Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in Portuguese women

Introduction - Obesity became a major public health problem as a result of its increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to protect membranes and lipoproteins from oxidative modifications. At the PON1 gene, several polymorphisms in the promoter and coding regions have been identified. The aims of this study were i) to assess PON1 L55M and Q192R polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity according to the expression of each allele in L55M and Q192R polymorphisms; iii) to compare PON1 activity between obese and normal-weight women. Materials and methods - We studied 75 healthy (35.9±8.2 years) and 81 obese women (34.3±8.2 years). Inclusion criteria for obese subjects were body mass index ≥30 kg/m2 and absence of inflammatory/neoplasic conditions or kidney/hepatic dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric methods, using paraoxon as a substrate. Results - No significant differences were found for PON1 activity between normal and obese women. Nevertheless, PON1 activity was greater (P<0.01) for the RR genotype (in Q192R polymorphism) and for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R polymorphism was significantly higher in obese women (P<0.05) and was associated with an increased risk of obesity (odds ratio=2.0 – 95% confidence interval (1.04; 3.87)). Conclusion - 55M and Q192R polymorphisms influence PON1 activity. The allele R of the Q192R polymorphism is associated with an increased risk for development of obesity among Portuguese Caucasian premenopausal women.

Limiting Internal Supply Voltage Spikes in DC-DC Converters

Implementing monolithic DC-DC converters for low power portable applications with a standard low voltage CMOS technology leads to lower production costs and higher reliability. Moreover, it allows miniaturization by the integration of two units in the same die: the power management unit that regulates the supply voltage for the second unit, a dedicated signal processor, that performs the functions required. This paper presents original techniques that limit spikes in the internal supply voltage on a monolithic DC-DC converter, extending the use of the same technology for both units. These spikes are mainly caused by fast current variations in the path connecting the external power supply to the internal pads of the converter power block. This path includes two parasitic inductances inbuilt in bond wires and in package pins. Although these parasitic inductances present relative low values when compared with the typical external inductances of DC-DC converters, their effects can not be neglected when switching high currents at high switching frequency. The associated overvoltage frequently causes destruction, reliability problems and/or control malfunction. Different spike reduction techniques are presented and compared. The proposed techniques were used in the design of the gate driver of a DC-DC converter included in a power management unit implemented in a standard 0.35 mu m CMOS technology.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

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.

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.

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.

Fast optimum-predictive control and capacitor voltage balancing strategy for bipolar back-to-back NPC converters in high-voltage direct current transmission systems

Multilevel power converters have been introduced as the solution for high-power high-voltage switching applications where they have well-known advantages. Recently, full back-to-back connected multilevel neutral point diode clamped converters (NPC converter) have been used inhigh-voltage direct current (HVDC) transmission systems. Bipolar-connected back-to-back NPC converters have advantages in long-distance HVDCtransmission systems over the full back-to-back connection, but greater difficulty to balance the dc capacitor voltage divider on both sending and receiving end NPC converters. This study shows that power flow control and dc capacitor voltage balancing are feasible using fast optimum-predictive-based controllers in HVDC systems using bipolar back-to-back-connected five-level NPC multilevel converters. For both converter sides, the control strategytakes in account active and reactive power, which establishes ac grid currents in both ends, and guarantees the balancing of dc bus capacitor voltages inboth NPC converters. Additionally, the semiconductor switching frequency is minimised to reduce switching losses. The performance and robustness of the new fast predictive control strategy, and its capability to solve the DC capacitor voltage balancing problem of bipolar-connected back-to-back NPCconverters are evaluated.

Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

Introduction and Objectives - Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression. Methods - We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls. Results - PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52). Conclusion - The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.

