Molecular epidemiology of African sleeping sickness

Human sleeping sickness in Africa, caused by Trypanosoma brucei spp. raises a number of questions. Despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity A key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease--knowledge that is difficult to achieve using traditional microscopy. The science of molecular epidemiology has developed a range of tools which have enabled us to accurately identify taxonomic groups at all levels (species, subspecies, populations, strains and isolates). Using these tools, we can now investigate the genetic interactions within and between populations of Trypanosoma brucei and gain an understanding of the distinction between human- and nonhuman-infective subspecies. In this review, we discuss the development of these tools, their advantages and disadvantages and describe how they have been used to understand parasite genetic diversity, the origin of epidemics, the role of reservoir hosts and the population structure. Using the specific case of T.b. rhodesiense in Uganda, we illustrate how molecular epidemiology has enabled us to construct a more detailed understanding of the origins, generation and dynamics of sleeping sickness epidemics

MESA: Message-Based System Analysis Using Runtime Verification

In this paper, we present a novel approach and framework for run-time verication of large, safety critical messaging systems. This work was motivated by verifying the System Wide Information Management (SWIM) project of the Federal Aviation Administration (FAA). SWIM provides live air traffic, site and weather data streams for the whole National Airspace System (NAS), which can easily amount to several hundred messages per second. Such safety critical systems cannot be instrumented, therefore, verification and monitoring has to happen using a nonintrusive approach, by connecting to a variety of network interfaces. Due to a large number of potential properties to check, the verification framework needs to support efficient formulation of properties with a suitable Domain Specific Language (DSL). Our approach is to utilize a distributed system that is geared towards connectivity and scalability and interface it at the message queue level to a powerful verification engine. We implemented our approach in the tool called MESA: Message-Based System Analysis, which leverages the open source projects RACE (Runtime for Airspace Concept Evaluation) and TraceContract. RACE is a platform for instantiating and running highly concurrent and distributed systems and enables connectivity to SWIM and scalability. TraceContract is a runtime verication tool that allows for checking traces against properties specified in a powerful DSL. We applied our approach to verify a SWIM service against several requirements.We found errors such as duplicate and out-of-order messages

Model Checking Real Time Java Using Java PathFinder

The Real Time Specification for Java (RTSJ) is an augmentation of Java for real time applications of various degrees of hardness. The central features of RTSJ are real time threads; user defined schedulers; asynchronous events, handlers, and control transfers; a priority inheritance based default scheduler; non-heap memory areas such as immortal and scoped, and non-heap real time threads whose execution is not impeded by garbage collection. The Robust Software Systems group at NASA Ames Research Center has JAVA PATHFINDER (JPF) under development, a Java model checker. JPF at its core is a state exploring JVM which can examine alternative paths in a Java program (e.g., via backtracking) by trying all nondeterministic choices, including thread scheduling order. This paper describes our implementation of an RTSJ profile (subset) in JPF, including requirements, design decisions, and current implementation status. Two examples are analyzed: jobs on a multiprogramming operating system, and a complex resource contention example involving autonomous vehicles crossing an intersection. The utility of JPF in finding logic and timing errors is illustrated, and the remaining challenges in supporting all of RTSJ are assessed

Seeing the Invisible: Embedding Tests in Code That Cannot be Modified

The difficulty of characterizing and observing valid software behavior during testing can be very difficult in flight systems. To address this issue, we evaluated several approaches to increasing test observability on the Shuttle Abort Flight Management (SAFM) system. To increase test observability, we added probes into the running system to evaluate the internal state and analyze test data. To minimize the impact of the instrumentation and reduce manual effort, we used Aspect-Oriented Programming (AOP) tools to instrument the source code. We developed and elicited a spectrum of properties, from generic to application specific properties, to be monitored via the instrumentation. To evaluate additional approaches, SAFM was ported to Linux, enabling the use of gcov for measuring test coverage, Valgrind for looking for memory usage errors, and libraries for finding non-normal floating point values. An in-house C++ source code scanning tool was also used to identify violations of SAFM coding standards, and other potentially problematic C++ constructs. Using these approaches with the existing test data sets, we were able to verify several important properties, confirm several problems and identify some previously unidentified issues

Asymptotic stationarity and regularity for nonsmooth optimization problems

Based on the tools of limiting variational analysis, we derive a sequential necessary optimality condition for nonsmooth mathematical programs which holds without any additional assumptions. In order to ensure that stationary points in this new sense are already Mordukhovich-stationary, the presence of a constraint qualification which we call AM-regularity is necessary. We investigate the relationship between AM-regularity and other constraint qualifications from nonsmooth optimization like metric (sub-)regularity of the underlying feasibility mapping. Our findings are applied to optimization problems with geometric and, particularly, disjunctive constraints. This way, it is shown that AM-regularity recovers recently introduced cone-continuity-type constraint qualifications, sometimes referred to as AKKT-regularity, from standard nonlinear and complementarity-constrained optimization. Finally, we discuss some consequences of AM-regularity for the limiting variational calculus.Comment: 30 pages, 2 figur

Contributions to complementarity and bilevel programming in Banach spaces

In this thesis, we derive necessary optimality conditions for bilevel programming problems (BPPs for short) in Banach spaces. This rather abstract setting reflects our desire to characterize the local optimal solutions of hierarchical optimization problems in function spaces arising from several applications. Since our considerations are based on the tools of variational analysis introduced by Boris Mordukhovich, we study related properties of pointwise defined sets in function spaces. The presence of sequential normal compactness for such sets in Lebesgue and Sobolev spaces as well as the variational geometry of decomposable sets in Lebesgue spaces is discussed. Afterwards, we investigate mathematical problems with complementarity constraints (MPCCs for short) in Banach spaces which are closely related to BPPs. We introduce reasonable stationarity concepts and constraint qualifications which can be used to handle MPCCs. The relations between the mentioned stationarity notions are studied in the setting where the underlying complementarity cone is polyhedric. The results are applied to the situations where the complementarity cone equals the nonnegative cone in a Lebesgue space or is polyhedral. Next, we use the three main approaches of transforming a BPP into a single-level program (namely the presence of a unique lower level solution, the KKT approach, and the optimal value approach) to derive necessary optimality conditions for BPPs. Furthermore, we comment on the relation between the original BPP and the respective surrogate problem. We apply our findings to formulate necessary optimality conditions for three different classes of BPPs. First, we study a BPP with semidefinite lower level problem possessing a unique solution. Afterwards, we deal with bilevel optimal control problems with dynamical systems of ordinary differential equations at both decision levels. Finally, an optimal control problem of ordinary or partial differential equations with implicitly given pointwise state constraints is investigated

Model Based Analysis and Test Generation for Flight Software

We describe a framework for model-based analysis and test case generation in the context of a heterogeneous model-based development paradigm that uses and combines Math- Works and UML 2.0 models and the associated code generation tools. This paradigm poses novel challenges to analysis and test case generation that, to the best of our knowledge, have not been addressed before. The framework is based on a common intermediate representation for different modeling formalisms and leverages and extends model checking and symbolic execution tools for model analysis and test case generation, respectively. We discuss the application of our framework to software models for a NASA flight mission