In recent years, worldwide obesity rates have risen dramatically, putting major strain on public health systems and the economy. Obesity is a multifaceted disease and its development can be influenced by a variety of factors including genetic, psychological and environmental influences. One area of current focus in obesity research is that of early life programming. It has been well-established that certain early life factors can impact the physiology and behaviour of the offspring. Because of this, early life programming has become increasingly well studied in order to develop a deeper understanding of how early life can influence obesity development. Another area of interest lies in positive mood. While there has been much research into the effects of negative states such as stress and anxiety on feeding behaviour, there is still very little known about how positive states can influence food choice. Using rat models of prenatal stress, neonatal overnutrition and positive affect, this thesis aimed to investigate the effects of early life and mood factors on feeding behaviour and food choice. Prenatal stress has been extensively studied and is characterised by an enhanced stress response in the offspring. Using two rat models of prenatal stress- social and restraint stress, the effects of prenatal stress on feeding behaviour and food choice in the offspring were examined. In both models, no effects of prenatal stress on either food intake or food choice were observed. However, in both cases the expected alterations to the offspring's stress responses when exposed to an acute stressor were not replicated. This may suggest that models of prenatal stress are not as robust as often cited in the literature. As well as the prenatal environment, the early postnatal environment is also able to influence physiology and behaviour. In terms of obesity, a well-studied model is that of small litter size. Rats from small litters are over-nourished as neonates and because of this illustrate an increased body weight that persists throughout life. While this increase in weight gain has been well-established, there is no evidence examining the impact of neonatal overnutrition on long-term food choice. Therefore, food intake and food choice were measured in small and control litter rats over a 10-week period. When placed on an ad lib diet of bland chow, sucrose and lard, small litter rats consumed significantly more chow than control litter rats, whilst maintaining similar consumption of lard and sucrose. However, when offered a high-fat high-sugar (HFHS) pellet for two hours a day alongside ad lib chow, small litter rats illustrated increased consumption of the HFHS pellet compared to controls. This suggests that small litter rats may be programmed to adjust their food choices to enable them to maintain their increased body weight in comparison to controls. To examine the effects of positive affect on feeding behaviour, ultrasonic vocalisations (USVs, specifically those at 50 kHz) were used as a measure of positive affect in rats. In order to examine whether access to a food reward could induce a positive affect (as measured by an increase in 50 kHz USVs), rats were schedule-fed sweetened condensed milk and USVs measured before, during and after consumption. No differences in 50 kHz USVs were observed suggesting that a palatable food, whilst rewarding, does not alter affective state in the rat. Using heterospecific social contact (a tickling interaction simulating rough and tumble play) to induce positive affect, rats were presented with an hour-long sucrose preference test following social contact in order to examine the impact of positive affect on food choice. While no differences in sucrose consumption were found, a reduced sucrose preference was observed in rats receiving social contact compared to controls, suggesting that positive affect may play a role in mediating food choice. Finally, the effects of fasting (a negative stimulus thought to reduce 50 kHz USVs) and a food reward on motivation for social contact were examined. Both fasting and access to a food reward resulted in no differences in conditioned place preference to receive social interaction. Overall, the results obtained in this thesis implicate both neonatal overnutrition and, for the first time, positive affect as possible mediators of food choice, although further studies are required to fully establish these effects. Importantly, these results also raise questions regarding the reproducibility of some early life models, such as prenatal stress, and highlights the importance of sharing precise experimental protocols across laboratories. Through further investigation of the effects of early life and affective states on food consumption and choice, and the mechanisms behind these, this may enable the development of therapeutic interventions and preventative measures that can help slow, or even reverse, the global obesity epidemic.

Thesis. 1976. Sc.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Vita. / Includes bibliographical references. / Sc.D.

