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PubMed2005

Kinematic evaluation in Parkinson's disease using a hand-held position transducer and computerized signal analysis.

BACKGROUND: The objective of this work was to develop a device for quantification of akinesia in Parkinson's disease, for the use in home monitoring of PD patients, as a part of home telecare programs. For this purpose a simple movement task is to be preferred, and the measurement devices must be small, lightweight, and easy to use, so patients may perform the measurements unattended. Another intended application was optimisation of the electrode position during implantations of neuromodulation systems for treatment of Parkinson. METHOD: A hand held transducer was used to measure the position of the thumb while the patient repeatedly flexed and extended the thumb. The position data was sampled and stored on a personal computer with a plug in converter card and software. Measurements were performed on 15 PD patients and 6 age-matched controls. Signal analysis procedures were developed in order to automatically derive numerical parameters that quantify the movement performance. In order to select the most relevant parameters, they were correlated to Unified Parkinson Disease Rating Scale (UPDRS) motor scores (Spearman's rank, single sided, p < 0.05). FINDINGS: In reviews of the raw position signals the amplitude and frequency was found to be lower in patients than in controls. In patients the movement was frequently interrupted by short periods of hesitation. The calculated parameters of covered distance (correlation coefficient r = -0.63), hesitation (r = 0.64) and frequency (r = -0.6) were found to be most relevant, as they correlated best to the UPDRS hand pronation/supination score. DISCUSSION: The equipment proved to be fast to setup and easy to use. The signal analysis methods provided meaningful numerical parameters for quantification of akinesia, represented in hand pronation/supination. These results suggest that the described methods may be useful for telemedicine and intraoperative use.

Aged↗

PubMed2003

An information theoretic approach for analyzing temporal patterns of gene expression.

MOTIVATION: Arrays allow measurements of the expression levels of thousands of mRNAs to be made simultaneously. The resulting data sets are information rich but require extensive mining to enhance their usefulness. Information theoretic methods are capable of assessing similarities and dissimilarities between data distributions and may be suited to the analysis of gene expression experiments. The purpose of this study was to investigate information theoretic data mining approaches to discover temporal patterns of gene expression from array-derived gene expression data. RESULTS: The Kullback-Leibler divergence, an information-theoretic distance that measures the relative dissimilarity between two data distribution profiles, was used in conjunction with an unsupervised self-organizing map algorithm. Two published, array-derived gene expression data sets were analyzed. The patterns obtained with the KL clustering method were found to be superior to those obtained with the hierarchical clustering algorithm using the Pearson correlation distance measure. The biological significance of the results was also examined. AVAILABILITY: Software code is available by request from the authors. All programs were written in ANSI C and Matlab (Mathworks Inc., Natick, MA).

Algorithms↗

PubMed2002

Comparison of visual acuities at different distances and defocus curves.

PURPOSE: To evaluate how visual acuities at different distances correlate with results from defocus curves. SETTING: Department of Ophthalmology and Institute of Medical Physics, University of Vienna, Medical School, Vienna, and Department of Ophthalmology, Krankenhaus St. Pölten, St. Pölten, Austria. METHODS: This study comprised 15 eyes of 14 patients with a mean age of 67.9 years +/- 9.7 (SD) with a monofocal silicone intraocular lens (911A, Pharmacia). The best corrected distance visual acuity was determined at viewing distances of 6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, and 33 cm using logMAR charts. Defocus curves were then evaluated from -3.0 to -0.5 diopter (D) at 0.5 D increments from the best distance correction at a viewing distance of 6 m. RESULTS: The mean distance visual acuity was logMAR 0.08 +/- 0.07. The visual acuity graph from the testing at different distances was above the defocus graph at all testing points. Comparison of the visual acuity results from the 2 tests revealed statistically significant differences in the range from 2 m (-0.5 D) to 33 cm (-3.0 D). CONCLUSIONS: Results of defocus curves disregard the diminutions of minus glasses, the normally restricted viewing distance to 6 m for distance acuity determination, and in particular the physiological miosis caused by the near-point reaction.

Aged↗

PubMedDate not supplied

Biochemical changes in response to intensive resistance exercise training in the elderly.

