Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “dwell time”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2003

[Spatial and temporal characteristic of eye movement in human-computer interface design].

OBJECTIVE: To examine the related spatial and temporal characteristics of eye movement in HCI design and to provide ergonomic parameters to optimize the HCI design based on eye tracking. METHOD: Task time, selected error and timeout numbers were recorded automatically, when 12 participants were performing the task of target selection, with different object size, space and dwell time. RESULT: It was significantly found that task time was influenced by object size and dwell time, the selected error was influenced by object space and dwell time significantly. CONCLUSION: The dwell time, object size and object space are all important to optimize the HCI design based on eye tracking. We recommend that the dwell time should be 500 ms, the object size and object space should be not less than 1.5 degrees and 1.0 degrees respectively for the normal interactive systems.

Adult↗
PubMed2004

Visual scan patterns during simulated control of an uninhabited aerial vehicle (UAV).

BACKGROUND: This study investigated pilots' visual scan patterns on an uninhabited aerial vehicle (UAV) flight display that used moving textbox symbology to emulate vertical moving pointers for the primary flight instruments. METHODS: Eye tracking measurements were recorded for five instrument-rated pilots. Dwell frequencies and mean dwell times were calculated for each instrument. The efficiency of instrument information presentation was evaluated based on mean dwell times and dwell histograms. The heading indicator, a strict digital readout, was used as the reference for pair-wise comparison with the moving textbox instruments. RESULTS: Instrument dwell frequencies differed significantly (p < 0.005, alpha = 0.006) with the attitude indicator being the most frequently scanned instrument followed by the vertical speed indicator, then the airspeed, heading, and altitude indicators. There was no difference in mean dwell times (p = 0.04-0.79, alpha = 0.008) or dwell histograms between the heading indicator and the primary moving textbox instruments. Pilot scan behavior was not significantly affected (p > 0.17) by workload. Also, subjects and historical controls did not differ (p > 0.30) in their frequency of engine instrument dwells. CONCLUSION: The dwell frequencies for the primary flight instruments, particularly the vertical speed indicator, differed from those reported for more traditional aircraft. The moving textboxes required visual fixations that were typical of quantitative instruments, which is a cognitively inefficient way to present information. Pilots failed to increase engine instrument dwells in the absence of non-visual cues of engine performance, making them potentially vulnerable to missing early changes in engine performance.

Adult↗
PubMed1989

Triple-barrel structure of inwardly rectifying K+ channels revealed by Cs+ and Rb+ block in guinea-pig heart cells.

1. The hypothesis that the inwardly rectifying K+ channel consists of a triple-barrel structure was investigated. Inward currents were recorded under the blocking effects of external Cs+ or Rb+ in the cell-attached configuration of the patch-clamp technique using single ventricular cells enzymatically isolated from guinea-pig hearts. 2. Cs+ (10-100 microM) or Rb+ (20-100 microM) added to the 150 mM-K+ pipette solution induced rapid open-blocked transitions in the inward open-channel currents. In about 20% of experiments the inward current showed two intermediate current levels equally spaced between the unit amplitude and the zero-conductance level. The current fluctuated between these four levels. In the remaining experiments no obvious sublevels were observed except spontaneous ones, whose amplitudes were not always equal to one-third or two-thirds of the unit amplitude. 3. In experiments showing sublevels, the probability that the open-channel current stayed at each level was measured at various concentrations of blockers and membrane potentials. In both Cs+ and Rb+ block, the distribution of the current levels showed reasonable agreement with the binomial theorem. This finding suggests that the inwardly rectifying K+ channel is composed of three equally conductive subunits and each subunit is independently blocked by Cs+ or Rb+. 4. The dwell-time histogram in each substate was well fitted with a single-exponential function. On the assumption of the binomial model, the blocking (mu) and unblocking (lambda) rate for Cs+ and Rb+ were calculated. The value of mu was linearly proportional to the concentration of the blocking ion at a given membrane potential and increased with hyperpolarization (e-fold increase with a change of -43.5 mV in the Cs+ block). lambda was almost independent of the concentration of the blocking ion and less dependent on the membrane potential than mu. 5. The open and blocked times were calculated in experiments showing no clear sublevels. The mean open time was almost equal to the mean dwell time at the full open level in experiments showing sublevels under the same conditions. On the other hand, the mean blocked time was about two or three times longer than the mean dwell time at the zero-conductance level measured in experiments with sublevels. These results may suggest that the instant one of the three subunits is plugged by blocking ions, the remaining two subunits are closed by unknown mechanisms. 6. Our results support the hypothesis that the cardiac inwardly rectifying K+ channel is composed of three equally conductive subunits.

