Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo

INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.

Control system for actuation and sensing in digital microfluidics devices

Digital Microfluidics (DMF) is a second generation technique, derived from the conventional microfluidics that instead of using continuous liquid fluxes, it uses only individual droplets driven by external electric signals. In this thesis a new DMF control/sensing system for visualization, droplet control (movement, dispensing, merging and splitting) and real time impedance measurement have been developed. The software for the proposed system was implemented in MATLAB with a graphical user interface. An Arduino was used as control board and dedicated circuits for voltage switching and contacts were designed and implemented in printed circuit boards. A high resolution camera was integrated for visualization. In our new approach, the DMF chips are driven by a dual-tone signal where the sum of two independent ac signals (one for droplet operations and the other for impedance sensing) is applied to the electrodes, and afterwards independently evaluated by a lock-in amplifier. With this new approach we were able to choose the appropriated amplitudes and frequencies for the different proposes (actuation and sensing). The measurements made were used to evaluate the real time droplet impedance enabling the knowledge of its position and velocity. This new approach opens new possibilities for impedance sensing and feedback control in DMF devices.

Learning new tricks: Corticostriatal dynamics during novel skill learning

Learning novel actions and skills is a prevalent ability across multiple species and a critical feature for survival and competence in a constantly changing world. Novel actions are generated and learned through a process of trial and error, where an animal explores the environment around itself, generates multiple patterns of behavior and selects the ones that increase the likelihood of positive outcomes. Proper adaptation and execution of the selected behavior requires the coordination of several biomechanical features by the animal. Cortico-basal ganglia circuits and loops are critically involved in the acquisition, learning and consolidation of motor skills.(...)

Efetividade de um programa de educação baseado na neurofisiologia da dor e exercício aquático em comparação com um programa de exercício aquático isolado em indivíduos com dor lombar crónica

RESUMO: Introdução e Objetivos: O exercício é uma das modalidades mais utilizadas no tratamento da Dor Lombar Crónica (DLC) mas também a mais recomendada pela literatura atual. Apesar de efetivo, o exercício não parece responder às características cognitivas e comportamentais identificadas nesta população. Assim, existem recomendações para que seja coadjuvado por educação de forma a minimizar a influência nos resultados de variáveis como o medo do movimento. Porém não é conhecido o real impacto nos resultados de um programa educacional quando acrescentado a um programa de exercício. O objetivo deste estudo foi investigar os efeitos de um programa de exercício aquático coadjuvado por educação baseada na neurofisiologia da dor (grupo experimental) comparado a um programa de exercício aquático isolado (grupo controlo), ao nível da intensidade da dor, incapacidade funcional e medo do movimento, em indivíduos com DLC. Metodologia: Sessenta e dois indivíduos com DLC foram aleatoriamente distribuídos pelo grupo experimental (n= 30) e pelo grupo controlo (n= 32). Os participantes de ambos os grupos realizaram um programa de 6 semanas constituído por 12 sessões de exercício aquático. No caso do grupo experimental foram realizadas duas sessões de educação baseada na neurofisiologia da dor (EBN) antes do programa de exercício aquático. As medidas de avaliação primárias foram a intensidade da dor (Escala Visual Análoga) e a incapacidade funcional (Quebec Back Pain Disability Scale). Secundariamente avaliou-se o medo do movimento através da Tampa Scale of Kinesiophobia. Os participantes foram avaliados antes da intervenção, 3 semanas após o início do programa de exercício aquático, no final da intervenção e 3 meses após o final da intervenção. Resultados: Foram encontradas melhorias significativas no final da intervenção ao nível da intensidade da dor e incapacidade funcional em ambos os grupos. Após 3 meses, apenas o grupo experimental apresentou melhorias significativas nas variáveis primárias. Na comparação entre grupos, os resultados foram favoráveis ao grupo experimental para a intensidade da dor nas avaliações após a intervenção (p= 0,032) e após 3 meses (p= 0,007). Quanto à incapacidade funcional e medo do movimento não se verificaram diferenças significativas entre grupos em nenhum momento. Também as medidas de relevância clínica utilizadas (tamanho do efeito; risco relativo; number needed to treat) favoreceram o grupo experimental. Conclusões: Os resultados mostram que um programa de exercício aquático e EBN foi mais efetivo na melhoria da intensidade da dor a curto e médio prazo do que um programa de exercício aquático isolado. Apesar de serem necessárias mais investigações sobre este tema, este estudo demonstra que a EBN pode otimizar os resultados quando associada a outras intervenções ativas como o exercício aquático.----------------ABSTRACT: Introduction and Objectives: Exercise is one of the most used modalities in the treatment of Chronic Low Back Pain (CLBP) but also the most recommended in current literature. Although it’s effective, exercise does not seem to respond to the cognitive and behavioural characteristics identified in this population. Thus, it is recommended to be assisted by education in order to minimize the influence of variables on the results such as the fear of movement. However, the real impact on the results of an educational program when added to an exercise program is not known. The aim of this study was to investigate the effects of a program of aquatic exercise and neurophysiology pain education (experimental group) compared to aquatic exercise program alone (control group), on the outcomes of pain intensity, functional disability and fear of movement in individuals with CLBP. Methodology: Sixty two individuals with CLBP were randomly distributed in the experimental group (n = 30) and in the control group (n = 32). Participants in both groups performed a 6-week program consisting of 12 sessions of aquatic exercise. In the case of the experimental group two sessions of neurophysiology pain education (NPE) were performed before the aquatic exercise program. The primary outcomes were pain intensity (Visual Analogue Scale) and functional disability (Quebec Back Pain Disability Scale). Secondarily, the fear of movement through the Tampa Scale of Kinesiophobia was assessed. Participants were assessed before the intervention, three weeks after the start of the aquatic exercise program, at the end of the intervention and 3 months after the end of the intervention. Results: Significant improvements were found at the end of the intervention in both groups in what intensity of pain and functional disability were concerned. After 3 months, only the experimental group showed significant improvements in the primary outcomes. Comparing both groups, the results favoured to the experimental group for intensity of pain scores after the intervention (p = 0.032) and after 3 months (p = 0.007). The functional disability and fear of movement had no significant differences between groups at any time. In addition, the measures of clinical relevance used (size effect; relative risk; number needed to treat) favoured the experimental group. Conclusions: The results show that a program of aquatic exercise and NPE were more effective in improving pain intensity at a short and medium term than an aquatic exercise program alone. Although more research on this topic is needed, this study demonstrates that the NPE can optimize results when combined with other active interventions such as aquatic exercise.

