Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

A Generalized Fuzzy Linguistic Model for Predicting Component Concentrations in an Optical Gas Sensing System

Motivated by environmental protection concerns, monitoring the flue gas of thermal power plant is now often mandatory due to the need to ensure that emission levels stay within safe limits. Optical based gas sensing systems are increasingly employed for this purpose, with regression techniques used to relate gas optical absorption spectra to the concentrations of specific gas components of interest (NOx, SO2 etc.). Accurately predicting gas concentrations from absorption spectra remains a challenging problem due to the presence of nonlinearities in the relationships and the high-dimensional and correlated nature of the spectral data. This article proposes a generalized fuzzy linguistic model (GFLM) to address this challenge. The GFLM is made up of a series of “If-Then” fuzzy rules. The absorption spectra are input variables in the rule antecedent. The rule consequent is a general nonlinear polynomial function of the absorption spectra. Model parameters are estimated using least squares and gradient descent optimization algorithms. The performance of GFLM is compared with other traditional prediction models, such as partial least squares, support vector machines, multilayer perceptron neural networks and radial basis function networks, for two real flue gas spectral datasets: one from a coal-fired power plant and one from a gas-fired power plant. The experimental results show that the generalized fuzzy linguistic model has good predictive ability, and is competitive with alternative approaches, while having the added advantage of providing an interpretable model.

Fuzzy logic-based implicit authentication for mobile access control

In order to address the increasing compromise of user privacy on mobile devices, a Fuzzy Logic based implicit authentication scheme is proposed in this paper. The proposed scheme computes an aggregate score based on selected features and a threshold in real-time based on current and historic data depicting user routine. The tuned fuzzy system is then applied to the aggregated score and the threshold to determine the trust level of the current user. The proposed fuzzy-integrated implicit authentication scheme is designed to: operate adaptively and completely in the background, require minimal training period, enable high system accuracy while provide timely detection of abnormal activity. In this paper, we explore Fuzzy Logic based authentication in depth. Gaussian and triangle-based membership functions are investigated and compared using real data over several weeks from different Android phone users. The presented results show that our proposed Fuzzy Logic approach is a highly effective, and viable scheme for lightweight real-time implicit authentication on mobile devices.

A generalized fuzzy linguistic model for predicting component concentrations in an optical gas sensing system

Motivated by environmental protection concerns, monitoring the flue gas of thermal power plant is now often mandatory due to the need to ensure that emission levels stay within safe limits. Optical based gas sensing systems are increasingly employed for this purpose, with regression techniques used to relate gas optical absorption spectra to the concentrations of specific gas components of interest (NO_x, SO₂ etc.). Accurately predicting gas concentrations from absorption spectra remains a challenging problem due to the presence of nonlinearities in the relationships and the high-dimensional and correlated nature of the spectral data. This article proposes a generalized fuzzy linguistic model (GFLM) to address this challenge. The GFLM is made up of a series of “If-Then” fuzzy rules. The absorption spectra are input variables in the rule antecedent. The rule consequent is a general nonlinear polynomial function of the absorption spectra. Model parameters are estimated using least squares and gradient descent optimization algorithms. The performance of GFLM is compared with other traditional prediction models, such as partial least squares, support vector machines, multilayer perceptron neural networks and radial basis function networks, for two real flue gas spectral datasets: one from a coal-fired power plant and one from a gas-fired power plant. The experimental results show that the generalized fuzzy linguistic model has good predictive ability, and is competitive with alternative approaches, while having the added advantage of providing an interpretable model.

