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PubMed1998

Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence.

PURPOSE: This study evaluates the cost-effectiveness of dynamic graciloplasty for intractable fecal incontinence. PATIENTS AND METHODS: The costs and effects of dynamic graciloplasty were measured in a prospective, longitudinal study and in a clinical trial. Forty-three patients with intractable fecal incontinence were evaluated before and after dynamic graciloplasty. Costs were obtained from the hospital information system and from patient-oriented questionnaires. We compared the costs of a dynamic graciloplasty with the costs of a colostomy. Colostomy costs were evaluated using a group of seven patients who had a stoma in place for incontinence for several years. Sensitivity analyses were included. RESULTS: Total direct costs of lifelong dynamic graciloplasty were $31,733 (United States dollars), costs of lifelong conventional treatment were $12,180 (United States), and costs of colostomy, including lifelong stoma care, were $71,576 (United States). The clinical success rate of dynamic graciloplasty was 74 percent. Quality of life after successful dynamic graciloplasty was better than with conventional treatment. CONCLUSION: We found that dynamic graciloplasty was more expensive than conventional treatment but resulted in a significantly higher quality of life. Stoma treatment was the least attractive alternative regarding both costs and effects. The Dutch Health Insurance Executive Board recommended reimbursement for the dynamic graciloplasty procedure.

Adult↗
PubMed2000

Tumor cell adhesion of human colon carcinoma cells with different metastatic properties to extracellular matrix under dynamic conditions of laminar flow.

PURPOSE: Shear forces have an important influence on cell adhesion and other cellular functions, and malignant cell lines appear to possess different adhesive properties under static and dynamic conditions. Thus, we analyzed human colon carcinoma cell adhesion under dynamic conditions and examined the interactions of HT-29 colon carcinoma cells of different metastatic properties with various immobilized ECM components. METHODS: Wall shear adhesion threshold (WSAT), dynamic adhesion rate (DAR), and adhesion stabilization rate (ASR) were compared between the cell lines using dynamic conditions in a laminar flow chamber by decreasing the flow (wall shear stress) of cell suspensions. Patterns of cell adhesion under dynamic conditions were compared to adhesive interactions in static microtiterplate assays. RESULTS: Poorly metastatic HT-29P cells adhered six times more than highly metastatic cells to type I collagen under laminar fluid flow, whereas only highly metastatic HT-29LMM showed adhesive interactions with fibronectin under static and dynamic conditions. High rates of cell adhesion to collagen IV were found under static, but not under dynamic, conditions. CONCLUSIONS: Although poorly and highly metastatic HT-29 cells express similar patterns of integrins, they differ in their adhesive properties to ECM components under static and dynamic conditions. Hydrodynamic shear forces appear to influence adhesive properties of HT-29 cells, and differences between dynamic and static cell adhesion were found.

Carcinoma↗
PubMed2007

Comparison of the effects of bilateral posterior dynamic and rigid fixation devices on the loads in the lumbar spine: a finite element analysis.

A bilateral dynamic stabilization device is assumed to alter favorable the movement and load transmission of a spinal segment without the intention of fusion of that segment. Little is known about the effect of a posterior dynamic fixation device on the mechanical behavior of the lumbar spine. Muscle forces were disregarded in the few biomechanical studies published. The aim of this study was to determine how the spinal loads are affected by a bilateral posterior dynamic implant compared to a rigid fixator which does not claim to maintain mobility. A paired monosegmental posterior dynamic implant was inserted at level L3/L4 in a validated finite element model of the lumbar spine. Both a healthy and a slightly degenerated disc were assumed at implant level. Distraction of the bridged segment was also simulated. For comparison, a monosegmental rigid fixation device as well as the effect of implant stiffness on intersegmental rotation were studied. The model was loaded with the upper body weight and muscle forces to simulate the four loading cases standing, 30 degrees flexion, 20 degrees extension, and 10 degrees axial rotation. Intersegmental rotations, intradiscal pressure and facet joint forces were calculated at implant level and at the adjacent level above the implant. Implant forces were also determined. Compared to an intact spine, a dynamic implant reduces intersegmental rotation at implant level, decreases intradiscal pressure in a healthy disc for extension and standing, and decreases facet joint forces at implant level. With a rigid implant, these effects are more pronounced. With a slightly degenerated disc intersegmental rotation at implant level is mildly increased for extension and axial rotation and intradiscal pressure is strongly reduced for extension. After distraction, intradiscal pressure values are markedly reduced only for the rigid implant. At the adjacent level L2/L3, a posterior implant has only a minor effect on intradiscal pressure. However, it increases facet joint forces at this level for axial rotation and extension. Posterior implants are mostly loaded in compression. Forces in the implant are generally higher in a rigid fixator than in a dynamic implant. Distraction strongly increases both axial and shear forces in the implant. A stiffness of the implant greater than 1,000 N/mm has only a minor effect on intersegmental rotation. The mechanical effects of a dynamic implant are similar to those of a rigid fixation device, except after distraction, when intradiscal pressure is considerably lower for rigid than for dynamic implants. Thus, the results of this study demonstrate that a dynamic implant does not necessarily reduce axial spinal loads compared to an un-instrumented spine.

