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PubMed2006

Evaluation of energetic and dynamic coupling networks in a PDZ domain protein.

A number of computational and experimental studies have identified intramolecular communication "pathways" or "networks" important for transmitting allostery. Here, we have used mutagenesis and NMR relaxation methods to investigate the scope and nature of the communication networks found in the second post-synaptic density-95/discs large/zonula occludens-1 (PDZ) domain of the human protein tyrosine phosphatase 1E protein (hPTP1E) (PDZ2). It was found that most mutations do not have a significant energetic contribution to peptide ligand binding. Three mutants that showed significant changes in binding also displayed context-dependent dynamic effects. Both a mutation at a partially exposed site (H71Y) and a buried core position (I35V) had a limited response in side-chain (2)H-based dynamics when compared to wild-type PDZ2. In contrast, a change at a second core position (I20F) that had previously been shown to be part of an energetic and dynamic network, resulted in extensive changes in side-chain dynamics. This response is reminiscent to that seen previously upon peptide ligand binding. These results shed light on the nature of the PDZ2 dynamic network and suggest that position 20 in PDZ2 acts as a "hub" that is energetically and dynamically critical for transmitting changes in dynamics throughout the PDZ domain.

Amino Acid Sequence↗
PubMed2006

Dynamic magnetic resonance angiography of the aneurysm neck: conformational changes during the cardiac cycle with possible consequences for endograft sizing and future design.

OBJECTIVE: Proper proximal fixation and stent-graft sealing within the aneurysm neck are critical for endovascular aneurysm repair (EVAR) durability. Computed tomography angiography (CTA) is the gold standard for preoperative sizing of endograft diameters, but the accuracy of these measurements is uncertain because they rely on static images of a dynamic process. The aortic configuration and diameter may change during the cardiac cycle. We studied these phenomena using dynamic electrocardiograph-triggered magnetic resonance angiography (MRA). METHODS: Eleven consecutive EVAR patients were included. Dynamic MRA was used to perform preoperative and postoperative measurements. Changes were measured in transverse aortic sections 10 mm below the lowest renal artery (level A), at the level of the renal arteries (level B), and 3 cm above the lowest renal artery (level C). Data were analyzed using image segmentation software. Aortic area and diameter changes along 256 axes were determined. RESULTS: Dynamic MRA demonstrated significant aortic area changes during the cardiac cycle before and after EVAR at all three measured levels. Pre-EVAR aortic area significantly increased per cardiac cycle: 8.4% at level A; 9.3% at level B; and 13.3% at level C (P < .001 for all levels). Post-EVAR aortic area increased 9.7% at level A, 9.6% at level B, and 15.8% at level C per cardiac cycle (P < .001 for all levels). Significant diameter changes during cardiac cycles were also observed at all three levels. Pre-EVAR mean diameter changed up to 8.9% (P < .001) compared with post-EVAR aortic changes of up to 11.5% (P < .001). EVAR had no effect on change in aortic area and diameter. Dynamic MRA also demonstrated that pulsatile aortic distension was not equal in all axes, but rather occurred as an asymmetrical expansion and contraction. CONCLUSION: In patients with (atherosclerotic) aneurysm disease, the aortic dimensions at the level of and proximal to the aneurysm neck change during the cardiac cycle. This phenomenon is preserved after EVAR. Therefore, maximum diameter using dynamic MRA may not be similar to the maximum diameter with static CTA in all patients, and a standard regimen of 10% to 15% oversizing of an endograft based on static CTA images may be inadequate for some patients. Further studies using dynamic MRA to evaluate effects of different endografts are anticipated, with possible consequences for endograft designs.

Aged↗
PubMed2005

Effects of atrial contraction, atrioventricular interaction and heart valve dynamics on human cardiovascular system response.