Animals↗
PubMed1998

Catheter deadspace: a source of error during tonometry.

Tonometry of PCO2 is a promising method for assessing the oxygen supply to demand ratio of the gastrointestinal mucosa in critically ill patients. A balloon-tipped tonometer is introduced into the stomach or sigmoid colon, and saline is instilled into the balloon. After a time to allow partial equilibration with intraluminal PCO2, saline is aspirated and PCO2 is measured. Intermittent instillation and aspiration of saline allows serial PCO2 measurements, provided correction factors are used to calculate the PCO2 value expected at full equilibration from the PCO2 values measured after short dwell times. The technique is not yet widely applied, partly because of methodological controversies. We evaluated the role of the catheter deadspace as a source of error during PCO2 tonometry. The increase in PCO2 in sigmoid-type tonometers with a normal length (normal tonometer (NT)) and in those with a 50% increase in length and thus deadspace (extended tonometer (ET)), in a saline bath at a PCO2 of 4.8 kPa was assessed. Saline dwell times were 10, 20, 30, 45, 60 and 90 min and the time-dependent PCO2 increase was determined at deadspace PCO2 values of approximately 4.0 and 8.0 kPa following contamination of the catheter deadspace after immersion in saline baths at PCO2 values of 4.8 and 9.6 kPa, respectively, before each measurement cycle. In another experiment, the tonometer was rinsed between measurement cycles to remove deadspace saline containing carbon dioxide and to obviate contamination of instilled saline. PCO2 was measured in a blood-gas analyser, taking into account measurement bias in saline. Failure to remove deadspace saline between measurement cycles resulted in an overestimation of 10% and 6% for the NT and 16% and 10% for the ET, at saline dwell times of 10 and 20 min, respectively, at a deadspace PCO2 of approximately 4.0 kPa. At a deadspace PCO2 of approximately 8.0 kPa, PCO2 was overestimated by 17%, 11% and 5% for the NT and 31%, 20% and 11% for the ET, at dwell times of 10, 20 and 30 min, respectively. Rinsing the NT/ET resulted in accurate assessment of PCO2 at all dwell times, but the dwell time-dependent increase in PCO2 was slightly slower in the ET, particularly at 10 min, after a sink effect of the increased deadspace. Hence, a previously unrecognized deadspace effect caused error during PCO2 tonometry, particularly with short dwell times. This potentially large error can be avoided by rinsing the tonometer before each measurement cycle, allowing accurate PCO2 tonometry even at 10-min saline dwell times, provided that correction factors are used that are specific for catheter size. These findings may help to widen the clinical applicability of tonometry.

Carbon Dioxide↗
PubMed1996

Determination of individual ultrafiltration time (APEX) and purification phosphate time by peritoneal equilibration test: application to individual peritoneal dialysis modality prescription in children.

Efficiency of peritoneal dialysis (PD) is dependent on adequate ultrafiltration (UF) and purification (solute clearance). These two goals apparently seem to conflict in terms of duration of dwells: short dwell time enhances UF capacity and, conversely, long dwell time enhances solute clearance. Peritoneal equilibration test (PET) allows an approach to the ultrafiltration time: the point at which the over time dialysate urea saturation and glucose desaturation curves cross, call APEX time. PET also allows an approach to the purification time: the point at which dialysate-to-plasma (D/P) concentration ratios over time are high. Because of the value of phosphate as a uremic factor of morbidity, we have chosen the time at which D/P phosphate is equal to 0.6 as a purification phosphate dwell time (PPT). A total of 17 patients were studied, over a five-year period, allowing 142 determinations. APEX times (range 18-71 min) and PPT (range 105-238 min) were spread over a wide distribution. PPT and APEX times were significantly shorter in children younger than three years of age than in children older than ten years of age. PPT were nearly four times longer than APEX times. Knowledge of these conflicting ultrafiltration and purification times should help, in our view, in the individual choice of the PD modality: if UF is the major goal, short dwell times should be used (automated PD); if purification is the major goal, long dwell times should be used, as in continuous ambulatory peritoneal dialysis; if both are the target goal, tidal PD should be discussed.