Biomechanical Phenomena↗
PubMed2006

Slow-fast decoupling of the disparity convergence eye movements dynamics.

In this paper we show how to separate the slow and fast dynamics of the disparity convergence of the eye movements dynamic model. The dynamic equations obtained determine the modified slow dynamics that takes into account the impact of the fast dynamics and the modified fast dynamics that takes into account the impact of the slow dynamics. The slow fast decoupling is achieved by finding analytical solutions of the transformation equations used. The transformed slow and fast subsystems have very simple forms. Having separated the slow and fast dynamics completely, neural control problems for the slow and fast eye movements dynamics can be independently studied and better understood.

Algorithms↗
PubMed1995

Dosimetry and clinical implementation of dynamic wedge.

PURPOSE: Wedge-shaped isodoses are desired in a number of clinical situations. Physical wedge filters have provided nominal angled isodoses with dosimetric consequences of beam hardening, increased peripheral dosing, nonidealized gradients at deep depths, along with the practical consequences of filter handling and placement problems. Dynamic wedging uses a combination of a moving jaw and changing dose rate to achieve angled isodoses. The clinical implementation of dynamic wedge and an accompanying quality assurance program are discussed in detail. METHODS AND MATERIALS: The accelerator at our facility has two photon energies (6 MV and 18 MV), currently with dynamic wedge angles of 15 degrees, 30 degrees, 45 degrees, and 60 degrees. The segmented treatment tables (STT) that drive the jaw in concert with a changing dose rate are unique for field sizes ranging from 4.0 cm to 20.0 cm in 0.5 cm steps, resulting in 256 STTs. Transmission wedge factors were measured for each STT with an ion chamber. Isodose profiles were accumulated with film after dose conversion. For treatment-planning purposes, dmax orthogonal dose profiles were measured for open and dynamic fields. Physical filters were assigned empirically via the ratio of open and wedge profiles. RESULTS: A nonlinear relationship with wedge factor and field size was found. The factors were found to be independent of the stationary field setting or second order blocking. Dynamic wedging provided more consistent gradients across the field compared with physical filters. Percent depth doses were found to be closer to open field. The created physical filters provided planned isodoses that closely resembled measured isodoses. Comparative isodose plans show improvement with dynamic wedging. CONCLUSIONS: Dynamic wedging has practical and dosimetric advantages over physical filters. Table collisions with physical filters are alleviated. Treatment planning has been solved with an empirical solution. Dynamic wedge is a positive replacement for physical filters, and a first step for commercial introduction of dynamic conformal therapy.

Humans↗
PubMed2004

A dynamic supraclavicular field-matching technique for head-and-neck cancer patients treated with IMRT.