Various simulation models of different complexity have been proposed to model the dynamic response of the human cardiovascular system. In a related paper we proposed an improved numerical model to study the dynamic response of the cardiovascular system, and the pressures, volumes and flow-rates in the four chambers of the heart, which included the effects of atrial contraction, atrioventricular interaction, and heart valve dynamics. This paper investigates the effects of each one of these aspects of the model on the overall dynamic system response. The dynamic response is studied under different situations, with and without including the effect of various features of the model, and these situations are studied and compared among themselves and to detailed aspects of expected healthy-system response. As an important contribution with potential clinical applications, this paper examines the corresponding effects of atrioventricular interaction, and heart valve opening and closing dynamics to the general system dynamic response. This isolation of physical cause-effect relationships is difficult to study with purely experimental methods. The simulation results agree well with results in the open literature. Comparison shows that introduction of these new features greatly improves the simulation accuracy of the effects of a, v and c waves, and in predicting regurgitant valve flow, the dichrotic notch, and E/A velocity ratio.

Animals↗
PubMed2006

In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation.

The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were monitored by HSV1-TK or by the firefly luciferase reporter gene using HSV1-TK enzyme activity assay and luciferase assay, respectively. The results of dynamic gene expression studies showed that the luciferase gene is an optimal reporter gene for monitoring short-timescale, dynamic transcriptional events mediating a series of Dox inductions, whereas the HSV1-tk is not optimal to achieve this purpose. Furthermore, the enzyme half-life of HSV1-TK in NG4TL4 cells is about 35 h after cycloheximide-induced protein inhibition. On the other hand, the results of an efflux assay of [(131)I] FIAU and [(3)H] GCV revealed that the molecular probe phosphorylated by HSV1-TK can be trapped long term within HSV1-TK stably transformed cells. Therefore, a long half-life radionuclide is not suitable for dynamic gene expression studies. Based on these results, we suggest that the HSV1-TK reporter system is not optimal for monitoring short-timescale dynamic processes such as kinetic gene expression controlled by inducible promoters or a less stable protein with a more rapid turnover due to the limitations of the half-life of the HSV1-TK enzyme and the cellular retention time of their phosphorylated molecular probes.

Arabinofuranosyluracil↗
PubMed2004

Use of sorption and extraction tests to predict the dynamics of the interaction of trace elements in agricultural soils contaminated by a mine tailing accident.

Over 2000 ha of agricultural soils were contaminated by a pyritic sludge and acidic waste waters coming from a spill from a mining exploitation. The affected soils were acidic with sandy-loam texture (SL), loamy with neutral pH (L), and calcareous, saline, with clay texture (Cs). The Cs soils were contaminated only with acidic waste waters. Sorption and extraction tests were applied to examine the medium-term dynamics of the interaction of trace elements (As, Cd, Cu, Pb and Zn) in the soils. The solid-soil solution distribution coefficient (KD) was determined in soil samples taken 3 months (initial stage, 3M samples) and then nearly 2 years (final stage, 21M samples) after the accident. Distribution coefficient values ranged from the lowest values in the SL samples (from 0.2 l kg(-1) for Cd and Zn to 25 l kg(-1) for As) to higher values in the L and Cs soils. Lead and As had the highest KD in all soils (over 10(5) l kg(-1) in the L soils). No clear dynamics pattern could be derived from these data because of the low heavy metal concentrations in the soil solution. As a complementary approach, four single extractions (0.01 and 1 mol l(-1) CaCl2; 0.05 mol l(-1) EDTA; 0.43 mol l(-1) CH3COOH) were applied to soil and sludge samples. Samples derived from submitting field 3M samples to drying-wetting (DW) cycles were included to define a complete laboratory approach to predict field dynamics. Results from extraction tests indicated that changes of the trace element interaction over time depended on the soil pH and on the source of contamination. For those soils affected only by the acidic waste waters, where an increase in fixation occurred, natural processes such as diffusion controlled dynamics. For those soils contaminated by a mixed source, the dynamics of the interaction was the resultant process of the combination of the natural attenuation and the oxidation of the pyritic sludge. This latter process led to an increase in the remobilization for those elements associated with soluble secondary minerals (Cd and Zn) and to an increase in the fixation for those elements coprecipitating with insoluble secondary minerals (Pb and As). Drying-wetting cycles were useful to predict the dynamics in the field at month-year scale. The CH3COOH was recommended as the best test among those studied here to derive conclusions about dynamics pattern because it provided significant desorption yields in most scenarios. Acidic soils with sludge contamination represented the scenarios with the highest risk, while calcareous soils better attenuated contamination. In a longer time scale, the depletion of calcareous components needs to be controlled.