Adolescent↗
PubMed2002

Down-regulation of CD43 molecule expression on intraperitoneal neutrophils in CAPD patients with peritonitis.

To assess the release of proteases from neutrophils infiltrated into the peritoneal cavity in continuous ambulatory peritoneal dialysis (CAPD), we investigated the regulation of CD43, LAM-1 and Mac-1 expression on the neutrophil plasma membrane using FACS analysis in CAPD patients with peritonitis. Five CAPD patients with peritonitis and five CAPD patients without peritonitis were studied. CD43 expression was immunohistochemically determined in both groups of patients using flow cytometry, and comparisons were made between the two groups. Down-regulation of CD43 and LAM-1, and up-regulation of Mac-1 were demonstrated on neutrophils obtained from CAPD dialysate of peritonitis patients after 1-h dwell time. Further up-regulation of Mac-1 developed until a dwell time of 4 h. Immunoblot analysis for neutrophil lysate from dialysate showed the presence of the asialo form of CD43 molecules and their fragments, which may be produced by cleavage of the CD43 molecule at extracellular sites. The intraperitoneal neutrophils in dialysate from CAPD patients with peritonitis are continuously activated during dwell time, and proteases may be released from neutrophils into dialysate after only a short dwell time.

Adult↗
PubMed2003

Ipsilateral deficits of targeted movements after stroke.

OBJECTIVE: To test the hypotheses that targeted movements of both the ipsilateral and the contralateral extremities of stroke survivors would be prolonged compared with those from a control group without stroke, and that the ipsilateral deficit would occur in movements toward small, but not large, targets. DESIGN: Descriptive study. SETTING: Motor performance laboratory. PARTICIPANTS: Convenience sample of right-handed individuals including 10 who were more than 6 months poststroke with Fugl-Meyer Motor Assessment scores greater than 75% for the upper (UEs) and lower (LEs) extremities, and a comparison group of 20 age-matched adults without stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The average time required for the stylus, held with the hand or strapped to the foot, to travel from leaving 1 target to contacting the second target (ie, movement time) and the average time the stylus rested on the target (ie, dwell time). RESULTS: Regardless of target size, movement and dwell times for both UEs of the stroke group were prolonged compared with those of the comparison group. Regardless of target size, dwell time for both LEs of the stroke group was prolonged compared with that of the comparison group. CONCLUSIONS: After stroke, the ipsilateral extremities may show subtle deficits in targeted movements.

Activities of Daily Living↗
PubMed1984

Long-term changes in transperitoneal water transport during continuous ambulatory peritoneal dialysis.

9 patients were observed prospectively during 14-40 months 003 continuous ambulatory peritoneal dialysis (CAPD) treatment. From start of CAPD, each patient recorded dwell time, drained ultrafiltration volume (delta V), initial glucose concentration in dialysate, dialy fluid intake, body weight and blood pressure on a special form. These data, together with monthly values for albumin, urea, creatinin, phosphate, glucose and beta 2-microglobulin in plasma and in instilled dialysate, were later fed into a specially designed computer program to compare changes in the monthly mean (+/- SEM) values. During 5 episodes of peritonitis, daily changes in delta V were also computed. A long-term increase in delta V was found in 4 and a decrease in 5 patients. In all 9 patients delta V changed intermittently. All changes were most pronounced for long dwell times as compared to shorter dwell exchanges. The decrease in delta V started within the first 12 months of treatment. In the daily routine were aware of decreased ultrafiltration capacity in 3 patients only. Intermittent monthly changes in delta V could partly be correlated to changes in daily fluid intake. No correlations were found between long-term changes in delta V and fluid intake. All except 1 patient gained progressively in body weight, but without correlations to fluid balance, blood pressure and plasma albumin concentration. At the start of the observation period, most patients loosing delta V during this study appeared to have a more permeable membrane with a higher absorption rate of glucose and higher equilibration ratios for creatinine and beta 2-microglobulin in 5-hours drained dialysate as compared with the other patients. However, this was not statistically different between the two groups of patients. During the observation period, most patients with decreased delta V also increased transperitoneal solute transport, while the solute transport decreased in patients with increasing delta V, but these changes were only significant for some patients. During peritonitis, delta V decreased significantly 1 day before any other signs of peritonitis. All changes in delta V were most pronounced for long dwell times as compared with short dwell times. It is suggested that changes in ultrafiltration can be related to altered permeability of the peritoneal membrane, which appear earlier and more frequent than suggested by others, and any loss of delta V can be explained by a more permeable ('open') peritoneal membrane. It is also possible that different diseases act differently on the permeability of the peritoneal membrane.

