylic acid ketonic carbonyl group. This was confirmed Cu(II) complex, however, for Au(III) and Bi (III) complexes, the results of IR and 1H and 13C NMR showed that the coordination was trough the nitrogen using the piperazine ring, a coordination not usually found for fluoroquinolones. The complexes of Au(III) shown to be active against the A20 tumor cell lines (murine lymphoma), B16-F10 (murine melanoma) and K562 (human myeloid leukemia). Complexes of Cu(II) showed significant antiparasitic activity, whereas complexes of Bi(III) have shown antibacterial activity.

Studying newborns in the first days of life prior to experiencing the world provides remarkable insights into the neurocognitive predispositions that humans are endowed with. First, it helps us to improve our current knowledge of the development of a typical brain. Secondly, it potentially opens new pathways for earlier diagnosis of several developmental neurocognitive disorders such as Autism Spectrum Disorder (ASD). While most studies investigating early cognition in the literature are purely behavioural, recently there has been an increasing number of neuroimaging studies in newborns and infants. Electroencephalography (EEG) is one of the most optimal neuroimaging technique to investigate neurocognitive functions in human newborns because it is non-invasive and quick and easy to mount on the head. Since EEG offers a versatile design with custom number of channels/electrodes, an ergonomic wearable solution could help study newborns outside clinical settings such as their homes. Compared to adult EEG, newborn EEG data are different in two main aspects: 1) In experimental designs investigating stimulus-related neural responses, collected data is extremely short in length due to the reduced attentional span of newborns; 2) Data is heavily contaminated with noise due to their uncontrollable movement artifacts. Since EEG processing methods for adults are not adapted to very short data length and usually deal with well-defined, stereotyped artifacts, they are unsuitable for newborn EEG. As a result, researchers manually clean the data, which is a subjective and time-consuming task. This thesis work is specifically dedicated to developing (semi-) automated novel signal processing methods for noise removal and for extracting reliable neural responses specific to this population. The solutions are proposed for both high-density EEG for traditional lab-based research and wearable EEG for clinical applications. To this end, this thesis, first, presents novel signal processing methods applied to newborn EEG: 1) Local Outlier Factor (LOF) for detecting and removing bad/noisy channels; 2) Artifacts Subspace Reconstruction (ASR) for detecting and removing or correcting bad/noisy segments. Then, based on these algorithms and other preprocessing functionalities, a robust preprocessing pipeline, Newborn EEG Artifact Removal (NEAR), is proposed. Notably, this is the first time LOF is explored for EEG bad channel detection, despite being a popular outlier detection technique in other kinds of data such as Electrocardiogram (ECG). Even if ASR is already an established artifact real algorithm originally developed for mobile adult EEG, this thesis explores the possibility of adapting ASR for short newborn EEG data, which is the first of its kind. NEAR is validated on simulated, real newborn, and infant EEG datasets. We used the SEREEGA toolbox to simulate neurologically plausible synthetic data and contaminated a certain number of channels and segments with artifacts commonly manifested in developmental EEG. We used newborn EEG data (n = 10, age range: 1 and 4 days) recorded in our lab based on a frequency-tagging paradigm. The chosen paradigm consists of visual stimuli to investigate the cortical bases of facelike pattern processing, and the results were published in 2019. To test NEAR performance on an older population with an event-related design (ERP) and with data recorded in another lab, we also evaluated NEAR on infant EEG data recorded on 9-months-old infants (n = 14) with an ERP paradigm. The experimental paradigm for these datasets consists of auditory stimulus to investigate the electrophysiological evidence for understanding maternal speech, and the results were published in 2012. Since authors of these independent studies employed manual artifact removal, the obtained neural responses serve as ground truth for validating NEAR’s artifact removal performance. For comparative evaluation, we considered the performance of two state-of-the-art pipelines designed for older infants. Results show that NEAR is successful in recovering the neural responses (specific to the EEG paradigm and the stimuli) compared to the other pipelines. In sum, this thesis presents a set of methods for artifact removal and extraction of stimulus-related neural responses specifically adapted to newborn and infant EEG data that will hopefully contribute to strengthening the reliability and reproducibility of developmental cognitive neuroscience studies, both in research laboratories and in clinical applications.