BACKGROUND: It is assumed that low-grade inflammation, characterized by increased circulating IL-6 and TNF-alpha, is related to the development of sarcopenia. Physical exercise, especially high intensity resistance training, has been shown to be effective in restoring the strength deficit in the elderly. Intensive exercise is accompanied by significant release of IL-6 and TNF-alpha into the blood circulation, but does not result in muscle wasting. Exercise-induced changes in heat-shock protein (Hsp), responsible for cellular protection during stressful situations, might interfere with the acute phase reaction and muscle adaptation. OBJECTIVE: To investigate if intensive strength training in elderly persons induces changes in Hsp70 expression, and if these changes are related to changes in the acute phase reaction or muscle adaptation. METHODS: 31 elderly persons (aged 68.4+/-5.4 years) performed 6 weeks' intensive strength training. At baseline and after 6 weeks, muscle strength, functional performance (physical activity profile, 6-min walk, 30- second chair stand, grip strength, chair sit & reach and back scratch), linear isokinetic leg extension, circulating IL-6, TNF-alpha, IL-10 and TGF-beta, and Hsp70 in monocytes (M) and lymphocytes (L) immediately after sampling (IAS), after incubation at 37 and 42 degrees C were determined. In 12 participants, cytokines were determined in untrained and trained conditions before and after a single training session. RESULTS: After 6 weeks' training, muscle strength and functional performance improved significantly, together with decreased Hsp70 IAS and Hsp70 37 degrees C and increased Hsp70 42 degrees C (all p<0.05). Strength gains correlated positively with baseline Hsp70 37 degrees C and training-induced changes of Hsp70 42 degrees C in M and L. In an untrained condition, training induced an increase of IL-6 (p<0.05) and a tendency of IL-10 to decrease (p=0.06). In a trained condition the decrease of IL-10 disappeared. Baseline physical activity and 6-min walk distance correlated negatively with circulating IL-6 (p<0.05); except for a negative correlation between TGF-beta and Hsp70 37 degrees C L (p<0.05), no significant relationships were found between cytokines and Hsp70. After the training program, Hsp70 37 degrees C was negatively related to circulating TNF-alpha, IL-10 and TGF-beta. CONCLUSION: Strength training in the elderly induces changes in Hsp70 expression, associated to strength gains and circulating cytokines.

Acute-Phase Reaction↗

PubMed2000

Modulation instability and pattern formation in spatially incoherent light beams.

We report on the experimental observation of modulation instability of partially spatially incoherent light beams in noninstantaneous nonlinear media and show that in such systems patterns can form spontaneously from noise. Incoherent modulation instability occurs above a specific threshold that depends on the coherence properties (correlation distance) of the wave packet and leads to a periodic train of one-dimensional filaments. At a higher value of nonlinearity, the incoherent one-dimensional filaments display a two-dimensional instability and break up into self-ordered arrays of light spots. This discovery of incoherent pattern formation reflects on many other nonlinear systems beyond optics. It implies that patterns can form spontaneously (from noise) in diverse nonlinear many-body systems involving weakly correlated particles, such as atomic gases at (or near) Bose-Einstein condensation temperatures and electrons in semiconductors at the vicinity of the quantum Hall regime.

Journal Article↗

PubMed2006

[Tissue contrast in MRI owing to intermolecular multiple-quantum coherences (iMQC)].

Dipole-dipole interactions in 1H NMR of liquids permit a new tissue contrast in MR imaging (MRI). For this purpose, the CRAZED (COSY Revamped by Asymmetric Z-gradient Echo Detection) sequence which simply consists of two radiofrequency pulses of delay tau and a magnetic field gradient pulse of strength G, is applied to create intermolecular multiple-quantum coherences of dipolar-coupled ensembles of water protons with spatial distance d = pi/(gammaGtau). As a consequence, the measured signal originates from "sources" that have a tunable dimension. CRAZED was first applied to MR imaging at 1.5 T by Zhong et al. To study the contrast properties and influence of sequence parameters of this technique, we implemented different sequences of this type on a clinical 1.5-T whole-body tomograph. The sequences were optimized in experiments with agar gel phantoms. We obtained images with dipolar contrast from the brain of healthy volunteers. The gradient system enabled correlation distances d in the range of 0.05 mm to 1 mm.

Image Processing, Computer-Assisted↗

PubMed2003

Comparisons and validation of statistical clustering techniques for microarray gene expression data.