Desenvolvimento de aplicações de Sistemas de Informação Geográfica WEB para gestão de resíduos urbanos.

A gestão do território contribui para o desenvolvimento socioeconómico e para o alcance de necessidades coletivas. A gestão de recursos, por sua vez, é uma das vias para atingir tais propósitos, convocando agentes, entidades e serviços para a administração de um território. O crescimento social e económico e a expansão urbana das últimas décadas tiveram um impacto significativo no consumo de recursos e na decorrente produção de resíduos, fazendo da gestão dos mesmos um importante meio para a gestão de recursos, com contributo para a gestão do território. Neste contexto, surgem serviços de gestão de resíduos urbanos, que dependem de informação geográfica referente ao seu sistema e ao do ambiente territorial em que o mesmo se insere. Face ao dinamismo e às relações entre diversos fenómenos e elementos presentes no referido ambiente, o processo de gestão de resíduos urbanos torna-se um desafio cada vez mais exigente e heterogéneo, em matéria de decisão espacial. Por esse motivo, é indispensável possuir ferramentas que integrem vários dados e que possibilitem abordagens metodológicas orientadas para uma intervenção territorial mais realista. Para tal, existem diversos métodos e técnicas, assentes em Tecnologias de Informação e Comunicação, com uma considerável adesão a soluções de Sistemas de Informação Geográfica, dada a necessidade de manipular informação com carácter espacial referente à gestão de resíduos urbanos. No quadro atual da produção e da prestação de serviços através de rede digital, as plataformas Web desses Sistemas de Informação Geográfica constituem-se como um instrumento para gestão de resíduos. Considerando o exemplo do Gabinete de Estudos, Planeamento e Controlo, dos Serviços Intermunicipalizados de Águas e Resíduos dos Municípios de Loures e Odivelas, no presente Trabalho de Projeto, pretende-se avaliar a situação atual das metodologias e dos recursos tecnológicos que um serviço deste tipo possui, percebendo o contributo que aplicações de Sistemas de Informação Geográfica Web podem ter para a concretização da sua missão, na conjuntura atual da tecnologia, da informação e da comunicação na Administração Pública. Assim, o presente Trabalho de Projeto propõe também um modelo de desenvolvimento das referidas aplicações, assentes em Sistemas de Informação Geográfica Desktop e Web de código aberto, livres e gratuitos. As aplicações abarcam informação interna, referente ao sistema de resíduos urbanos, dos Serviços Intermunicipalizados de Águas e Resíduos dos Municípios de Loures e Odivelas, e informação externa diversa, referente ao seu território de intervenção. A integração e relação da informação interna e externa, com resultados nas aplicações, são apresentadas como possíveis meios de assistência aos procedimentos efetuados no Gabinete de Estudos, Planeamento e Controlo e à prestação efetiva do serviço de gestão de resíduos urbanos. Igualmente, é possível inferir a versatilidade, a aplicabilidade e o potencial de aplicações de Sistemas de Informação Geográfica, em diversas vertentes e escalas de gestão do território.