PURPOSE: The conventional single-isocenter and half-beam (SIHB) technique for matching supraclavicular fields with head-and-neck (HN) intensity-modulated radiotherapy (IMRT) fields is subject to substantial dose inhomogeneities from imperfect accelerator jaw/MLC calibration. It also limits the isocenter location and restricts the useful field size for IMRT. We propose a dynamic field-matching technique to overcome these limitations. METHODS AND MATERIALS: The proposed dynamic field-matching technique makes use of wedge junctions for the abutment of supraclavicular and HN IMRT fields. The supraclavicular field was shaped with a multileaf collimator (MLC), which was orientated such that the leaves traveled along the superoinferior direction. The leaves that defined the superior field border moved continuously during treatment from 1.5 cm below to 1.5 cm above the conventional match line to generate a 3-cm-wide wedge-shaped junction. The HN IMRT fields were optimized by taking into account the dose contribution from the supraclavicular field to the junction area, which generates a complementary wedge to produce a smooth junction in the abutment region. This technique was evaluated on a polystyrene phantom and 10 HN cancer patients. Treatment plans were generated for the phantom and the 10 patients. Dose profiles across the abutment region were measured in the phantom on films. For patient plans, dose profiles that passed through the center of the neck lymph nodes were calculated using the proposed technique and the SIHB technique, and dose uniformity in the abutment region was compared. Field mismatches of +/- 1 mm and +/- 2 mm because of imperfect jaw/MLC calibration were simulated, and the resulting dose inhomogeneities were studied for the two techniques with film measurements and patient plans. Three-dimensional volumetric doses were analyzed, and equivalent uniform doses (EUD) were computed. The effect of field mismatches on EUD was compared for the two match techniques. RESULTS: For a perfect jaw/MLC calibration, dose profiles for the 10 patients in the 3-cm match zone had an average inhomogeneity range of -1.6% to +1.6% using the dynamic-matching technique and -3.7% to +3.8% according to the SIHB technique. Measurements showed that dose inhomogeneities that resulted from 1-mm and 2-mm jaw/MLC calibration errors were reduced from as large as 27% and 45% with the SIHB technique to less than 2% and 5.7% with the dynamic technique, respectively. For -1-mm, -2-mm, +1-mm, and +2-mm jaw/MLC calibration errors, respectively, treatment plans for the 10 patients yielded average dose inhomogeneities of -5.9%, -3.0%, +2.7%, and +5.8% with the dynamic technique as compared to -22.8%, -11.1%, +9.8%, and +22.1% with the SIHB technique. Calculation based on a dose-volume histogram (DVH) showed that the SIHB technique resulted in larger changes in EUD of the PTV in the junction area than did the dynamic technique. CONCLUSION: Compared with the conventional SIHB technique, the dynamic field-matching technique provides superior dose homogeneity in the abutment region between the supraclavicular and HN IMRT fields. The dynamic feathering mechanism substantially reduces dose inhomogeneities that result from imperfect jaw/MLC calibration. In addition, isocenter location in the dynamic field-matching technique can be chosen for reproducible patient setup and for adequate IMRT field size rather than being dictated by the match position. It also allows angling of the supraclavicular field to reduce the volume of healthy lung irradiated, which is impractical with the SIHB technique. In principle, this technique should be applicable to any treatment site that requires the abutment of static and intensity-modulated fields.

Calibration↗
PubMed2005

Confined dynamics, forms and transitions in colloidal systems: from clay to DNA.

Colloidal suspensions are a classic example of confining systems developing large specific surfaces, presenting a rich variety of shapes and exhibiting complex organization on a length scale ranging from 1 nm to several micrometers. Two distinct confined dynamics are generally considered in such systems: (1) the embedded fluid dynamics entrapped in the pore network with two main contributions, surface interaction and long-range connectivity, and (2) the dynamics of the host matrix, associated with a time evolution of the interfacial geometry. This last contribution is particularly important during dynamic and structural transitions of colloidal suspensions such as jamming, glass transition, phase separations and flocculation. It is generally believed that the characteristic time scale needed to describe colloidal movement and interfacial geometrical reorganization is much slower than the dynamics of the embedded fluid (except in the trivial situation where the fluid molecule is irreversibly adsorbed to a colloidal surface). Thus, few connections are made between these two distinct dynamics. In this presentation, we show how the slow and confined water dynamics at proximity of a colloidal surface provides an original way to probe colloidal shape and colloidal orientation dynamics. Two topics are presented. First of all, water field-cycling NMR relaxometry is used to probe the glass transition and the strong rotational slowing down of a colloidal system made of plate-like particles, a synthetic clay (laponite). Second, we analyze the case of long colloidal thin rods (either mineral or biologic such as DNA cylinders) dispersed in very diluted suspensions. At large distance and/or long time, these particles appear as a portion of a line. We discuss how the embedded fluid dynamics can be sensitive to this morphological crossover and may provide information about the particle shape. Some comparisons with recent experiments are presented.