Real-time analytics on large dynamic graphs

In today's fast-paced and interconnected digital world, the data generated by an increasing number of applications is being modeled as dynamic graphs. The graph structure encodes relationships among data items, while the structural changes to the graphs as well as the continuous stream of information produced by the entities in these graphs make them dynamic in nature. Examples include social networks where users post status updates, images, videos, etc.; phone call networks where nodes may send text messages or place phone calls; road traffic networks where the traffic behavior of the road segments changes constantly, and so on. There is a tremendous value in storing, managing, and analyzing such dynamic graphs and deriving meaningful insights in real-time. However, a majority of the work in graph analytics assumes a static setting, and there is a lack of systematic study of the various dynamic scenarios, the complexity they impose on the analysis tasks, and the challenges in building efficient systems that can support such tasks at a large scale. In this dissertation, I design a unified streaming graph data management framework, and develop prototype systems to support increasingly complex tasks on dynamic graphs. In the first part, I focus on the management and querying of distributed graph data. I develop a hybrid replication policy that monitors the read-write frequencies of the nodes to decide dynamically what data to replicate, and whether to do eager or lazy replication in order to minimize network communication and support low-latency querying. In the second part, I study parallel execution of continuous neighborhood-driven aggregates, where each node aggregates the information generated in its neighborhoods. I build my system around the notion of an aggregation overlay graph, a pre-compiled data structure that enables sharing of partial aggregates across different queries, and also allows partial pre-computation of the aggregates to minimize the query latencies and increase throughput. Finally, I extend the framework to support continuous detection and analysis of activity-based subgraphs, where subgraphs could be specified using both graph structure as well as activity conditions on the nodes. The query specification tasks in my system are expressed using a set of active structural primitives, which allows the query evaluator to use a set of novel optimization techniques, thereby achieving high throughput. Overall, in this dissertation, I define and investigate a set of novel tasks on dynamic graphs, design scalable optimization techniques, build prototype systems, and show the effectiveness of the proposed techniques through extensive evaluation using large-scale real and synthetic datasets.

Gráficos de controle: aspectos teóricos e práticos a partir da ótica da lógica formal e da lógica fuzzy

O presente trabalho faz um enlace de teorias propostas por dois trabalhos: Transformação de valores crisp em valores fuzzy e construção de gráfico de controle fuzzy. O resultado desse enlace é um gráfico de controle fuzzy que foi aplicado em um processo de produção de iogurte, onde as variáveis analisadas foram: Cor, Aroma, Consistência, Sabor e Acidez. São características que dependem da percepção dos indivíduos, então a forma utilizada para coletar informações a respeito de tais característica foi a análise sensorial. Nas analises um grupo denominado de juízes, atribuía individualmente notas para cada amostra de iogurte em uma escala de 0 a 10. Esses valores crisp, notas atribuídas pelos juízes, foram então, transformados em valores fuzzy, na forma de número fuzzy triangular. Com os números fuzzy, foram construídos os gráficos de controle fuzzy de média e amplitude. Com os valores crisp foram construídos gráficos de controle de Shewhart para média e amplitude, já consolidados pela literatura. Por fim, os resultados encontrados nos gráficos tradicionais foram comparados aos encontrados nos gráficos de controle fuzzy. O que pode-se observar é que o gráfico de controle fuzzy, parece satisfazer de forma significativa a realidade do processo, pois na construção do número fuzzy é considerada a variabilidade do processo. Além disso, caracteriza o processo de produção em alguns níveis, onde nem sempre o processo estará totalmente em controle ou totalmente fora de controle. O que vai ao encontro da teoria fuzzy: se não é possível prever com exatidão determinados resultados é melhor ter uma margem de aceitação, o que implicará na redução de erros.

Problems in number theory and hyperbolic geometry

In the first part of this thesis we generalize a theorem of Kiming and Olsson concerning the existence of Ramanujan-type congruences for a class of eta quotients. Specifically, we consider a class of generating functions analogous to the generating function of the partition function and establish a bound on the primes ℓ for which their coefficients c(n) obey congruences of the form c(ℓn + a) ≡ 0 (mod ℓ). We use this last result to answer a question of H.C. Chan. In the second part of this thesis [S2] we explore a natural analog of D. Calegari’s result that there are no hyperbolic once-punctured torus bundles over S^1 with trace field having a real place. We prove a contrasting theorem showing the existence of several infinite families of pairs (−χ, p) such that there exist hyperbolic surface bundles over S^1 with trace field of having a real place and with fiber having p punctures and Euler characteristic χ. This supports our conjecture that with finitely many known exceptions there exist such examples for each pair ( −χ, p).

A mitochondrial species identification assay for Australian blacktip sharks (Carcharhinus tilstoni, C. limbatus and C. amblyrhynchoides) using real-time PCR and high-resolution melt analysis

