Denial of service attacks (DoS) are a common threat to many online services. These attacks aim to overcome the availability of an online service with massive traffic from multiple sources. By spoofing legitimate users, an attacker floods a target system with a high quantity of packets or connections to crash its network resources, bandwidth, equipment, or servers. Packet filtering methods are the most known way to prevent these attacks via identifying and blocking the spoofed attack from reaching its target. In this project, the extent of the DoS attacks problem and attempts to prevent it are explored. The attacks categories and existing countermeasures based on preventing, detecting, and responding are reviewed. Henceforward, a neural network learning algorithms and statistical analysis are utilized into the designing of our proposed packet filtering system.

Multiple regression models play an important role in analyzing and making predictions about data. Prediction accuracy becomes lower when two or more explanatory variables in the model are highly correlated. One solution is to use ridge regression. The purpose of this thesis is to study the performance of available ridge regression estimators for Poisson regression models in the presence of moderately to highly correlated variables. As performance criteria, we use mean square error (MSE), mean absolute percentage error (MAPE), and percentage of times the maximum likelihood (ML) estimator produces a higher MSE than the ridge regression estimator. A Monte Carlo simulation study was conducted to compare performance of the estimators under three experimental conditions: correlation, sample size, and intercept. It is evident from simulation results that all ridge estimators performed better than the ML estimator. We proposed new estimators based on the results, which performed very well compared to the original estimators. Finally, the estimators are illustrated using data on recreational habits.

Imagine your local creamery administers a survey asking their patrons to choose their five favorite ice cream flavors. Any data collected by this survey would be an example of partially ranked data, as the set of all possible flavors is only ranked into subsets of the chosen flavors and the non-chosen flavors. If the creamery asks you to help analyze this data, what approaches could you take? One approach is to use the natural symmetries of the underlying data space to decompose any data set into smaller parts that can be more easily understood. In this work, I describe how to use permutation representations of the symmetric group to create and study efficient algorithms that yield such decompositions.

miRNAs are non-coding RNAs of approx. 22 nucleotides in length that inhibit gene expression at the post-transcriptional level. By virtue of this gene regulation mechanism, miRNAs play a critical role in several biological processes and patho-physiological conditions, including cancers. miRNA behavior is a result of a multi-level complex interaction network involving miRNA-mRNA, TF-miRNA-gene, and miRNA-chemical interactions; hence the precise patterns through which a miRNA regulates a certain disease(s) are still elusive. Herein, I have developed an integrative genomics methods/pipeline to (i) build a miRNA regulomics and data analytics repository, (ii) create/model these interactions into networks and use optimization techniques, motif based analyses, network inference strategies and influence diffusion concepts to predict miRNA regulations and its role in diseases, especially related to cancers. By these methods, we are able to determine the regulatory behavior of miRNAs and potential causal miRNAs in specific diseases and potential biomarkers/targets for drug and medicinal therapeutics.

Modern application domains such as Composite Event Recognition (CER) and real-time Analytics require the ability to dynamically refresh query results under high update rates. Traditional approaches to this problem are based either on the materialization of subresults (to avoid their recomputation) or on the recomputation of subresults (to avoid the space overhead of materialization). Both techniques have recently been shown suboptimal: instead of materializing results and subresults, one can maintain a data structure that supports efficient maintenance under updates and can quickly enumerate the full query output, as well as the changes produced under single updates. Unfortunately, these data structures have been developed only for aggregate-join queries composed of equi-joins, limiting their applicability in domains such as CER where temporal joins are commonplace. In this paper, we present a new approach for dynamically evaluating queries with multi-way θ-joins under updates that is effective in avoiding both materialization and recomputation of results, while supporting a wide range of applications. To do this we generalize Dynamic Yannakakis, an algorithm for dynamically processing acyclic equi-join queries. In tandem, and of independent interest, we generalize the notions of acyclicity and free-connexity to arbitrary θ-joins. We instantiate our framework to the case where θ-joins are only composed of equalities and inequalities (<, ≤, =, >, ≥) and experimentally compare this algorithm, called IEDyn, to state of the art CER systems as well as incremental view maintenance engines. IEDyn performs consistently better than the competitor systems with up to two orders of magnitude improvements in both time and memory consumption.

The human immunodeficiency virus type 1 (HIV-1) protease (PR) is a critical drug target as it is responsible for virion maturation. Mutations within the active site (1°) of the PR directly interfere with inhibitor binding while mutations distal to the active site (2°) to restore enzymatic fitness. Increasing mutation number is not directly proportional to the severity of resistance, suggesting that resistance is not simply additive but that it is interdependent. The interdependency of both primary and secondary mutations to drive protease inhibitor (PI) resistance is grossly understudied. To structurally and dynamically characterize the direct role of secondary mutations in drug resistance, I selected a panel of single-site mutant protease crystal structures complexed with the PI darunavir (DRV). From these studies, I developed a network hypothesis that explains how mutations outside the active site are able to perpetuate changes to the active site of the protease to disrupt inhibitor binding. I then expanded the panel to include highly mutated multi-drug resistant variants. To elucidate the interdependency between primary and secondary mutations I used statistical and machine-learning techniques to determine which specific mutations underlie the perturbations of key inter-molecular interactions. From these studies, I have determined that mutations distal to the active site are able to perturb the global PR hydrogen bonding patterns, while primary and secondary mutations cooperatively perturb hydrophobic contacts between the PR and DRV. Discerning and exploiting the mechanisms that underlie drug resistance in viral targets could proactively ameliorate both current treatment and inhibitor design for HIV-1 targets.

