Exponential Decay Equation Research Articles

“Blind” testing of models for predicting the 90Sr activity concentration in river systems using post-Chernobyl monitoring data

Two different models for predicting the time-dependent mobility of 90Sr in river systems have been evaluated using post-Chernobyl monitoring data for five large Belarusian rivers (Dnieper, Pripyat, Sozh, Besed and Iput) in the period between 1990 and 2004. The results of model predictions are shown to be in good agreement (within a factor of 5) with the measurements of 90Sr activity concentration in river waters over a long period of time after the accident. This verifies the relatively good accuracy of the generalised input parameters of these models which were derived primarily from measurements of 90Sr deposited after atmospheric nuclear weapons testing (NWT). For the cases studied here, the simpler AQUASCOPE model performed just as well as the more complex “Global” model which used GIS-based catchment data as an input. The reasons for this are discussed. Exponential decay equations were also curve-fitted to the data for each river to help assess the uncertainties in the predictive models.

A comparative study of the cytoskeleton binding drugs nocodazole and taxol with a mammalian cell quartz crystal microbalance biosensor: Different dynamic responses and energy dissipation effects

The quartz crystal microbalance (QCM) was used to create piezoelectric whole-cell biosensors utilizing either living endothelial cells (ECs) or the metastatic human mammary cancer cell line MDA-MB-231 adhering to the gold QCM surface under in vitro growth conditions. We utilized the whole-cell QCM biosensors for the detection of the effects of varying concentrations of the microtubule binding drugs taxol and nocodazole by measuring changes in the QCM steady state frequency (Δ f) and motional resistance (Δ R), shift values. Using 0.11–50 μM nocodazole, we observed the Δ f shift values of the biosensors, consisting of 20,000 ECs, to decrease significantly in magnitude (nearly 100%) to a limiting value, in a dose-dependent fashion, over a 5- to 6-h incubation period following drug addition. This effect is consistent with nocodazole’s known disruption of intracellular microtubules. On the other hand, 10 μM taxol caused little alteration in Δ f over the same time period, consistent with its microtubule hyperstabilization effect. When the EC QCM biosensor Δ f shift values were normalized by the number of ECs found firmly attached to the QCM surface via trypsin removal and electronic counting, the dose curve was shifted to lower nocodazole concentrations, resulting in a more sensitive drug biosensor. The kinetics of the Δ f decrease with increasing nocodazole concentrations measured by the EC QCM biosensor was found to be similar at all drug concentrations and was well fit by a single first-order exponential decay equation. For all nocodazole doses, t 0.5 was invariant, averaging t 0.5 = 0.83 ± 0.14 h. These data demonstrate that a single dynamic sensing system within the cell, the microtubules, is disrupted by the addition of nocodazole and this process is sensed by the cell QCM biosensor. This interpretation of the data was confirmed by a fluorescence light microscopy investigation of ECs undergoing treatment with increasing nocodazole doses using a fluorescent antibody to α-tubulin. These studies revealed a corresponding loss of the spread morphology of the cells, concomitant with a rearrangement of the extended native microtubules into increasingly large aggregates with the cells eventually lifting from the surface in significant numbers at 50 μM. At 6 μM nocodazole, partial reversibility of the EC QCM biosensor was demonstrated. These results indicate that the EC QCM biosensor can be used to detect and study EC cytoskeleton alterations and dynamics. We suggest the potential of this cellular biosensor for the real-time identification or screening of all classes of biologically active drugs or biological macromolecules that affect cellular attachment and cellular spreading, regardless of their molecular mechanism of action.

Do gravel bed river size distributions record channel network structure?

