A análise de fármacos e outras moléculas relacionadas em fluidos biológicos é essencial no âmbito farmacêutico. Atualmente, a demanda por análises rápidas e mais complexas impulsiona a química analítica para o desenvolvimento de soluções inovadoras. A cromatografia líquida multidimensional com acoplamento de colunas para injeção direta de fluidos biológicos tem ganhado atenção nos últimos anos. Ao mesmo tempo, o acoplamento entre cromatografia líquida e espectrometria de massas proporcionou marcante desenvolvimento científico na área biomédica e bioquímica. Esta tese apresenta os diversos estágios na redução da escala em sistemas de column switching utilizando colunas RAM, para a análise de fármacos em fluidos biológicos. Na escala convencional, com colunas de 4,6 mm de diâmetro interno, desenvolveu-se um sistema para a análise de fluoxetina em plasma. A metodologia desenvolvida foi adequadamente validada para aplicação na monitorização terapêutica, com tempo de análise de 20 minutos (incluído o preparo de amostras) e consumo de apenas 100 µL de amostra. Avaliou-se a escala microbore (2,1 mm), a qual apresentou excelente potencialidade para o acoplamento com a espectrometria de massas utilizando ionização por electrospray. Na primeira etapa em escala capilar, com colunas de 520 µm de diâmetro interno, desenvolveu-se um sistema para análise de fluoxetina em plasma. Esse sistema proporcionou análises em 25 minutos, também aplicáveis à monitorização terapêutica, consumindo poucos microlitros de amostra. Finalmente, foi desenvolvido um sistema de column switching capilar com colunas na ordem de 200 µm. Esse sistema foi acoplado à espectrometria de massas em tandem proporcionando, inovadoramente, análises altamente sensíveis e simultâneas, com baixo consumo de amostras. Um grupo de cinco antidepressivos e o albendazol, com seus produtos de biotransformação, tiveram suas análises validadas em menos de 8 minutos, consumindo menos de um microlitro de amostra. Esse sistema capilar contrasta com os sistemas convencionais comumente utilizados, os quais consomem entre centenas e milhares de vezes mais amostra para atingir a mesma detectabilidade. / Analysis of drugs and other related molecules in biofluids is essential in the pharmaceutical field. Nowadays, the development of innovative solutions in analytical chemistry has been pushed by the needs for speed and more complex analysis. Lately, multidimensional liquid chromatography using column switching for direct injection of biofluids has gained attention. At the same time, liquid chromatography hyphenated with mass spectrometry provided remarkable scientific development in biomedical and biochemical area. This thesis presents the scale reduction steps in RAM column switching, for drug analysis in biofluids. In the conventional scale, using 4.6 mm i.d. columns, a system was developed, providing fluoxetine analysis in plasma. The developed method resulted in a 20 min long run, including the sample preparation step, which consumed 100 µL of sample. The method was adequately validated, being applicable to therapeutic drug monitoring. The microbore scale (2.1 mm) was evaluated, presenting great potentiality for coupling with electrospray-mass spectrometry. In the first capillary scale step, using 520 µm columns, a system was developed for fluoxetine analysis. Fluoxetine analysis was achieved in 25 min, within the application range for therapeutic drug monitoring, and consuming few microliters of sample. Finally, a RAM capillary column switching system employing columns on the order of 200 µm was developed, in an innovative way. This system was coupled with a tandem mass spectrometer, rendering sensitive and simultaneous analysis with reduced sample volume. The analysis of one group containing five antidepressants, as well as the analysis of albendazol and its metabolites was validated. These analyses took only 8 minutes and consumed less than one microliter of sample. In contrast with conventional systems, this system consumes about hundreds or thousands times less sample, with the same detectability.

