Via de sinalização mTOR no carcinoma urotelial da bexiga

Trabalho de Projeto apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Análises Laboratoriais Especializadas, área de especialização em Análise Biomédica

Avaliação dos perfis de resistência a antibióticos em Escherichia coli provenientes de infeções urinárias adquiridas na comunidade

As infeções do trato urinário (ITU) são das infeções mais frequentes na comunidade, sendo E. coli o principal agente etiológico. O conhecimento da realidade epidemiológica no que concerne aos padrões de suscetibilidade aos vários antibióticos utilizados no tratamento de ITU é de extrema importância, permitindo assim a escolha mais adequada em contexto de terapia empírica. No tratamento da ITU são utilizados antibióticos de eliminação urinária, nomeadamente

Efficiently and Fairly Allocating Bandwidth at a Highly Congested Link

We consider the problem of efficiently and fairly allocating bandwidth at a highly congested link to a diverse set of flows, including TCP flows with various Round Trip Times (RTT), non-TCP-friendly flows such as Constant-Bit-Rate (CBR) applications using UDP, misbehaving, or malicious flows. Though simple, a FIFO queue management is vulnerable. Fair Queueing (FQ) can guarantee max-min fairness but fails at efficiency. RED-PD exploits the history of RED's actions in preferentially dropping packets from higher-rate flows. Thus, RED-PD attempts to achieve fairness at low cost. By relying on RED's actions, RED-PD turns out not to be effective in dealing with non-adaptive flows in settings with a highly heterogeneous mix of flows. In this paper, we propose a new approach we call RED-NB (RED with No Bias). RED-NB does not rely on RED's actions. Rather it explicitly maintains its own history for the few high-rate flows. RED-NB then adaptively adjusts flow dropping probabilities to achieve max-min fairness. In addition, RED-NB helps RED itself at very high loads by tuning RED's dropping behavior to the flow characteristics (restricted in this paper to RTTs) to eliminate its bias against long-RTT TCP flows while still taking advantage of RED's features at low loads. Through extensive simulations, we confirm the fairness of RED-NB and show that it outperforms RED, RED-PD, and CHOKe in all scenarios.

Exploiting the Transients of Adaptation for RoQ Attacks on Internet Resources

In this paper, we expose an unorthodox adversarial attack that exploits the transients of a system's adaptive behavior, as opposed to its limited steady-state capacity. We show that a well orchestrated attack could introduce significant inefficiencies that could potentially deprive a network element from much of its capacity, or significantly reduce its service quality, while evading detection by consuming an unsuspicious, small fraction of that element's hijacked capacity. This type of attack stands in sharp contrast to traditional brute-force, sustained high-rate DoS attacks, as well as recently proposed attacks that exploit specific protocol settings such as TCP timeouts. We exemplify what we term as Reduction of Quality (RoQ) attacks by exposing the vulnerabilities of common adaptation mechanisms. We develop control-theoretic models and associated metrics to quantify these vulnerabilities. We present numerical and simulation results, which we validate with observations from real Internet experiments. Our findings motivate the need for the development of adaptation mechanisms that are resilient to these new forms of attacks.

Characterization of Network-Wide Anomalies in Traffic Flows

Detecting and understanding anomalies in IP networks is an open and ill-defined problem. Toward this end, we have recently proposed the subspace method for anomaly diagnosis. In this paper we present the first large-scale exploration of the power of the subspace method when applied to flow traffic. An important aspect of this approach is that it fuses information from flow measurements taken throughout a network. We apply the subspace method to three different types of sampled flow traffic in a large academic network: multivariate timeseries of byte counts, packet counts, and IP-flow counts. We show that each traffic type brings into focus a different set of anomalies via the subspace method. We illustrate and classify the set of anomalies detected. We find that almost all of the anomalies detected represent events of interest to network operators. Furthermore, the anomalies span a remarkably wide spectrum of event types, including denial of service attacks (single-source and distributed), flash crowds, port scanning, downstream traffic engineering, high-rate flows, worm propagation, and network outage.