Tropical Australian shark fisheries target two morphologically indistinguishable blacktip sharks, the Australian blacktip (Carcharhinus tilstoni) and the common blacktip (C. limbatus). Their relative contributions to northern and eastern Australian coastal fisheries are unclear because of species identification difficulties. The two species differ in their number of precaudal vertebrae, which is difficult and time consuming to obtain in the field. But, the two species can be distinguished genetically with diagnostic mutations in their mitochondrial DNA ND4 gene. A third closely related sister species, the graceful shark C. amblyrhynchoides, can also be distinguished by species-specific mutations in this gene. DNA sequencing is an effective diagnostic tool, but is relatively expensive and time consuming. In contrast, real-time high-resolution melt (HRM) PCR assays are rapid and relatively inexpensive. These assays amplify regions of DNA with species-specific genetic mutations that result in PCR products with unique melt profiles. A real-time HRM PCR species-diagnostic assay (RT-HRM-PCR) has been developed based on the mtDNA ND4 gene for rapid typing of C. tilstoni, C. limbatus and C. amblyrhynchoides. The assay was developed using ND4 sequences from 66 C. tilstoni, 33. C. limbatus and five C. amblyrhynchoides collected from Indonesia and Australian states and territories; Western Australia, the Northern Territory, Queensland and New South Wales. The assay was shown to be 100% accurate on 160 unknown blacktip shark tissue samples by full mtDNA ND4 sequencing.

Adaptação do paradigma orientado a notificações para desenvolvimento de sistemas fuzzy

This work proposes to adjust the Notification Oriented Paradigm (NOP) so that it provides support to fuzzy concepts. NOP is inspired by elements of imperative and declarative paradigms, seeking to solve some of the drawbacks of both. By decomposing an application into a network of smaller computational entities that are executed only when necessary, NOP eliminates the need to perform unnecessary computations and helps to achieve better logical-causal uncoupling, facilitating code reuse and application distribution over multiple processors or machines. In addition, NOP allows to express the logical-causal knowledge at a high level of abstraction, through rules in IF-THEN format. Fuzzy systems, in turn, perform logical inferences on causal knowledge bases (IF-THEN rules) that can deal with problems involving uncertainty. Since PON uses IF-THEN rules in an alternative way, reducing redundant evaluations and providing better decoupling, this research has been carried out to identify, propose and evaluate the necessary changes to be made on NOP allowing to be used in the development of fuzzy systems. After that, two fully usable materializations were created: a C++ framework, and a complete programming language (LingPONFuzzy) that provide support to fuzzy inference systems. From there study cases have been created and several tests cases were conducted, in order to validate the proposed solution. The test results have shown a significant reduction in the number of rules evaluated in comparison to a fuzzy system developed using conventional tools (frameworks), which could represent an improvement in performance of the applications.

Efficient Secure Computation for Real-world Settings and Security Models

Secure computation involves multiple parties computing a common function while keeping their inputs private, and is a growing field of cryptography due to its potential for maintaining privacy guarantees in real-world applications. However, current secure computation protocols are not yet efficient enough to be used in practice. We argue that this is due to much of the research effort being focused on generality rather than specificity. Namely, current research tends to focus on constructing and improving protocols for the strongest notions of security or for an arbitrary number of parties. However, in real-world deployments, these security notions are often too strong, or the number of parties running a protocol would be smaller. In this thesis we make several steps towards bridging the efficiency gap of secure computation by focusing on constructing efficient protocols for specific real-world settings and security models. In particular, we make the following four contributions: - We show an efficient (when amortized over multiple runs) maliciously secure two-party secure computation (2PC) protocol in the multiple-execution setting, where the same function is computed multiple times by the same pair of parties. - We improve the efficiency of 2PC protocols in the publicly verifiable covert security model, where a party can cheat with some probability but if it gets caught then the honest party obtains a certificate proving that the given party cheated. - We show how to optimize existing 2PC protocols when the function to be computed includes predicate checks on its inputs. - We demonstrate an efficient maliciously secure protocol in the three-party setting.

Evaluation of the conductor-like screening model for real solvents for the prediction of the water activity coefficient at infinite dilution in ionic liquids

Ionic liquids (ILs) have attracted great attention, from both industry and academia, as alternative fluids for very different types of applications. The large number of cations and anions allow a wide range of physical and chemical characteristics to be designed. However, the exhaustive measurement of all these systems is impractical, thus requiring the use of a predictive model for their study. In this work, the predictive capability of the conductor-like screening model for real solvents (COSMO-RS), a model based on unimolecular quantum chemistry calculations, was evaluated for the prediction water activity coefficient at infinite dilution, gamma(infinity)(w), in several classes of ILs. A critical evaluation of the experimental and predicted data using COSMO-RS was carried out. The global average relative deviation was found to be 27.2%, indicating that the model presents a satisfactory prediction ability to estimate gamma(infinity)(w) in a broad range of ILs. The results also showed that the basicity of the ILs anions plays an important role in their interaction with water, and it considerably determines the enthalpic behavior of the binary mixtures composed by Its and water. Concerning the cation effect, it is possible to state that generally gamma(infinity)(w) increases with the cation size, but it is shown that the cation-anion interaction strength is also important and is strongly correlated to the anion ability to interact with water. The results here reported are relevant in the understanding of ILs-water interactions and the impact of the various structural features of its on the gamma(infinity)(w) as these allow the development of guidelines for the choice of the most suitable lLs with enhanced interaction with water.