Non-gyrator type active inductors

Modern CMOS radio frequency (RF) Receivers have enabled efficient and increasing applications. The main requirement is to have system in a single chip, in order to minimize area and cost. For the purpose it is required the development of inductorless circuits for the key blocks of an RF receiver. Examples of this key blocks are RC oscillators, RF band pass filters, and Low Noise Amplifiers. The present dissertation presents an inductorless wideband MOSFET-only RF Non-Gyrator Type of Active Inductors with low area, low cost, and very low power, capable of covering the whole WMTS, and ISM, band and intended for biomedical applications. The proposed circuit is based on a floating capacitor connected between two controlled current sources. The first current source, which is controlled by the circuit input voltage, has two objectives: supply current to the capacitor (

Using an LED as a sensor and visible light communication device in a smart illumination system

The need for more efficient illumination systems has led to the proliferation of Solid-State Lighting (SSL) systems, which offer optimized power consumption. SSL systems are comprised of LED devices which are intrinsically fast devices and permit very fast light modulation. This, along with the congestion of the radio frequency spectrum has paved the path for the emergence of Visible Light Communication (VLC) systems. VLC uses free space to convey information by using light modulation. Notwithstanding, as VLC systems proliferate and cost competitiveness ensues, there are two important aspects to be considered. State-of-the-art VLC implementations use power demanding PAs, and thus it is important to investigate if regular, existent Switched-Mode Power Supply (SMPS) circuits can be adapted for VLC use. A 28 W buck regulator was implemented using a off-the-shelf LED Driver integrated circuit, using both series and parallel dimming techniques. Results show that optical clock frequencies up to 500 kHz are achievable without any major modification besides adequate component sizing. The use of an LED as a sensor was investigated, in a short-range, low-data-rate perspective. Results show successful communication in an LED-to-LED configuration, with enhanced range when using LED strings as sensors. Besides, LEDs present spectral selective sensitivity, which makes them good contenders for a multi-colour LED-to-LED system, such as in the use of RGB displays and lamps. Ultimately, the present work shows evidence that LEDs can be used as a dual-purpose device, enabling not only illumination, but also bi-directional data communication.

Analysis and implementation of a multi-ratio switched capacitor DC-DC converter for a supercapacitor power supply

An energy harvesting system requires an energy storing device to store the energy retrieved from the surrounding environment. This can either be a rechargeable battery or a supercapcitor. Due to the limited lifetime of rechargeable batteries, they need to be periodically replaced. Therefore, a supercapacitor, which has ideally a limitless number of charge/discharge cycles can be used to store the energy; however, a voltage regulator is required to obtain a constant output voltage as the supercapacitor discharges. This can be implemented by a Switched-Capacitor DC-DC converter which allows a complete integration in CMOS technology, although it requires several topologies in order to obtain a high efficiency. This thesis presents the complete analysis of four different topologies in order to determine expressions that allow to design and determine the optimum input voltage ranges for each topology. To better understand the parasitic effects, the implementation of the capacitors and the non-ideal effect of the switches, in 130 nm technology, were carefully studied. With these two analysis a multi-ratio SC DC-DC converter was designed with an output power of 2 mW, maximum efficiency of 77%, and a maximum output ripple, in the steady state, of 23 mV; for an input voltage swing of 2.3 V to 0.85 V. This proposed converter has four operation states that perform the conversion ratios of 1/2, 2/3, 1/1 and 3/2 and its clock frequency is automatically adjusted to produce a stable output voltage of 1 V. These features are implemented through two distinct controller circuits that use asynchronous time machines (ASM) to dynamically adjust the clock frequency and to select the active state of the converter. All the theoretical expressions as well as the behaviour of the whole system was verified using electrical simulations.