Heart disease has remained the deadliest disease in the United States for the past 100 years. Imaging methods are frequently employed in cardiology in order to help clinicians diagnose the specific type of heart disease and to guide treatment decisions. Ultrasound is the most frequently used imaging modality in cardiology because it is inexpensive, portable, easy to use, and extremely safe for patients. Using a variety of imaging processing techniques, deformations exhibited by the cardiac tissue during contraction can be imaged with ultrasound and used as an indicator of myocardial health. This dissertation will demonstrate the clinical implementation of two ultrasound-based strain estimation techniques developed in the Ultrasound and Elasticity Imaging Laboratory at Columbia University. Each of the two imaging methods will be tailored for clinical applications using techniques for optimal strain estimation derived from ultrasound and imaging processing theory. The motion estimation rate (MER) used for strain estimation is examined in the context of the theoretical Strain Filter and used to increase the precision of axial strain estimation. Diverging beam sequences are used to achieve full-view high MER imaging within a single heartbeat. At approximately 500 Hz, the expected elastographic signal-to-noise ratio (E(SNRe|ε)) of the axial strain becomes single-peaked, indicating an absence of “peak-hopping” errors which can severely corrupt strain estimation. In order to mediate the tradeoff in spatial resolution resulting from the use of diverging beams, coherent spatial compounding is used to increase the accuracy of the lateral strain estimation, resulting in a more physiologic strain profile. A sequence with 5 coherently compounded diverging waves is used at 500 Hz to improve the radial SNRe of the strain estimation compared to a single-source diverging sequence at 500 Hz. The first technique, Myocardial Elastography (ME), is used in conjunction with an intracardiac echocardiography (ICE) system to image the formation of thermal ablation lesions in vivo using a canine model (n=6). By comparing the systolic strain before and after the formation of a lesion, lesion maps are generated which allow for the visualization of the lesion in real-time during the procedure. A good correlation is found between the lesion maps and the actual lesion volume as measured using gross pathology (r2=0.86). The transmurality of the lesions are also shown to be in good agreement with gross pathology. Finally, the feasibility of imaging gaps between neighboring lesions is established. Lesion size and the presence of gaps have been associated with the success rate of cardiac ablation procedures, demonstrating the value of ME as a potentially useful technique for clinicians to help improve patient outcomes following ablation procedures. The second technique, Electromechanical Wave Imaging (EWI), is implemented using a transthoracic echocardiography system in a study of heart failure patients (n=16) and healthy subjects (n=4). EWI uses the transient inter-frame strains to generate maps of electromechanical activation, which are then used to distinguish heart failure patients from healthy controls (p<.05). EWI was also shown to be capable of distinguishing responders from non-responders to cardiac resynchronization therapy (CRT) on the basis of the activation time of the lateral wall. These results indicate that EWI could be used as an adjunct tool to monitor patient response to CRT, in addition to helping guide lead placement prior to device implantation.

Desde o ano 2000, o Grupo de Alta Tensão e Materiais (GATM) tem contribuído com suas pesquisas no desenvolvimento de processos para produção de novos transdutores piezoelétricos de materiais poliméricos, baseados na tecnologia dos piezoeletretos. Essa intensa investigação se justifica pelas excelentes propriedades piezoelétricas desses dispositivos, com atividade na ordem de centenas e até milhares de pC/N, ultrapassando o desempenho de algumas tradicionais cerâmicas. Destacam-se também nestes sensores, sua estrutura flexível e robusta, sua resposta na faixa de frequências ultrassônicas e seu baixo custo. Características estas que os tornam muito competitivos com os transdutores convencionais, cerâmicos e poliméricos, a exemplo do PZT e PVDF, respectivamente. Neste contexto, desenvolveu-se em 2009 no GATM um novo arranjo polimérico de múltiplos canais, em que filmes de teflon FEP foram termicamente moldados e depois expostos a um intenso campo elétrico (na ordem de kV), criando sensores com elevado coeficiente piezoelétrico. Esse novo dispositivo, batizado de Piezoeletreto de Canais Tubulares (PCT) foi construído por meio de um processo de fabricação organizado e controlado, diferentemente dos piezoeletretos vistos