XRCC3 THR241MET polymorphism influence on nuclear buds frequency in exposed to formaldehyde

Formaldehyde (FA), also known as formalin, formal and methyl aldehydes, is a colorless, flammable, strong-smelling gas. It has an important application in embalming tissues and that result in exposures for workers in the pathology anatomy laboratories and mortuaries. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. Manifold in vitro studies clearly indicated that FA is genotoxic. FA induced various genotoxic effects in proliferating cultured mammalian cells. The cytokinesis-block micronucleus (CBMN) assay was originally developped as an ideal system form easuring micronucleus (MN), however it can also be used to measure nucleoplasmic bridges (NBP) and nuclear buds (NBUD). Over the past decade another unique mechanism of micronucleus formation, known as nuclear budding has emerged. NBUDS is considered as a marker of gene amplification and/or altered gene dosage because the nuclear budding process is the mechanism by which cells removed amplified and/excess DNA.

Lifestyle factors influence in the frequency in buccal micronucleus

Genomic damage is probably the most important fundamental cause of development and degenerative disease. It is also well established that genomic damage is produced by environmental exposure to genotoxins, medical procedures (e.g. radiation and chemicals), micronutrient deficiency (e.g. folate), lifestyle factors (e.g. alcohol, smoking, drugs and stress), and genetic factors such as inherited defects in DNA metabolism and/or repair. Tobacco smoke has been associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Alcohol is definitely a recognized agent that influence cells in a genotoxic form, been citied as a strong agent with potential in the development of carcinogenic lesions. Epidemiological evidence points to a strong synergistic effect between cigarette smoking and alcohol consumption in the induction of cancers in the oral cavity. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The MN assay in buccal cells was also used to study cancerous and precancerous lesions and to monitor the effects of a number of chemopreventive agents.

XRCC3241 Polymorphism influence on genotoxicity biomarkers frequency in workers occupationaly exposed to formaldehyde

Formaldehyde (FA) is ubiquitous in the environment and is a chemical agent that possesses high reactivity. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. The exposure to this substance 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 micronucleus (biomarkers of chromosomes breakage or loss), nucleoplasmic bridges (biomarker of chromosome rearrangement, poor repair and / or telomeres fusion) and nuclear buds (biomarker of elimination of amplified DNA). The gene X-ray repair cross-complementing group 3 (XRCC3) is involved in homologous recombination repair of cross-links and chromosomal double-strand breaks and at least one polymorphism has been reported in codon 241, a substitution of a methionine for a threonine.

Evaluation of the influence of the ADH3 ILE349VAL polymorphism in the frequency of genotoxicity biomarkers in workers exposed to formaldehyde and tobacco smoking

Formaldehyde (FA) is a colourless gas widely used in the industry and hospitals as an aqueous solution, formalin. It is extremely reactive and induces various genotoxic effects in proliferating cultured mammalian cells. Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Genetic polymorphisms in enzymes involved in the metabolism are very important and can make changes in the individual susceptibility to disease. Alcohol dehydrogenase class 3 (ADH3), also known as formaldehyde dehydrogenase dependent of glutathione, is the major enzyme involved in the formaldehyde oxidation, especially in the buccal mucosa. The polymorphism in study is a substitution of an isoleucine for a valine in codon 349. The cytokinesis-blocked micronucleus assay (CBMN) in human lymphocytes is one of the most commonly used methods for measuring DNA damage, namely the detection of micronucleus, nucleoplasmic bridges, and nuclear buds, classified as genotoxicity biomarkers.

Occupational exposure to formaldehyde: effects of years of exposure in the frequency of micronucleus

Formaldehyde: an important industrial compound used in the manufacture of synthetic resins and chemical compounds such as lubricants and adhesives; also applied as a disinfectant, preservative and in cosmetics productions; relevant workplace exposure to FA also occurs in anatomy, pathology and in mortuaries; classified by IARC as carcinogenic to humans (Group 1), based on sufficient evidence in humans and experimental animals; manifold in vitro studies indicated that FA can induce genotoxic effects in proliferating cultured mammalian cells. Aim of the study: to evaluate if years of exposure induced a genotoxic biomarkers increase, namely MN in lymphocytes and buccal cells, in workers occupationally exposed to FA (factory and pathology anatomy laboratory).

Interaction of formaldehyde and tobacco smoking in the frequency of micronucleus and the XRCC3 Thr241Met polymorphism

Formaldehyde is classified by IARC as carcinogenic to humans (nasopharyngeal cancer). Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. XRCC3 is involved in homologous recombination repair of cross-links and chromosomal double-strand breaks (Thr241Met polymorphism). The aim of the study is to determine whether there is an in vivo association between genetic polymorphism of the gene XRCC3 and the frequency of genotoxicity biomarkers in subjects exposed or not to formaldehyde and with or without tobacco consumption.

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.