Journal Article↗
PubMed2000

Flow dynamics of stenotic aortic valves assessed by signal processing of Doppler spectrograms.

Clinical assessment of aortic stenosis (AS) is sometimes challenging, because all hemodynamic indexes of severity are modified by flow rate. However, the mechanisms underlying flow dependence remain controversial. Analysis of instantaneous flow dynamics has provided crucial information in a number of cardiovascular disorders and may add new insight into this phenomenon. This study was designed to analyze in vivo the effects of flow interventions on instantaneous valvular dynamics of stenotic valves. For this purpose, a custom algorithm for signal processing of Doppler spectrograms was developed and validated against a control population. Digital Doppler recordings at the aortic valve and left ventricular outflow tract were obtained in 15 patients with AS, at baseline and during low-dose dobutamine infusion; 10 normal subjects were studied as controls. Spectrograms were processed by signal averaging, time alignment, modal-velocity enhancement, envelope tracing, and numerical interpolation. Instantaneous relative aortic valve area (rAVA) was obtained by the continuity equation and plotted against normalized ejection time. Curves were classified as either type A (rapid, early-systolic opening) or type B (slow, end-systolic opening). Curves from controls closely matched prior knowledge of normal valve dynamics, but curves from patients were clearly different: all controls except 2 (80%) had type A, whereas all patients except 3 (80%) had a type B pattern (p = 0.03). Dobutamine infusion in patients increased and slightly anticipated peak rAVA by accelerating valve opening. Despite similar values of area and pressure difference, type B dynamics were associated with lower blood pressure (p = 0.01) and worse long-term outcome (>3 years) than type A flow dynamics (p = 0.02). Signal processing of Doppler spectrograms allows a comprehensive assessment of aortic flow dynamics. Differences in timing of valve aperture and in maximal leaflet excursion account for flow-mediated changes in valve area, suggesting complementary effects of inertia and elasticity on the kinetics of stenotic aortic valves. Flow-dynamic analysis provides novel clinical information regarding physiology of AS unavailable to conventional indexes.

Aged↗
PubMed2003

Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants.

Biophysical forces and biochemical factors play crucial roles in the maintenance of the integrity of articular cartilage. In this study, we explored the effect of dynamic tissue shear deformation and insulin-like growth factor I (IGF-I) on matrix synthesis by chondrocytes within native cartilage explants. Dynamic tissue shear in the range of 0.5-6% strain amplitude at 0.1 Hz was applied to cartilage explants cultured in serum-free medium. Dynamic tissue shear above 1.5% strain amplitude significantly stimulated protein and proteoglycan synthesis, by maximum values of 35 and 25%, respectively, over statically held control specimens. In the absence of tissue shear, IGF-I augmented protein and proteoglycan synthesis up to twofold at IGF-I concentrations in the range of 100-300 ng/ml. When tissue shear and IGF-I stimuli were combined, matrix biosynthesis levels were significantly higher than the maximal effect caused by either stimulus alone. However, there was no significant interaction between tissue shear and IGF-I as determined by two-way ANOVA. We then quantified the effect of dynamic tissue shear on the transport of IGF-I into and within cartilage explants. [125I]IGF-I was added to the medium, and the levels of intratissue [125I]IGF-I were directly measured as a function of time over 48 h in the presence and absence of continuous dynamic shear strain. Dynamic shear did not alter the rate of uptake of [125I]IGF-I into the explants, suggesting that convective diffusion of [125I]IGF-I is negligible under the shear strain conditions used. This is in marked contrast to the enhancement of transport reported in response to uniaxial dynamic compression. Taken together, these data suggest that (1) the stimulatory effect of tissue shear is via mechanotransduction pathways and not by facilitated transport of biochemical factors and (2) chondrocytes may possess complementary signal transduction pathways for biophysical and biochemical factors leading to changes in metabolic activity.

Analysis of Variance↗
PubMed1997

Dynamic balance testing with electrically evoked perturbation: a test of reliability.