Quadrature generators based on ring oscillators and shift registers

Quadrature oscillators are key elements in modern radio frequency (RF) transceivers and very useful nowadays in wireless communications, since they can provide: low quadrature error, low phase-noise, and wide tuning range (useful to cover several bands). RC oscillators can be fully integrated without the need of external components (external high Q-inductors), optimizing area, cost, and power consumption. The conventional structure of ring oscillator offers poor frequency stability and phasenoise, low quality factor (Q), and besides being vulnerable to process, voltage and temperature (PVT) variations, its performance degrades as the frequency of operation increases. This thesis is devoted to quadrature oscillators and presents a detailed comparative study of ring oscillator and shift register (SR) approaches. It is shown that in SRs both phase-noise and phase error are reduced, while ring oscillators have the advantage of occupying less area and less consumption due to the reduced number of components in the circuit. Thus, although ring oscillators are more suitable for biomedical applications, SRs are more appropriate for wireless applications, especially when specification requirements are more stringent and demanding. The first architecture studied consists in a simple CMOS ring oscillator employing an odd number of static single-ended inverters as delay cells. Subsequently, the quadrature 4-stage ring oscillator concept is shown and post-layout simulations are presented. The 3 and 4-phase single-frequency local oscillator (LO) generators employing SRs are presented, the latter with 50% and 25% duty-cycles. The circuits operate at 600 MHz and 900 MHz, and were designed in a 130 nm standard CMOS technology with a voltage supply of 1.2 V.

Switching mode power amplifier for bluetooth applications

Modern fully integrated transceivers architectures, require circuits with low area, low cost, low power, and high efficiency. A key block in modern transceivers is the power amplifier, which is deeply studied in this thesis. First, we study the implementation of a classical Class-A amplifier, describing the basic operation of an RF power amplifier, and analysing the influence of the real models of the reactive components in its operation. Secondly, the Class-E amplifier is deeply studied. The different types of implementations are reviewed and theoretical equations are derived and compared with simulations. There were selected four modes of operation for the Class-E amplifier, in order to perform the implementation of the output stage, and the subsequent comparison of results. This led to the selection of the mode with the best trade-off between efficiency and harmonics distortion, lower power consumption and higher output power. The optimal choice was a parallel circuit containing an inductor with a finite value. To complete the implementation of the PA in switching mode, a driver was implemented. The final block (output stage together with the driver) got 20 % total efficiency (PAE) transmitting 8 dBm output power to a 50 W load with a total harmonic distortion (THD) of 3 % and a total consumption of 28 mW. All implementations are designed using standard 130 nm CMOS technology. The operating frequency is 2.4 GHz and it was considered an 1.2 V DC power supply. The proposed circuit is intended to be used in a Bluetooth transmitter, however, it has a wider range of applications.

Minimal computation structures for visual information applications based on printed electronics

In the early nineties, Mark Weiser wrote a series of seminal papers that introduced the concept of Ubiquitous Computing. According to Weiser, computers require too much attention from the user, drawing his focus from the tasks at hand. Instead of being the centre of attention, computers should be so natural that they would vanish into the human environment. Computers become not only truly pervasive but also effectively invisible and unobtrusive to the user. This requires not only for smaller, cheaper and low power consumption computers, but also for equally convenient display solutions that can be harmoniously integrated into our surroundings. With the advent of Printed Electronics, new ways to link the physical and the digital worlds became available. By combining common printing techniques such as inkjet printing with electro-optical functional inks, it is starting to be possible not only to mass-produce extremely thin, flexible and cost effective electronic circuits but also to introduce electronic functionalities into products where it was previously unavailable. Indeed, Printed Electronics is enabling the creation of novel sensing and display elements for interactive devices, free of form factor. At the same time, the rise in the availability and affordability of digital fabrication technologies, namely of 3D printers, to the average consumer is fostering a new industrial (digital) revolution and the democratisation of innovation. Nowadays, end-users are already able to custom design and manufacture on demand their own physical products, according to their own needs. In the future, they will be able to fabricate interactive digital devices with user-specific form and functionality from the comfort of their homes. This thesis explores how task-specific, low computation, interactive devices capable of presenting dynamic visual information can be created using Printed Electronics technologies, whilst following an approach based on the ideals behind Personal Fabrication. Focus is given on the use of printed electrochromic displays as a medium for delivering dynamic digital information. According to the architecture of the displays, several approaches are highlighted and categorised. Furthermore, a pictorial computation model based on extended cellular automata principles is used to programme dynamic simulation models into matrix-based electrochromic displays. Envisaged applications include the modelling of physical, chemical, biological, and environmental phenomena.