Climatology of the Iberia coastal low-level wind jet: weather research forecasting model high-resolution results

Coastal low-level jets (CLLJ) are a low-tropospheric wind feature driven by the pressure gradient produced by a sharp contrast between high temperatures over land and lower temperatures over the sea. This contrast between the cold ocean and the warm land in the summer is intensified by the impact of the coastal parallel winds on the ocean generating upwelling currents, sharpening the temperature gradient close to the coast and giving rise to strong baroclinic structures at the coast. During summertime, the Iberian Peninsula is often under the effect of the Azores High and of a thermal low pressure system inland, leading to a seasonal wind, in the west coast, called the Nortada (northerly wind). This study presents a regional climatology of the CLLJ off the west coast of the Iberian Peninsula, based on a 9km resolution downscaling dataset, produced using the Weather Research and Forecasting (WRF) mesoscale model, forced by 19 years of ERA-Interim reanalysis (1989-2007). The simulation results show that the jet hourly frequency of occurrence in the summer is above 30% and decreases to about 10% during spring and autumn. The monthly frequencies of occurrence can reach higher values, around 40% in summer months, and reveal large inter-annual variability in all three seasons. In the summer, at a daily base, the CLLJ is present in almost 70% of the days. The CLLJ wind direction is mostly from north-northeasterly and occurs more persistently in three areas where the interaction of the jet flow with local capes and headlands is more pronounced. The coastal jets in this area occur at heights between 300 and 400 m, and its speed has a mean around 15 m/s, reaching maximum speeds of 25 m/s.

A VLF to UHF propagation model for evaluation of high-speed railway electromagnetic interference in RF monitoring base-stations

Considering that recent european high-speed railway system has a traction power system of kV 50 Hz, which causes electromagnetic emission for the outside world, it is important to dimension the railway system emissions, using a frequency/distance dependent propagation model. This paper presents an enhanced theoretical model for VLF to UHF propagation, railway system oriented. It introduces the near field approach (crucial in low frequency propagation) and also considers the source characteristics and type of measuring antenna. Simulations are presented, and comparisons are set with earlier far field models. Using the developed model, a real case study was performed in partnership with Refer Telecom (portuguese telecom operator for railways). The new propagation model was used in order to predict the future high-speed railway electromagnetic emissions in the Lisbon north track. The results show the model's prediction capabilities and also its applicability to realistic scenarios.

Efficient feature selection filters for high-dimensional data

Feature selection is a central problem in machine learning and pattern recognition. On large datasets (in terms of dimension and/or number of instances), using search-based or wrapper techniques can be cornputationally prohibitive. Moreover, many filter methods based on relevance/redundancy assessment also take a prohibitively long time on high-dimensional. datasets. In this paper, we propose efficient unsupervised and supervised feature selection/ranking filters for high-dimensional datasets. These methods use low-complexity relevance and redundancy criteria, applicable to supervised, semi-supervised, and unsupervised learning, being able to act as pre-processors for computationally intensive methods to focus their attention on smaller subsets of promising features. The experimental results, with up to 10(5) features, show the time efficiency of our methods, with lower generalization error than state-of-the-art techniques, while being dramatically simpler and faster.

A comprehensive high-throughput FTIR spectroscopy-based method for evaluating the transfection event: estimating the transfection efficiency and extracting associated metabolic responses

Reporter genes are routinely used in every laboratory for molecular and cellular biology for studying heterologous gene expression and general cellular biological mechanisms, such as transfection processes. Although well characterized and broadly implemented, reporter genes present serious limitations, either by involving time-consuming procedures or by presenting possible side effects on the expression of the heterologous gene or even in the general cellular metabolism. Fourier transform mid-infrared (FT-MIR) spectroscopy was evaluated to simultaneously analyze in a rapid (minutes) and high-throughput mode (using 96-wells microplates), the transfection efficiency, and the effect of the transfection process on the host cell biochemical composition and metabolism. Semi-adherent HEK and adherent AGS cell lines, transfected with the plasmid pVAX-GFP using Lipofectamine, were used as model systems. Good partial least squares (PLS) models were built to estimate the transfection efficiency, either considering each cell line independently (R 2 ≥ 0.92; RMSECV ≤ 2 %) or simultaneously considering both cell lines (R 2 = 0.90; RMSECV = 2 %). Additionally, the effect of the transfection process on the HEK cell biochemical and metabolic features could be evaluated directly from the FT-IR spectra. Due to the high sensitivity of the technique, it was also possible to discriminate the effect of the transfection process from the transfection reagent on KEK cells, e.g., by the analysis of spectral biomarkers and biochemical and metabolic features. The present results are far beyond what any reporter gene assay or other specific probe can offer for these purposes.