OBJECTIVE: To investigate the reliability of a newly developed perturbation protocol for assessing dynamic balance. DESIGN: Each subject was tested in two experimental balance conditions, static and dynamic. The dependent variables for the static condition were sway area (SA), sway path length (SPL), sagittal sway standard deviation (SSD), and lateral sway standard deviation (LaSD). During the dynamic condition trials a stimulus was delivered to the tibial nerves of both legs to perturb the subjects. The subjects were instructed to return to the pre-perturbation level of steadiness as soon as possible after the stimulation. The dependent variables for the dynamic condition were dynamic phase duration (DPD), sway path mean (SPM), linear sway standard deviation (LiSD), and sagittal sway standard deviation (SSD). SETTING: The motor control laboratory of a university department of kinesiology. PATIENTS: Ten subjects from a population-based sample of healthy adults. MAIN OUTCOME MEASURE: An intraclass reliability estimate for all dependent measures in the static and dynamic conditions. RESULTS: In the static condition, the variables SA, SPL, SSD, and LaSD had reliabilities of .94, .98, .86, and .92, respectively, and in the dynamic condition the reliability estimates for DPD. SPM, LiSD, and SSD were .90, .71, .80, and .92, respectively. CONCLUSIONS: The results indicate the current technique provides a means of objectively measuring a subject's ability to regain static postural stability following electrically induced perturbation.

Adult↗
PubMed2002

Sequence-dependent dynamics of duplex DNA: the applicability of a dinucleotide model.

The short-time (submicrosecond) bending dynamics of duplex DNA were measured to determine the effect of sequence on dynamics. All measurements were obtained from a single site on duplex DNA, using a single, site-specific modified base containing a rigidly tethered, electron paramagnetic resonance active spin probe. The observed dynamics are interpreted in terms of single-step sequence-dependent bending force constants, determined from the mean squared amplitude of bending relative to the end-to-end vector using the modified weakly bending rod model. The bending dynamics at a single site are a function of the sequence of the nucleotides constituting the duplex DNA. We developed and examined several dinucleotide-based models for flexibility. The models indicate that the dominant feature of the dynamics is best explained in terms of purine- and pyrimidine-type steps, although distinction is made among all 10 unique steps: It was found that purine-purine steps (which are the same as pyrimidine-pyrimidine steps) were near average in flexibility, but the pyrimidine-purine steps (5' to 3') were nearly twice as flexible, whereas purine-pyrimidine steps were more than half as flexible as average DNA. Therefore, the range of stepwise flexibility is approximately fourfold and is characterized by both the type of base pair step (pyrimidine/purine combination) and the identity of the bases within the pair (G, A, T, or C). All of the four models considered here underscore the complexity of the dependence of dynamics on DNA sequence with certain sequences not satisfactorily explainable in terms of any dinucleotide model. These findings provide a quantitative basis for interpreting the dynamics and kinetics of DNA-sequence-dependent biological processes, including protein recognition and chromatin packaging.

Animals↗
PubMed2004

Temperature derivative fluorescence spectroscopy as a tool to study dynamical changes in protein crystals.

Motions through the energy landscape of proteins lead to biological function. At temperatures below a dynamical transition (150-250 K), some of these motions are arrested and the activity of some proteins ceases. Here, we introduce the technique of temperature-derivative fluorescence microspectrophotometry to investigate the dynamical behavior of single protein crystals. The observation of glass transitions in thin films of water/glycerol mixtures allowed us to demonstrate the potential of the technique. Then, protein crystals were investigated, after soaking the samples in a small amount of fluorescein. If the fluorophore resides within the crystal channels, temperature-dependent changes in solvent dynamics can be monitored. Alternatively, if the fluorophore binds to the protein, local dynamical transitions within the biomolecule can be probed directly. A clear dynamical transition was observed at 175 K in the active site of crystalline human butyrylcholinesterase. The results suggest that the dynamics of crystalline proteins is strongly dependent on solvent composition and confinement in the crystal channels. Beyond applications in the field of kinetic crystallography, the highly sensitive temperature-derivative fluorescence microspectrophotometry technique opens the way to many studies on the dynamics of biological nanosamples.

