Control Charts with Variable Dimension for Linear Combination of Poisson Variables

This article analyzes the simultaneous control of several correlated Poisson variables by using the Variable Dimension Linear Combination of Poisson Variables (VDLCP) control chart, which is a variable dimension version of the LCP chart. This control chart uses as test statistic, the linear combination of correlated Poisson variables in an adaptive way, i.e. it monitors either p₁ or p variables (p₁ < p) depending on the last statistic value. To analyze the performance of this chart, we have developed software that finds the best parameters, optimizing the out‐of‐control average run length (ARL) for a shift that the practitioner wishes to detect as quickly as possible, restricted to a fixed value for in‐control ARL. Markov chains and genetic algorithms were used in developing this software. The results show performance improvement compared to the LCP chart. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimization of biochemical systems through mathematical programming: Methods and applications

In this work we present a general (mono and multiobjective) optimization framework for the technological improvement of biochemical systems. The starting point of the method is a mathematical model in ordinary differential equations (ODEs) of the investigated system, based on qualitative biological knowledge and quantitative experimental data. In the method we take advantage of the special structural features of a family of ODEs called power-law models to reduce the computational complexity of the optimization program. In this way, the genetic manipulation of a biochemical system to meet a certain biotechnological goal can be expressed as an optimization program with some desired properties such as linearity or convexity.The general method of optimization is presented and discussed in its linear and geometric programming versions. We furthermore illustrate the use of the method by several real case studies. We conclude that the technological improvement of microorganisms can be afforded using the combination of mathematical modelling and optimization. The systematic nature of this approach facilitates the redesign of biochemical systems and makes this a predictive exercise rather than a trial-and-error procedure.     

Two-stage cascaded classification approach based on genetic fuzzy learning for speech/music discrimination

Automatic discrimination of speech and music is an important tool in many multimedia applications. The paper presents a robust and effective approach for speech/music discrimination, which relies on a two-stage cascaded classification scheme. The cascaded classification scheme is composed of a statistical pattern recognition classifier followed by a genetic fuzzy system. For the first stage of the classification scheme, other widely used classifiers, such as neural networks and support vector machines, have also been considered in order to assess the robustness of the proposed classification scheme. Comparison with well-proven signal features is also performed. In this work, the most commonly used genetic learning algorithms (Michigan and Pittsburgh) have been evaluated in the proposed two-stage classification scheme. The genetic fuzzy system gives rise to an improvement of about 4% in the classification accuracy rate. Experimental results show the good performance of the proposed approach with a classification accuracy rate of about 97% for the best trial.     

Thesaurus enrichment for query expansion in audiovisual archives

It is common practice in audiovisual archives to disclose documents using metadata from a structured vocabulary or thesaurus. Many of these thesauri have limited or no structure. The objective of this paper is to find out whether retrieval of audiovisual resources from a collection indexed with an in-house thesaurus can be improved by enriching the thesaurus structure. We propose a method to add structure to a thesaurus by anchoring it to an external, semantically richer thesaurus. We investigate the added value of this enrichment for retrieval purposes. We first anchor the thesaurus to an external resource, WordNet. From this anchoring we infer relations between pairs of terms in the thesaurus that were previously unrelated. We employ the enriched thesaurus in a retrieval experiment on a TRECVID 2007 dataset. The results are promising: with simple techniques we are able to enrich a thesaurus in such a way that it adds to retrieval performance.     

Lower and upper bounds for the two-echelon capacitated location-routing problem

In this paper, we introduce two algorithms to address the two-echelon capacitated location-routing problem (2E-CLRP). We introduce a branch-and-cut algorithm based on the solution of a new two-index vehicle-flow formulation, which is strengthened with several families of valid inequalities. We also propose an adaptive large-neighbourhood search (ALNS) meta-heuristic with the objective of finding good-quality solutions quickly. The computational results on a large set of instances from the literature show that the ALNS outperforms existing heuristics. Furthermore, the branch-and-cut method provides tight lower bounds and is able to solve small- and medium-size instances to optimality within reasonable computing times.     

Diagnosing Czech Patients with Inherited Platelet Disorders

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.     

A Role of DNA Methylation within the CYP17A1 Gene in the Association of Genetic and Environmental Risk Factors with Stress-Related Manifestations of Schizophrenia

As genetic and environmental influences on schizophrenia might converge on DNA methylation (DNAm) within loci which are both associated with the disease and implicated in response to environmental stress, we examined whether DNAm within CYP17A1, a hypothalamus–pituitary–adrenal axis gene which is situated within the schizophrenia risk locus 10q24.32, would mediate genetic and environmental effects on stress-related schizophrenia symptoms. DNAm within an exonic–intronic fragment of CYP17A1 was assessed in the blood of 66 schizophrenia patients and 63 controls using single-molecule real-time bisulfite sequencing. Additionally, the VNTR polymorphism of the AS3MT gene, a plausible causal variant within the 10q24.32 locus, was genotyped in extended patient and control samples (n = 700). The effects of local haplotype, VNTR and a polyenviromic risk score (PERS) on DNAm, episodic verbal memory, executive functions, depression, and suicidality of patients were assessed. Haplotype and PERS differentially influenced DNAm at four variably methylated sites identified within the fragment, with stochastic, additive, and allele-specific effects being found. An allele-specific DNAm at CpG-SNP rs3781286 mediated the relationship between the local haplotype and verbal fluency. Our findings do not confirm that the interrogated DNA fragment is a place where genetic and environmental risk factors converge to influence schizophrenia symptoms through DNAm.     

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of ACE*Ya5ACE, CDH4*Yb8NBC516, COL13A1*Ya5ac1986, HECW1*Ya5NBC182, LAMA2*Ya5-MLS19, PLAT*TPA25, PKHD1L1*Yb8AC702, SEMA6A*Yb8NBC597, STK38L*Ya5ac2145 and TEAD1*Ya5ac2013 Alu elements to longevity. The study group included 2054 unrelated individuals aged from 18 to 113 years who are ethnic Tatars from Russia. We analyzed the dynamics of the allele and genotype frequencies of the studied Alu polymorphic loci in the age groups of young (18–44 years old), middle-aged (45–59 years old), elderly (60–74 years old), old seniors (75–89 years old) and long-livers (90–113 years old). Most significant changes in allele and genotype frequencies were observed between the long-livers and other groups. The search for polygenic predictors of longevity was performed using the APSampler program. Attaining longevity was associated with the combinations LAMA2*ID + CDH4*D (OR = 2.23, P_Bonf = 1.90 × 10⁻²) and CDH4*DD + LAMA2*ID + HECW1*D (OR = 4.58, P_Bonf = 9.00 × 10⁻³) among persons aged between 18 and 89 years, LAMA2*ID + CDH4*D + SEMA6A*I for individuals below 75 years of age (OR = 3.13, P_Bonf = 2.00 × 10⁻²), LAMA2*ID + HECW1*I for elderly people aged 60 and older (OR = 3.13, P_Bonf = 2.00 × 10⁻²) and CDH4*DD + LAMA2*D + HECW1*D (OR = 4.21, P_Bonf = 2.60 × 10⁻²) and CDH4*DD + LAMA2*D + ACE*I (OR = 3.68, P_Bonf = 1.90 × 10⁻²) among old seniors (75–89 years old). The key elements of combinations associated with longevity were the deletion alleles of CDH4 and LAMA2 genes. Our results point to the significance for human longevity of the Alu polymorphic loci in CDH4, LAMA2, HECW1, SEMA6A and ACE genes, involved in the integration systems.