até então. No presente trabalho construiu-se um protótipo de hidrofone com elemento ativo dado por um filme de PCT, para aplicações de até 100 kHz e com uma eletrônica de pré-amplificação em 24 dB. O primeiro teste com o protótipo restringiu-se à obtenção da sua sensibilidade. Realizaram-se ainda testes de caracterização quanto ao padrão de diretividade e a relação sinal-ruído. A calibração foi feita em três diferentes modalidades de geração do sinal: AM, CW e Burst, todas de maneira comparativa com o auxílio de um hidrofone comercial. A sensibilidade média encontrada nas medidas foi de 0,142 mV/Pa (-196,93 dB re 1 V/&#956Pa) e, na ressonância (40 kHz) de 1,698 mV/Pa (-175,4 dB re 1 V/&#956Pa). A segunda fase de testes destinou-se a geração de imagens para diagnóstico clínico, baseada na técnica de Vibroacustografia (VA). Verificou- se a viabilidade do uso da VA com o mapeamento de dois objetos distintos, uma pequena esfera metálica de 1 mm de diâmetro e uma estrutura óssea. / Since 2000, the High-Voltage and Materials Group (GATM) has focused its research on developing new processes for manufacture piezoelectric transducers, from polymeric materials based on the piezoelectret technology. This intense research is justified by the excellent electromechanical properties of these devices, with piezoelectric coefficient in the order of hundreds up to thousands of pC/N, exceeding the performance of the most traditional ceramics. Other highlights of these sensors are the flexible and robust structure, its wide range response in ultrasonic frequencies and low cost. These characteristics make them very competitive with those conventional ceramic and polymeric transducers, such as the PZT and PVDF, respectively. In this context, in 2009 a new polymeric multiple film arrangement was laminated to create an open channel structure that after been exposed to an intense electric field (on the order of kV), produces a piezoelectric sensor with high piezoelectricity. This new device was built by an organized and controlled process, unlike the piezoelectrets seen so far. The main features inherent to tubular channels piezoelectret are the constructive uniformity, control of the resonance frequency and greater thermal stability, when compared to other piezoelectric polymers. Based on these tubular piezoelectrets, in the current study, a prototype of a 24dB preamplifier ultrasonic hydrophone was built. The first test with the prototype restricted to obtaining its sensitivity. Further tests were performed to characterize the pattern of directivity and signal-to-noise ratio. The calibration tests were conducted on three different approaches to signal generation AM, CW and Burst; all in a comparative manner with the aid of a calibration standard hydrophone. The results showed a transducer with average sensitivity of 0.142 mV/Pa (-196.93 dB re 1 V/&#956Pa), and the resonance region at 40 kHz with a sensitivity of 1,698 mV/Pa (-175.4 dB re 1 V/&#956Pa) and a unidirectional sensitive region. The feasibility of producing images by VA has been verified by mapping two distinct objects, a small metal sphere of 1 mm diameter and a bone structure.

Assegurar o bem-estar dos animais de laboratório e evitar a dor e o sofrimento desnecessários são as principais considerações na experimentação. Por isso, a investigação em busca de novos protocolos anestésicos que garantam um mínimo ou nulo desconforto dos animais tem-se convertido num tema prioritário. Neste estudo realizou-se a comparação do efeito da combinação de xilazina (X) e ketamina (K) com acepromazina (A) e opióides [metadona (Me), morfina (Mo) e tramadol (T)] com a finalidade de avaliar sua influência nos parâmetros fisiológicos de ratos de laboratório, para ambos os sexos, bem como seu poder analgésico e o efeito da oxigenação sobre os mesmos. A associação XKA para ratos machos e fêmeas e a associação XKMe para fêmeas foram as mais seguras e eficazes para procedimentos anestésicos. Porém, os resultados do teste de formalina com a medição da vocalização ultrassônica (VUS) sugerem que o protocolo de XKA tem um poder analgésico baixo, não sendo indicado para procedimentos que possam gerar dor moderada ou severa. Todas as associações anestésicas tiveram efeitos importantes como diurese, manutenção dos olhos abertos e hiperglicemia, os quais devem ser considerados quando possam influenciar nos resultados experimentais. Também, se conseguiu demonstrar que a oxigenação melhora a saturação de oxigênio (SO2) e os valores da pressão parcial de oxigênio (pO2) confirmando que sua utilização deveria ser sempre parte dos procedimentos experimentais com anestesia injetável para evitar a hipoxemia. Não obstante, observou-se uma acidose respiratória por aumento da pressão parcial do CO2 (pCO2) e diminuição do pH, cuja causa se relacionou