Acetylcholinesterase↗
PubMed1997

Overall and internal dynamics of DNA as monitored by five-atom-tethered spin labels.

Electron paramagnetic resonance (EPR) spectra of the two-atom-tethered six-membered ring thymidylate spin label (DUMTA) incorporated into duplexes of different sizes were found to display a helix length dependence and a local-order parameter S = 0.32 +/- 0.01 for B-DNA based on the dynamic cylinder model (Keyes, R. S., and A. M. Bobst. 1995. Detection of internal and overall dynamics of a two-atom-tethered spin-labeled DNA. Biochemistry. 34:9265-9276). This sensitivity to size, which reflects global tumbling, is now reported for the more flexible five-atom-tethered five-membered ring thymidylate spin label (DUAP) that can be readily incorporated enzymatically and sequence specifically into nucleic acids of different sizes. The DUAPs containing B-DNA systems were simulated with the same dynamic cylinder model, giving S = 0.20 +/- 0.01 for the more flexibly tethered spin label. This shows that S is dependent on tether length but not on global motion. An analysis with the same motional model of the B-Z transition in a (dG-dC)n polymer containing the five-atom-tethered six-membered ring cytidylate spin label (DCAT) (Strobel, O. K., R. S. Keyes, and A. M. Bobst. 1990b. Base dynamics of local Z-DNA conformations as detected by electron paramagnetic resonance with spin-labeled deoxycytidine analogues. Biochemistry. 29:8522-8528) revealed an increase in S from 0.15 +/- 0.01 to 0.26 +/- 0.01 in response to the B- to Z-DNA transition. This indicates that S is not only sensitive to tether length, but also to conformational changes in DNA. Both the DUAP- and the DCAT-labeled systems were also simulated with a base disk model. From the DUAP spectral series, the perpendicular component of the correlation time tau perpendicular describing the spin-labeled base diffusion was found to be sensitive to global tumbling, confirming earlier results obtained with DUMTA. The DCAT polymer results demonstrated that tau perpendicular monitors a conformational change from B- to Z-DNA, indicating that tau perpendicular is also sensitive to local base dynamics. These results confirm that the dynamics of five-atom-tethered nitroxides are coupled to the nucleic acid dynamics and, as with two-atom-tethered spin labels, can be characterized by S and tau perpendicular. The analyses of both spin-labeled systems provide good evidence for spin-labeled base motions within double-stranded DNA occurring on the nanosecond time scale, and establish that both labels can be used to monitor changes in global tumbling and local order parameter due to variations in DNA conformation and protein-DNA interactions.

Base Sequence↗
PubMed1998

Enzyme activity below the dynamical transition at 220 K.

Enzyme activity requires the activation of anharmonic motions, such as jumps between potential energy wells. However, in general, the forms and time scales of the functionally important anharmonic dynamics coupled to motion along the reaction coordinate remain to be determined. In particular, the question arises whether the temperature-dependent dynamical transition from harmonic to anharmonic motion in proteins, which has been observed experimentally and using molecular dynamics simulation, involves the activation of motions required for enzyme function. Here we present parallel measurements of the activity and dynamics of a cryosolution of glutamate dehydrogenase as a function of temperature. The dynamical atomic fluctuations faster than approximately 100 ps were determined using neutron scattering. The results show that the enzyme remains active below the dynamical transition observed at approximately 220 K, i.e., at temperatures where no anharmonic motion is detected. Furthermore, the activity shows no significant deviation from Arrhenius behavior down to 190 K. The results indicate that the observed transition in the enzyme's dynamics is decoupled from the rate-limiting step along the reaction coordinate.

Catalysis↗
PubMed2003

Molecular dynamics simulations of a K+ channel blocker: Tc1 toxin from Tityus cambridgei.