Adult↗
PubMed2000

Glucose absorption in acute peritoneal dialysis.

OBJECTIVE: During acute peritoneal dialysis (APD), it is known that glucose found in the dialysate solution contributes to the provision of significant calories. It has been well documented in continuous ambulatory peritoneal dialysis (CAPD) that glucose absorption occurs. In APD, however, it remains unclear how much glucose absorption actually does occur. Therefore, the purpose of this study was to determine whether it is appropriate to use the formula used to calculate glucose absorption in CAPD (Grodstein et al) among patients undergoing APD. METHODS: Actual measurements of glucose absorption (Method I) were calculated in 9 patients undergoing APD treatment for >24 hours who were admitted to the intensive care unit. Glucose absorption using the Grodstein et al formula (Method II) was also determined and compared with the results of actual measurements. The data was then further analyzed based on the factors that influence glucose absorption, specifically dwell time and concentration. RESULTS: The mean total amount of glucose absorbed was 43% +/- 15%. However, when dwell time and concentration were further examined, significant differences were noted. Method I showed a cumulative increase over time. Method II showed that absorption was fixed. This suggests that with the variation in dwell time commonly seen in the acute care setting, the use of Method II may not be accurate. In each of the 2 methods, a significant difference in glucose absorption was noted when comparing the use of 1.5% and 4.25% dialysate concentrations. CONCLUSION: The established formula designed for CAPD should not be used for calculating glucose absorption in patients receiving APD because variation in dwell time and concentration should be taken into account. Because of the time constraints and staffing required to calculate each exchange individually, combined with the results of the study, we recommend the use of the percentage estimate of 40% to 50%.

Absorption↗
PubMed2006

Optimization of HDR brachytherapy dose distributions using linear programming with penalty costs.

Prostate cancer is increasingly treated with high-dose-rate (HDR) brachytherapy, a type of radiotherapy in which a radioactive source is guided through catheters temporarily implanted in the prostate. Clinicians must set dwell times for the source inside the catheters so the resulting dose distribution minimizes deviation from dose prescriptions that conform to patient-specific anatomy. The primary contribution of this paper is to take the well-established dwell times optimization problem defined by Inverse Planning by Simulated Annealing (IPSA) developed at UCSF and exactly formulate it as a linear programming (LP) problem. Because LP problems can be solved exactly and deterministically, this formulation provides strong performance guarantees: one can rapidly find the dwell times solution that globally minimizes IPSA's objective function for any patient case and clinical criteria parameters. For a sample of 20 prostates with volume ranging from 23 to 103 cc, the new LP method optimized dwell times in less than 15 s per case on a standard PC. The dwell times solutions currently being obtained clinically using simulated annealing (SA), a probabilistic method, were quantitatively compared to the mathematically optimal solutions obtained using the LP method. The LP method resulted in significantly improved objective function values compared to SA (P = 1.54 x 10(-7)), but none of the dosimetric indices indicated a statistically significant difference (P < 0.01). The results indicate that solutions generated by the current version of IPSA are clinically equivalent to the mathematically optimal solutions.

Algorithms↗
PubMed1986

Factors affecting Staphylococcus epidermidis growth in peritoneal dialysis solutions.