Aluminum Silicates↗
PubMed1998

Mechanisms of cardiomyoplasty: comparative effects of adynamic versus dynamic cardiomyoplasty.

BACKGROUND: The apparent paradox seen in patients who have undergone dynamic cardiomyoplasty and shown substantial clinical and functional improvements with only modest hemodynamic changes may be due to inappropriate end points chosen for study, a result of incomplete understanding of mechanisms involved. The purpose of this study was to compare the relative role of the passive "girdling effect" and the dynamic "systolic squeezing effect" of the wrapped muscle in cardiomyoplasty. METHODS: The control group of 6 dogs underwent 4 weeks of rapid pacing (250 beats/min) to induce severe heart failure followed by 8 weeks of observation without rapid pacing. The trajectory of recovery in hemodynamics and cardiac dimensions was followed with echocardiography and Swan-Ganz catheters. In the "adynamic" cardiomyoplasty group (n=4), the left latissimus dorsi muscle was wrapped around the ventricles and allowed to stabilize and mature for 4 weeks. This was followed by rapid pacing and recovery as in the control group. In the "dynamic" cardiomyoplasty group (n=3), the same protocol for the adynamic group was followed except that a synchronizable cardiomyostimulator was attached to the thoracodorsal nerve of the muscle wrap. This allowed the latter to be transformed during the rapid-pacing phase and permitted dynamic squeezing of the muscle wrap to be generated by burst stimulation synchronized with cardiac contraction in a 1:2 ratio. RESULTS: Baseline data were comparable in all groups prior to rapid pacing. After 4 weeks of rapid pacing, the left ventricular ejection fraction was higher in the adynamic (27.0%+/-3.9%; p < 0.05) and dynamic (33.3%+/-2.3%; p < 0.02) cardiomyoplasty groups compared with controls (18.8%+/-8.3%). Similarly, ventricular dilatation in both systole and diastole was less in the adynamic (51.8+/-8.7 mL, [p < 0.002] and 38.2+/-7.2 mL [p < 0.001], respectively) and dynamic (62.0+/-7.2 [p < 0.02] and 41.3+/-3.5 mL [p < 0.005], respectively) cardiomyoplasty groups compared with controls. In the dynamic group, on and off studies were carried out after cessation of rapid pacing while the heart was still in severe failure, and they demonstrated a systolic squeezing effect in stimulated beats. Only this group recovered fully to baseline after 8 weeks. CONCLUSIONS: By reducing myocardial stress, both the passive girdling effect and the dynamic systolic squeezing effect have complementary roles in the mechanisms of dynamic cardiomyoplasty.

Animals↗
PubMed2001

Pore network modelling: determination of the dynamic profiles of the pore diffusivity and its effect on column performance as the loading of the solute in the adsorbed phase varies with time.