Toxins that block voltage-gated potassium (Kv) channels provide a possible template for improved homology models of the Kv pore. In assessing the interactions of Kv channels and their toxins it is important to determine the dynamic flexibility of the toxins. Multiple 10 ns duration molecular dynamics simulations combined with essential dynamics analysis have been used to explore the flexibility of four different Kv channel-blocking toxins. Three toxins (Tc1, AgTx and ChTx) share a common fold. They also share a common pattern of conformational dynamics, as revealed by essential dynamics analysis of the simulation results. This suggests that some aspects of dynamic behaviour are conserved across a single protein fold class. In each of these three toxins, the residue exhibiting minimum flexibility corresponds to a conserved lysine residue that is suggested to interact with the filter domain of the channel. Thus, comparative simulations reveal functionally important conservation of molecular dynamics as well as protein fold across a family of related toxins.

Animals↗
PubMed2000

Thresholds for step initiation induced by support-surface translation: a dynamic center-of-mass model provides much better prediction than a static model.

The need to initiate a step in order to recover balance could, in theory, be predicted by a static model based solely on displacement of the center of mass (COM) with respect to the base of support (BOS), or by a dynamic model based on the interaction between COM displacement and velocity. The purpose of this study was to determine whether the dynamic model provides better prediction than the static model regarding the need to step in response to moving-platform perturbation. The COM phase plane trajectories were determined for 10 healthy young adults for trials where the supporting platform was translated at three different acceleration levels in anterior and posterior directions. These trajectories were compared with the thresholds for step initiation predicted by the static and dynamic COM models. A single-link-plus-foot biomechanical model was employed to mathematically simulate termination of the COM movement, without stepping, using the measured platform acceleration as the input. An optimization routine was used to determine the stability boundaries in COM state space so as to establish the dynamic thresholds where a compensatory step must be initiated in order to recover balance. In the static model, the threshold for step initiation was reached if the COM was displaced beyond the BOS limits. The dynamic model showed substantially better accuracy than the static model in predicting the need to step in order to recover balance: 71% of all stepping responses predicted correctly by the dynamic model versus only 11% by the static model. These results support the proposition that the central nervous system must react to and control dynamic effects, i.e. COM velocity, as well as COM displacement in order to maintain stability with respect to the existing BOS without stepping.

Adult↗
PubMed1997

New method for monitoring the functional state of a dynamic cardiomyoplasty.

OBJECTIVE: To assess the impact of a dynamic cardiomyoplasty on failing hearts, it is essential to estimate the contraction force of the skeletal muscle and how its contraction is synchronized with the heart cycle. METHODS: In a 6-month study a small fluid-filled, balloon-mounted catheter was placed between the myocardium and the muscular wrap in five adult female Boor goats and two female domestic pigs. The catheter was connected to a subcutaneous measuring chamber whereby pressure monitoring could be accomplished. Distinct pressure signals as a result of function of the dynamic cardiomyoplasty and the heart were detected initially in all animals. RESULTS: Maximal relative pressure from the dynamic cardiomyoplasty was calculated as 336.2% +/- 69.4% on day 24 +/- 6.1 (n = 7) and end-stage pressure as 59.8% +/- 9.7% on day 174.6 +/- 13.1 (n = 4). A functional loss of pressure signals from the dynamic cardiomyoplasty was correlated to severe histologic muscle damage (n = 3). Pressure signals transferred from the contracting myocardium to the catheter showed defined segments of contraction, ejection, and filling periods, allowing a mechanical synchronization of the dynamic cardiomyoplasty to the heart cycle. CONCLUSIONS: This monitoring catheter enabled the assessment of the functional state of the dynamic cardiomyoplasty and allowed a synchronization to the heart cycle. It will promote understanding and might help to avoid muscle damage in dynamic cardiomyoplasty for an improved outcome of the surgical treatment of end-stage heart failure.

Animals↗
PubMed1997

Dynamic cardiac compression improves contractile efficiency of the heart.