Este estudo apresenta um modelo matemático fenomenológico para um sistema convencional de Eletrodiálise (ED) para dessalinização de água, com operação contínua em estágios. O modelo, elaborado a partir de balanços materiais em cada compartimento de um estágio genérico, foi aplicado para separação dos seguintes sais em solução aquosa: NaCl, KCl, Na2SO4 e MgCl2. A restrição operacional de sistemas de ED devida à densidade de corrente limite é particular para cada sistema e depende da configuração geométrica do equipamento, características das membranas seletivas e das propriedades do soluto. Para sua determinação, foram realizados experimentos em uma unidade de ED em escala laboratório, construída no Departamento de Engenharia Química da EPUSP. Essa unidade experimental foi utilizada para validação do modelo. A sensibilidade do modelo foi analisada para diferentes solutos em relação às seguintes variáveis: resistência elétrica da membrana, temperatura, vazão do fluido na célula, espessura da célula e concentração da alimentação, visando estabelecer seu efeito nos custos totais do sistema. O modelo foi aplicado em simulações para sistemas de ED operando em diferentes configurações: em contracorrente, com reciclo e em batelada. A partir de um caso base, foi elaborado um algoritmo de otimização pelo método de busca direta para determinar a configuração geométrica e potencial elétrico ótimo que minimizem os custos operacionais e de investimento do processo. A melhor configuração do ponto de vista econômico corresponde a um sistema em concorrente com reciclo. Os estudos de sensibilidade indicaram que o custo de remoção de Na2SO4 foi maior do que o custo de remoção de NaCl e KCl, aparentemente devido ao fato de se tratar de íons divalentes. Finalmente, apesar de haver diminuição do custo com o aumento da velocidade do fluido através das membranas, esse custo passa a aumentar para altas velocidades, devido ao maior efeito do custo de bombeamento. / This study presents a phenomenological mathematical model for an electrodialysis system (ED) for water desalination, operating continuously in stages. The model is based on material balances for the species in each compartment of a generic stage, and was applied to the separation of the following salts from water solutions: NaCl, KCl, Na2SO4, and MgCl2. One major operational restriction in ED systems is the limiting current density, which is specific for each system and depends on the equipment configuration, membrane characteristics, and solute properties. The limiting current density was determined by means of a series of laboratory scale experiments in an ED unit designed and assembled in the Chemical Engineering Department, University of São Paulo. This same experimental unit was used to validate the model. A sensitivity analysis was carried out for solutions containing different solutes, with relation to the following variables: membrane electrical resistance, temperature, fluid flow rate in the cell, cell thickness, and feed concentration, aiming at evaluating their effect on the total cost. The model was applied to simulate ED systems with different configurations: countercurrent, with recycle stream, or operating in batch mode. Based on a reference configuration, a direct search algorithm was used to estimate optimal values of design variables and electrical potential that minimize the investment and operational costs of an ED plant. The most feasible process configuration from the economic point of view corresponds to a co-current system with recycle, which has minimum membrane area. No effect of the temperature on the processing cost was detected. The desalination cost is larger for Na2SO4 than for NaCl or KCl, possibly due to the fact that these are monovalent ions. The increase in the velocity of the solution in the cell compartments causes a decrease in the processing cost due to the increase in the transfer rates, but large velocities result in high pumping costs, which contribute to the increase in processing costs.

Regression analyses constitutes an important part of the statistical inference and has great applications in many areas. In some applications, we strongly believe that the regression function changes monotonically with some or all of the predictor variables in a region of interest. Deriving analyses under such constraints will be an enormous task. In this work, the restricted prediction interval for the mean of the regression function is constructed when two predictors are present. I use a modified likelihood ratio test (LRT) to construct prediction intervals.