à hipoventilação por depressão respiratória e acúmulo de CO2 durante o transcorrer da anestesia. Tal situação demonstra a necessidade de oxigenar os animais desde a indução da anestesia e de administrar medicamentos para reverter a depressão respiratória como a naloxona, bem como utilizar animais que não apresentem nenhum tipo de comprometimento respiratório. Portanto, a inclusão de analgesia e a oxigenação nos protocolos anestésicos injetáveis devem ser utilizadas de forma rotineira garantindo a mínima presença de dor e, com isso, resultados mais confiáveis nos procedimentos experimentais. / Ensuring the wellbeing of laboratory animals and avoiding unnecessary pain and suffering is one of the main considerations in experimentation. Therefore, the investigation of new anesthetic protocols that guarantee a minimum or null discomfort of the animals has become a priority theme. In this study, it was made an evaluation of the effect of the combination of xylazine (X) and ketamine (K) with acepromazina (A) and opioids [methadone (Me), morphine (Mo) e tramadol (T)] with the purpose of comparing their influence on the physiological parameters of laboratory rats, for both sexes, and evaluating their analgesic power and the effect of the oxygenation on them. The XKA protocol for male and females rats and the XKMe protocol for females were the safest and most effective for anesthetic procedures. However, the results of the formalin test with the measurement of the ultrasonic vocalization (VUS) suggest that the XKA protocol had a low analgesic power, and it is not indicated for procedures that can generate moderate or severe pain. All anesthetic protocols had important effects as diuresis, maintenance of open eyes, and hyperglycemia; these effects should be considered when they could influence in the experimental results. It was demonstrated that oxygenation improves oxygen saturation (SO2) and oxygen partial pressure (pO2) confirming that its use should be considered in the experimental procedures with injectable anesthesia to avoid hypoxemia. Nevertheless, a respiratory acidosis was observed due to the increase in partial pressure of CO2 (pCO2) and the decrease in pH, that could be caused for the hypoventilation due to respiratory depression and CO2 accumulation during the course of anesthesia. This leads to consider the need to pre-oxygenate animals from induction, to use drugs to reverse respiratory depression such as naloxone, and to work with animals that are not respiratory compromised. Therefore the inclusion of analgesia and oxygenation in anesthesia protocols should begin to be used routinely ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

Demands to handle individual particles or particle agglomerates have been emerging in the fields of biology and chemistry, and particle trapping and manipulation with mechanical waves generated from ultrasound sources, known as “acoustic tweezing”, has gained great interest by researchers and been proved useful for its unique advantages. With an analogy to optical tweezing, research has demonstrated the possibility to use modulated acoustic fields generated by ultrasound arrays for trapping individual particles and groups of particles at length scales from hundreds of µm to a few mm. This thesis explores and demonstrates particle trapping and manipulation with electronically-controlled miniaturized ultrasound arrays (element pitch around 500 µm or less), focusing on the development of dexterous electronic systems. Generally, in acoustic manipulation applications, low voltage outputs with continuous mode operation are required to create stable acoustic energy potential “landscapes” for trapping without damaging particles or cells. The research work of this thesis is oriented towards integration of control electronics with miniaturized ultrasound arrays. Test fixtures have been carefully designed and fabricated for the characterization of transducer arrays developed by collaborating researchers and array-controlled particle manipulation experiments have been demonstrated with customized fluorescence microscopy equipment. Most importantly, this thesis has established two versions of prototype Field programmable gate array (FPGA) based electronics to drive ultrasound arrays. One is a computer-controlled 16-channel system, with adjustable output frequencies, phases and amplitudes. Another is a 40-channel switching electronics for manual controlled output switching or time-shared output multiplexing. The electronic systems that have been developed are highly scalable and easily adapted for different acoustic tweezing applications. In conclusion, this thesis has proposed prototype electronic toolkits as research platforms to explore diverse possibilities for acoustic tweezing with miniaturized ultrasound arrays.

