Rare manifestation of a c.290 C\u3eT, p.Gly97Glu VCP mutation

Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50’s was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics. Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation

Faster Mutation Analysis via Equivalence Modulo States

Mutation analysis has many applications, such as asserting the quality of test suites and localizing faults. One important bottleneck of mutation analysis is scalability. The latest work explores the possibility of reducing the redundant execution via split-stream execution. However, split-stream execution is only able to remove redundant execution before the first mutated statement. In this paper we try to also reduce some of the redundant execution after the execution of the first mutated statement. We observe that, although many mutated statements are not equivalent, the execution result of those mutated statements may still be equivalent to the result of the original statement. In other words, the statements are equivalent modulo the current state. In this paper we propose a fast mutation analysis approach, AccMut. AccMut automatically detects the equivalence modulo states among a statement and its mutations, then groups the statements into equivalence classes modulo states, and uses only one process to represent each class. In this way, we can significantly reduce the number of split processes. Our experiments show that our approach can further accelerate mutation analysis on top of split-stream execution with a speedup of 2.56x on average.Comment: Submitted to conferenc

Towards Smart Hybrid Fuzzing for Smart Contracts

Smart contracts are Turing-complete programs that are executed across a blockchain network. Unlike traditional programs, once deployed they cannot be modified. As smart contracts become more popular and carry more value, they become more of an interesting target for attackers. In recent years, smart contracts suffered major exploits, costing millions of dollars, due to programming errors. As a result, a variety of tools for detecting bugs has been proposed. However, majority of these tools often yield many false positives due to over-approximation or poor code coverage due to complex path constraints. Fuzzing or fuzz testing is a popular and effective software testing technique. However, traditional fuzzers tend to be more effective towards finding shallow bugs and less effective in finding bugs that lie deeper in the execution. In this work, we present CONFUZZIUS, a hybrid fuzzer that combines evolutionary fuzzing with constraint solving in order to execute more code and find more bugs in smart contracts. Evolutionary fuzzing is used to exercise shallow parts of a smart contract, while constraint solving is used to generate inputs which satisfy complex conditions that prevent the evolutionary fuzzing from exploring deeper paths. Moreover, we use data dependency analysis to efficiently generate sequences of transactions, that create specific contract states in which bugs may be hidden. We evaluate the effectiveness of our fuzzing strategy, by comparing CONFUZZIUS with state-of-the-art symbolic execution tools and fuzzers. Our evaluation shows that our hybrid fuzzing approach produces significantly better results than state-of-the-art symbolic execution tools and fuzzers

Particle Swarm Optimization Framework for Low Power Testing of VLSI Circuits

Power dissipation in sequential circuits is due to increased toggling count of Circuit under Test, which depends upon test vectors applied. If successive test vectors sequences have more toggling nature then it is sure that toggling rate of flip flops is higher. Higher toggling for flip flops results more power dissipation. To overcome this problem, one method is to use GA to have test vectors of high fault coverage in short interval, followed by Hamming distance management on test patterns. This approach is time consuming and needs more efforts. Another method which is purposed in this paper is a PSO based Frame Work to optimize power dissipation. Here target is to set the entire test vector in a frame for time period 'T', so that the frame consists of all those vectors strings which not only provide high fault coverage but also arrange vectors in frame to produce minimum toggling

SlowFuzz: Automated Domain-Independent Detection of Algorithmic Complexity Vulnerabilities

Algorithmic complexity vulnerabilities occur when the worst-case time/space complexity of an application is significantly higher than the respective average case for particular user-controlled inputs. When such conditions are met, an attacker can launch Denial-of-Service attacks against a vulnerable application by providing inputs that trigger the worst-case behavior. Such attacks have been known to have serious effects on production systems, take down entire websites, or lead to bypasses of Web Application Firewalls. Unfortunately, existing detection mechanisms for algorithmic complexity vulnerabilities are domain-specific and often require significant manual effort. In this paper, we design, implement, and evaluate SlowFuzz, a domain-independent framework for automatically finding algorithmic complexity vulnerabilities. SlowFuzz automatically finds inputs that trigger worst-case algorithmic behavior in the tested binary. SlowFuzz uses resource-usage-guided evolutionary search techniques to automatically find inputs that maximize computational resource utilization for a given application.Comment: ACM CCS '17, October 30-November 3, 2017, Dallas, TX, US

Population-based incremental learning with associative memory for dynamic environments

Copyright © 2007 IEEE. Reprinted from IEEE Transactions on Evolutionary Computation. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In recent years there has been a growing interest in studying evolutionary algorithms (EAs) for dynamic optimization problems (DOPs) due to its importance in real world applications. Several approaches, such as the memory and multiple population schemes, have been developed for EAs to address dynamic problems. This paper investigates the application of the memory scheme for population-based incremental learning (PBIL) algorithms, a class of EAs, for DOPss. A PBIL-specific associative memory scheme, which stores best solutions as well as corresponding environmental information in the memory, is investigated to improve its adaptability in dynamic environments. In this paper, the interactions between the memory scheme and random immigrants, multi-population, and restart schemes for PBILs in dynamic environments are investigated. In order to better test the performance of memory schemes for PBILs and other EAs in dynamic environments, this paper also proposes a dynamic environment generator that can systematically generate dynamic environments of different difficulty with respect to memory schemes. Using this generator a series of dynamic environments are generated and experiments are carried out to compare the performance of investigated algorithms. The experimental results show that the proposed memory scheme is efficient for PBILs in dynamic environments and also indicate that different interactions exist between the memory scheme and random immigrants, multi-population schemes for PBILs in different dynamic environments

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker