Analysis of Renal Cell Carcinoma Cell Response to the Enhancement of 5-aminolevulinic Acid-mediated Protoporphyrin IX Fluorescence by Iron Chelator Deferoxamine†

As a tumor photodiagnostic agent, 5-aminolevulinic acid (ALA) is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with fluorescence. ALA-PpIX fluorescence was evaluated in human renal cell carcinoma (RCC) cell lines and non-tumor HK-2 cell lines. We found that extracellular PpIX level was correlated with ABCG2 activity, illustrating its importance as a PpIX efflux transporter. Extracellular PpIX was also related to the K_m of ferrochelatase (FECH) that chelates PpIX with ferrous iron to form heme. The V_max of FECH was higher in all RCC cell lines tested than in the HK-2 cell line. TCGA dataset analysis indicates a positive correlation between FECH expression and RCC patient survival. These findings suggest FECH as an important biomarker in RCC. Effects of iron chelator deferoxamine (DFO) on the enhancement of PpIX fluorescence were assessed. DFO increased intracellular PpIX in both tumor and non-tumor cells, resulting in no gain in tumor/non-tumor fluorescence ratios. DFO appeared to increase ALA-PpIX more at 1-h than at 4-h treatment. There was an inverse correlation between ALA-PpIX fluorescence and the enhancement effect of DFO. These results suggest that enhancement of ALA-PpIX by DFO may be limited by the availability of ferrous iron in mitochondria following ALA administration.     

Measurement of the Rates of Diffusion of Halomethanes into Polymer Films Using ATR-FTIR Spectroscopy

Polymer-modified attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and FEWS (fibre-optic evanescent wave) spectroscopy have been very successful to date for sensitive detection of organic pollutants in water utilising the mid-infrared (MIR) region of the electromagnetic spectrum (4000-400 cm^?1). This sensing approach involves the use of different polymer films for preconcentration with optimisation of the sensor related to the rate of diffusion of solvent molecules into these polymer films. Compounds such as chloroform, bromoform, bromodichloromethane and dibromochloromethane which are collectively referred to as trihalomethanes (THMs) were analysed in this work. A gaseous phase experimental design was used and from experimental data the rate of diffusion of each of the halomethanes was quantified based on a Fickian type diffusion model. Individual diffusion coefficient values were found to be in the range 3.38 E-10 ± 0.01 E-10 to 4.72 E-08 ± 0.42 E-08 cm² s^?1. Multicomponent effects were observed for mixtures of compounds diffusing into polyisobutylene and ethylene-propylene copolymer.     

Positively and negatively charged ionic modifications to cellulose assessed as cotton-based protease-lowering and hemostatic wound agents

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapping but distinct phases of wound healing wherein different dressing material properties are required to bring pathological events under control when they present as a result of trauma or chronic wounds. Thus, we have designed cellulose wound dressings with properties that function through modified fiber surface properties to lower protease levels in the chronic wound and promote clotting in hemorrhaging wounds. With this in mind three finishing chemistries utilizing traditional pad-dry-cure approaches were explored for their potential to confer charged properties to cotton dressings. Cellulose dressings designed to remove cationic serine proteases from highly exudative chronic wounds were created to present negatively charged fibers as an ion exchange mechanism of protease-lowering. Phosphorylated cotton and polycarboxylic acid crosslinked cotton were prepared to examine their ability to remove human neutrophil elastase (HNE) from surrogate wound fluid. A cellulose phosphorylation reaction utilizing sodium hexametaphosphate: urea was explored to optimize cellulose phosphorylation as a function of HNE sequestration efficacy. Acid catalyzed cross linking of cellulose with butane-tetracarboxylic acid also resulted in a negatively charged dressing that removed HNE from solution more effectively than phosphorylated cellulose. Collagenase sequestration was also assessed with phosphorylated cellulose and polycarboxylic acid cross linked cellulose derivatives. Butanetetracarboxylic acid and phosphorylated cellulose functioned to remove collagenase from solution most effectively. Cellulose dressings designed to accelerate thrombosis and aggregation of blood platelets were prepared with a view to examining derivatized cotton fibers bearing a net positive charge to promote hemostasis. Cellulose and chitosan dressings bearing an aminoglucan functionality were created by grafting chitosan on cotton and preparing aminized cotton. The preparation of chitosan-grafted cotton dressings was completed with a citric acid grafting onto cellulose. Aminized cotton was functionalized as an ethylamino-ether cellulose derivative. The chitosan-grafted and aminized cotton demonstrated a dose response gelling of citrated sheep blood.     

Modeling of MIG/MAG welding with experimental validation using an active contour algorithm applied on high speed movies

This paper investigates some issues in physical modeling of metal inert gas/metal active gas (MIG/MAG) welding process in the short arc mode. In this mode, a metal supply is molten in the arc state and then transferred to the weld pool during the short-circuit state. A hybrid model having two distinct continuous states whose switchings are controlled by two guard conditions is proposed. Due to the complexity of the physical phenomena involved in the welding process, simplifications are used to obtain a model accounting for the main physical contributions but simple enough to yield an efficient, fast and numerically tractable simulator which can be used intensively for evaluating different control strategies. In an attempt to validate the proposed model, different measurements have been made including supply voltage and current sampled synchronously with high speed digital video. In order to extract some relevant quantities representative of the metal transfer from image sequences, an active contour algorithm is developed and tested. The effectiveness of the proposed model in the prediction of major tendencies of a welding process, especially in the arc state, is shown using experimental data. Some limitations of the model during the metal transfer are also stressed and possible remedies are then proposed.     