Simplified decoding techniques for linear block codes

Error correcting codes are combinatorial objects, designed to enable reliable transmission of digital data over noisy channels. They are ubiquitously used in communication, data storage etc. Error correction allows reconstruction of the original data from received word. The classical decoding algorithms are constrained to output just one codeword. However, in the late 50’s researchers proposed a relaxed error correction model for potentially large error rates known as list decoding. The research presented in this thesis focuses on reducing the computational effort and enhancing the efficiency of decoding algorithms for several codes from algorithmic as well as architectural standpoint. The codes in consideration are linear block codes closely related to Reed Solomon (RS) codes. A high speed low complexity algorithm and architecture are presented for encoding and decoding RS codes based on evaluation. The implementation results show that the hardware resources and the total execution time are significantly reduced as compared to the classical decoder. The evaluation based encoding and decoding schemes are modified and extended for shortened RS codes and software implementation shows substantial reduction in memory footprint at the expense of latency. Hermitian codes can be seen as concatenated RS codes and are much longer than RS codes over the same aphabet. A fast, novel and efficient VLSI architecture for Hermitian codes is proposed based on interpolation decoding. The proposed architecture is proven to have better than Kötter’s decoder for high rate codes. The thesis work also explores a method of constructing optimal codes by computing the subfield subcodes of Generalized Toric (GT) codes that is a natural extension of RS codes over several dimensions. The polynomial generators or evaluation polynomials for subfield-subcodes of GT codes are identified based on which dimension and bound for the minimum distance are computed. The algebraic structure for the polynomials evaluating to subfield is used to simplify the list decoding algorithm for BCH codes. Finally, an efficient and novel approach is proposed for exploiting powerful codes having complex decoding but simple encoding scheme (comparable to RS codes) for multihop wireless sensor network (WSN) applications.

Biomethane production from food waste and organic residues

Anaerobic digestion (AD) of biodegradable waste is an environmentally and economically sustainable solution which incorporates waste treatment and energy recovery. The organic fraction of municipal solid waste (OFMSW), which comprises mostly of food waste, is highly degradable under anaerobic conditions. Biogas produced from OFMSW, when upgraded to biomethane, is recognised as one of the most sustainable renewable biofuels and can also be one of the cheapest sources of biomethane if a gate fee is associated with the substrate. OFMSW is a complex and heterogeneous material which may have widely different characteristics depending on the source of origin and collection system used. The research presented in this thesis investigates the potential energy resource from a wide range of organic waste streams through field and laboratory research on real world samples. OFMSW samples collected from a range of sources generated methane yields ranging from 75 to 160 m3 per tonne. Higher methane yields are associated with source segregated food waste from commercial catering premises as opposed to domestic sources. The inclusion of garden waste reduces the specific methane yield from household organic waste. In continuous AD trials it was found that a conventional continuously stirred tank reactor (CSTR) gave the highest specific methane yields at a moderate organic loading rate of 2 kg volatile solids (VS) m-3 digester day-1 and a hydraulic retention time of 30 days. The average specific methane yield obtained at this loading rate in continuous digestion was 560 ± 29 L CH4 kg-1 VS which exceeded the biomethane potential test result by 5%. The low carbon to nitrogen ratio (C: N <14:1) associated with canteen food waste lead to increasing concentrations of volatile fatty acids in line with high concentrations of ammonia nitrogen at higher organic loading rates. At an organic loading rate of 4 kg VS m-3day-1 the specific methane yield dropped considerably (381 L CH4 kg-1 VS), the pH rose to 8.1 and free ammonia (NH3 ) concentrations reached toxicity levels towards the end of the trial (ca. 950 mg L-1). A novel two phase AD reactor configuration consisting of a series of sequentially fed leach bed reactors connected to an upflow anaerobic sludge blanket (UASB) demonstrated a high rate of organic matter decay but resulted in lower specific methane yields (384 L CH4 kg-1 VS) than the conventional CSTR system.

An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (cex) as primary treatment for large operable or locally advanced/inflammatory breast cancer.

In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation.

Crime in College Park: understanding crime levels, perceptions, and environmental design in an off-campus student-occupied neighborhood

Gemstone Team Crime Prevention and Perception

A recurrent F8 mutation in Irish haemophilia A patients: evidence for a founder effect.

Haemophilia A is a mutationally heterogeneous disorder with approximately 1,000 unique mutations of the Factor VIII (F8) gene recorded to date [1]. With the exception of the intron 22 inversion mutation, which occurs in ~45% of individuals with clinically severe disease, recurrent mutations causing haemophilia A are rare. This reflects a high rate of spontaneous mutation within the F8 gene generally resulting in private mutations within individual kindreds. We have identified a recurrent F8 gene mutation in Irish haemophilia A patients and have used haplotype analysis to investigate its origins.

Experimentally elevated plasma testosterone levels do not influence singing behaviour of male blue tits (Parus caeruleus) during the early breeding season

Sexual selection theory suggests that females might prefer males on the basis of testosterone (T)-dependent secondary sexual traits such as song. Correlational studies have linked high plasma T-levels to high diurnal song output. This has been confirmed in experiments where T-levels were kept high at times when natural T-levels have decreased. However, surprisingly little is known about the relation between T-levels during the early breeding season and song. In many passerine birds males sing at a high rate at dawn early in the breeding season, referred to as the dawn chorus. In blue tits (Parus caeruleus), the dawn chorus coincides with the fertile period of the female, whereas diurnal song occurs throughout the breeding season. Previous studies on blue tits showed that characteristics of the dawn chorus correlate with male reproductive success. We experimentally elevated plasma T-levels in male blue tits during the pre-fertile and fertile period. Our aim was to test whether increased plasma T-levels affect dawn song characteristics and increase the amount of diurnal song. Although T-implants successfully raised circulating T-levels, we did not find any difference between T- and control males in temporal performance measures of dawn song or in diurnal song output. Our results suggest that either there is no direct causal link between song output or quality and individual T-levels, or experimental manipulations of T-levels using implants do not permit detection of such effects during the early breeding season. Although we cannot exclude that individual T-levels are causally linked to other (e.g. structural) song parameters, our results cast doubt on T-dependence as the mechanisms that enforces honesty on song as a sexually selected trait.