MOTIVATION: With the advent of microarray chip technology, large data sets are emerging containing the simultaneous expression levels of thousands of genes at various time points during a biological process. Biologists are attempting to group genes based on the temporal pattern of their expression levels. While the use of hierarchical clustering (UPGMA) with correlation 'distance' has been the most common in the microarray studies, there are many more choices of clustering algorithms in pattern recognition and statistics literature. At the moment there do not seem to be any clear-cut guidelines regarding the choice of a clustering algorithm to be used for grouping genes based on their expression profiles. RESULTS: In this paper, we consider six clustering algorithms (of various flavors!) and evaluate their performances on a well-known publicly available microarray data set on sporulation of budding yeast and on two simulated data sets. Among other things, we formulate three reasonable validation strategies that can be used with any clustering algorithm when temporal observations or replications are present. We evaluate each of these six clustering methods with these validation measures. While the 'best' method is dependent on the exact validation strategy and the number of clusters to be used, overall Diana appears to be a solid performer. Interestingly, the performance of correlation-based hierarchical clustering and model-based clustering (another method that has been advocated by a number of researchers) appear to be on opposite extremes, depending on what validation measure one employs. Next it is shown that the group means produced by Diana are the closest and those produced by UPGMA are the farthest from a model profile based on a set of hand-picked genes. AVAILABILITY: S+ codes for the partial least squares based clustering are available from the authors upon request. All other clustering methods considered have S+ implementation in the library MASS. S+ codes for calculating the validation measures are available from the authors upon request. The sporulation data set is publicly available at http://cmgm.stanford.edu/pbrown/sporulation

Algorithms↗

PubMed2005

Identification of neutrophil gelatinase-associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte-secreted protein response to IL-1beta: a proteomic analysis.

The liver is the major source of proteins used throughout the body for various functions. Upon injury or infection, an acute phase response (APR) is initiated in the liver that is primarily mediated by inflammatory cytokines such as interleukin-1beta (IL-1beta) and interleukin-6. Among others, the APR is characterized by an altered protein synthetic profile. We used two-dimensional gel electrophoresis to study the dynamics of changes in protein synthesis in hepatocytes exposed to these inflammatory cytokines. Protein profiles were quantified using image analysis and further analyzed using multivariate statistical methods. Our results indicate that IL-1beta and IL-6 each induces secreted protein responses with distinct dynamics and dose-dependence. Parallel stimulation by IL-1beta and IL-6 results in a protein pattern indistinguishable from the IL-1beta pattern, indicating a dominant effect of IL-1beta over IL-6 at the doses tested. Multidimensional scaling (MDS) of correlation distances between protein secretion levels revealed two protein pairs that are robustly co-secreted across the various cytokine stimulation conditions, suggesting shared regulatory pathways. Finally, we also used multivariate alternating conditional expectation (MACE) to identify transformation functions that discriminated the cytokine-stimulated and untreated hepatocyte-secreted protein profiles. Our analysis indicates that the expression of neutrophil gelatinase-associated lipocalin (NGAL) was sufficient to discriminate between IL-1beta and IL-6 stimulation. The combination of proteomics and multivariate analysis is expected to provide new information on the cellular regulatory networks involved in generating specific cellular responses.

Acute-Phase Proteins↗

PubMed2005

Thermal- and photoinduced spin-state switching in an unprecedented three-dimensional bimetallic coordination polymer.

The compound {Fe(pmd)[Ag(CN)2][Ag2(CN)3]} (pmd=pyrimidine) was synthesized and characterized. Magnetic, calorimetric and single crystal visible spectroscopic studies demonstrate the occurrence of a two-step high-spin (HS) right arrow over left arrow low-spin (LS) transition. The critical temperatures are T(c1)=185 and T(c2)=148 K. Each step involves approximately 50 % of the iron centers, with the low-temperature step showing a hysteresis of 2.5 K. The enthalpy and entropy variations associated with the two steps are DeltaH(1)=3.6+/-0.4 kJ mol(-1) and DeltaS(1)=19.5+/-3 J K(-1) mol(-1); DeltaH(2)=4.8+/-0.4 kJ mol(-1) and DeltaS(2)=33.5+/-3 J K(-1) mol(-1). Photomagnetic and visible spectroscopy experiments show that below 50 K, where the LS state is the thermodynamically stable state, the compound can be switched quantitatively to the HS state using green-red light (550-650 nm). HS-to-LS relaxation experiments in the dark at temperatures between 15 and 55 K show that the relaxation takes place via a two-step cooperative process, which was analyzed in the context of the mean field theory. The crystal structure has been studied at 290, 220, 170, 90 and 30 K together with 30 K after irradiation. The compound adopts monoclinic symmetry (P2(1)/c, Z=16) at all temperatures. There are five [FeN6] pseudo-octahedral sites linked by pmd, [Ag(CN)2]- and [Ag2(CN)3]- bridging ligands to form an unprecedented three-dimensional (6,6) topology. The structural analysis allows for an understanding of the microscopic mechanism of the two-step behavior of the thermally induced spin transition as well as the corresponding relaxation of the photoexcited compound based on the individual changes of the five sites. Synergy between metallophilic interactions and the spin transition is also shown by the variation of the AgAg distances. Correlations between the variation of the unit-cell volume and the change of AgAg interactions within each step with the asymmetric change of the anomalous heat capacity have also been inferred.