Wideband CMOS low noise amplifiers

Modern fully integrated receiver architectures, require inductorless circuits to achieve their potential low area, low cost, and low power. The low noise amplifier (LNA), which is a key block in such receivers, is investigated in this thesis. LNAs can be either narrowband or wideband. Narrowband LNAs use inductors and have very low noise figure, but they occupy a large area and require a technology with RF options to obtain inductors with high Q. Recently, wideband LNAs with noise and distortion cancelling, with passive loads have been proposed, which can have low NF, but have high power consumption. In this thesis the main goal is to obtain a very low area, low power, and low-cost wideband LNA. First, it is investigated a balun LNA with noise and distortion cancelling with active loads to boost the gain and reduce the noise figure (NF). The circuit is based on a conventional balun LNA with noise and distortion cancellation, using the combination of a common-gate (CG) stage and common-source (CS) stage. Simulation and measurements results, with a 130 nm CMOS technology, show that the gain is enhanced by about 3 dB and the NF is reduced by at least 0.5 dB, with a negligible impact on the circuit linearity (IIP3 is about 0 dBm). The total power dissipation is only 4.8 mW, and the active area is less than 50 x 50 m2 . It is also investigated a balun LNA in which the gain is boosted by using a double feedback structure.We propose to replace the load resistors by active loads, which can be used to implement local feedback loops (in the CG and CS stages). This will boost the gain and reduce the noise figure (NF). Simulation results, with the same 130 nm CMOS technology as above, show that the gain is 24 dB and NF is less than 2.7 dB. The total power dissipation is only 5.4 mW (since no extra blocks are required), leading to a figure-of-merit (FoM) of 3.8 mW

A minimal version of a Protein Tyrosine Phosphatase

Phosphatase and tensin homologue (PTEN) protein belongs to the family of protein tyrosine phos-phatase. Mutations on the phosphatase and tensin homologue (PTEN) protein are highly observed in diverse types of human tumors, being mostly identified on the phosphatase domain of the protein. Although PTEN is a modular protein composed by a phosphatase domain and a C2 domain for mem-brane anchoring, this work aimed at developing a minimal version of PTEN´s phosphatase domain. The minimal version (Small Domain) comprises a 28 residue peptide, with the PTEN 8-mer catalytic peptide accommodated between a α-helix and β-turn as observed in PTEN native structure. Firstly, a de novo prediction of the Small Domain´s secondary structure was carried out by molecular modeling tools. The stability of the predicted structures were then evaluated by Molecular Dynamics. Automated molecular docking of PTEN natural substrate PIP3, its analogue (Inositol) and a PTEN inhibitor (L-tar-tare) were performed with the modeled structure, and PTEN used as a positive control. The gene en-coding for Small Domain was designed and cloned into an expression vector at N-terminal of Green Fluorescence Protein (GFP) encoding gene. The fusion protein was then expressed in Escherichia coli cells. Different expression conditions have been explored for the production of the fusion protein to minimize the formation of inclusion bodies.

Predictive control of a current-source inverter for solar photovoltaic grid interface

Solar photovoltaic systems are an increasing option for electricity production, since they produce electrical energy from a clean renewable energy resource, and over the years, as a result of the research, their efficiency has been increasing. For the interface between the dc photovoltaic solar array and the ac electrical grid is necessary the use of an inverter (dc-ac converter), which should be optimized to extract the maximum power from the photovoltaic solar array. In this paper is presented a solution based on a current-source inverter (CSI) using continuous control set model predictive control (CCS-MPC). All the power circuits and respective control systems are described in detail along the paper and were tested and validated performing computer simulations. The paper shows the simulation results and are drawn several conclusions.

Extracting kinetic information from literature with KineticRE

To better understand the dynamic behavior of metabolic networks in a wide variety of conditions, the field of Systems Biology has increased its interest in the use of kinetic models. The different databases, available these days, do not contain enough data regarding this topic. Given that a significant part of the relevant information for the development of such models is still wide spread in the literature, it becomes essential to develop specific and powerful text mining tools to collect these data. In this context, this work has as main objective the development of a text mining tool to extract, from scientific literature, kinetic parameters, their respective values and their relations with enzymes and metabolites. The approach proposed integrates the development of a novel plug-in over the text mining framework @Note2. In the end, the pipeline developed was validated with a case study on Kluyveromyces lactis, spanning the analysis and results of 20 full text documents.