Staphylococcus epidermidis is the most frequent cause of peritonitis complicating continuous ambulatory peritoneal dialysis. We studied factors that might influence the growth of S. epidermidis in commercially available peritoneal dialysis solution (PDS). Test strains were inoculated into PDS and incubated overnight at 37 degrees C. Samples were removed at appropriate intervals, bacterial counts were performed, and growth curves were constructed. We studied the effects of various osmolarities, the neutralization and acidification of fresh and spent PDS, and the effect of intraperitoneal dwell time on the ability PDS to support growth of S. epidermidis. In fresh PDS, numbers of bacteria remained constant after 24 h. No significant differences in growth were observed among PDS with 0.5, 1.5, 2.5, and 4.25% glucose. Neutralizing acidic fresh PDS had no effect on bacterial growth. However, growth did occur in spent PDS. PDS which was recovered after only 2 h in the peritoneal cavity supported growth to the same extent as did PDS recovered after 4 to 6 h. Mean log10 changes after 24 h of incubation were as follows: for fresh PDS, -1.3; after 2 h dwell time, 2.9; after 4 h dwell time, 1.9; and after 6 h dwell time, 1.3. Acidification of spent PDS to less than pH 6.35 produced less rapid growth; mean log10 increases after 24 h of incubation were 1.9 for pH 7.75, 1.6 for pH 6.35, 0.6 for pH 5.75, and 0.7 for pH 4.95. Fresh PDS of all available osmolarities neither supported the growth of S. epidermidis nor was bactericidal. Spent PDS supported bacterial growth, and this growth was partly independent of the neutralization which occurred during the dialysis.

Amino Acids↗
PubMed2001

Ultrasound to decontaminate heavy metals in dredged sediments.

Sediments contaminated with heavy metals due to past disposal practices threaten the environment and require remediation. This study was an attempt to develop a technology to decontaminate heavy metals in dredged sediments using ultrasound coupled with vacuum pressure. A set of laboratory scale experiments were conducted using dredged sediments obtained from New York/New Jersey harbor. This sediment sample is considered as category III, a material that failed to meet USEPA requirements for toxicity or bioaccumulation, and required secure disposal. Acoustic cavitation due to ultrasound energy coupled with vacuum pressure was used to facilitate the removal of chromium (the selected metal contaminant) from the sediments. Full factorial experimental designs were performed to evaluate the above treatment technique and to optimize the processes. Two coupled processes were used to separate and to treat both coarse (Process #1) and fine (Process #2) fractions of sediments. Selected variables for evaluation of Process #1 were ultrasound power, soil-to-water ratio, vacuum pressure and dwell time, and for Process #2 were ultrasound power, soil-to-water ratio and dwell time. Laboratory scale experiments were carried out with various combinations of these parameters according to the factorial design. The optimum removal was found to be 92% with the parameter levels at 1200W power, 1:15 soil-to-water ratio, 15 psi vacuum pressure and 15 min of dwell time. After the application of Process #2 for fine sediments it was found that the fines were separated into silt and clay. Only the silt faction had a considerable metal removal while the clay fraction was insensitive to the treatment. A maximum removal of 83% was obtained for silt fraction when factor levels were at 1200W power, 1:50 soil-to-water ratio and 90 min of dwell time. Further analysis of clay fraction showed that the chromium in clay is immobile and stable. The toxicity characteristic leaching procedure (TCLP) test on clay fraction confirmed that the treated clay fraction is safe to dispose. The study showed that the proposed treatment technique is effective and economical for sediments with lower clay contents.

Cost-Benefit Analysis↗
PubMed2003

Discrete and cyclical units of action in a mixed target pair aiming task.

Two experiments addressed the issue of discrete and cyclical units as possible basic units of action that might be used to construct complex actions based on task constraints. The experiments examined the influence of low and high accuracy constraints on the end-effector's motion in rhythmical aiming movements. Both experiments utilized a Fitts-type task under three accuracy constraints: (1) big target pairing-low index of movement difficulty (ID), (2) small target pairing-high ID, and (3) mixed target pairing-one target high ID and the other target low ID. Experiment I was a 1-degree-of-freedom ( df) task that required subjects to crossover the inside edge of targets in a target pair using elbow flexion-extension motions. Experiment II used a 2- df task that required subjects to tap back and forth between targets in a target pair using a hand-held stylus. In both experiments, end-effector motion in the low ID condition was cyclical with the end-effector's motion consistent with a limit-cycle attractor description, while in the high ID condition end-effector motion was discrete and consistent with a fixed-point attractor description. The mixed target pairing produced both discrete and cyclical features in the end-effector's dynamics that suggested a functional linking of discrete and cyclical units of action as the optimal movement solution. Evidence supporting the above statements was found in the kinematic measures of movement time (MT), dwell time, proportion of MT accelerating and decelerating, and in a measure of harmonicity (Guiard 1993, Acta Psychol 82:139-159; Guiard 1997, Hum Mov Sci 16:97-131). Extended practice in the mixed target condition revealed a bias towards cyclical motion with practice. The results demonstrate that discrete and cyclical motion, represented as limit-cycle and fixed-point attractors, are basic units of action that the motor system uses in constructing more complex action sequences. The results are discussed with reference to coordinative structures and the generalized motor program as basic units of action. Issues pertaining to visual feedback processing and movement braking in rapid aiming tasks are also discussed.