Journal Article↗

PubMed2004

Diffusion measurements free of motion artifacts using intermolecular dipole-dipole interactions.

Diffusion encoding, or diffusion weighting, is commonly achieved by applying a pair of balanced pulsed-field gradients during spin evolution. An alternative way to obtain diffusion measurements is to select dipolar correlation distances using the distant dipolar field (DDF) in systems with abundant spin density, such as water in tissues. Diffusion weighting using this effect is unique in that the refocusing "gradient" is carried within the sample, and thus the macroscopic motion of the sample is not expected to interfere with signal formation. The experiments presented here demonstrate that in moving phantoms, the phase shift of the signal due to linear motion is minimal in diffusion-weighted (DW) DDF measurements, and that motion artifacts in images of moving phantoms and the abdomen of live mice are small compared to standard pulsed-field-gradient methods. The technique may facilitate the use of DWI in typically motion-prone regions such as the abdomen, lungs, and heart.

Abdomen↗

PubMed2006

Proteomic pattern-based analyses of light responses in Arabidopsis thaliana wild-type and photoreceptor mutants.

Light critically affects the physiology of plants. Using two-dimensional gel electrophoresis, we used a proteomics approach to analyze the responses of Arabidopsis thaliana to red (660 nm), far-red (730 nm) and blue (450 nm) light, which are utilized by type II and type I phytochromes, and blue light receptors, respectively. Under specific light treatments, the proteomic profiles of 49 protein spots exhibited over 1.8-fold difference in protein abundance, significant at p <0.05. Most of these proteins were metabolic enzymes, indicating metabolic changes induced by light of specific wavelengths. The differentially-expressed proteins formed seven clusters, reflecting co-regulation. We used the 49 differentially-regulated proteins as molecular markers for plant responses to light, and by developing a procedure that calculates the Pearson correlation distance of cluster-to-cluster similarity in expression changes, we assessed the proteome-based relatedness of light responses for wild-type and phytochrome mutant plants. Overall, this assessment was consistent with the known physiological responses of plants to light. However, we also observed a number of novel responses at the proteomic level, which were not predicted from known physiological changes.

Arabidopsis↗

PubMed1984

Capillarization, mitochondrial densities, oxygen diffusion distances and innervation of red and white muscle of the lizard Dipsosaurus dorsalis.

The white and red regions of the iliofibularis muscle of the lizard Dipsosaurus dorsalis were analyzed using histologic and morphometric analysis. These regions are composed of fast glycolytic (FG) and both fast oxidative, glycolytic (FOG) and tonic fibers, respectively. Endplate morphology and number of endplates per fiber were estimated from fibers from both areas. Capillary volume densities of the red and white regions were quantified from transverse sections. Mitochondrial volume of fibers from the red and white regions were estimated from electron micrographs. All fibers from the white region of the iliofibularis possessed a single, well defined endplate, as did most red region fibers. The remaining red fibers (28 +/- 5%) possessed an average of 14.7 +/- 3 endplates each, distributed along the entire length of the fiber at intervals of approximately 1124 micron. Red fibers possessed twice the mitochondrial volume of white fibers (7.6 +/- 0.4%, red; 3.8 +/- 0.3%, white). Mitochondria were distributed uniformly through the fibers from both regions. Capillary anisotropy was low (gamma = 1.018) in both regions. Capillary densities of the red region (629 +/- 35 mm-2) were much greater than those of the corresponding white region (73 +/- 8 mm-2). The data indicate that capillary densities, mitochondrial volumes and theoretical diffusion distances correlate well with the oxidative capacity of lizard muscle fibers. Tonic fibers of this species appear oxidative and therefore metabolically capable of functioning during locomotion. The similar mitochondrial volumes and capillary densities of reptilian and mammalian muscles suggest that the greater oxidative capacity of mammalian muscle is due in part to possession of more oxidatively active mitochondria rather than to possession of more mitochondria per se.