Bed load sediment particles supplied to channels by hillslopes are reduced in size by abrasion during downstream transport. The branching structure of the channel network creates a distribution of downstream travel distances to a given reach of river and thus may strongly influence the grain size distribution of the long‐term bed load flux through that reach. Here we investigate this hypothesis, using mass conservation and the Sternberg exponential decay equation for particle abrasion, to predict bed material variability at multiple scales for both natural and artificial drainage networks. We assume that over a sufficiently long timescale, no net deposition occurs and that grains less than 2 mm are swept away in suspension. We find that abrasion during fluvial transport has a surprisingly small effect on the bed load sediment grain size distribution, for the simple case of spatially uniform supply of poorly sorted hillslope sediments. This occurs because at any point in the channel network, local resupply offsets the size reduction of material transported from upstream. Thus river bed material may essentially mirror the coarse component of the size distribution of hillslope sediment supply. Furthermore, there is a predictable distance downstream at which the bed load grain size distribution reaches a steady state. In the absence of net deposition due to selective transport, large‐scale variability in bed material, such as downstream fining, must then be due primarily to spatial gradients in hillslope sediment production and transport characteristics. A second key finding is that average bed load flux will tend to stabilize at a constant value, independent of upstream drainage area, once the rate of silt production by bed load abrasion per unit travel distance is equal to the rate of coarse sediment supply per unit channel length (q). Bed load flux equilibrates over a distance that scales with the inverse of the fining coefficient in the abrasion rate law (α) and can be approximated simply as q/3α. Thus the efficiency of particle abrasion sets a fundamental length scale, shorter for weaker rocks and longer for harder rocks, which controls the expression in the river bed of variability in sediment supply. We explore the role of the abrasion length scale in modulating the influence of sediment supply variability in a number of channel network contexts, including individual tributary junctions, a sequence of tributary inputs along a main stem channel, and variable basin shapes and network architecture as expressed by the width function. These findings highlight the need for both data and theory that can be used to predict the grain size distributions supplied to channels by hillslopes.

Fault-scarp degradation modeling in central Greece: The Kaparelli and Eliki faults (Gulf of Corinth) as a case study

Abstract Morphologic analysis of fault-scarps of known age, combined with data from palaeoseismological trenches, is used to determine the mass diffusivity ( c ) for central Greece. Seventeen scarp profiles were accurately measured, in areas ruptured during two strong seismic events: the Eliki and Kaparelli areas within the Gulf of Corinth. Application of the linear diffusion model to our data showed that the diffusion coefficient c decreases with time from a mean value of 6.99 ± 2.03 m 2 /ka in fault-scarps formed 23 years ago (Kaparelli fault) to 1.167 ± 1.038 m 2 /ka in scarps formed 145 years ago (Eliki area), consistent with an exponential decay equation. The relatively high values of c indicate a young fault-scarp, representing the initial stages of the degradation process. Mass diffusivity values display irregularities and increase locally in composite fault-scarps (from 0.2 to 2.45 m 2 /ka). The mass diffusivity coefficient in a specific area appears to retain a memory of the geometric features of the most recent events. In the case of multiple-event fault-scarps, the mass diffusivity constant c yields lower values for a long-term estimate than that of the most recent event taken individually. We conclude that morphotectonic analysis of fault-scarps integrated with palaeoseismic reconstructions can be a valuable method for age determination of active structures and the estimation of potential hazards in tectonically active areas.

Role of Chloride Ions in Modulation of the Interaction between von Willebrand Factor and ADAMTS-13

The degradation of von Willebrand factor (VWF) depends on the activity of a zinc protease (referred to as ADAMTS-13), which cleaves VWF at the Tyr(1605)-Met(1606) peptide bond. Little information is available on the physiological mechanisms involved in regulation of AD-AMTS-13 activity. In this study, the role of ions on the ADAMTS-13/VWF interaction was investigated. In the presence of 1.5 m urea, the protease cleaved multimeric VWF in the absence of NaCl at pH 8.00 and 37 degrees C, with an apparent k(cat)/K(m) congruent with 3.4 x 10(4) M(-1) s(-1), but this value decreased by approximately 10-fold in the presence of 0.15 M NaCl. Using several monovalent salts, the inhibitory effect was attributed mostly to anions, whose potency was inversely related to the corresponding Jones-Dole viscosity B coefficients (ClO(4)(-) > Cl(-) > F(-)). The specific inhibitory effect of anions was due to their binding to VWF, which caused a conformational change responsible for quenching the intrinsic fluorescence of the protein and reducing tyrosine exposition to bulk solvent. Ristocetin binding to VWF could reduce the apparent affinity and reverse the inhibitory effect of chloride. We hypothesize that, after secretion into the extracellular compartment, VWF is bound by chloride ions abundantly present in this milieu, becoming unavailable to proteolysis by AD-AMTS-13. Shear forces, which facilitate GpIbalpha binding (this effect being artificially obtained by ristocetin), can reverse the inhibitory effect of chloride, whose concentration gradient across the cell membrane may represent a simple but efficient strategy to regulate the enzymatic activity of ADAMTS-13.