A three-dimensional pore network model for diffusion in porous adsorbent particles was employed in a dynamic adsorption model that simulates the adsorption of a solute in porous particles packed in a chromatographic column. The solution of the combined model yielded the dynamic profiles of the pore diffusion coefficient of beta-galactosidase along the radius of porous ion-exchange particles and along the length of the column as the loading of the adsorbate molecules on the surface of the pores occurred, and, the dynamic adsorptive capacity of the chromatographic column as a function of the design and operational parameters of the chromatographic system. The pore size distribution of the porous adsorbent particles and the chemistry of the adsorption sites were unchanged in the simulations. It was found that for a given column length the dynamic profiles of the pore diffusion coefficient were influenced by: (i) the superficial fluid velocity in the column, (ii) the diameter of the adsorbent particles and (iii) the pore connectivity of the porous structure of the adsorbent particles. The effect of the magnitude of the pore connectivity on the dynamic profiles of the pore diffusion coefficient increased as the diameter of the adsorbent particles and the superficial fluid velocity in the column increased. The dynamic adsorptive capacity of the column increased as: (a) the particle diameter and the superficial fluid velocity in the column decreased, and (b) the column length and the pore connectivity increased. In preparative chromatography, it is desirable to obtain high throughputs within acceptable pressure gradients, and this may require the employment of larger diameter adsorbent particles. In such a case, longer column lengths satisfying acceptable pressure gradients with adsorbent particles having higher pore connectivity values could provide high dynamic adsorptive capacities. An alternative chromatographic system could be comprised of a long column packed with large particles which have fractal pores (fractal particles) that have high pore connectivities and which allow high intraparticle diffusional and convective flow mass transfer rates providing high throughputs and high dynamic adsorptive capacities. If large scale monoliths could be made to be reproducible and operationally stable, they could also offer an alternative mode of operation that could provide high throughputs and high dynamic adsorptive capacities.

Adsorption↗
PubMed1990

Modulation of abnormal defecation dynamics by biofeedback treatment in chronically constipated children with encopresis.

To determine whether outcome in chronically constipated and encopretic children with abnormal defecation dynamics could be improved with biofeedback training, we randomly assigned patients, 5 to 16 years of age, to receive conventional treatment alone (n = 19) or conventional plus biofeedback treatment (n = 22) and evaluated physiologic outcome at 7 months and clinical outcome at 7 and 12 months. Eighty-six percent of patients learned normal defecation dynamics with up to six biofeedback sessions. At 7 months, 13% of conventionally treated and 77% of biofeedback-treated patients had normal defecation dynamics (p less than 0.01); one conventionally treated (5%) and 12 biofeedback-treated patients (55%) had recovered (p less than 0.01). Learning normal defecation dynamics was correlated with clinical recovery (p less than 0.01). At 7 months, 11% of patients with normal defecation dynamics after biofeedback treatment had abnormal defecation dynamics, and 71% of the biofeedback-treated patients with normal defecation dynamics recovered. At 12 months, 16% of conventionally treated and 50% of biofeedback-treated patients had recovered (p less than 0.05). Balloon defecation did not improve significantly in those who learned normal defecation dynamics. Therefore the ability to defecate balloons is apparently not dependent on the normal function of the external and sphincter and pelvic floor muscles alone. Biofeedback treatment is complementary to a good conventional therapeutic regimen in patients with abnormal defecation dynamics.

Adolescent↗
PubMed2001

Pore network modelling of affinity chromatography: determination of the dynamic profiles of the pore diffusivity of beta-galactosidase and its effect on column performance as the loading of beta-galactosidase onto anti-beta-galactosidase varies with time.

A three-dimensional pore network model for diffusion in porous adsorbent particles was employed in a dynamic adsorption model that simulates the adsorption of a solute in porous particles packed in a chromatographic column. The solution of the combined model yielded the dynamic profiles of the pore diffusion coefficient of beta-galactosidase along the radius of porous adsorbent particles and along the length of the column as the loading of beta-galactosidase onto anti-beta-galactosidase immobilized on the surface of the pores of the particles occurred, and, the dynamic adsorptive capacity of the chromatographic column as a function of the design and operational parameters of the chromatographic system. It was found that for a given column length the dynamic profiles of the pore diffusion coefficient were influenced by (a) the superficial fluid velocity in the column, (b) the diameter of the adsorbent particles, and (c) the pore connectivity of the porous structure of the adsorbent particles. The effect of the magnitude of the pore connectivity on the dynamic profiles of the pore diffusion coefficient of beta-galactosidase increased as the diameter of the adsorbent particles and the superficial fluid velocity in the column increased. The dynamic adsorptive capacity of the column increased as (i) the particle diameter and the superficial fluid velocity in the column decreased, and (ii) the column length and the pore connectivity increased. In preparative affinity chromatography, it is desirable to obtain high throughputs within acceptable pressure gradients, and this may require the employment of larger diameter adsorbent particles. In such a case, longer column lengths satisfying acceptable pressure gradients with adsorbent particles having higher pore connectivity values could provide high dynamic adsorptive capacities. An alternative chromatographic system could be comprised of a long column packed with large particles which have fractal pores (fractal particles) that have high pore connectivities and which allow high intraparticle diffusional and convective flow mass transfer rates providing high throughputs and high dynamic adsorptive capacities. If large scale monoliths could be made to be reproducible and operationally stable, they could also offer an alternative mode of operation that could provide high throughputs and high dynamic adsorptive capacities.

