Wavelet analysis of human DNA

This paper studies the human DNA in the perspective of signal processing. Six wavelets are tested for analyzing the information content of the human DNA. By adopting real Shannon wavelet several fundamental properties of the code are revealed. A quantitative comparison of the chromosomes and visualization through multidimensional and dendograms is developed.

The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde

The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is “sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans”. Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053–14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673–18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies.

Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

Identification of a 0.4 Kb deletion region in 10q26 associated with endometrial carcinoma

We have identified an allelic deletion common region in the q26 region of chromosome 10 in endometrial carcinomas, which has been reported previously as a potential target of genetic alterations related to this neoplasia. An allelotyping analysis of 19 pairs of tumoral and non-tumoral samples was accomplished using seven microsatellite polymorphic markers mapping in the 10q26 chromosomal region. Loss of heterozygosity for one or more loci was detected in 29% of the endometrial carcinoma samples. The observed pattern of loss enabled the identification of a 3.5 Mb common deleted region located between the D10S587 and D10S186 markers. An additional result from an endometrial sample with evidence of a RER phenotype may suggest a more centromeric region of loss within the above-mentioned interval. This 401.84 Kb interval flanked by the D10S587 and D10S216 markers may be a plausible location for a putative suppressor gene involved in early stage endometrial carcinogenesis.

Cytostatics occupational exposure: genotoxic effects assessment

The use of cytostatics drugs in anticancer therapy is increasing. Health care workers can be occupationally exposed to these drugs classified as carcinogenic, mutagenic or teratogenic. Workers may be exposed to this drug, being in the hospital settings the main focus dwelled upon the pharmacy, and nursing personnel. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers can have the same side effects with no therapeutic benefit. The exposure to these substances is epidemiologically linked to cancer and nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.

Biomonitorization in hospital settings with cytostatics occupational exposure

Exposure in a hospital setting is normally due to the use of several antineoplastic drugs simultaneously. Nevertheless, the effects of such mixtures at the cell level and on human health in general are unpredictable and unique due to differences in practice of hospital oncology departments, in the number of patients, protection devices available, and the experience and safety procedures of medical staff. Health care workers who prepare or administer hazardous drugs or who work in areas where these drugs are used may be exposed to these agents in the air, on work surfaces, contaminated clothing, medical equipment, patient excreta, and other surfaces. These workers include specially pharmacists, pharmacy technicians, and nursing personnel. Exposures may occur through inhalation resulting from aerosolization of powder or liquid during reconstitution and spillage taking place while preparing or administering to patients, through Cytokinesis-block micronucleus test (CBMN) is extensively used in biomonitoring, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.

Shannon entropy analysis of the genome code

This paper studies the chromosome information of twenty five species, namely, mammals, fishes, birds, insects, nematodes, fungus, and one plant. A quantifying scheme inspired in the state space representation of dynamical systems is formulated. Based on this algorithm, the information of each chromosome is converted into a bidimensional distribution. The plots are then analyzed and characterized by means of Shannon entropy. The large volume of information is integrated by averaging the lengths and entropy quantities of each species. The results can be easily visualized revealing quantitative global genomic information.

Accessing complexity from genome information

This paper studies the information content of the chromosomes of 24 species. In a first phase, a scheme inspired in dynamical system state space representation is developed. For each chromosome the state space dynamical evolution is shed into a two dimensional chart. The plots are then analyzed and characterized in the perspective of fractal dimension. This information is integrated in two measures of the species’ complexity addressing its average and variability. The results are in close accordance with phylogenetics pointing quantitative aspects of the species’ genomic complexity.

Selenium role in an human biomonitoring study applied to occupational health

Selenium functions as a co-factor for the reduction of antioxidant enzymes and is an important component of antioxidant enzymes. Dietary selenium significantly inhibits the induction of skin, liver, colon, and mammary tumours in experimental animals by a number of different carcinogens, as well as the induction of mammary tumours by viruses. Selenium shows a “U” shaped curve for functionality, whereby too little is as damaging as too much. At optimal levels, selenium may protect against the formation of DNA adducts, DNA or chromosome breakage, chromosome gain or loss, mitochondrial DNA, and telomere length and function. Aim of study: Investigate the relation between selenium and genotoxic effects in a human biomonitoring study applied to occupational health.