The theory of Brownian motion is a cornerstone of modern physics. In this thesis, we introduce a nonequilibrium extension to this theory, namely an effective Markovian theory of the Brownian motion of a heated nanoparticle. This phenomenon belongs to the class of nonequilibrium steady states (NESS) and is characterized by spatially inhomogeneous temperature and viscosity fields extending in the solvent surrounding the nanoparticle. The first chapter provides a pedagogic introduction to the subject and a concise summary of our main results and summarizes their implications for future developments and innovative applications. The derivation of our main results is based on the theory of fluctuating hydrodynamics, which we introduce and extend to NESS conditions, in the second chapter. We derive the effective temperature and the effective friction coefficient for the generalized Langevin equation describing the Brownian motion of a heated nanoparticle. As major results, we find that these parameters obey a generalized Stokes–Einstein relation, and that, to first order in the temperature increment of the particle, the effective temperature is given in terms of a set of universal numbers. In chapters three and four, these basic results are made explicit for various realizations of hot Brownian motion. We show in detail, that different degrees of freedom are governed by distinct effective parameters, and we calculate these for the rotational and translational motion of heated nanobeads and nanorods. Whenever possible, analytic results are provided, and numerically accurate approximation methods are devised otherwise. To test and validate all our theoretical predictions, we present large-scale molecular dynamics simulations of a Lennard-Jones system, in chapter five. These implement a state-of-the-art GPU-powered parallel algorithm, contributed by D. Chakraborty. Further support for our theory comes from recent experimental observations of gold nanobeads and nanorods made in the the groups of F. Cichos and M. Orrit. We introduce the theoretical concept of PhoCS, an innovative technique which puts the selective heating of nanoscopic tracer particles to good use. We conclude in chapter six with some preliminary results about the self-phoretic motion of so-called Janus particles. These two-faced hybrids with a hotter and a cooler side perform a persistent random walk with the persistence only limited by their hot rotational Brownian motion. Such particles could act as versatile laser-controlled nanotransporters or nanomachines, to mention just the most obvious future nanotechnological applications of hot Brownian motion.

The theory of Brownian motion is a cornerstone of modern physics. In this thesis, we introduce a nonequilibrium extension to this theory, namely an effective Markovian theory of the Brownian motion of a heated nanoparticle. This phenomenon belongs to the class of nonequilibrium steady states (NESS) and is characterized by spatially inhomogeneous temperature and viscosity fields extending in the solvent surrounding the nanoparticle. The first chapter provides a pedagogic introduction to the subject and a concise summary of our main results and summarizes their implications for future developments and innovative applications. The derivation of our main results is based on the theory of fluctuating hydrodynamics, which we introduce and extend to NESS conditions, in the second chapter. We derive the effective temperature and the effective friction coefficient for the generalized Langevin equation describing the Brownian motion of a heated nanoparticle. As major results, we find that these parameters obey a generalized Stokes–Einstein relation, and that, to first order in the temperature increment of the particle, the effective temperature is given in terms of a set of universal numbers. In chapters three and four, these basic results are made explicit for various realizations of hot Brownian motion. We show in detail, that different degrees of freedom are governed by distinct effective parameters, and we calculate these for the rotational and translational motion of heated nanobeads and nanorods. Whenever possible, analytic results are provided, and numerically accurate approximation methods are devised otherwise. To test and validate all our theoretical predictions, we present large-scale molecular dynamics simulations of a Lennard-Jones system, in chapter five. These implement a state-of-the-art GPU-powered parallel algorithm, contributed by D. Chakraborty. Further support for our theory comes from recent experimental observations of gold nanobeads and nanorods made in the the groups of F. Cichos and M. Orrit. We introduce the theoretical concept of PhoCS, an innovative technique which puts the selective heating of nanoscopic tracer particles to good use. We conclude in chapter six with some preliminary results about the self-phoretic motion of so-called Janus particles. These two-faced hybrids with a hotter and a cooler side perform a persistent random walk with the persistence only limited by their hot rotational Brownian motion. Such particles could act as versatile laser-controlled nanotransporters or nanomachines, to mention just the most obvious future nanotechnological applications of hot Brownian motion.:1 Introduction and Overview 2 Theory of Hot Brownian Motion 3 Various Realizations of Hot Brownian Motion 4 Toy Model and Numerical Methods 5 From Experiments and Simulations to Applications 6 Conclusion and Outlook