Sistema fuzzy para estimativa do bem-estar de matrizes pesadas

Entender o comportamento e suas pequenas variações decorrentes das mudanças do ambiente térmico e desenvolver modelos que simulem o bem-estar a partir de respostas das aves ao ambiente constituem o primeiro passo para a criação de um sistema de monitoramento digital de aves em galpões de produção. Neste trabalho, foi desenvolvido um sistema de suporte à decisão com base na teoria dos conjuntos fuzzy para a estimativa do bem-estar de matrizes pesadas em função de frequências e duração dos comportamentos expressos pelas aves. O desenvolvimento do sistema passou por cinco etapas distintas: 1) organização dos dados experimentais; 2) apresentação dos vídeos em entrevista com especialista; 3) criação das funções de pertinência com base nas entrevistas e na revisão da literatura; 4) simulação de frequências de ocorrências e tempos médios de expressão dos comportamentos classificados como indicadores de bem-estar utilizando equações de regressão obtidas na literatura, e 5) construção das regras, simulação e validação do sistema. O sistema fuzzy desenvolvido estimou satisfatoriamente o bem-estar de matrizes pesadas, tendo na sua última versão, com maior número de regras, acertado 77,8% dos dados experimentais, comparados com as respostas esperadas por um especialista. O sistema pode ser utilizado como instrumento matemático-computacional para apoiar decisões em galpões de produção de matrizes pesadas.

Evaluating tests for convergence of economic series using Monte Carlo methods with an application to real GDP's per head.

Doutoramento em Economia.

Real-time load-side control of electric power systems

Two trends are emerging from modern electric power systems: the growth of renewable (e.g., solar and wind) generation, and the integration of information technologies and advanced power electronics. The former introduces large, rapid, and random fluctuations in power supply, demand, frequency, and voltage, which become a major challenge for real-time operation of power systems. The latter creates a tremendous number of controllable intelligent endpoints such as smart buildings and appliances, electric vehicles, energy storage devices, and power electronic devices that can sense, compute, communicate, and actuate. Most of these endpoints are distributed on the load side of power systems, in contrast to traditional control resources such as centralized bulk generators. This thesis focuses on controlling power systems in real time, using these load side resources. Specifically, it studies two problems.

(1) Distributed load-side frequency control: We establish a mathematical framework to design distributed frequency control algorithms for flexible electric loads. In this framework, we formulate a category of optimization problems, called optimal load control (OLC), to incorporate the goals of frequency control, such as balancing power supply and demand, restoring frequency to its nominal value, restoring inter-area power flows, etc., in a way that minimizes total disutility for the loads to participate in frequency control by deviating from their nominal power usage. By exploiting distributed algorithms to solve OLC and analyzing convergence of these algorithms, we design distributed load-side controllers and prove stability of closed-loop power systems governed by these controllers. This general framework is adapted and applied to different types of power systems described by different models, or to achieve different levels of control goals under different operation scenarios. We first consider a dynamically coherent power system which can be equivalently modeled with a single synchronous machine. We then extend our framework to a multi-machine power network, where we consider primary and secondary frequency controls, linear and nonlinear power flow models, and the interactions between generator dynamics and load control.

(2) Two-timescale voltage control: The voltage of a power distribution system must be maintained closely around its nominal value in real time, even in the presence of highly volatile power supply or demand. For this purpose, we jointly control two types of reactive power sources: a capacitor operating at a slow timescale, and a power electronic device, such as a smart inverter or a D-STATCOM, operating at a fast timescale. Their control actions are solved from optimal power flow problems at two timescales. Specifically, the slow-timescale problem is a chance-constrained optimization, which minimizes power loss and regulates the voltage at the current time instant while limiting the probability of future voltage violations due to stochastic changes in power supply or demand. This control framework forms the basis of an optimal sizing problem, which determines the installation capacities of the control devices by minimizing the sum of power loss and capital cost. We develop computationally efficient heuristics to solve the optimal sizing problem and implement real-time control. Numerical experiments show that the proposed sizing and control schemes significantly improve the reliability of voltage control with a moderate increase in cost.