Adsorption↗
PubMed2001

Dynamic gadolinium-enhanced MR imaging of pituitary adenomas: usefulness of sequential sagittal and coronal plane images.

Dynamic magnetic resonance (MR) imaging for pituitary adenomas is usually performed in a coronal direction; however, small lesions between slices, or lesions located at the anterior or posterior aspect of the pituitary gland might be overlooked on MR images in only the coronal direction. The purpose of our study was to evaluate whether consecutive dynamic MR images in the coronal and sagittal planes improve detection of pituitary adenomas. Eighteen patients with pituitary microadenomas and nine with healthy pituitary glands were included in this study. MR images were performed with 1.5 T superconductive units and commercially-available head coils. After a 5 ml gadolinium contrast injection, eight serial dynamic sagittal images were obtained. Within 3 or 6 min, this was followed by a 10-15 ml gadolinium injection and acquisition of eight serial dynamic coronal images. Dynamic MR images and conventional noncontrast- and contrast-enhanced sagittal and coronal T1-weighted images were evaluated independently in a blind fashion by two neuroradiologists regarding the depiction of pituitary microadenomas. The sensitivities of dynamic enhanced MR imaging in the detection of microadenomas were 61.1% in sagittal direction, 72.2% in coronal direction respectively, and were superior to those of conventional noncontrast- and contrast-enhanced T1-weighted imaging (22.2-50%). The sensitivity of a combination of sagittal and coronal dynamic enhanced MR imaging for the detection of microadenomas was 88.9% and was superior to those of conventional noncontrast- and contrast-enhanced T1-weighted imaging combining sagittal and coronal directions (61.1%, 61.1%) (P<0.05, P<0.05, respectively). The specificity and accuracy of dynamic enhanced MR imaging with combination of sagittal and coronal images was 88.9% respectively. Dynamic gadolinium-enhanced MR imaging, especially using both sagittal and coronal planes, was concluded to be useful for the detection of pituitary microadenomas.

Adenoma↗
PubMed2002

The role of dynamic imaging in sentinel lymph node biopsy in breast cancer.

The aim of this study was to evaluate the role of dynamic imaging in sentinel lymph node (SLN) biopsy in breast cancer. Patients with T1/T2, N0 invasive breast cancer underwent SLN localisation using intra-dermal injection of 15 MBq of 99mTc-nanocolloid. Gamma camera anterior-oblique dynamic imaging commenced simultaneously with tracer administration for 45 min, and was followed by anterior and lateral static imaging. Dynamic imaging data was reformatted into image files of different time-frames. Patterns of uptake were analysed using the sequences of dynamic frames and time-activity curve (TAC). SLN localisation was successful in 70/73 studies (96%) in 72 patients. Imaging information was present within the first 15 min of dynamic imaging in 67/70 studies (96%). Critical analysis of dynamic data helped to differentiate true SLN from secondary echelon nodes in eight studies and transient foci of radioactivity in six studies. In 17 studies, SLN contained metastatic disease. The detection of SLN metastasis was independent from the use of dynamic imaging. Dynamic imaging improves the interpretation of preoperative SLN imaging for breast cancer, but does not contribute significantly to the successful detection of SLN. Hence, preoperative dynamic imaging is not necessary in SLN biopsy for breast cancer.

Breast Neoplasms↗
PubMed1995

Detection of internal and overall dynamics of a two-atom-tethered spin-labeled DNA.

