Effect of APE1 T2197G (Asp148Glu) Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer

It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.     

Optimal location of piezoelectric actuators for active vibration control of thin axially functionally graded beams

Up to now, optimal location for active control studies concern principally multilayers or homogeneous structures. In the case of functionally graded materials, very few papers exist and they only concern cross section variations. In this way, this paper deals with the optimization of piezoelectric actuators locations on axially functionally graded beams for active vibration control. For this kind of structures, the free vibration problem is more complicated as the governing equations have variable coefficients. Here, the eigenproblem is solved using Fredholm integral equations. The optimal locations of actuators are determined using an optimization criterion, ensuring good controllability of each eigenmode of the structure. The linear quadratic regulator, including a state observer, is used for active control simulations. Two numerical examples are presented for two kinds of boundary conditions.     

Processing radio frequency ultrasound images: a robust method for local spectral features estimation by a spatially constrained parametric approach

Spectral estimation is a major component in studies aiming at characterizing biological tissues through the analysis of backscattered radio frequency (RF) ultrasonic signals and images. However, conventional spectral estimation techniques yield a well-known trade-off between spatial resolution and variance. The backscattered signals are stochastic by nature, so short-term local analysis results in a high variance of the estimates, which cannot efficiently be reduced through conventional spatial averaging. We address this issue by describing a spectral estimation technique that reduces the variance of the estimates (by smoothing the local estimates in spectrally homogeneous regions) while preserving spectral discontinuities (i.e., the smoothing is not performed across regions with different spectral contents). The proposed approach is set in a Bayesian framework and is based on local autoregressive (AR) estimation, constrained by smoothness priors. These smoothness priors are introduced through a Markov random field in which the associated potential functions are nonquadratic, allowing thereby to preserve discontinuity. The method is validated on simulated RF images and tested on echocardiographic images acquired in vivo. The results are compared to the estimates provided by the conventional Burg technique. These results clearly demonstrate the ability of the proposed approach to improve spectral estimation in terms of variance reduction and discontinuity detection.     

INTRODUCTION TO THE SPECIAL ISSUE ON CASE-BASED REASONING IN THE HEALTH SCIENCES

There has been an explosion of interest in health sciences applications of case-based reasoning (CBR), not only in the traditional CBR in medicine domain, but also in bioinformatics, enabling home health-care technologies, CBR integration, and synergies between CBR and knowledge discovery. This special issue features the best papers from the third workshop on CBR in the health sciences, held at ICCBR-05 in Madrid. It is the third in a series of exciting workshops, the first two of which were held at ICCBR-03, in Trondheim, Norway, and at ECCBR-04, in Madrid, Spain. The nine high-quality papers introduced here represent the research and experience of twenty-two authors working in eight different countries on a wide range of problems and projects. These papers illustrate some of the major trends of current research in CBR in the health sciences, and represent overall an excellent sample of the most recent advances of CBR in the health sciences.     

PP/EMA TPV: Dynamic cross‐linking through an alcoholysis reaction

Dynamically cross‐linked polypropylene/ethylene‐methyl acrylate copolymer (PP/EMA) blends were prepared by reactive extrusion in a twin‐screw extruder. A transesterification reaction catalyzed by an organotin compound and involving the acrylic moieties of EMA with the hydroxyl functions of pentanediol was used to cross‐link the elastomeric EMA. The extent of cross‐linking was estimated through the insoluble content of the blend. The alcohol‐to‐acrylic ratio and the dibutyltin oxide content were both found to increase the extent of EMA cross‐linking. Processing conditions such as screw rotation rate and extrusion temperature profile also had large effects on the reaction extent. Conditions leading to improved pentanediol dispersion were found to generate larger insoluble fraction. Gel contents of EMA phase as high as 75% to 85% were obtained. Interestingly, the stress‐strain curves of the cross‐linked PP/EMA TPV are very well represented by a single master curve. Dynamically cross‐linked blends show systematically better tensile properties than the non‐reactive system. Blends with higher insoluble content show strain at break in the 650%–750% range. Material processability was maintained, even for the systems with high insoluble content.     