IEEE 802.11ah is designed to support battery powered devices that are required to serve for several years in the Internet of Things networks. The Restricted Access Window (RAW) has been introduced in IEEE 802.11ah to address the scalability of thousands of densely deployed devices. As the RAW sizes entail the consumed energy to support the transmitting devices in the network, hence the control mechanism for RAW should be carefully devised for improving the overall energy e ciency of IEEE 802.11ah. This thesis presents a two-stage adaptive RAW scheme for IEEE 802.11ah to optimise the energy efficiency of massive channel access and transmission in the uplink communications for highly dense networks. The proposed scheme adaptively controls the RAW sizes and device transmission access by taking into account the number of devices per RAW, retransmission mechanism, harvested-energy and prioritised access. The scheme has four completely novel control blocks: RAW size control that adaptively adjusts the RAW sizes according to different number of devices and application types in the networks. RAW retransmission control that improves the channel utilisation by retransmitting the collided packets at the subsequent slot in the same RAW. Harvested-energy powered access control that adjusts the RAW sizes with the consideration of the uncertain amount of harvested-energy in each device and channel conditions. Priority-aware channel access control that reduces the collisions of high-priority packets in the time-critical networks. The performance of the proposed controls is evaluated in Matlab under different net work scenarios. Simulation results show that the proposed controls improve the network performances in terms of energy efficiency, packet delivery ratio and delay as compared to the existing window control.

Introdução: A patogênese da apneia obstrutiva do sono envolve estreitamento da faringe causado por deslocamento de líquido das pernas para o pescoço durante a noite. Objetivo: Determinar o efeito de intervenções que depletem líquido corporal na gravidade da apneia obstrutiva do sono. Métodos: Em ensaio randomizado controlado com placebo, homens diagnosticados com apneia obstrutiva do sono grave, segundo os critérios da Academia Americana de Medicina do Sono, foram aleatoriamente designados para receber diariamente diurético Lasilactona (espironolactona 100 mg + furosemida 20 mg) ou pílula placebo ou aconselhamento nutricional para dieta com restrição de sódio mais pílula placebo. O período de intervenção foi de uma semana. Todos os participantes realizaram a polissonografia portátil tipo III no início e no final do estudo. A mudança no índice de apneia hipopneia (IAH) foi o desfecho primário. Resultados: O estudo incluiu 54 participantes com média de idade (±DP) de 45±8,8 anos, IMC de 29,9±2,9 kg/m2 e IAH de 49±19 eventos/h. A mudança no IAH foi -11 eventos/h de sono (intervalo de confiança de 95% [IC], -15,59 para -5,74) no grupo de dieta, -7,33 (IC 95%, -13,75 para -0,91) no grupo diurético e 0,33 (IC 95%, -2,51 para 3,17) no grupo placebo (P=0,001 para interação tempo × grupo). A redução de água corporal total foi 2,2±2,2 L no grupo diurético (P<0,001) e 1,0±1,6 L no grupo dieta (P=0,002). Os sintomas de sonolência e a circunferência do pescoço reduziram significativamente somente no grupo dieta (P=0,007 e P<0,001 para interação, respectivamente). O uso de diurético aumentou a concentração de aldosterona e a atividade da renina plasmática (P<0,001 para interação). Conclusões: Em homens com apneia obstrutiva do sono grave, intervenções dietéticas e farmacológicas que depletam líquido corporal diminuem o IAH. Esse estudo fornece evidências de que a retenção de líquido corporal desempenha papel na patogênese da apneia do sono. / Rationale: The pathogenesis of obstructive sleep apnea involves pharyngeal narrowing caused by overnight fluid displacement from the legs to the neck. Objective: To determine the effect of interventions that reduced the body fluid content on obstructive sleep apnea severity. Methods: In this placebo-controlled study, men diagnosed with severe obstructive sleep apnea according American Academy of Sleep Medicine clinical criteria were randomized to receive daily diuretic lasilactone (spironolactone 100 mg + furosemide 20 mg) or placebo pill or nutritional counseling to sodium-restricted diet plus placebo pill. The intervention period was one week. All participants underwent out-of-center polysomnographies at baseline and follow-up. The change in apnea-hypopnea index (AHI) was the main outcome. Results: The study included 54 participants with mean age (±SD) of 45±8.8 years, body mass index of 29.9±2.9 kg/m2, and AHI of 49±19 events/h. From baseline to follow-up, the AHI delta value was −11 (95% confidence interval [CI], −15.59 to −5.74) in the diet group, −7.33 (95% CI, −13.75 to −0.91) in the diuretic group, and 0.33 (95% CI, −2.51 to 3.17) in the placebo group (P=0.001 for time × group interaction). The reduction in the total body water was 2.2±2.2 L in the diuretic group (P<0.001) and 1.0±1.6 L in the diet group (P=0.002). Sleepiness and neck circumference reduced only in the diet group (P=0.007 and P<0.001 for the interaction, respectively). The diuretic use augmented aldosterone concentration and plasma renin activity (P<0.001 for the interaction). Conclusions: Among men with severe OSA, dietary and pharmacological interventions that decrease bodily fluid content reduce the AHI. This trial provides a finding that fluid retention plays a role in apnea pathogenesis.