A genetic algorithm for the resource constrained multi-project scheduling problem

This paper presents a genetic algorithm for the resource constrained multi-project scheduling problem. The chromosome representation of the problem is based on random keys. The schedules are constructed using a heuristic that builds parameterized active schedules based on priorities, delay times, and release dates defined by the genetic algorithm. The approach is tested on a set of randomly generated problems. The computational results validate the effectiveness of the proposed algorithm.

Project scheduling under multiple resources constraints using a genetic algorithm

The resource constrained project scheduling problem (RCPSP) is a difficult problem in combinatorial optimization for which extensive investigation has been devoted to the development of efficient algorithms. During the last couple of years many heuristic procedures have been developed for this problem, but still these procedures often fail in finding near-optimal solutions. This paper proposes a genetic algorithm for the resource constrained project scheduling problem. The chromosome representation of the problem is based on random keys. The schedule is constructed using a heuristic priority rule in which the priorities and delay times of the activities are defined by the genetic algorithm. The approach was tested on a set of standard problems taken from the literature and compared with other approaches. The computational results validate the effectiveness of the proposed algorithm.

Project scheduling using a competitive genetic algorithm

- The resource constrained project scheduling problem (RCPSP) is a difficult problem in combinatorial optimization for which extensive investigation has been devoted to the development of efficient algorithms. During the last couple of years many heuristic procedures have been developed for this problem, but still these procedures often fail in finding near-optimal solutions. This paper proposes a genetic algorithm for the resource constrained project scheduling problem. The chromosome representation of the problem is based on random keys. The schedule is constructed using a heuristic priority rule in which the priorities and delay times of the activities are defined by the genetic algorithm. The approach was tested on a set of standard problems taken from the literature and compared with other approaches. The computational results validate the effectiveness of the proposed algorithm

A biased random-key genetic algorithm with forward-backward improvement for the resource constrained project scheduling problem

This paper presents a biased random-key genetic algorithm for the resource constrained project scheduling problem. The chromosome representation of the problem is based on random keys. Active schedules are constructed using a priority-rule heuristic in which the priorities of the activities are defined by the genetic algorithm. A forward-backward improvement procedure is applied to all solutions. The chromosomes supplied by the genetic algorithm are adjusted to reflect the solutions obtained by the improvement procedure. The heuristic is tested on a set of standard problems taken from the literature and compared with other approaches. The computational results validate the effectiveness of the proposed algorithm.

Uma metaheurística para a programação de projectos com multi-modos e recursos limitados

Este artigo apresenta uma nova abordagem (MM-GAV-FBI), aplicável ao problema da programação de projectos com restrições de recursos e vários modos de execução por actividade, problema conhecido na literatura anglo-saxónica por MRCPSP. Cada projecto tem um conjunto de actividades com precedências tecnológicas definidas e um conjunto de recursos limitados, sendo que cada actividade pode ter mais do que um modo de realização. A programação dos projectos é realizada com recurso a um esquema de geração de planos (do inglês Schedule Generation Scheme - SGS) integrado com uma metaheurística. A metaheurística é baseada no paradigma dos algoritmos genéticos. As prioridades das actividades são obtidas a partir de um algoritmo genético. A representação cromossómica utilizada baseia-se em chaves aleatórias. O SGS gera planos não-atrasados. Após a obtenção de uma solução é aplicada uma melhoria local. O objectivo da abordagem é encontrar o melhor plano (planning), ou seja, o plano que tenha a menor duração temporal possível, satisfazendo as precedências das actividades e as restrições de recursos. A abordagem proposta é testada num conjunto de problemas retirados da literatura da especialidade e os resultados computacionais são comparados com outras abordagens. Os resultados computacionais validam o bom desempenho da abordagem, não apenas em termos de qualidade da solução, mas também em termos de tempo útil.

A random key based genetic algorithm for the resource constrained project scheduling problem

This paper presents a genetic algorithm for the Resource Constrained Project Scheduling Problem (RCPSP). The chromosome representation of the problem is based on random keys. The schedule is constructed using a heuristic priority rule in which the priorities of the activities are defined by the genetic algorithm. The heuristic generates parameterized active schedules. The approach was tested on a set of standard problems taken from the literature and compared with other approaches. The computational results validate the effectiveness of the proposed algorithm.