Modular specification of forbidden states for supervisory control

A method for solving the forbidden state problem in the Supervisory Control Theory framework is presented. In many real-world applications both the plant and specification is given as a set of interacting automata or processes. In this work, we enable specification of forbidden states within such a modular structure. The aim with the method is to make each forbidden modular state combination uncontrollable. It is then possible to use efficient modular synthesis algorithms for calculation of a modular supervisor where the forbidden states are removed

Towards Secure Data Flow Oriented Multi-Vendor ICT Governance Model

Today, still, ICT Governance is being regarded as a departmental concern, not an overall organizational concern. History has shown us that implementation strategies, which are based on departments, results in fractional implementations leading to ad hoc solutions with no central control and stagnation for the in-house ICT strategy. Further, this recently has created an opinion trend; many are talking about the ICT department as being redundant, a dying out breed, which should be replaced by on-demand specialized external services. Clearly, the evermore changing surroundings do force organizations to accelerate the pace of new adaptations within their ICT plans, more vivacious than most organizations currently is able to. This leads to that ICT departments tend to be reactive rather than acting proactively and take the lead in the increased transformation pace in which organizations find themselves. Simultaneously, the monolithic systems of the 1980ies/1990ies is often very dominating in an organization, consume too much of the yearly IT budget, leaving healthy system development behind. These systems were designed before data became an organizational all-encompassing resource; the systems were designed more or less in isolation in regards to the surrounding environment. These solutions make data sharing costly and not at all optimal. Additionally, in strives to adapt to the organization’s evolution, the initial architecture has become disrupted and built up in shreds. Adding to this, on May 25, 2018, an upgraded EU Privacy Regulation on General Data Protection Regulation (GDPR) will be activated. This upgraded privacy regulation includes a substantial strengthening of 1994’s data privacy regulation, which will profoundly affect EU organizations. This regulation will, among other things, limit the right to collect and process personal data and will give the data subject all rights to his/her data sets, independentof where this data is/has been collected and by whom. Such regulation force data collecting and processingorganizations to have total control over any personal data collected and processed. This includes detailedunderstanding of data flows, including who did what and when and under who’s authorization, and how data istransported and stored. Concerning data/information flows, maps are a mandatory part of the system documentation. This encompasses all systems, including outsourced such as cloud services. Hence, individual departments cannot any longer claim they “own” data. Further, since mid-2000, we have seen aglobal inter-organizational data integration, independent of organizations, public or private. If this integration ceasesto exist, the result will be a threat to the survival of the organization. Additionally, if the organization fails to providea transparent documentation according to the GDPR, substantial economic risk is at stake. So, the discussion aboutthe ICT departments’ demise is inapt. Any organizational change will require costly and time-consuming ICTdevelopment efforts to adapt to the legislation of today’s situation. Further, since data nowadays is interconnectedand transformed at all levels, interacting at multiple intersections all over the organization, and becoming a unifiedbase of all operative decisions, an ICT governance model for the organization is required

Towards Secure Data Flow Oriented Multi-Vendor ICT Governance Model

Today, still, ICT Governance is being regarded as a departmental concern, not an overall organizational concern. History has shown us that implementation strategies, which are based on departments, results in fractional implementations leading to ad hoc solutions with no central control and stagnation for the in-house ICT strategy. Further, this recently has created an opinion trend; many are talking about the ICT department as being redundant, a dying out breed, which should be replaced by on-demand specialized external services. Clearly, the evermore changing surroundings do force organizations to accelerate the pace of new adaptations within their ICT plans, more vivacious than most organizations currently is able to. This leads to that ICT departments tend to be reactive rather than acting proactively and take the lead in the increased transformation pace in which organizations find themselves. Simultaneously, the monolithic systems of the 1980ies/1990ies is often very dominating in an organization, consume too much of the yearly IT budget, leaving healthy system development behind. These systems were designed before data became an organizational all-encompassing resource; the systems were designed more or less in isolation in regards to the surrounding environment. These solutions make data sharing costly and not at all optimal. Additionally, in strives to adapt to the organization’s evolution, the initial architecture has become disrupted and built up in shreds. Adding to this, on May 25, 2018, an upgraded EU Privacy Regulation on General Data Protection Regulation (GDPR) will be activated. This upgraded privacy regulation includes a substantial strengthening of 1994’s data privacy regulation, which will profoundly affect EU organizations. This regulation will, among other things, limit the right to collect and process personal data and will give the data subject all rights to his/her data sets, independentof where this data is/has been collected and by whom. Such regulation force data collecting and processingorganizations to have total control over any personal data collected and processed. This includes detailedunderstanding of data flows, including who did what and when and under who’s authorization, and how data istransported and stored. Concerning data/information flows, maps are a mandatory part of the system documentation. This encompasses all systems, including outsourced such as cloud services. Hence, individual departments cannot any longer claim they “own” data. Further, since mid-2000, we have seen aglobal inter-organizational data integration, independent of organizations, public or private. If this integration ceasesto exist, the result will be a threat to the survival of the organization. Additionally, if the organization fails to providea transparent documentation according to the GDPR, substantial economic risk is at stake. So, the discussion aboutthe ICT departments’ demise is inapt. Any organizational change will require costly and time-consuming ICTdevelopment efforts to adapt to the legislation of today’s situation. Further, since data nowadays is interconnectedand transformed at all levels, interacting at multiple intersections all over the organization, and becoming a unifiedbase of all operative decisions, an ICT governance model for the organization is required