Switches play an important regulatory role at all levels of biology, from molecular switches triggering signaling cascades to cellular switches regulating cell maturation and apoptosis. Medical therapies are often designed to toggle a system from one state to another, achieving a specified health outcome. For instance, small doses of subpathologic viruses activate the immune system’s production of antibodies. Electrical stimulation revert cardiac arrhythmias back to normal sinus rhythm. In all of these examples, a major challenge is finding the optimal stimulus waveform necessary to cause the switch to flip. This thesis develops, validates, and applies a novel model-independent stochastic algorithm, the Extrema Distortion Algorithm (EDA), towards finding the optimal stimulus. We validate the EDA’s performance for the Hodgkin-Huxley model (an empirically validated ionic model of neuronal excitability), the FitzHugh-Nagumo model (an abstract model applied to a wide range of biological systems that that exhibit an oscillatory state and a quiescent state), and the genetic toggle switch (a model of bistable gene expression). We show that the EDA is able to not only find the optimal solution, but also in some cases excel beyond the traditional analytic approaches. Finally, we have computed novel optimal stimulus waveforms for aborting epileptic seizures using the EDA in cellular and network models of epilepsy. This work represents a first step in developing a new class of adaptive algorithms and devices that flip biological switches, revealing basic mechanistic insights and therapeutic applications for a broad range of disorders.

Worldwide globalization has made supply chains more vulnerable to risk factors, increasing the associated costs of outsourcing goods. Outsourcing is highly beneficial for any company that values building upon its core competencies, but the emergence of the COVID-19 pandemic and other crises have exposed significant vulnerabilities within supply chains. These disruptions forced a shift in the production of goods from outsourcing to domestic methods. This paper considers a multi-echelon supply chain model with global and domestic raw material suppliers, manufacturing plants, warehouses, and markets. All levels within the supply chain network are evaluated from a holistic perspective, calculating a total cost for all levels with embedded risk. We formulate the problem as a mixed-integer linear model programmed in Excel Solver linear to solve smaller optimization problems. Then, we create a Tabu Search algorithm that solves problems of any size. Excel Solver considers three small-scale supply chain networks of varying sizes, one of which maximizes the decision variables the software can handle. In comparison, the Tabu Search program, programmed in Python, solves an additional ten larger-scaled supply chain networks. Tabu Search’s capabilities illustrate its scalability and replicability. A quadratic multi-regression analysis interprets the input parameters (iterations, neighbors, and tabu list size) associated with total supply chain cost and run time. The analysis shows iterations and neighbors to minimize total supply chain cost, while the interaction between iterations x neighbors increases the run time exponentially. Therefore, increasing the number of iterations and neighbors will increase run time but provide a more optimal result for total supply chain cost. Tabu Search’s input parameters should be set high in almost every practical case to achieve the most optimal result. This work is the first to incorporate risk and outsourcing into a multi-echelon supply chain, solved using an exact (Excel Solver) and metaheuristic (Tabu Search) solution methodology. From a practical case, managers can visualize supply chain networks of any size and variation to estimate the total supply chain cost in a relatively short time. Supply chain managers can identify suppliers and pick specific suppliers based on cost or risk. Lastly, they can adjust for risk according to external or internal risk factors. Future research directions include expanding or simplifying the supply chain network design, considering multiple parts, and considering scrap or defective products. In addition, one could incorporate a multi-product dynamic planning horizon supply chain. Overall, considering a hybrid method combining Tabu Search with genetic algorithms, particle swarm optimization, simulated annealing, CPLEX, GUROBI, or LINGO, could provide better results in a faster computational time.

Legislative committee meetings are an integral part of the lawmaking process for local and state bills. The testimony presented during these meetings is a large factor in the outcome of the proposed bill. This research uses Natural Language Processing and Machine Learning techniques to analyze testimonies from California Legislative committee meetings from 2015-2016 in order to identify what aspects of a testimony makes it successful. A testimony is considered successful if the alignment of the testimony matches the bill outcome (alignment is "For" and the bill passes or alignment is "Against" and the bill fails). The process of finding what makes a testimony successful was accomplished through data filtration, feature extraction, implementation of classification models, and feature analysis. Several features were extracted and tested to find those that had the greatest impact on the bill outcome. The features chosen provided information on the sentence complexity and type of words used (adjective, verb, nouns) for each testimony. Additionally all the testimonies were analyzed to find common phrases used within successful testimonies. Two types of classification models were implemented: ones that used the manually extracted feature as input and ones that used their own feature extraction process. The results from the classification models and feature analysis show that certain aspects within a testimony such as sentence complexity and using specific phrases significantly impact the bill outcome. The most successful models, Support Vector Machine and Multinomial Naive Bayes, achieved an accuracy of 91.79\% and 91.22\% respectively

We demonstrate TimeTravel, an efficient DBMS system for seamless integrated querying of past and (forecasted) future values of time series, allowing the user to view past and future values as one joint time series. This functionality is important for advanced application domain like energy. The main idea is to compactly represent time series as models. By using models, the TimeTravel system answers queries approximately on past and future data with error guarantees (absolute error and confidence) one order of magnitude faster than when accessing the time series directly. In addition, it efficiently supports exact historical queries by only accessing relevant portions of the time series. This is unlike existing approaches, which access the entire time series to exactly answer the query. To realize this system, we propose a novel hierarchical model index structure. As real-world time series usually exhibits seasonal behavior, models in this index incorporate seasonality. To construct a hierarchical model index, the user specifies seasonality period, error guarantees levels, and a statistical forecast method. As time proceeds, the system incrementally updates the index and utilizes it to answer approximate and exact queries. TimeTravel is implemented into PostgreSQL, thus achieving complete user transparency at the query level. In the demo, we show the easy building of a hierarchical model index for a real-world time series and the effect of varying the error guarantees on the speed up of approximate and exact queries.