The effect of dynamic cardiac compression on left ventricular contractile efficiency was assessed in terms of the pressure-volume relationship and myocardial oxygen consumption. In 11 excised cross-circulated dog hearts, the ventricle was directly compressed during systole (dynamic cardiac compression). Measurements for pressure-volume area (a measure of total mechanical energy), external work, and myocardial oxygen consumption were done before and during dynamic cardiac compression. Dynamic cardiac compression increased pressure-volume area by 28% +/- 17% (mean plus or minus the standard deviation) and external work by 24% +/- 20% (p = 0.0000185 and 0.0000212, respectively) at given end-diastolic and stroke volumes without affecting myocardial oxygen consumption. As a result, the oxygen cost of pressure-volume area, that is, the slope of the myocardial oxygen consumption-pressure-volume area relationship, significantly decreased by 16% +/- 13% (p = 0.0000135) whereas the pressure-volume area-independent myocardial oxygen consumption was unchanged. Then, contractile efficiency, that is, the reciprocal of the slope of the myocardial oxygen consumption-pressure-volume area relationship in joules significantly improved from 45% +/- 8% to 53% +/- 13% (p = 0.0000437). When the native myocardial oxygen consumption-pressure-volume area relationship was assessed by subtracting the dynamic cardiac compression pressure applied to the heart, the slope of the myocardial oxygen comsumption-pressure-volume area relationship returned to the control level. This indicates that the contractile efficiency of the native heart was not affected by dynamic cardiac compression. We conclude that dynamic cardiac compression enhances left ventricular pump function by improving the contractile efficiency of the overall heart leaving the energetics of the native heart unchanged.

Animals↗
PubMed2003

The RAGENA dynamic model of radon generation, entry and accumulation indoors.

The complexity generated by the existence of a great number of parameters and processes affecting the generation of radon in the source, its transport in the source medium, its entry into a dwelling and its accumulation in the different rooms of a dwelling has led to the development of partial models and experimental studies that are focused on a given aspect. However, in order to model radon levels and dynamics in real houses, it is necessary to take into account all the parameters and processes affecting radon levels. This is the objective of the dynamic RAGENA model of radon generation, entry and accumulation indoors. The model has been adapted to a Mediterranean climate house under dynamic conditions, and the indoor radon and soil radon dynamics have been compared to experimental results. It has been found (i) that the model gives a soil radon dynamics similar to that obtained experimentally, (ii) a remarkable model-experiment agreement indoors and (iii) that the indoor radon dynamics is given by a permanent radon entry from building materials and a dynamic removal through ventilation, which is driven by indoor-outdoor temperature differences and wind speed.

Air Movements↗
PubMed2003

A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials.

Dynamic flexure is a major mode of deformation in the native heart valve cusp, and may effect the mechanical and biological development of tissue engineered heart valves (TEHV). To explore this hypothesis, a novel bioreactor was developed to study the effect of dynamic flexural stimulation on TEHV biomaterials. It was implemented in a study to compare the effect of uni-directional cyclic flexure on the effective stiffness of two candidate TEHV scaffolds: a non-woven mesh of polyglycolic acid (PGA) fibers, and a non-woven mesh of PGA and poly L-lactic acid (PLLA) fibers, both coated with poly 4-hydroxybutyrate (P4HB). The bioreactor has the capacity to dynamically flex 12 rectangular samples (25 x 7.5 x 2mm) under sterile conditions in a cell culture incubator. Sterility was maintained in the bioreactor for at least 5 weeks of incubation. Flexure tests to measure the effective stiffness in the "with-flexure" (WF) and opposing "against-flexure" (AF) directions indicated that dynamically flexed PGA/PLLA/P4HB scaffolds were approximately 72% (3 weeks) and 76% (5 weeks) less stiff than static controls (p<0.01), and that they developed directional anisotropy by 3 weeks of incubation (stiffer AF, p<0.01). In contrast, both dynamically flexed and static PGA/P4HB scaffolds exhibited a trend of decreased stiffness with incubation, with no development of directional anisotropy. Dynamically flexed PGA/P4HB scaffolds were significantly less stiff than static controls at 3 weeks (p<0.05). Scanning electron microscopy revealed signs of heterogeneous P4HB coating and fiber disruption, suggesting possible explanations for the observed mechanical properties. These results indicate that dynamic flexure can produce quantitative and qualitative changes in the mechanical properties of TEHV scaffolds, and suggest that these differences need to be accounted for when comparing the effects of mechanical stimulation on the development of cell-seeded TEHV constructs.

Absorbable Implants↗