Perseverative conversation is a problem vocal behavior that is unique to individuals with Asperger's disorder. It is characterized by long-winded monologues revolving around circumscribed interests. The current research literature suggests that perseverative conversation may exacerbate already poor social relations, impede productivity at work and home, and lead to disruptive behavior when it is restricted. Despite the negative repercussions there is a lack of research related to the assessment and treatment of this behavior. In the field of applied behavior analysis, concurrent operants assessments have been used effectively to identify relative preference for concurrently available reinforcers. In the current study, choice assessments using concurrent operants arrangements were used to evaluate the reinforcing properties of perseverative conversation in children and adolescents with Asperger's disorder. Five participants, all with Asperger's disorder and reported difficulties with perseverative conversation, were assessed in three phases: A preference assessment for conversation topics; an assessment of preference for reinforcer dimensions; and an assessment of preference for competing dimensions. In the first phase a two-stage preference assessment separated high-preferred from less-preferred conversation topics and in the second and third phases participants were asked to make choices regarding their preference for conversation content, conversational style, and conversation duration. Phase II results suggested that participants preferred conversing about their respective circumscribed interests over neutral topics, actively conversing rather than listening, and conversing for longer duration rather than shorter duration. Phase III, which assessed relative preference for the three reinforcer dimensions, resulted in a hierarchy of preference for all but one participant. Two participants demonstrated the strongest preference for conversation content and two participants demonstrated the strongest preference for conversational style. Conversation duration was least preferred by four of the five participants. Perseverative conversation occurred at a relatively high rate across all assessment phases. The results are discussed in terms of current theoretical explanations for perseverative thinking and behavior, implications for treatment, and future research of this problem vocal behavior.

Although the captive reproduction of non-avian reptiles has increased steadily since the 1970’s, a dearth of information exists on successful management practices for large captive populations of these species. The data reported here come from a captive population of ball pythons (Python regius) maintained by a commercial breeding company, The Snake Keeper, Inc. (Spanish Fork, UT). Reproductive data are available for 6,480 eggs from 937 ball python clutches. The data presented suggest that proper management practices should include the use of palpation and/or ultrasound to ensure breeding occurs during the proper time of the female reproductive cycle, and that maintenance of proper humidity during the incubation of eggs is vitally important. Ball python reproduction traits (clutch size, clutch mass, relative clutch mass, egg mass, hatch rate, egg length, egg width, hatchling mass, healthy offspring per clutch, week laid, and days of incubation) were recorded for the clutches laid during this study. For the 937 clutches, the identity of the dam and sire were known for 862 (92%) and 777 (83%) of the clutches, respectively. A multivariate model that included nine of the 11 traits listed above was compiled. Heritability and genetic and phenotypic correlations were calculated from the multivariate analysis. The trait that showed the most promise for use in artificial selection to increase reproduction rates was clutch size due to considerable genetic variation, high heritability, and favorable genetic correlations with other reproduction traits. Although large datasets have been published for twinning in avian species, relatively few are available for non-avian reptiles. Reported here are 14 sets of twins produced from 6,480 eggs from 937 ball python clutches. The survival rate for twins during the first 3 months of life in our study was 97%. Interestingly, 11 of the sets of twins were identical in sex and phenotype, and additional genetic data suggested the rate of monozygotic twinning within this captive population of ball pythons was higher than that of dizygotic twinning. Further, using microsatellite analysis we were able to generate data that shows three sets of python twins were genetically identical.