Re-evaluation of a reported increased micronucleus frequency in lymphocytes of workers occupationally exposed to formaldehyde

A replicate evaluation of increased micronucleus (MN) frequencies in peripheral lymphocytes of workers occupationally exposed to formaldehyde (FA) was undertaken to verify the observed effect and to determine scoring variability. May–Grünwald–Giemsa-stained slides were obtained from a previously performed cytokinesis-block micronucleus test (CBMNT) with 56 workers in anatomy and pathology laboratories and 85 controls. The first evaluation by one scorer (scorer 1) had led to a highly significant difference between workers and controls (3.96 vs 0.81 MN per 1000 cells). The slides were coded before re-evaluation and the code was broken after the complete re-evaluation of the study. A total of 1000 binucleated cells (BNC) were analysed per subject and the frequency of MN (in ‰) was determined. Slides were distributed equally and randomly between two scorers, so that the scorers had no knowledge of the exposure status. Scorer 2 (32 exposed, 36 controls) measured increased MN frequencies in exposed workers (9.88 vs 6.81). Statistical analysis with the two-sample Wilcoxon test indicated that this difference was not significant (p = 0.17). Scorer 3 (20 exposed, 46 controls) obtained a similar result, but slightly higher values for the comparison of exposed and controls (19.0 vs 12.89; p = 0.089). Combining the results of the two scorers (13.38 vs 10.22), a significant difference between exposed and controls (p = 0.028) was obtained when the stratified Wilcoxon test with the scorers as strata was applied. Interestingly, the re-evaluation of the slides led to clearly higher MN frequencies for exposed and controls compared with the first evaluation. Bland–Altman plots indicated that the agreement between the measurements of the different scorers was very poor, as shown by mean differences of 5.9 between scorer 1 and scorer 2 and 13.0 between scorer 1 and scorer 3. Calculation of the intra-class correlation coefficient (ICC) revealed that all scorer comparisons in this study were far from acceptable for the reliability of this assay. Possible implications for the use of the CBMNT in human biomonitoring studies are discussed.

Compact, frequency reconfigurable, printed monopole antenna

This paper proposes a possible implementation of a compact printed monopole antenna, useful to operate in UMTS and WLAN bands. In order to accomplish that, a miniaturization technique based on the application of chip inductors is used in conjunction with frequency reconfiguration capability. The chip inductors change the impedance response of the monopole, allowing to reduce the resonant frequency. In order to be able to operate the antenna in these two different frequencies, an antenna reconfiguration technique based on PIN diodes is applied. This procedure allows the change of the active form of the antenna leading to a shift in the resonant frequency. The prototype measurements show good agreement with the simulation results.

On performance of distributed model predictive control in power system frequency regulation

This paper describes the implementation of a distributed model predictive approach for automatic generation control. Performance results are discussed by comparing classical techniques (based on integral control) with model predictive control solutions (centralized and distributed) for different operational scenarios with two interconnected networks. These scenarios include variable load levels (ranging from a small to a large unbalance generated power to power consumption ratio) and simultaneously variable distance between the interconnected networks systems. For the two networks the paper also examines the impact of load variation in an island context (a network isolated from each other).

Complementary filter design with three frequency bands: robot attitude estimation

This paper extents the by now classic sensor fusion complementary filter (CF) design, involving two sensors, to the case where three sensors that provide measurements in different bands are available. This paper shows that the use of classical CF techniques to tackle a generic three sensors fusion problem, based solely on their frequency domain characteristics, leads to a minimal realization, stable, sub-optimal solution, denoted as Complementary Filters3 (CF3). Then, a new approach for the estimation problem at hand is used, based on optimal linear Kalman filtering techniques. Moreover, the solution is shown to preserve the complementary property, i.e. the sum of the three transfer functions of the respective sensors add up to one, both in continuous and discrete time domains. This new class of filters are denoted as Complementary Kalman Filters3 (CKF3). The attitude estimation of a mobile robot is addressed, based on data from a rate gyroscope, a digital compass, and odometry. The experimental results obtained are reported.

Establishment of optimal physical assets inspection frequency based on risk principles

Risk Based Inspection (RBI) is a risk methodology used as the basis for prioritizing and managing the efforts for an inspection program allowing the allocation of resources to provide a higher level of coverage on physical assets with higher risk. The main goal of RBI is to increase equipment availability while improving or maintaining the accepted level of risk. This paper presents the concept of risk, risk analysis and RBI methodology and shows an approach to determine the optimal inspection frequency for physical assets based on the potential risk and mainly on the quantification of the probability of failure. It makes use of some assumptions in a structured decision making process. The proposed methodology allows an optimization of inspection intervals deciding when the first inspection must be performed as well as the subsequent intervals of inspection. A demonstrative example is also presented to illustrate the application of the proposed methodology.

Estimation of rotational frequency response functions

As it is widely known, in structural dynamic applications, ranging from structural coupling to model updating, the incompatibility between measured and simulated data is inevitable, due to the problem of coordinate incompleteness. Usually, the experimental data from conventional vibration testing is collected at a few translational degrees of freedom (DOF) due to applied forces, using hammer or shaker exciters, over a limited frequency range. Hence, one can only measure a portion of the receptance matrix, few columns, related to the forced DOFs, and rows, related to the measured DOFs. In contrast, by finite element modeling, one can obtain a full data set, both in terms of DOFs and identified modes. Over the years, several model reduction techniques have been proposed, as well as data expansion ones. However, the latter are significantly fewer and the demand for efficient techniques is still an issue. In this work, one proposes a technique for expanding measured frequency response functions (FRF) over the entire set of DOFs. This technique is based upon a modified Kidder's method and the principle of reciprocity, and it avoids the need for modal identification, as it uses the measured FRFs directly. In order to illustrate the performance of the proposed technique, a set of simulated experimental translational FRFs is taken as reference to estimate rotational FRFs, including those that are due to applied moments.