The analytical separation of phosphate from natural water by ion exchange

An ion exchange method has been developed for separating inorganic orthophosphate from natural water samples. The technique makes it possible to determine orthophosphate by the molybdophosphate blue procedure without interference from phosphate esters or certain other forms of bound phosphorus. Experiments to examine the conditions under which phosphate is found in natural waters suggest that adsorption by high molecular weight organic substances such as lignins may account for a large fraction of the soluble phosphorus.     

A microfluidic platform using molecular beacon-based temperature calibration for thermal dehybridization of surface-bound DNA

This work presents a simple microfluidic device with an integrated thin-film heater for studies of DNA hybridization kinetics and double-stranded DNA melting temperature measurements. The heating characteristics of the device were evaluated with a novel, noninvasive indirect technique using molecular beacons as temperature probes inside reaction chambers. This is the first microfluidic device in which thermal dehybridization of surface-bound oligonucleotides was performed for measurement of double-stranded DNA melting temperatures with +/- 1 degrees C precision. Surface modification and oligonucleotide immobilization were performed by continuously flowing reagents through the microchannels. The resulting reproducibility of oligonucleotide surface densities, at 9% RSD, was better than for the same modification chemistries on glass slides in unstirred reagent solutions (RSD=20%). Moreover, the surface density of immobilized DNA probe molecules could be varied controllably by changing the concentration of the reagent solution used for immobilization. Thus, excellent control of surface characteristics was made possible, something which is often difficult to achieve with larger devices. Solid-phase hybridization reactions, a fundamental aspect of microarray technologies often taking several hours in conventional systems, were reduced to minutes in this device. It was also possible to determine forward rate constants for hybridization, k. These varied from 820,000 to 72,000 M(-1) s(-1), decreasing as surface densities increased. Surface densities could therefore be optimized to obtain rapid hybridization using such an approach. Taken together, this combined microfluidic/small-volume heating approach represents a powerful tool for surface-based DNA analysis.     

In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro

Raman microspectroscopy was used to determine biochemical markers during the differentiation of embryonic murine stem cells (mES) in vitro. Such markers are useful to determine the differentiation status of ES cells cultured on biomaterials. Raman spectra of mES cells as undifferentiated, spontaneously differentiated (4 days), and differentiated cells via formation of embryoid bodies (16, 20 days) were analyzed. Unsupervised hierarchical cluster analysis and principal component analysis were used to determine biochemical differences between mES cells in various states of differentiation. The undifferentiated cells were characterized by high scores of the first principal component (PC1, 49% variance). Similarity between the PC1 loading and the Raman spectrum of RNA indicated a high concentration of RNA in mES cells compared to differentiated cells. The ratio between the peak areas of RNA and proteins was used as a measure of mRNA translation. Using the same peak area ratio, it was possible to differentiate even between mES as undifferentiated and in early stages of differentiation (4 days). These findings were correlated with biological studies reporting high levels of nontranslated mRNA during early embryonic development. Therefore, the RNA translation obtained from the Raman spectra can be used as marker of differentiation state of mES cells.     

Structural change of water with solutes and temperature up to 100 degrees C in aqueous solutions as revealed by attenuated total reflectance infrared spectroscopy

The attenuated total reflectance infrared (ATR-IR) spectra of several aqueous solutions have been measured by using a newly developed heatable rod-type ATR cell. The OH stretching bands showed systematic change with increasing solute concentrations and these changes can be explained by four different OH components based on curve-fitting results. NaCl solutions show longer H-bond distance character, while carbonate solutions present shorter ones. The Na2CO3 1 M solution conserves this shorter H-bond nature up to 100 degrees C. On the other hand, the loose nature of NaCl solutions becomes less pronounced at higher temperatures because of the dissociation of pure water clusters. These in situ observations of water structures are generally in agreement with the expected nature of fluids within the earth.