Mutation T-->C of nucleotide 2238 in the gene of atrial natriuretic peptide (ANP) precursor and heterogeneity of sodium-sensitive hypertension. Preliminary report

Atrial natriuretic peptide (ANP) is involved in the pathogenesis of sodium-sensitive hypertension. The loss of Sca I restriction site in the ANP precursor gene abolishes the regular stop codon. The aim of our study was the analysis of the Sca I gene polymorphism in 23 patients with sodium-sensitive hypertension, the molecular characteristic of the mutation and the comparison of the blood pressure values, plasma renin activity, plasma ANP and aldosterone concentration between patients with or without mutation. Applying the polymerase chain reaction (PCR), followed by digestion with Sca I, the heterozygous mutation has been found in 9 (39%) patients. The sequencing of PCR products indicated that the loss of Sca I restriction site is caused by T2238-->C transition leading to the translation of ANP with two additional arginines. The higher concentration of ANP in plasma has been found in T2238-->C transition patients on normal and high sodium diet as compared with patients without mutation. These preliminary results suggest that the heterogeneity of sodium-sensitive hypertension is associated with the T2238-->C mutation of the ANP precursor gene.     

Evaluation of multitransducer arrays for the determination of organic vapor mixtures

A study of vapor recognition and quantification by polymer-coated multitransducer (MT) arrays is described. The primary data set consists of experimentally derived sensitivities for 11 organic vapors obtained from 15 microsensors comprising five cantilever, capacitor, and calorimeter devices coated with five different sorptive-polymer films. These are used in Monte Carlo simulations coupled with principal component regression models to assess expected performance. Recognition rates for individual vapors and for vapor mixtures of up to four components are estimated for single-transducer (ST) arrays of up to five sensors and MT arrays of up to 15 sensors. Recognition rates are not significantly improved by including more than five sensors in an MT array for any specific analysis, regardless of difficulty. Optimal MT arrays consistently outperform optimal ST arrays of similar size, and with judiciously selected 5-sensor MT arrays, one-third of all possible ternary vapor mixtures are reliably discriminated from their individual components and binary component mixtures, whereas none are reliably determined with any of the ST arrays. Quaternary mixtures could not be analyzed effectively with any of the arrays. A "universal" MT array consisting of eight sensors is defined, which provides the best possible performance for all analytical scenarios. Accurate quantification is predicted for correctly identified vapors.     

Characterization of Fuel Properties and Fire Spread Rates for Little Bluestem Grass

Rapid urban sprawl and population decentralization in recent decades have increased the size of the wildland-urban interface and resulted in higher community risk and vulnerability to wildfire. This paper primarily focuses on understanding grass-fueled fires common to Texas and improving the understanding of the physics and fire dynamics that are inherent in the grassland and prairie flame spread problem. Little bluestem (Schizachyrium scoparium) grass was chosen as the grassland fuel due to its prevalent coverage in the Texas area and its relevance to grassland fires in Texas. The methodology in this study relies on a framework to characterize fuel properties of little bluestem grass using small- and intermediate-scale experiments to better predict full-scale fire behavior. An intermediate-scale numerical flame spread model was developed for grass fuels that accounts for fuel moisture content to calculate the mass versus time of a burning little bluestem plant. The results of the small- and intermediate-scale experiments were used to develop input parameters for a field-scale numerical simulation of a grass field using a physics-based computational fire model, Wildland-urban interface Fire Dynamics Simulator (WFDS). A sensitivity analysis was performed to determine the effect of varying WFDS input parameters on the fire spread rate. The results indicate that the fuel moisture content had the most significant impact on the fire spread rate.     

Detection and discrimination capabilities of a multitransducer single-chip gas sensor system

The performance of a single-chip, three-transducer, complementary metal oxide semiconductor gas sensor microsystem has been thoroughly evaluated. The monolithic gas sensor system includes three polymer-coated transducers, a mass-sensitive cantilever, a thermoelectric calorimetric sensor, and an interdigitated capacitive sensor that are integrated along with all electronic circuits needed to operate these sensors. The system additionally includes a temperature sensor and a serial interface unit so that it can be directly connected to, for example, a microcontroller. Several multitransducer chips have been coated with various partially selective polymers and then have been exposed to different volatile organic compounds. The sensitivities of the three different polymer-coated transducers to defined sets of gaseous analytes have been determined. The obtained sensitivity values have then been normalized with regard to the partition coefficients of the respective analyte/polymer combination to reveal the transducer-specific effects. The results of this investigation show that the three different transducers respond to fundamentally different molecular properties, such as the analyte molecular mass (mass-sensitive), its dielectric coefficient (capacitive), and its sorption heat (calorimetric) so that correlations between the determined sensitivity values and the different molecular properties of the absorbed analytes could be established. The information as provided by the system, hence, represents a body of orthogonal data that can serve as input to appropriate signal processing and pattern recognition techniques to address issues such as the quantification of analytes in mixtures.     