Growth versus metabolic tissue replacement in mouse tissues determined by stable carbon and nitrogen isotope analysis

Stable-isotope signatures in animal tissues presumably reflect the local food web. However, that assumption may be complicated by differential nutrient routing, fractionation, and the possibility that large organisms are not in isotopic equilibrium with seasonally available food sources. Additionally, the rate at which organisms incorporate the isotopic signature of a food is largely unknown. In this study we assessed the rate of carbon- and nitrogen-isotope turnover in liver, muscle, and blood in mice (Mus musculus L., 1758) following a diet change. We report the proportion of tissue turnover caused by growth versus that caused by metabolic tissue replacement. Growth accounted for approximately 10% of observed tissue turnover in adult mice. Blood carbon had the shortest half-life (16.9 days), followed by muscle carbon (23.9 days). Liver carbon turnover, which was slower than blood and muscle carbon turnovers, was not as well described by the exponential decay equations. All tissues primarily reflect the protein carbon signature rather than the carbohydrate carbon signature. The nitrogen signature in all tissues was enriched by 3‰–5‰ over their diets' nitrogen signature, depending on tissue type, and the isotopic turnover rates of nitrogen in blood and muscle were comparable with those observed for carbon.

Validation of the Arya and Paris Water Retention Model for Brazilian Soils

The Arya and Paris (AP) model predicts soil water retention curves from soil particle‐size distribution (PSD) data based on the similarity between these two functions. The AP model estimates pore radius (ri) from the radius (Ri) of spherical particles by scaling pore length with a parameter α. This paper evaluates the performance of the AP model with representative Brazilian soil types using three constant α values: α = 1.38, 0.938 (literature values), and 0.977, (obtained in the present work); and a α‐variable approach, where α is determined as a function of soil water content (θ). The study was performed with 104 soil samples collected in three sites. The soil PSD curves were obtained with an automatic soil particle analyzer based on the attenuation of γ‐ray by dispersed soil particles falling in a liquid medium and the soil water retention were measured with tension table and Richard chamber methods. The best mathematical representation of the α = f(θ) relationship was obtained with a first‐order exponential decay equation [α = 0.947 + 0.427exp(−θ/0.129)] that provided values of α in the range from 1.37 (θ = 0 m3 m−3) to 0.96 (θ = 0.6 m3 m−3). The root mean square deviation values of estimated and measured θ were 0.062 m3 m−3 for α = f(θ), 0.073 m3 m−3 for α = 0.977, 0.080 m3 m−3 for α = 0.938, and 0.136 m3 m−3 for α = 1.38. Therefore, for these set of soils the α‐variable approach and the constant ones using 0.977 and 0.938 presented the best estimation for the soil water retention relationships.

Novel Mechanism of Inhibition of HIV-1 Reverse Transcriptase by a New Non-nucleoside Analog, KM-1

2-Naphthalenesulfonic acid (4-hydroxy-7-[[[[5-hydroxy-6-[(4 cinnamylphenyl)azo]-7-sulfo-2-naphthalenyl]amino]-carbonyl]amino]-3-[(4-cinnamylphenyl)]azo (KM-1)) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that was designed to bind at an unconventional site on human immunodeficiency virus type 1 reverse transcriptase (RT) (Skillman, A. G., Maurer, K. W., Roe, D. C., Stauber, M. J., Eargle, D., Ewing, T. J., Muscate, A., Davioud-Charvet, E., Medaglia, M. V., Fisher, R. J., Arnold, E., Gao, H. Q., Buckheit, R., Boyer, P. L., Hughes, S. H., Kuntz, I. D., and Kenyon, G. L. (2002) Bioorg. Chem. 30, 443-458). We have investigated the mechanism by which KM-1 inhibits wild-type human immunodeficiency virus type 1 RT by using pre-steady state kinetic methods to examine the effect of KM-1 on the parameters governing the single nucleotide incorporation catalyzed by RT. Analysis of the pre-steady-state burst phase of dATP incorporation showed that KM-1 decreased the amplitude of the reaction as previously shown for other NNRTIs, because of the slow equilibration of the inhibitor with RT. In the ternary enzyme-DNA-KM-1 complex (E-DNA-I), incorporation of the next nucleotide onto the primer is blocked. However, unlike conventional NNRTIs, the inhibitory effect was caused primarily by weakening the DNA binding affinity and displacing DNA from the enzyme. Wild-type RT binds a 25/45-mer DNA duplex with an apparent K(d) of 3 nm, which was increased to 400 nm upon saturation with KM-1. Likewise, the apparent K(d) for KM-1 binding to RT increased at higher DNA concentrations. We therefore conclude that KM-1 represents a new class of inhibitor distinct from nevirapine and related NNRTIs. KM-1 can bind to RT in both the absence and presence of DNA but weakens the affinity for DNA 140-fold so that it favors DNA dissociation. The data suggest that KM-1 distorts RT conformation and misaligns DNA at the active site.

Turbulent Drag Reduction Efficiency and Mechanical Degradation of Poly(Acrylamide)

Turbulent drag reduction (DR) efficiency and mechanical degradation of high‐molecular‐weight poly(acrylamide) (PAAM) was investigated in a rotating disk apparatus. Drag reduction efficiency of PAAM was measured as a function of rotational speed, polymer concentration, and temperature and then compared with that of poly(ethylene oxide) (PEO). The PAAM exhibited relatively high shear resistance, and its mechanical degradation behavior in a turbulent flow was examined by using both an exponential and a fractional exponential decay equation.

Effect of management history and temperature on the mineralization of methylene urea in soil

A soil incubation and a greenhouse study on processing tomato were used to test the effects of soil temperature and the size and activity of the soil microbial biomass (SMB) on the degradation (mineralization) rate of a slow-release N fertilizer, methylene urea (MU), a condensation product of urea and formaldehyde. The mineralization rates of three MUs: Short (S), Medium (M), and Long (L) with different water solubilities were measured at two temperatures in a soil with low (fallow, F) and high (cover crop, CC) microbial activity. In the greenhouse study, the fate of fertilizer N was followed using 15N-urea and 15N-MU. The fertilizer N efficiency calculated for urea using the 15N mass balance approach was 93 and 85% compared with 65 and 67% for MU-S in F and CC soils, respectively. During six months of incubation, 52 and 63% of MU-S N was mineralized at 20 and 30 °C, respectively. The accumulated N data suggested that the degradation of all three MU types followed first-order reaction kinetics. The reaction rates were similar for all three MUs and increased with increasing temperature. However, fitting discrete, non-accumulated data revealed that MU mineralization is more complex and cannot be modeled with simple exponential decay equations. The size and activity of SMB did not affect the mineralization rate of MU-N under laboratory or greenhouse conditions. Interestingly, Activity Index (AI), defined as the slowly available pool of MU-N, was not a reliable indicator for the mineralization rate and plant availability of MU-N.

Modeling Wound‐induced Respiration of Fresh‐cut Carrots (Daucus carota L.)

ABSTRACT A mechanistic model based on synthesis and inactivation of enzymes, associated to the respiration pathway, was proposed to describe wound‐induced respiration of fresh‐cut produce. Carrots (Daucus carota L.) were cut into slices, sticks, a combination of both, and shreds to obtain different wounding intensities, defined by the ratio of new area created to tissue weight (A/W). Respiration rates obtained at 10°C showed a typical increase, a maximum peak, and a decrease until reaching steady state. A 2‐phase exponential decay equation described the process, with the obtained key parameters relating to A/W. This model can be used to understand wound‐induced respiration and the possible implications in produce quality changes and packaging design.

Effects of intensity of repetitive acoustic stimuli on neural adaptation in the ventral cochlear nucleus of the rat.

To study neural adaptation as a function of stimulus intensity, auditory near-field evoked potentials were recorded from the ventral cochlear nucleus in awake Long Evans rats. Responses to 250-ms trains of repetitive clicks (pulse rates ranging from 100 to 1000 pulses per second) were collected at stimulus intensities of 5, 10, 30, 50 and 70 dB SPL. The amplitude of the first negative (N1) component of the average evoked potentials to individual pulses in the train was measured by using a subtraction method. The N1 responses were normalized with respect to the highest cochlear nucleus potential observed in the train, and then plotted as a function of click position in the train. As expected, the general trend of the curves was an exponential decay reaching a plateau more or less rapidly as a function of both intensity and rate of stimulation. Fitting these curves with exponential decay equations revealed that the rapid time constant decreased for increasing stimulus intensities whereas the short-term time constant is relatively independent of intensity. The amount of adaptation (expressed as the ratio of the plateau to the first peak amplitude) was substantially less prominent at low intensities (5-10 dB SPL) and low rates (100-200 pulses per second) than at higher intensities and high rates. These results indicate that adaptation patterns obtained in the ventral cochlear nucleus by using near-field evoked potentials exhibit properties comparable to those already present at the level of the auditory nerve.

A note on the suitability of an exponential equation to characterize pH decline corrected for muscle temperature in bovine muscle early post mortem

Identifying rates of pH and temperature decline associated with bovine M. longissimus thoracis et lumborum (LTL) tenderness would assist beef carcass processors to produce a high quality product. An exponential decay equation was used to describe the early post mortem declines of pH values adjusted to 20 °C and their concomitant temperature data from 371 bovine LTL muscles. Approximately 10% of the muscles in the database exhibited non-exponential pH decline post mortem and the model did not converge for these muscles. For convergent muscles, the model predicted pH values homoscedastically with no significant bias. Limits of agreement analysis showed that the model predicted the adjusted pH value within 0.14 pH units. Prediction error was evenly distributed and the intra-class correlation coefficent was high ( r I=0.98). When applied to the muscle temperature data, the exponential equation predicted temperature values heteroscedastically. These results indicated that this exponential equation characterised the post mortem pH decline in LTL muscle sufficiently well for researchers to use the exponential constant ( k) of decay to describe this decline with time or muscle temperature. The equation was not appropriate for describing the decline of muscle temperature with time post mortem in this data set.

The Influence of Hydrogen and Tensile Stress on Passivity of Type 304 Stainless Steel

The effects of hydrogen and applied tensile stress on the passivity of type 304 stainless steel were investigated in borate buffer solutions containing chloride ions. Hydrogen was cathodically charged into specimens by applying a cathodic constant current density. Applied tensile stress is found to have no obvious effect on the breakdown potential of uncharged specimens unless the concentration of chloride ions in the borate buffer solution is high. Hydrogen significantly decreases the breakdown potential. For charged specimens at various tensile stress levels, breakdown potentials are well fitted as a function of charging current density using the second-order exponential decay equation. At a certain charging current density, the breakdown potential and applied tensile stress approximately follow a linear relationship. The slope of the straight line becomes more negative in the intermediate charging current density range than in both low and high current density ranges, indicating that tensile stress has a more obvious promoting effect on the breakdown of passive films formed on specimens charged in this current density range. It was observed that hydrogen increases the anodic current density in the passive range. Applied tensile stress affects the anodic current density in various degrees for the specimens charged at different charging current densities. © 2003 The Electrochemical Society. All rights reserved.

The blood volumes of the primary and secondary circulatory system in the Atlantic cod Gadus morhua L, using plasma bound Evans Blue and compartmental analysis.