Acceleration↗
PubMed2006

A hand-over-hand diffusing model for myosin-VI molecular motors.

Single molecules of dimeric myosin-VI have been demonstrated to be able to move processively towards the pointed end of actin filament with a mean step size of approximately 36 nm. Here we present a hand-over-hand diffusing mechanism for this unidirectional movement. Based on this mechanism, its dynamical behaviors such as the step-size distribution, dwell-time distributions and mean dwell time at various ATP and ADP concentrations and under various loads are studied in detail. The calculated results show good agreement with previous experimental results. The processive movement of mutant myosin-V with its neck domains truncated to only one IQ motif can also be explained by using this hand-over-hand diffusing model.

Actins↗
PubMed2002

Optimizing the multielement analysis capabilities of an ICP quadrupole mass spectrometer using electrothermal vaporization sample introduction.

A mathematical solution and an experimental procedure are described for calculating the maximum number of transient signals, such as those obtained using ETV sample introduction into an ICPMS, that can be monitored by a scanning spectrometer, such as a quadrupole mass analyzer. The total number of masses that can be monitored per ETV firing is shown to be dependent on the values chosen for data collection (i.e., scan time and dwell time) and the necessary limits of detection required by the method. The theory shows the effect that statistical noise, peak shapes, and inconsistent peak appearance times have on the overall variance calculated for the sample concentration based on total counts or "peak area". Also included in the variance calculation is the contribution made by the autosampler as an example of one type of error that is not associated with the data collection parameters. The theory is validated by two experiments where 21 and 68 transient signals are monitored per ETV firing; and as predicted, a 10 ppb sample is accurately quantified with precision better than 9% in both cases.

Journal Article↗
PubMed2006

The SPECTRUM population model of the impact of screening and treatment on U.S. breast cancer trends from 1975 to 2000: principles and practice of the model methods.

OBJECTIVE: This stochastic simulation model was developed to estimate the impact of screening and treatment diffusion on U.S. breast cancer mortality between 1975 and 2000. MODELING APPROACH: We use an event-driven continuous-time state transition model. Women who are destined to develop breast cancer may be screen detected, present with symptoms, or die of other causes before cancer is diagnosed. At presentation, the cancer has a stage assigned on the basis of mode of detection. Cancers are assumed to be estrogen receptor (ER) positive or negative. Data on screening and treatment diffusion are based on national datasets; other parameters are based on a synthesis of the evidence available in the literature. MODEL METHODS: The model is calibrated to predict incidence and stage distribution (in situ, local, regional, and distant). Other than screening or treatment, background events that affect mortality are not explicitly modeled but are captured in the deviation between model projections of mortality trends and actual trends. We assume that: 1) tumors progress more slowly in older age groups, 2) screen- and clinically detected disease have the same survival conditional on age and stage, 3) women do not die of breast cancer within the "lead time" period, 4) screening benefits are captured by shifts in stage at diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical sojourn time and dwell times in each of the clinical stages are stochastically independent. MODEL RESULTS: Dissemination of screening and therapeutic advances had a substantial impact on mortality trends. We estimate that, by the year 2000, diffusion of screening lowered mortality by 12.4% and treatment improvements and dissemination lowered mortality by 14.6%. CONCLUSIONS: Models such as this one can be useful to translate clinical trial findings to general populations. This model can also be used inform policy debates about how to best achieve targeted reductions in breast cancer morbidity and mortality.

Adult↗
PubMed2001

Dihydroxyeicosatrienoic acids are potent activators of Ca(2+)-activated K(+) channels in isolated rat coronary arterial myocytes.