Dilute acid hydrolysis of cellulose and cellulosic bio-waste using a microwave reactor system

The dilute acid hydrolysis of grass and cellulose with phosphoric acid was undertaken in a microwave reactor system. The experimental data and reaction kinetic analysis indicate that this is a potential process for cellulose and hemi-cellulose hydrolysis, due to a rapid hydrolysis reaction at moderate temperatures. The optimum conditions for grass hydrolysis were found to be 2.5% phosphoric acid at a temperature of 175 degrees C. It was found that sugar degradation occurred at acid concentrations greater than 2.5% (v/v) and temperatures greater than 175 degrees C. In a further series of experiments, the kinetics of dilute acid hydrolysis of cellulose was investigated varying phosphoric acid concentration and reaction temperatures. The experimental data indicate that the use of microwave technology can successfully facilitate dilute acid hydrolysis of cellulose allowing high yields of glucose in short reaction times. The optimum conditions gave a yield of 90% glucose. A pseudo-homogeneous consecutive first order reaction was assumed and the reaction rate constants were calculated as: k(1) = 0.0813 s(-1); k(2) = 0.0075 s(-1), which compare favourably with reaction rate constants found in conventional non-microwave reaction systems. The kinetic analysis would indicate that the primary advantages of employing microwave heating were to: achieve a high rate constant at moderate temperatures: and to prevent 'hot spot' formation within the reactor, which would have cause localised degradation of glucose.

Plant-wide predictive control for a thermal power plant based on a physical plant model

A constrained non-linear, physical model-based, predictive control (NPMPC) strategy is developed for improved plant-wide control of a thermal power plant. The strategy makes use of successive linearisation and recursive state estimation using extended Kalman filtering to obtain a linear state-space model. The linear model and a quadratic programming routine are used to design a constrained long-range predictive controller One special feature is the careful selection of a specific set of plant model parameters for online estimation, to account for time-varying system characteristics resulting from major system disturbances and ageing. These parameters act as nonstationary stochastic states and help to provide sufficient degrees-of-freedom to obtain unbiased estimates of controlled outputs. A 14th order non-linear plant model, simulating the dominant characteristics of a 200 MW oil-fired pou er plant has been used to test the NPMPC algorithm. The control strategy gives impressive simulation results, during large system disturbances and extremely high rate of load changes, right across the operating range. These results compare favourably to those obtained with the state-space GPC method designed under similar conditions.

Iterative Multiuser Detection and Decoding for DS-CDMA System With Space-Time Linear Dispersion

This paper considers a Q-ary orthogonal direct-sequence code-division multiple-access (DS-CDMA) system with high-rate space-time linear dispersion codes (LDCs) in time-varying Rayleigh fading multiple-input-multiple-output (MIMO) channels. We propose a joint multiuser detection, LDC decoding, Q-ary demodulation, and channel-decoding algorithm and apply the turbo processing principle to improve system performance in an iterative fashion. The proposed iterative scheme demonstrates faster convergence and superior performance compared with the V-BLAST-based DS-CDMA system and is shown to approach the single-user performance bound. We also show that the CDMA system is able to exploit the time diversity offered by the LDCS in rapid-fading channels.

Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option.

Keloid scars are common benign fibroproliferative reticular dermal lesions with unknown etiology and ill-defined management with high rate of recurrence post surgery. The progression of keloids is characterized by increased deposition of extracellular matrix proteins, invasion into the surrounding healthy skin and inflammation. Fibroblasts are considered to be the key cellular mediators of fibrogenesis in keloid scars. Fibroblast activation protein alpha (FAP-a) and dipeptidyl peptidase IV (DPPIV) are proteases located at the plasma membrane promoting cell invasiveness and tumor growth and have been previously associated with keloid scars. Therefore, in this study we analyzed in further detail the expression of FAP-a in keloid fibroblasts compared to control skin fibroblasts. Dermal fibroblasts were obtained from punch-biopsies from the active margin of four keloids and four control skin samples. Flow cytometry was used to analyze FAP-a expression and the CytoSelect(®) 24-Well Collagen I Cell Invasion Assay was applied to study fibroblast invasion. Secretion of extracellular matrix (ECM) proteins was investigated by multiplexed particle-based flow cytometric assay and enzyme-linked immunosorbent assay. We found an increased expression of FAP-a in keloid fibroblasts compared to control skin fibroblasts (p