The volume of the primary (PCS) and secondary (SCS) circulatory system in the Atlantic cod Gadus morhua was determined using a modified dye dilution technique. Cod (N=10) were chronically cannulated in the second afferent branchial artery with PE-50 tubing. Evans Blue dye was bound to harvested fish plasma at a concentration of 1 mg dye ml(-1) plasma, and injected at a concentration of 1 mg kg(-1) body mass. Serial sampling from the cannula produced a dye dilution curve, which could be described by a double exponential decay equation. Curve analysis enabled the calculation of the primary circulatory and total distribution volume. The difference between these volumes is assumed to be the volume of the SCS. From the dilution curve, it was also possible to calculate flow rates between and within the systems. The results of these experiments suggest a plasma volume in the PCS of 3.42+/-0.89 ml 100 g(-1) body mass, and in the SCS of 1.68+/-0.35 ml 100 g(-1) body mass (mean +/- S.D.) or approximately 50% that of the PCS. Flow rates to the SCS were calculated as 2.7% of the resting cardiac output. There was an allometric relationship between body mass and blood volumes. Increasing condition factor showed a tendency towards smaller blood volumes of the PCS, expressed as percentage body mass, but this was not evident for the volume of the SCS.

Stress Relaxation during Isothermal Annealing at Elevated Temperatures in Electroplated Cu Films

ABSTRACTDeformation mechanisms of electroplated Cu thin films on TaN/SiO2/Si were investigated by performing isothermal annealing above 200 °C. Stress relaxation behavior during isothermal annealing was analyzed by curve fitting using exponential decay equations. During heating, fast relaxation and subsequent slow relaxation processes were observed. In contrast, during cooling, only slow relaxation process was observed. Among possible mechanisms for stress relaxation, diffusion creep was found to be the most plausible mechanism based on the obtained values of the activation energy. It was suggested that the slow relaxation process observed both in the heating and in the cooling processes was attributed to a grain-boundary diffusion creep. On the other hand, the fast relaxation process observed during heating was attributed to a surface-diffusion controlled mechanism. The surface diffusion mechanism was considered to be characteristic to Cu thin films that did not form stable surface oxide.

Determination of toxicokinetic parameters for bioconcentration of water-soluble fraction of petroleum hydrocarbon associated with no. 0 diesel in Changjiang estuary and Jiaozhou bay: model versus mesocosm experiments.

A method is proposed for determination of toxicokinetic parameters for bioconcentration by phytoplankton of the water-soluble fraction (WSF) of petroleum hydrocarbon (PH) associated with No. 0 diesel, in which WSF-PH concentration in phytoplankton cells, C(A(d)), is estimated by subtracting concentration in water (S-bottle) containing a phytoplankton sample from that in a C-bottle without phytoplankton. It was demonstrated that C(A(d)) agrees well with the concentration found by direct ultrasonication extraction of collected cells, C(A(ind)) ( r = 0.88, p < 0.0001), and its uncertainty was about 17.6%. Mesocosms in 25-m3 ethylene vinyl acetate or 4-m3 polyethylene bags were performed at two sites in China: Changjiang Estuary in spring/summer 1998 and Jiaozhou Bay in autumn 1999 and spring/summer 2000. The experiments were designed to determine toxicokinetic parameters, including specific rates of uptake and elimination, and bioconcentration factor (BCF), for bioconcentration of WSF-PH by phytoplankton. A modified kinetic two-compartment model for bioconcentration of WSF-PH by phytoplankton was developed to estimate the toxicokinetic parameters. In the model, the influence of phytoplankton growth on bioconcentration and WSF-PH decline due to biotic and abiotic processes other than bioconcentration, such as volatilization, microbial degradation, phytolysis, and sorption expressed as an exponential-decay equation, are taken into account. Size-dependent BCF was observed in the laboratory experiment. BCFs were 1.0 x 10(4) in summer in Changjiang Estuary, 1.6 x 10(4) in summer, and 1.1 x 10(4) in autumn in Jiaozhou Bay. The difference in BCF may be interpreted by its size dependence.