DNA motions consist of several components which couple, making their investigation difficult. This study describes an approach for obtaining dynamical information by EPR when spin-labeled nucleic acids are examined. The analysis is accomplished by implementing two motional models. The first model (i.e., dynamic cylinder model) views the spin-labeled helix as a diffusing cylinder containing internal dynamics which are characterized by an order parameter. The second model (i.e., base disk model) provides correlation times describing the diffusion of the spin-labeled base. In each model, the nitroxide motion consists of both global and internal contributions. Dynamic cylinder and base disk simulations of four duplexes containing nitroxides attached to thymidine by a two-atom tether (DUMTA)-(dT)7DUMTA-(dT)7.(dA)15, [(dT)7DUMTA(dT)7]2.(dA)30, [(dT)7DUMTA(dT)7]3.(dA)45, and [(dT)7DUMTA(dT)7]m.-(dA)n--demonstrate the useful application of this approach. From dynamic cylinder simulations, the order parameter for internal motions is found to be independent of the helix length (S = 0.32 +/- 0.01). Previous base disk simulations of a DNA 26mer and polymer labeled with a five-atom-tethered nitroxide seemed to indicate that tau perpendicular was only sensitive to internal dynamics. Results from base disk simulations of DUMTA-labeled DNA indicate that the perpendicular component of the base disk correlation time (tau perpendicular = 1.4-6.2 ns) is sensitive to global dynamics. Thus, tau perpendicular is a quantitative indicator of both internal and global dynamics. Comparison of the two models reveals that tau perpendicular infinity S2 tau rb, where tau rb represents the rigid-body diffusion of the DNA helix. This relationship between S and tau perpendicular provides a framework for studying conformational changes and size-dependent phenomena in spin-labeled nucleic acids. Application of the dynamic cylinder model to a B-Z transition generates distinct values of S for each of the conformations, indicating that Z-DNA is more rigid than B-DNA.

Base Sequence↗
PubMed2004

Molecular control of recombination dynamics in dye-sensitized nanocrystalline TiO2 films: free energy vs distance dependence.

In this paper we address the dependence of the charge recombination dynamics in dye-sensitized, nanocrystalline TiO2 films upon the properties of the sensitizer dye employed. In particular we focus upon dependence of the charge recombination kinetics upon the dye oxidation potential E0(D+/D), determined electrochemically, and the spatial separation r of the dye cation HOMO orbital from the metal oxide surface, determined by semiempirical calculations. Our studies employed a series of ruthenium bipyridyl dyes in addition to porphyrin and phthalocyanine dyes. A strong correlation is observed between the recombination dynamics and the spatial separation r, with variation in r by 3 A resulting in a more than 10-fold change in the recombination half-time t(50%). This correlation is found to be in agreement with electron tunneling theory, t(50%) proportional, variant exp(-betar) with beta = 0.95 +/- 0.2 A-1. In contrast, the recombination dynamics were found to be relatively insensitive to variations in E0D+/D), indicative of the recombination reaction lying near the peak of the Marcus free energy curve, DeltaG approximately lambda, and with lambda approximately 0.8 eV. A correlation is also observed between the recombination half-time and the temporal shape of the kinetics, with faster recombination dynamics being more dispersive (less monoexponential). Comparison with numerical Monte Carlo type simulations suggests this correlation is attributed to a shift from fast recombination dynamics primarily limited by dispersive electron transport within the metal oxide film to slower dynamics primarily limited by the interfacial electron-transfer reaction. We conclude that the primary factor controlling the charge recombination dynamics in dye-sensitized, nanocrystalline TiO2 films is the spatial separation of the dye cation from the electrode surface. In particular, we show that for the Ru(dcbpy)2NCS2 dye series, the use of X = NCS rather than X = CN results in a 2 A shift in the dye cation HOMO orbital away from the electrode surface, causing a 7-fold retardation of the recombination dynamics, resulting in the remarkably slow recombination dynamics observed for this sensitizer dye.

Journal Article↗
PubMed2006

Collective Langevin dynamics of conformational motions in proteins.

