Model-Based Security Testing

Security testing aims at validating software system requirements related to security properties like confidentiality, integrity, authentication, authorization, availability, and non-repudiation. Although security testing techniques are available for many years, there has been little approaches that allow for specification of test cases at a higher level of abstraction, for enabling guidance on test identification and specification as well as for automated test generation. Model-based security testing (MBST) is a relatively new field and especially dedicated to the systematic and efficient specification and documentation of security test objectives, security test cases and test suites, as well as to their automated or semi-automated generation. In particular, the combination of security modelling and test generation approaches is still a challenge in research and of high interest for industrial applications. MBST includes e.g. security functional testing, model-based fuzzing, risk- and threat-oriented testing, and the usage of security test patterns. This paper provides a survey on MBST techniques and the related models as well as samples of new methods and tools that are under development in the European ITEA2-project DIAMONDS.Comment: In Proceedings MBT 2012, arXiv:1202.582

Guidance for laboratories performing molecular pathology for cancer patients

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here

Robustness-Driven Resilience Evaluation of Self-Adaptive Software Systems

An increasingly important requirement for certain classes of software-intensive systems is the ability to self-adapt their structure and behavior at run-time when reacting to changes that may occur to the system, its environment, or its goals. A major challenge related to self-adaptive software systems is the ability to provide assurances of their resilience when facing changes. Since in these systems, the components that act as controllers of a target system incorporate highly complex software, there is the need to analyze the impact that controller failures might have on the services delivered by the system. In this paper, we present a novel approach for evaluating the resilience of self-adaptive software systems by applying robustness testing techniques to the controller to uncover failures that can affect system resilience. The approach for evaluating resilience, which is based on probabilistic model checking, quantifies the probability of satisfaction of system properties when the target system is subject to controller failures. The feasibility of the proposed approach is evaluated in the context of an industrial middleware system used to monitor and manage highly populated networks of devices, which was implemented using the Rainbow framework for architecture-based self-adaptation

The Progress, Challenges, and Perspectives of Directed Greybox Fuzzing

Most greybox fuzzing tools are coverage-guided as code coverage is strongly correlated with bug coverage. However, since most covered codes may not contain bugs, blindly extending code coverage is less efficient, especially for corner cases. Unlike coverage-guided greybox fuzzers who extend code coverage in an undirected manner, a directed greybox fuzzer spends most of its time allocation on reaching specific targets (e.g., the bug-prone zone) without wasting resources stressing unrelated parts. Thus, directed greybox fuzzing (DGF) is particularly suitable for scenarios such as patch testing, bug reproduction, and specialist bug hunting. This paper studies DGF from a broader view, which takes into account not only the location-directed type that targets specific code parts, but also the behaviour-directed type that aims to expose abnormal program behaviours. Herein, the first in-depth study of DGF is made based on the investigation of 32 state-of-the-art fuzzers (78% were published after 2019) that are closely related to DGF. A thorough assessment of the collected tools is conducted so as to systemise recent progress in this field. Finally, it summarises the challenges and provides perspectives for future research.Comment: 16 pages, 4 figure

Clinical application of high throughput molecular screening techniques for pharmacogenomics.

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing

Evaluation of behavior in transgenic mouse models to understand human congenital pain conditions

BACKGROUND: Containing a brain for signal processing and decision making, and a peripheral component for sensation and response, the nervous system provides higher organisms a powerful method of interacting with their environment. The specific neurons involved in pain sensation are known as nociceptors and are the source of normal nociceptive pain signaling to prompt appropriate responses. Though acute hypersensitization can be advantageous by encouraging an organism to allow an injured area to heal, chronic pain conditions can be pathological and can markedly reduce quality of life. While a variety of genes have been associated with congenital pain conditions, two rare cases examined in this study have not had their mutated genes identified. Potassium voltage-gated channel subfamily H member 8, or KCNH8, is involved in regulating action potential production and propagation, and has not been linked with pain processing of any kind to date. Here, a male patient evaluated at Boston Children’s Hospital contains a novel single-base KCNH8 mutation and possesses an extremely low sensitivity to cold temperatures and mechanical pain, but a higher sensitivity to warmer temperatures. A separate protein, intersectin-2, or ITSN2, normally functions in clathrin-mediated endocytosis and exocytosis. A second patient at Boston Children’s Hospital expresses a previously-unseen point mutation in ITSN2 and experiences erythromelalgia, characterized by episodes of intense pain and red, swollen limbs during ambient warm temperatures. Through the use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing, this study will produce these specific genetic mutations in mouse lines to explore their effects on mammalian behavior. OBJECTIVES: This project employs two transgenic mouse models to study the behavioral phenotypes associated with rare potentially damaging mutations in KCNH8 and ITSN2 exhibited in the human patients. Through these experiments, a greater understanding of neural pain signaling and sensitivity changes can occur. METHODS: The differences in temperature preference of KCNH8 and ITSN2 mutant mice compared to wild type mice lacking these mutations was studied using thermal plates under cold and warm conditions. Direct application of acetone and von Frey filaments to mouse paws was used to study cold and mechanical sensitivity. Further testing of stamina, anxiety, coordination, and strength were also evaluated. RESULTS: A marked decrease in sensitivity to von Frey stimulation (p<0.01) and acetone administration (p<0.05) was observed in KCNH8 mutant mice. Thermal preference testing demonstrated a decreased preference for warmer temperatures as compared to wild type mice. In addition, anxiety levels were also observed to be slightly higher in these mutant KCNH8 mice (p<0.05). The mutant ITSN2 mice spent less time at cooler temperatures, though surprisingly they significantly preferred warmer conditions as compared to their wild type littermates. A full and partial reversal of these temperature preferences was demonstrated in cold and heat thermal conditions respectively after intraperitoneal gabapentin injection, which normalized the mice toward wild type behavior. CONCLUSIONS: Data from the KCNH8 mutant mouse model indicates an aversion to warmer temperatures and a decreased ability to detect cold or mechanical pressure, much like the human patient. The mutant ITSN2 mice were less likely to spend time at cooler temperatures, indicating heightened sensory sensitivity, but their preference for warmer temperatures suggests a possible desensitization of the affected nociceptors. These results often mirror the patient’s phenotype, but the preference for ambient warmer environments appears opposite to the patient. As the ITSN2 mice feel discomfort at cooler temperatures, a proposed desensitization at warmer temperatures would result in a more comfortable environment and could explain the observed preference. The trends toward normal neural firing rates achieved through gabapentin injection suggest that the aberrant responses in mutant ITSN2 mice is due to altered sensitization, but additional examination under these conditions with a larger group of mice is necessary to further unravel these signaling pathways. However, these extremely encouraging data introduce two new molecular targets for acute pain control