Planning transport sequences for flexible manufacturing systems

When designing a manufacturing system it is important to plan what the system should do. One important activity in most manufacturing systems is to transport products or resources between different positions. In a flexible manufacturing system it can be challenging to design and plan these transport operations due to their complex logical behavior. This paper presents a method that identifies, creates and visualizes these transport operations based on inputs from a standard virtual manufacturing tool and a high level product operation recipe. The planning of the created transport operations is transformed into a problem of finding a non-blocking solution for a discrete model of the product refinement

Heritability and the Equal Environments Assumption: Evidence from Multiple Samples of Misclassified Twins

The final publication is available at Springer via https://doi.org/10.1007/s10519-013-9602-1Classically derived estimates of heritability from twin models have been plagued by the possibility of genetic-environmental covariance. Survey questions that attempt to measure directly the extent to which more genetically similar kin (such as monozygotic twins) also share more similar environmental conditions represent poor attempts to gauge a complex underlying phenomenon of GE-covariance. The present study exploits a natural experiment to address this issue: Self-misperception of twin zygosity in the National Longitudinal Survey of Adolescent Health (Add Health). Such twins were reared under one “environmental regime of similarity” while genetically belonging to another group, reversing the typical GE-covariance and allowing bounded estimates of heritability for a range of outcomes. In addition, we examine twins who were initially misclassified by survey assignment—a stricter standard—in three datasets: Add Health, the Minnesota Twin Family Study and the Child and Adolescent Twin Study in Sweden. Results are similar across approaches and datasets and largely support the validity of the equal environments assumption

Heritability of Oral Microbiota and Immune Responses to Oral Bacteria

Maintaining a symbiotic oral microbiota is essential for oral and dental health, and host genetic factors may affect the composition or function of the oral microbiota through a range of possible mechanisms, including immune pathways. The study included 836 Swedish twins divided into separate groups of adolescents (n= 418) and unrelated adults (n= 418). Oral microbiota composition and functions of non-enzymatically lysed oral bacteria samples were evaluated using 16S rRNA gene sequencing and functional bioinformatics tools in the adolescents. Adaptive immune responses were assessed by testing for serum IgG antibodies against a panel of common oral bacteria in adults. In the adolescents, host genetic factors were associated with both the detection and abundance of microbial species, but with considerable variation between species. Host genetic factors were associated with predicted microbiota functions, including several functions related to bacterial sucrose, fructose, and carbohydrate metabolism. In adults, genetic factors were associated with serum antibodies against oral bacteria. In conclusion, host genetic factors affect the composition of the oral microbiota at a species level, and host-governed adaptive immune responses, and also affect the concerted functions of the oral microbiota as a whole. This may help explain why some people are genetically predisposed to the major dental diseases of caries and periodontitis

Shared etiology of type 1 diabetes and Hashimoto’s thyroiditis: a population-based twin study

Objective Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors. Design This study is a twin cohort study. Methods National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and vice-versa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5–15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2–15.1) and 1.7 (95% CI: 0.7–4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis. Conclusions Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets.publishedVersio

Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)

Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.NonePublishe

MethylPCA: a toolkit to control for confounders in methylome-wide association studies

Background In methylome-wide association studies (MWAS) there are many possible differences between cases and controls (e.g. related to life style, diet, and medication use) that may affect the methylome and produce false positive findings. An effective approach to control for these confounders is to first capture the major sources of variation in the methylation data and then regress out these components in the association analyses. This approach is, however, computationally very challenging due to the extremely large number of methylation sites in the human genome. Result We introduce MethylPCA that is specifically designed to control for potential confounders in studies where the number of methylation sites is extremely large. MethylPCA offers a complete and flexible data analysis including 1) an adaptive method that performs data reduction prior to PCA by empirically combining methylation data of neighboring sites, 2) an efficient algorithm that performs a principal component analysis (PCA) on the ultra high-dimensional data matrix, and 3) association tests. To accomplish this MethylPCA allows for parallel execution of tasks, uses C++ for CPU and I/O intensive calculations, and stores intermediate results to avoid computing the same statistics multiple times or keeping results in memory. Through simulations and an analysis of a real whole methylome MBD-seq study of 1,500 subjects we show that MethylPCA effectively controls for potential confounders. Conclusions MethylPCA provides users a convenient tool to perform MWAS. The software effectively handles the challenge in memory and speed to perform tasks that would be impossible to accomplish using existing software when millions of sites are interrogated with the sample sizes required for MWAS

A New Method for Detecting Associations with Rare Copy-Number Variants

Copy number variants (CNVs) play an important role in the etiology of many diseases such as cancers and psychiatric disorders. Due to a modest marginal effect size or the rarity of the CNVs, collapsing rare CNVs together and collectively evaluating their effect serves as a key approach to evaluating the collective effect of rare CNVs on disease risk. While a plethora of powerful collapsing methods are available for sequence variants (e.g., SNPs) in association analysis, these methods cannot be directly applied to rare CNVs due to the CNV-specific challenges, i.e., the multi-faceted nature of CNV polymorphisms (e.g., CNVs vary in size, type, dosage, and details of gene disruption), and etiological heterogeneity (e.g., heterogeneous effects of duplications and deletions that occur within a locus or in different loci). Existing CNV collapsing analysis methods (a.k.a. the burden test) tend to have suboptimal performance due to the fact that these methods often ignore heterogeneity and evaluate only the marginal effects of a CNV feature. We introduce CCRET, a random effects test for collapsing rare CNVs when searching for disease associations. CCRET is applicable to variants measured on a multi-categorical scale, collectively modeling the effects of multiple CNV features, and is robust to etiological heterogeneity. Multiple confounders can be simultaneously corrected. To evaluate the performance of CCRET, we conducted extensive simulations and analyzed large-scale schizophrenia datasets. We show that CCRET has powerful and robust performance under multiple types of etiological heterogeneity, and has performance comparable to or better than existing methods when there is no heterogeneity