Thermally tuned optical fiber for true time delay generation

A new technique for generating a continuous range of true time delay values is introduced. Heating optical fiber in order to change the effective index of the guided mode produces time delays. A 45-m section of single-mode silica fiber is demonstrated to produce a continuous range of time delay values from 0 to 211 ps over a temperature tuning range of 50°C (30–80°C). A thermal time delay factor is introduced and found to be 0.096 ps/m°C for Corning LEAF fiber. A 7.66-m section of multimode Lucina polymer fiber is demonstrated to produce a range of time delay values from 0 to 32 ps over a temperature tuning range of 30°C (30–60°C). The thermal time delay factor for this fiber is −0.1427 ps/m°C.     

Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins

Background  

The delivery of ubiquitinated proteins to the proteasome for degradation is a key step in the regulation of the ubiquitin-proteasome pathway, yet the mechanisms underlying this step are not understood in detail. The Rad23 family of proteins is known to bind ubiquitinated proteins through its two ubiquitin-associated (UBA) domains, and may participate in the delivery of ubiquitinated proteins to the proteasome through docking via the Rad23 ubiquitin-like (UBL) domain.     

The influence of random interactions and decision heuristics on norm evolution in social networks

In this paper we explore the effect that random social interactions have on the emergence and evolution of social norms in a simulated population of agents. In our model agents observe the behaviour of others and update their norms based on these observations. An agent’s norm is influenced by both their own fixed social network plus a second random network that is composed of a subset of the remaining population. Random interactions are based on a weighted selection algorithm that uses an individual’s path distance on the network to determine their chance of meeting a stranger. This means that friends-of-friends are more likely to randomly interact with one another than agents with a higher degree of separation. We then contrast the cases where agents make highest utility based rational decisions about which norm to adopt versus using a Markov Decision process that associates a weight with the best choice. Finally we examine the effect that these random interactions have on the evolution of a more complex social norm as it propagates throughout the population. We discover that increasing the frequency and weighting of random interactions results in higher levels of norm convergence and in a quicker time when agents have the choice between two competing alternatives. This can be attributed to more information passing through the population thereby allowing for quicker convergence. When the norm is allowed to evolve we observe both global consensus formation and group splintering depending on the cognitive agent model used.     

Recent measurements of 36Cl in Yucca Mountain rock, soil and seepage

Samples of rock, soil and seepage were collected from Yucca Mountain, USA, and analyzed for ³⁶Cl/Cl ratios by accelerator mass spectrometry (AMS). Rock excavated from the Drill Hole Wash fault at repository horizon depths produced a ratio suggesting that small amounts of water with “bomb-pulse” ³⁶Cl had percolated to that site over the past 50 years. Rock from four other sites within the exploratory studies facility did not yield bomb-pulse ratios. Ratios in the soil varied depending on depth and location, with some samples producing bomb-pulse signatures. Ratios for seep water were slightly elevated above the present cosmogenic background value. This paper also discusses results from a column study mimicking the passage of ³⁶Cl through volcanic rock and from an experiment using bromide instead of chloride as a carrier in sample preparation for AMS.     

The impulse photopyroelectric method for thermal characterization of electrically conducting polymers

For electrically conducting polypyrole films, the thermal diffusivity and thermal conductivity were obtained by modeling the signals from the photopyroelectric flash technique with a one-dimensional four-layer system. This method has a number of advantages over the sinusoidal excitation: wide thickness range, fast acquisition, simple and cheap setup. This first thermal characterization of polypyrole films shows an increasing thermal conductivity with dopant ion concentration.     

Association and phase behavior of hydrophobically modified photoresponsive poly(acrylamide)s in the presence of ionic surfactant

 The extent of association between the cationic surfactant TTAB and a series of hydrophobically modified polyacrylamides (HPAMs) containing an N-n-alkyl and substituted azobenzene hydrophobic sidegroup has been studied utilizing a cationic surfactant-selective membrane electrode. Binding of TTAB to the polymer hydrophobes is found to increase with increasing hydrophobicity of the hydrophobe. In the presence of electrolyte, aqueous solutions of HPAMs and ionic surfactant exhibit an associative phase separation. The temperature or clearing point (CP) at which the system goes from a one phase to two-phase system are reported. The area of the two-phase region is found to increase with increasing electrolyte concentration, hydrophobicity of the hydrophobe for the high molecular weight HPAMs, and decreasing hydrophobicity for low molecular weight HPAMs. Exposure of HPAMs containing an azobenzene hydrophobe to UV light results in a decrease in interaction between the hydrophobe and surfactant and a corresponding decrease in the CP due to conversion of azobenzene from the more hydrophobic trans form to the less hydrophobic cis isomer. Received: 23 September 1996 Accepted: 11 March 1997