<p>Symbolic resources transform in to social power and material resources through the educational system. This entails that all students should have equal access to it.</p><p>The essay compares Swedish didactics in “immigrant” and “white” schools, all situated in socio-economically underprivileged areas, analysing interviews with eight Swedish teachers about their didactics regarding restricted and elaborated language code.</p><p>Understanding teacher’s work in the class room requires attention to the intersections between race and class, and of both to the distribution of symbolic resources in general.</p><p>The essay finds that the practice of the” immigrant” school teachers differs from the “white” school teachers’. The former are active, providing intellectual tools, scaffolding and driving force while the later choose a more passive attitude, letting students decide for themselves what to do and what goals to reach. Consequently “white” schools allow the reproduction of unequal distribution of symbolic resources while practice in immigrant schools aim to compensate for disadvantages.</p><p>Practice seems to win legitimacy by different sets of conceptualisations. Immigrant students are envisaged like persons in need of help with low self-esteem and low drive. “White” students are looked upon as self-sufficient hedonists with a “natural” language competence.</p>

Symbolic resources transform in to social power and material resources through the educational system. This entails that all students should have equal access to it. The essay compares Swedish didactics in “immigrant” and “white” schools, all situated in socio-economically underprivileged areas, analysing interviews with eight Swedish teachers about their didactics regarding restricted and elaborated language code. Understanding teacher’s work in the class room requires attention to the intersections between race and class, and of both to the distribution of symbolic resources in general. The essay finds that the practice of the” immigrant” school teachers differs from the “white” school teachers’. The former are active, providing intellectual tools, scaffolding and driving force while the later choose a more passive attitude, letting students decide for themselves what to do and what goals to reach. Consequently “white” schools allow the reproduction of unequal distribution of symbolic resources while practice in immigrant schools aim to compensate for disadvantages. Practice seems to win legitimacy by different sets of conceptualisations. Immigrant students are envisaged like persons in need of help with low self-esteem and low drive. “White” students are looked upon as self-sufficient hedonists with a “natural” language competence.

Becoming a face expert takes years of learning and development. Many research programs are devoted to studying face perception, particularly given its prerequisite role in social interaction, yet its fundamental neural operations are poorly understood. One reason is that there are many possible explanations for a change in facial appearance, such as lighting, expression, or identity. Despite general agreement that the brain extracts multiple layers of feature detectors arranged into hierarchies to interpret causes of sensory information, very little work has been done to develop computational models of these processes, especially for complex stimuli like faces. The studies presented in this thesis used nonlinear generative models developed within machine learning to solve several face perception problems. Applying a deep hierarchical neural network, we showed that it is possible to learn representations capable of perceiving facial actions, expressions, and identities, better than similar non-hierarchical architectures. We then demonstrated that a generative architecture can be used to interpret high-level neural activity by synthesizing images in a top-down pass. Using this approach we showed that deep layers of a network can be activated to generate faces corresponding to particular categories. To facilitate training models to learn rich and varied facial features, we introduced a new expression database with the largest number of labeled faces collected to date. We found that a model trained on these images learned to recognize expressions comparably to human observers. Next we considered models trained on pairs of images, making it possible to learn how faces change appearance to take on different expressions. Modeling higher-order associations between images allowed us to efficiently match images of the same type according to a learned pairwise similarity measure. These models performed well on several tasks, including matching expressions and identities, and demonstrated performance superior to competing models. In sum, these studies showed that neural networks that extract highly nonlinear features from images using architectures inspired by the brain can solve difficult face perception tasks with minimal guidance by human experts.