Animals↗

PubMed1998

Phylogenetic analysis of reptilian hemoglobins: trees, rates, and divergences.

Phylogenetic relationships among reptiles were examined using previously published and newly determined hemoglobin sequences. Trees reconstructed from these sequences using maximum-parsimony, neighbor-joining, and maximum-likelihood algorithms were compared with a phylogenetic tree of Amniota, which was assembled on the basis of published morphological data. All analyses differentiated alpha chains into alphaA and alphaD types, which are present in all reptiles except crocodiles, where only alphaA chains are expressed. The occurrence of the alphaD chain in squamates (lizards and snakes only in this study) appears to be a general characteristic of these species. Lizards and snakes also express two types of beta chains (betaI and betaII), while only one type of beta chain is present in birds and crocodiles. Reconstructed hemoglobin trees for both alpha and beta sequences did not yield the monophyletic Archosauria (i.e., crocodilians + birds) and Lepidosauria (i.e., Sphenodon + squamates) groups defined by the morphology tree. This discrepancy, as well as some other poorly resolved nodes, might be due to substantial heterogeneity in evolutionary rates among single hemoglobin lineages. Estimation of branch lengths based on uncorrected amino acid substitutions and on distances corrected for multiple substitutions (PAM distances) revealed that relative rates for squamate alphaA and alphaD chains and crocodilian beta chains are at least twice as high as those of the rest of the chains considered. In contrast to these rate inequalities between reptilian orders, little variation was found within squamates, which allowed determination of absolute evolutionary rates for this subset of hemoglobins. Rate estimates for hemoglobins of lizards and snakes yielded 1.7 (alphaA) and 3.3 (beta) million years/PAM when calibrated with published divergence time vs. PAM distance correlates for several speciation events within snakes and for the squamate left and right arrow sphenodontid split. This suggests that hemoglobin chains of squamate reptiles evolved approximately 3.5 (alphaA) or approximately 1.7 times (beta) faster than their mammalian equivalents. These data also were used to obtain a first estimate of some intrasquamate divergence times.

Alligators and Crocodiles↗

PubMed1993

Vascular morphometry of KHT and RIF-1 murine sarcomas.

Although tumor oxygenation and vascular structure have been studied extensively, previous work has most often been qualitative in nature. To clarify underlying physiological mechanisms, a more quantitative approach is needed. The current work considers two murine tumor lines of differing radiobiological hypoxic fraction (HF), the RIF-1 and the KHT fibrosarcomas. Following intravascular injection of India ink, histological sections were prepared and quantitated in terms of anatomical blood vessel-tumor cell distance distributions and vessel diameters. Vessel diameters increased with increasing tumor volume for RIF-1 tumors, while not changing significantly for the KHT. The fraction of the tumor within a given distance of the nearest blood vessel, varied as a function of: (i) tumor line, (ii) distance from tumor surface, and (iii) tumor volume. For small-volume tumors, intertumor differences in vessel-tumor cell distances correlated with differences in radiobiological HF, while for large-volume tumors, vessel-tumor cell differences were not significantly different between tumor lines. Combining current findings with previously determined intravascular oxyhemoglobin distributions in the same two tumor lines, it was apparent that not only is a substantial portion of the tumor volume beyond the expected oxygen diffusion limits of blood vessels, but, in addition, a relatively low percentage of these vessels is capable of supplying oxygen.

Animals↗

PubMed1976

Association kinetics with coupled diffusional flows. Special application to the lac repressor--operator system.

The time development of the association of the lac repressor to the operator is considered in a model where the repressor is allowed to bind unspecifically to DNA and move along the DNA chain in a one-dimensional diffusion. The coupling to the three-dimensional diffusion outside the chain is introduced by letting the repressor associate and dissociate from the chain until it is finally bound to the operator. All distance correlations along the chain are included. The mean time of association is calculated and through a comparison with experimental data the molecular parameters are determined. The one-dimensional diffusion constant is found to be of the order of 10(-9) cm(2)s(-1). The model is sufficiently general to be applicable to other similar systems.