Functionally relevant slow conformational motions of proteins are, at present, in most cases inaccessible to molecular dynamics (MD) simulations. The main reason is that the major part of the computational effort is spend for the accurate description of a huge number of high frequency motions of the protein and the surrounding solvent. The accumulated influence of these fluctuations is crucial for a correct treatment of the conformational dynamics; however, their details can be considered irrelevant for most purposes. To accurately describe long time protein dynamics we here propose a reduced dimension approach, collective Langevin dynamics (CLD), which evolves the dynamics of the system within a small subspace of relevant collective degrees of freedom. The dynamics within the low-dimensional conformational subspace is evolved via a generalized Langevin equation which accounts for memory effects via memory kernels also extracted from short explicit MD simulations. To determine the memory kernel with differing levels of regularization, we propose and evaluate two methods. As a first test, CLD is applied to describe the conformational motion of the peptide neurotensin. A drastic dimension reduction is achieved by considering one single curved conformational coordinate. CLD yielded accurate thermodynamical and dynamical behaviors. In particular, the rate of transitions between two conformational states agreed well with a rate obtained from a 150 ns reference molecular dynamics simulation, despite the fact that the time scale of the transition (approximately 50 ns) was much longer than the 1 ns molecular dynamics simulation from which the memory kernel was extracted.

Biophysics↗
PubMed2002

Intrinsically slow dynamic instability of HeLa cell microtubules in vitro.

The dynamic behavior of mammalian microtubules has been extensively studied, both in living cells and with microtubules assembled from purified brain tubulin. To understand the intrinsic dynamic behavior of mammalian nonneural microtubules, we purified tubulin from cultured HeLa cells. We find that HeLa cell microtubules exhibit remarkably slow dynamic instability, spending most of their time in an attenuated state. The tempered dynamics contrast sharply with the dynamics of microtubules prepared from purified bovine brain tubulin under similar conditions. In accord with their minimal dynamic instability, assembled HeLa cell microtubules displayed a slow treadmilling rate and a low guanosine-5'-triphosphate hydrolysis rate at steady state. We find that unlike brain tubulin, which consists of a heterogeneous mixture of beta-tubulin isotypes (beta(II), beta(III), and beta(IV) and a low level of beta(I)), HeLa cell tubulin consists of beta(I) tubulin ( approximately 80%) and a minor amount of beta(IV) tubulin ( approximately 20%). The slow dynamic behavior of HeLa cell microtubules in vitro differs strikingly from the dynamic behavior of microtubules in living cultured mammalian cells, supporting the idea that accessory factors create the robust dynamics that occur in cells.

Animals↗
PubMed2004

In vivo measurement of microtubule dynamics using stable isotope labeling with heavy water. Effect of taxanes.

Microtubules are dynamic polymers with central roles in the mitotic checkpoint, mitotic spindle assembly, and chromosome segregation. Agents that block mitotic progression and cell proliferation by interfering with microtubule dynamics (microtubule-targeted tubulin-polymerizing agents (MTPAs)) are powerful antitumor agents. Effects of MTPAs (e.g. paclitaxel) on microtubule dynamics have not yet been directly demonstrated in intact animals, however. Here we describe a method that measures microtubule dynamics as an exchange of tubulin dimers into microtubules in vivo. The incorporation of deuterium ((2)H(2)) from heavy water ((2)H(2)O) into tubulin dimers and polymers is measured by gas chromatography/mass spectrometry. In cultured human lung and breast cancer cell lines, or in tumors implanted into nude mice, tubulin dimers and polymerized microtubules exhibited nearly identical label incorporation rates, reflecting their rapid exchange. Administration of paclitaxel during 24 h of (2)H(2)O labeling in vivo reduced (2)H labeling in polymers while increasing (2)H in dimers, indicating diminished flux of dimers into polymers (i.e. inhibition of microtubule dynamic equilibrium). In vivo inhibition of microtubule dynamics was dose-dependent and correlated with inhibition of DNA replication, a stable isotopic measure of tumor cell growth. In contrast, microtubule polymers from sciatic nerve of untreated mice were not in dynamic equilibrium with tubulin dimers, and paclitaxel increased label incorporation into polymers. Our results directly demonstrate altered microtubule dynamics as an important action of MTPAs in vivo. This sensitive and quantitative in vivo assay of microtubule dynamics may prove useful for pre-clinical and clinical development of the next generation of MTPAs as anticancer drugs.

Animals↗