Model Considerations for Fire Scene Reconstruction Using a Bayesian Framework

Towards the development of a more rigorous approach for coupling collected fire scene data to computational tools, a Bayesian computational strategy is presented in this work. The Bayesian inversion technique is exercised on synthetic, time-integrated data to invert for the location, size, and time-to-peak of an unknown fire using two well-known forward models; Consolidated Model of Fire and Smoke Transport (CFAST) and Fire Dynamics Simulator (FDS). A Gaussian process surrogate model was fit to coarse FDS simulations to facilitate Markov Chain Monte Carlo sampling. The inversion framework was able to predict the total energy release by all fire cases except for one CFAST forward model, a 1000 kW steady fire. It was found that insufficient information was available in the time-integrated data to distinguish the temporal variations in peak times. FDS performed better than CFAST in predicting the maximum energy release rate with the posterior mean of the best configurations being 0.05% and 2.77% of the true values respectively. Both models performed equally well on locating the fire in a compartment.     

Towards a versatile DRIE: silicon pit structures combined with electrochemical etch stop

A novel approach for fabricating low-pitch arrays of silicon membranes on standard CMOS wafers by combining deep-reactive ion etching (DRIE) and electrochemical etching (ECE) techniques is presented. These techniques have been used to fabricate membrane-based sensors and sensor arrays featuring different membrane sizes on a single wafer with a well defined etch stop. The described procedure is particularly useful in cases when the usage of SOI wafers is not an option. The combination of a grid-like mask pattern featuring uniform-size etch openings for the DRIE process with a reliable ECE technique allowed to fabricate silicon membranes with sizes ranging from 0.01 mm/sup 2/ to 2.2 mm/sup 2/. The development of this new method has been motivated by the need to design a compact n-well-based calorimetric sensor array, where the use of a standard ECE technique would have significantly increased the overall size of the device.     

Mass spectrometry-assisted protease substrate screening

Since sequencing of the human genome was completed, more than 500 genes have been annotated as proteases. Exploring the physiological role of each protease requires the identification of their natural substrates. However, the endogenous substrates of many of the human proteases are as yet unknown. Here we describe a new assay that addresses this problem. The assay, which easily can be automated, is based on the incubation of immobilized protein fractions, which may contain the natural substrate, with a defined protease. After concentrating the proteolytically released peptides by reversed-phase chromatography they are analyzed by tandem mass spectrometry and the substrates identified by database searching. The proof of principle in this study is demonstrated by incubating immobilized human plasma proteins with thrombin and by identifying by tandem mass spectrometry the fibrinopeptides, released by the action of thrombin from their natural substrate fibrinogen, in the reaction mixture.     

Deep-Learning Emulators of Transient Compartment Fire Simulations for Inverse Problems and Room-Scale Calorimetry

Fire Technology - This work describes a deep learning methodology for “emulating” temperature outputs produced by the Fire Dynamics Simulator (FDS), a CFD software. An array of...     

The Effects of Cadmium at Low Environmental Concentrations on THP-1 Macrophage Apoptosis

Cadmium at environmental concentrations is a risk factor for many diseases, including cardiovascular and neurodegenerative diseases, in which macrophages play an important role. The aim of this study was to evaluate the effects of cadmium at low environmental (nanomolar) concentrations on apoptotic processes in THP-1(acute monocytic leukemia cells line)-derived macrophages, with special focus on mitochondrial events involved. Macrophages were incubated with various cadmium chloride (CdCl₂) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM and 2 µM CdCl₂. Cell viability was measured using flow cytometry. Flow cytometric measurement (annexin V/FITC (annexin V/fluorescein isothiocyanate) and PI (propidium iodide) double staining) was used to quantify the extent of apoptosis. Fluorescence and confocal microscopy were used for imaging of apoptosis process. Changes in mitochondrial membrane potential were monitored using cytofluorimetry after cell staining with JC-1(5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol-carbocyane iodide) probe. Mitochondrial ROS (reactive oxygen species) levels were measured cytofluorimetrically after incubation of cells with mitochondrial superoxide indicator (MitoSOX) red fluorescent marker. The mRNA expression of Bcl-2 and Bax was analysed with qRT-PCR. Our study demonstrates that cadmium, even at low environmental concentrations, exerts mitochondrial toxicity in THP-1 macrophages. Forty-eight-hour exposure to very low concentrations reduces cell viability and results in cell death by apoptosis and necrosis. The decrease in mitochondrial membrane potential, increased ROS production, increased Bax and decreased Bcl-2 mRNA expression are mitochondrial events involved in cadmium-induced apoptosis.     

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine analogue (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC₅₀ equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.