Diffusion↗

PubMed2005

The composite vastus medialis-patellar complex osseomuscular flap as a salvage procedure after complex trauma of the knee--an anatomical study and clinical application.

BACKGROUND: In the setting of severe perigenicular trauma or complicated endoprosthetic knee surgery, primary knee fusion may be the last resort for salvage of the limp. In this case, the patella looses its destination as an anterior knee stabilizer and can become a substantial donor of bone substance, especially if osseous defects are involved. PATIENTS AND METHODS: 12 formalin fixated cadavers were studied in terms of vascular anatomy, pedicle reliability, arc of rotation and their relation to sex, age, and height. Moreover, the operation was performed on a suitable patient. RESULTS: The quadriceps with the vastus medialis and the patella can be raised from the tibial tuberosity up to the entrance of the osteoarticular branch of the superficial femoral artery into the vastus medialis muscle ca 16 cm (15-19 cm) from the inferior patellar pole. This distance correlated well to the overall height of the cadavers (P=0.009). The vascular prerequisites were always present. In the clinical case, there was a favorable outcome with knee fusion after 4 months, despite of the lateral condylar defect. DISCUSSION: The composite vastus medialis-patellar complex osseomuscular flap can be safely used as a source of vascularized femoral condyle substitute in the setting of primary knee fusion.

Arteries↗

PubMed2005

Spatial variability of shallow groundwater level, electrical conductivity and nitrate concentration, and risk assessment of nitrate contamination in North China Plain.

In recent years, nitrate (NO3) contamination of groundwater has become a growing concern for people in rural areas in North China Plain (NCP) where groundwater is used as drinking water. The objective of this study was to evaluate groundwater resource level, to determine groundwater quality and to assess the risk of NO3 pollution in groundwater in Quzhou County in the NCP. Ordinary Kriging (OK) method was used to analyze the spatial variability of shallow groundwater level, groundwater electrical conductivity (EC) and NO3-N concentrations, and Indictor Kriging (IK) method was used to analyze the data with NO3-N concentrations equal or greater than the groundwater NO3 pollution threshold (20 mg L(-1)). The results indicated that groundwater level averaged 9.81 m, a level 6 m lower than in 1990. The spatial correlation distances for groundwater level, EC and NO3-N concentration were 21.93, 2.19 and 3.55 km, respectively. The contour map showed that shallow groundwater level areas extended from north to south across the County. Groundwater EC was above 3 dS m(-1) in the most part of the northern county. Groundwater NO3 pollution (NO3-N> or =20 mg L(-1)) mainly occurred in the County Seat areas due to wastewater irrigation and excessive fertilizer leaching from agricultural fields. At Henantuang town, besides suburban of the County Seat, groundwater was also contaminated by NO3 shown by the map generated using the IK method, which was not reflected in the map generated using the OK method. The map generated using the OK method could not reflect correctly the groundwater NO3 pollution status. The IK method is useful to assess the risk of NO3 pollution by giving the conditional probability of NO3 concentration exceeding the threshold value. It is suggested that risk assessment of NO3 pollution is useful for better managing groundwater resource, preventing soil salinization and minimizing NO3 pollution in groundwater.

China↗

PubMed2005

Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusion.

A variety of experimental evidence suggests that rapid, long-range propagation of conformational changes through the core of proteins plays a vital role in allosteric communication. Here, we describe a non-equilibrium molecular dynamics simulation method, anisotropic thermal diffusion (ATD), which allowed us to observe a dominant intramolecular signaling pathway in PSD-95, a member of the PDZ domain protein family. The observed pathway is in good accordance with a pathway previously inferred using a multiple sequence analysis of 276 PDZ domain proteins. In comparison with conventional solution molecular dynamics methods, the ATD method provides greatly enhanced signal-to-noise, allowing long-distance correlations to be observed clearly. The ATD method requires neither a large number of homologous proteins, nor extremely long simulation times to obtain a complete signaling pathway within a protein. Therefore, the ATD method should prove to be a powerful and general complement to experimental efforts to understand the physical basis of intramolecular signaling.

Allosteric Site↗