Genotoxicity and Cytotoxicity Exerted by Pesticides in Different Biotic Matrices-An Overview of More Than a Decade of Experimental Evaluation

Agrochemicals represent one of the most important sources of environmental pollution. Although attempts to reduce agrochemical use through organic agricultural practices and the use of other technologies to control pests continue, the problem is still unsolved. Recent technological advances in molecular biology and analytical science have allowed the development of rapid, robust, and sensitive diagnostic tests (biomarkers) that can be used to monitor exposure to, and the effects of pollution. One of the major goals of our research laboratory is to evaluate comparatively the genotoxic and cytotoxic effects exerted by several pure agrochemicals and their technical formulations commonly used in Argentina on vertebrate cells in vitro and in vivo employing several end-points for geno and cytotoxicity. Among them are listed the herbicides dicamba and flurochloridone, the fungicide zineb, the insecticides pirimicarb and imidacloprid. Overall, the results clearly demonstrated that the damage induced by the commercial formulations is in general greater than that produced by the pure pesticides, suggesting the presence of deleterious components in the excipients with either a putative intrinsic toxic effect Larramendy et al. 4 or with the capacity of exacerbating 52 the toxicity of the pure agrochemicals, or both. Accordingly, the results highlight that: 1) A complete knowledge of the toxic effect/s of the active ingredient is not enough in biomonitoring studies; 2) Pesticide/s toxic effect/s should be evaluated assaying to the commercial formulation available in market; 3) The deleterious effect/s of the excipient/s present within the commercial formulation should not be either discarded nor underestimated, and 4) A single bioassay is not enough to characterize the toxicity of a agrochemical under study.Fil: Larramendy, Marcelo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Citología; ArgentinaFil: Nikoloff, Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Citología; ArgentinaFil: Ruiz de Arcaute, Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Citología; ArgentinaFil: Soloneski, Sonia Maria Elsa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Citología; Argentin

Emerging prenatal genetic tests : developing a health technology assessment (HTA) framework for informed decision-making

Delphi Process In preparation for the first Delphi exercise, a list of questions was produced from the academic literature, webbased sources and interviews with experts. These questions were structured into broad dimensions and a draft questionnaire piloted. A final list of 73 questions formed the basis of the first Delphi survey. Participants were asked to grade the perceived importance of each question for inclusion in HTA reports on new prenatal genetic tests (4 = Essential; 3 = Desirable, but not essential; 2 = Useful but should not be required; 1 = Of little/ no importance; 0 = I have no basis for judgement). Secondly, they were asked to indicate whether a question should be addressed during test development or whether the question could be addressed later once the technology is ready for implementation. Finally, Panel members were encouraged to identify any other questions which appeared to be missing from the initial list. For copy of questionnaire, see Annex 1: Delphi Round 1 Questionnaire. Respondents were also asked to provide personal details to give some indication of their HTA experience and specialist expertise. Analysis of responses demonstrated that SAFE Delphi panel members represent a highly experienced, multidisciplinary international group of experts with the knowledge required to define which key questions should be addressed in HTA reports on new prenatal genetic tests. Delphi Responses Responses were received from 77/90 (86%) of Panel members. These were analysed with a cut-off of 75% (±3%) applied as an indicator of Panel consensus for all questions. Thus, any question which three out of four respondents rated as essential or desirable was retained, whilst those not achieving this level of agreement were provisionally excluded. In addition, mean scores were also calculated (excluding 0 = I have no basis for judgement) for each question. A mean score >3.25 ± 0.05 was taken as an indication that the Panel had identified a particular question as being of the highest priority to address in HTA