Application of an exponential model to early postmortem bovine muscle pH decline

An exponential decay equation was used to describe the decline of pH in bovine M. longissimus thoracis et lumborum (LTL) muscle postmortem. Goodness of fit of the equation was tested by convergence of model criterion and contrasting predicted against expected pH values of LTL muscles from 24 Bos taurus steer carcasses measured 40, 60, 80, 120, 185 and 1440 min after stunning. The model was fitted to pH values measured, as well as to the measured pH values adjusted to arbitrary constant temperatures of 10, 20 or 30°C. The model failed to converge for 46% of the muscles sampled in the data sets with measured pH. The model converged for 100% of the muscles with pH values adjusted to 10, 20 or 30°C. Limits of agreement, heteroscedasticity and intraclass correlation analyses showed little difference in the fit of the model to pH values adjusted to either 10, 20 or 30°C. Fitting this model to pH data adjusted to 20°C will enable comparison of rates of pH decline between muscles of different temperatures postmortem or laboratory homogenates and facilitate relation of pH decline rate to aspects of beef quality.

A Quartz Crystal Microbalance Cell Biosensor: Detecting Nocodazole Dependent Microtubule Disruption Dynamics In Living Cells

ABSTRACTA Quartz Crystal Microbalance (QCM) was used to create a biosensor utilizing living adherent endothelial cells (ECs) as the biological sensing element. This EC QCM biosensor detected the effect of varying concentrations of nocodazole, a microtubule binding and disrupting drug, on the adherent cells as they altered the underlying QCM device state frequency, Δf, and motional Resistance, ΔR, shift values. Over the dose range 0.11-15 μM nocodazole, the Δf shift values decreased significantly in magnitude in a dose dependent fashion over a 5-6 hr incubation period following drug addition to a limiting value, with a 900 nM midpoint. This effect is consistent with nocodazole's known dose dependent effect on the disruption of microtubules. At all drug concentrations, the relative Δf decrease with time was found to be very similar and well fit by a single exponential decay equation. For all nocodazole doses, t 0.5 was invariant, averaging t 0.5 = 0.83 ± 0.14 hr. These data demonstrate that a single dynamic sensing system within the cell, the microtubules, responds to the addition of nocodazole and its response can be quantified by the biosensor. These results indicate that the EC QCM biosensor can be used to detect EC cytoskeletal alterations and dynamics and may be a valuable screening method for all classes of biologically active drugs or biological macromolecules that affect cytoskeleton perturbations or cellular attachment.

T2 Relaxometry Can Lateralize Mesial Temporal Lobe Epilepsy in Patients with Normal MRI

In unselected patients with intractable temporal lobe epilepsy (TLE), approximately 15% do not have detectable hippocampal atrophy on MRI. The purpose of this study was to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable TLE, who do not demonstrate hippocampal atrophy on volumetric MRI (MRIV). We selected 14 patients with unilateral TLE who had unilateral atrophy and 11 patients with unilateral TLE who had no evidence of atrophy on MRIV. Images were acquired on a 1.5 T MR scan using a dual echo sequence with 23 contiguous oblique coronal slices in all patients and in 14 healthy subjects. Fitting a single exponential decay equation to the imaging data generated T2 maps. Averages of six slices containing the head, body, and tail of the hippocampus were used to calculate hippocampal T2 relaxation times (HT2). The epileptic focus was defined by history, video-EEG, and surgical response. All TLE patients with hippocampal atrophy and 9/11 (82%) patients with normal MRI had abnormally high HT2 ipsilateral to the epileptic focus. Bilateral abnormal HT2 were found in 6/14 (43%) of patients with unilateral hippocampal atrophy and 2/11 (18%) of patients with normal MRI. However, this increase was always greater ipsilateral to the epileptic focus. Qualitative hippocampal pathology showed gliosis and neuronal loss in 10/14 operated patients with hippocampal atrophy on MRIV and in 5/7 operated patients with normal MRI. In conclusion, hippocampal T2 mapping provides evidence of hippocampal damage in the majority of patients with intractable TLE who have no evidence of atrophy on MRI and can correctly lateralize the epileptic focus in most patients.