Orientador: Jorge Nahás Neto / Coorientador: Eliana Aguiar Petri Nahás / Banca: Paulo Traiman / Banca: Eduardo Carvalho Pessoa / Resumo: Avaliar o efeito da isoflavona da soja sobre o tecido mamário em mulheres na pós-menopausa. Trata-se de estudo clínico, prospectivo, randomizado, duplo-cego, placebo controlado, envolvendo 80 mulheres na pós-menopausa com sintomas vasomotores, idade entre 45 a 70 anos, acompanhadas no Ambulatório de Climatério e Menopausa da Faculdade de Medicina de Botucatu-Unesp, de janeiro de 2005 a dezembro de 2006. Na randomização, 40 pacientes receberam 100 mg isoflavona da soja/dia (duas cápsulas de 125 mg de extrato seco de glicine Max) e 40 pacientes placebo (duas cápsulas de lactose) durante 10 meses. A densidade mamária (DM) foi avaliada pela mamografia e o parênquima mamário pela ultrassonografia de mamas no início e após dez meses de seguimento. Para análise estatística foram utilizados o teste t-Student, ANOVA, teste de Mann-Whitney e teste do Qui-Quadrado. Na comparação das características clínicas iniciais entre os grupos de usuárias de isoflavona e placebo, não houve diferenças significantes, com valores médios de idade de 55,1±6,0 e 56,2±7,7 anos, tempo de menopausa de 6,6±4,8 e 7,1±4,2 anos e IMC de 29,7±5,0 e 28,5±4,9 kg/m2, respectivamente (p>0,05). Concluíram o estudo 32 pacientes sob isoflavona e 34 sob placebo. Na comparação da densidade mamográfica entre os momentos inicial e final, não houve diferença estatisticamente significativa. Na avaliação do parênquima mamário pela ultrassonografia, não houve diferença entre os grupos. Na comparação entre os momentos dentro de cada grupo, não foram constatadas diferenças significativas nos parâmetros da mamografia e ultrassonografia. No período de 10 meses, o uso de isoflavona de soja não modificou o tecido mamário, avaliado pela mamografia e ultrassonografia, em mulheres na pós-menopausa / Abstract: To evaluate the effect of soy isoflavone on breast tissue in postmenopausal women. This study is a prospective, randomized, double-blind, placebo-controlled trial involving 80 postmenopausal women with vasomotor symptoms, aged 45-70 years, followed in Climacteric and Menopause Clinic of the Botucatu Medical School-UNESP, from January 2005 to December 2006. At randomization, 40 patients received 100 mg of soy isoflavone/day (two capsules of 125 mg standardized soy extract, Glicine max) and 40 patients, placebo (two capsules of lactose) for 10 months. The breast density was evaluated by mammography and breast parenchyma by ultrasound, at baseline and after ten months of follow-up. The Student t-test, ANOVA, Mann-Whitney and Chi-Square were used in the statistical analysis. In comparison of baseline clinical characteristics between the isoflavone and placebo groups, there were no significant differences, with mean age of 55.1 ± 6.0 and 56.2 ± 7.7 years, duration of menopause 6.6 ± 4.8 and 7.1 ± 4.2 years and BMI 29.7 ± 5.0 and 28.5 ± 4.9 kg/m2, respectively (p> 0.05). Concluded the study, 32 patients on isoflavone and 34 in the placebo group. In comparison in mammographic density (MD) between moments, baseline and final, there was no difference statistically significant. In the evaluation of breast parenchyma by ultrasound, there was no difference between groups. In comparing the moments within each group, there were no significant differences in the parameters of mammography and ultrasound. In 10 months, the use of soy isoflavone did not affect breast tissue, as assessed by mammography and ultrasound, in postmenopausal women / Doutor

Variable-rate technologies for sprayer applications stand to increase efficacy by ensuring the right amount of chemical is applied at the right location. However, external environmental factors such as droplet drift caused by variable ambient condition, are not yet integrated into modern sprayer systems. Real-time wind velocity measurements can be used to control droplet spectra for reducing spray drift by actuating a variable-orifice nozzle. This work aimed to develop data processing methods needed to filter noise and remove vehicle speed from wind velocity measurements collected with an ultrasonic anemometer aboard a moving platform. Using a global navigation satellite system (GNSS), vehicle speed was calculated in the field and subtracted from apparent wind velocity for comparison to static measurements. Experiments under stationary and dynamic sensor deployments were used to develop an algorithm to provide instantaneous local wind velocity and to better understand the local spatiotemporal variability of wind under field conditions.