1. Dihydroxyeicosatrienoic acids (DHETs), which are metabolites of arachidonic acid (AA) and epoxyeicosatrienoic acids (EETs), have been identified as highly potent endogenous vasodilators, but the mechanisms by which DHETs induce relaxation of vascular smooth muscle are unknown. Using inside-out patch clamp techniques, we examined the effects of DHETs on the large conductance Ca(2+)-activated K(+) (BK) channels in smooth muscle cells from rat small coronary arteries (150-300 microM diameter). 2. 11,12-DHET potently activated BK channels with an EC(50) of 1.87 +/- 0.57 nM (n = 5). Moreover, the three other regioisomers 5,6-, 8,9- and 14,15-DHET were equipotent with 11,12-DHET in activating BK channels. The efficacy of 11,12-DHET in opening BK channels was much greater than that of its immediate precursor 11,12-EET. In contrast, AA did not significantly affect BK channel activity. 3. The voltage dependence of BK channels was dramatically modulated by 11,12-DHET. With physiological concentrations of cytoplasmic Ca(2+) (200 nM), the voltage at which the channel open probability was half-maximal (V(1/2)) was shifted from a baseline of 115.6 +/- 6.5 mV to 95.0 +/- 10.1 mV with 5 nM 11,12-DHET, and to 60.0 +/- 8.4 mV with 50 nM 11,12-DHET. 4. 11,12-DHET also enhanced the sensitivity of BK channels to Ca(2+) but did not activate the channels in the absence of Ca(2+). 11,12-DHET (50 nM) reduced the Ca(2+) EC(50) of BK channels from a baseline of 1.02 +/- 0.07 microM to 0.42 +/- 0.11 microM. 5. Single channel kinetic analysis indicated that 11,12-DHET did not alter BK channel conductance but did reduce the first latency of BK channel openings in response to a voltage step. 11,12-DHET dose-dependently increased the open dwell times, abbreviated the closed dwell times, and decreased the transition rates from open to closed states. 6. We conclude that DHETs hyperpolarize vascular smooth muscle cells through modulation of the BK channel gating behaviour, and by enhancing the channel sensitivities to Ca(2+) and voltage. Hence, like EETs, DHETs may function as endothelium-derived hyperpolarizing factors.

8,11,14-Eicosatrienoic Acid↗
PubMed1992

Voltage-dependent gating mechanism for single fast chloride channels from rat skeletal muscle.

1. A voltage-dependent gating mechanism for the fast Cl- channel was developed from the analysis of single-channel current records obtained with the patch clamp technique from primary cultures of rat skeletal muscle. Up to 10(6) open and shut intervals were analysed from each of five different excised patches of membrane containing a single fast Cl- channel. 2. Rate constants for a kinetic scheme with six closed and two open states (scheme I) were estimated at a given voltage by maximum likelihood fitting of open and closed dwell-time distributions obtained at that voltage. This procedure was then repeated for data obtained at each of three to eight different membrane potentials for each channel. 3. Plots of the estimated rate constants against membrane potential typically appeared linear on semilogarithmic co-ordinates, consistent with rate constants that are exponentially dependent on voltage. 4. Regression analysis of these plots yielded two parameters for each rate constant: the value of the rate constant at -50 mV (B) and its voltage sensitivity (A). The dwell-time distributions predicted with these parameters and scheme I gave a good description of the experimental dwell-time distributions at all the studied voltages, lending further support for an exponential dependence of rate constants on membrane potential. 5. Estimates of A and B were also obtained by simultaneously fitting dwell-time distributions obtained at three to eight different voltages, in order to better define these parameters. Predicted dwell-time distributions obtained with these estimates and scheme I could approach the theoretical best description of the data for discrete-state Markov models. 6. Eight to twelve of the fourteen rate constants in scheme I appeared voltage sensitive, with effective gating charges ranging from about -1.5 to +1.0 units of electronic charge. 7. The estimated rate constants and their voltage sensitivities for the five analysed channels were generally similar, but showed some heterogeneity. 8. Gating mechanisms which had fewer kinetic states than scheme I, or equal and opposite effective gating charges over each transition barrier, or four or five identical and independent voltage-dependent subunits, all gave poorer descriptions of the data than scheme I. These simpler mechanisms were also ranked below scheme I by the Schwarz criterion, which applies a heavy penalty for additional free parameters. 9. These findings indicate that the voltage dependence of the fast Cl- channel is consistent with a kinetic scheme with six closed and two open states, in which a majority of transitions among the states are voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