The objective of this work is to optimize high-power low-frequency sonication (US) pretreatment of sludge, and especially to investigate for the first time possible improvements by higher pressure and audible frequency. After a preliminary examination of regular process conditions (sludge conditioning, sludge type, prior alkalization, temperature control, etc), effects of US parameters (power -PUS, intensity -IUS, specific energy input -ES, frequency -FS, etc.) and of hydrostatic pressure (Ph) were specifically looked into, separately and in combination, first under cooling at constant temperature (28°C), then under the progressive temperature rise provoked by sonication. First, it was confirmed that specific energy input (ES) plays a key role in sludge US disintegration (i.e. solubilisation of organic matter) and that temperature rise during adiabatic-like sonication is beneficial through additional effects of thermal hydrolysis and cavitation. At a given ES value, low FS (12 kHz vs. 20 kHz) and high PUS enhance soluble chemical oxygen demand (SCOD) due to more violent cavitation, while hydrostatic pressure gives rise to an optimum value due to its opposite effects on cavitation threshold and intensity. One major result is that optimal pressure depends on IUS (P¬US) as well as temperature profile, but not on ES, FS, nor sludge type. Setting the other parameters at the most favorable conditions expected, i.e. 12 kHz, 360 W , 28 gTS/L, and adiabatic conditions, final optimization was achieved by searching for this pressure optimum and examining sequential procedure to avoid too high temperature dampening cavitation intensity and damaging the transducer. Such conditions with sequential mode and Ph of 3.25 bar being selected succeeded in achieving very high SCOD, but only marginally improved subsequent methanization yield.

La fonctionnalisation des surfaces permet d’en modifier leur comportement vis-à-vis des propriétés physico-chimiques de fluides. Nous avons restreint notre étude à la caractérisation par méthode acoustique des interfaces microstructurées silicium-fluide pour lesquelles une gravure physique d’un réseau de piliers de petites dimensions a été réalisée. Les propriétés de ces interfaces vis-à-vis des liquides dépendent de la géométrie des gravures, des propriétés du fluide et des conditions d’interaction du fluide avec la surface. Notre objectif a été de confronter des modèles de comportement en terme de mouillabilité de ces surfaces aux mesures des coefficients de réflexion des ondes ultrasonores. Une première étape du travail a consisté à modéliser le coefficient de réflexion d’une onde ultrasonore incidente sur une surface microtexturée en fonction de l’état du liquide sur la surface. Deux états physiques caractéristiques ont étés étudiés : l’état où le liquide reste au sommet des piliers (état Cassie) et celui où le liquide pénètre dans le réseau de piliers (état Wenzel). Deux modèles numériques ont été développés : le premier repose sur la modélisation par éléments finis utilisant COMSOL MULTIPHYSICS et le second modèle numérique utilise une méthode explicite aux différences finies.La technique expérimentale est fondée sur une méthode de mesure du coefficient de réflexion électrique d’un transducteur ultrasonore haute fréquence à l’aide d’un analyseur de réseau, qui permet après traitement d’en déduire le coefficient de réflexion à l’interface.Les résultats originaux obtenus démontrent qu’une onde acoustique de compression est sensible à l’état d’un liquide sur une surface microtexturée. / Surfaces functionalization can change the wetting properties of the surface depending on the physico-chemical properties of fluids. We restricted our study to the characterization by acoustic method of microstructured silicon-fluid interfaces for which a physical etching of a network of small pillars was achieved. The properties of these interfaces depend on the geometry of the etched microtextures, the fluid properties and the interaction between the fluid and the surface. Our objective was to compare modeling and measurements of reflection coefficients of ultrasonic waves at theses interfaces. A first stage of work was to model the reflection coefficient of an ultrasonic wave incident on a microtextured surface depending on the state of the liquid on the surface. Two specific physical states have been studied: The state where the liquid remains at the top of the pillars (Cassie state) and when the liquid penetrates in the network of pillars (Wenzel state). Two numerical models were developed: one basedon finite element modeling using COMSOL Multiphysics and the second numerical model uses an explicit finite difference method. The experimental technique is based on a method measuring the electrical reflection coefficient ofan ultrasonic transducer according to the frequency using a high frequency network analyzer. Signal processing allows deducing the reflection coefficient at the interface. The original results obtained demonstrate that an acoustic compression wave is sensitive to the state of a liquid on a surface microtextured.