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PubMed1994

Giant cell reparative granuloma of the distal skeletal bones. A report of five cases with immunohistochemical findings.

Giant cell reparative granuloma (GCRG) is a reactive bone lesion that most often involves the jaws. However, occasional cases of GCRG in the distal extremities have been reported, to which we add five cases. All the patients were young to middle-aged adults and had sharply bordered, lytic lesions. Histologically, all the lesions had areas of osteoclast-like giant cells and osteoblast mantled osteoid. Two of the cases had foci of osteoclast-like giant cells lining vascular spaces. In extragnathic locations, GCRG may simulate other osteolytic giant cells lesions such as giant cell tumour of bone and aneurysmal bone cyst (AnBC). Immunohistochemically, all cases showed positive staining of the stromal spindle cells for vimentin and actin, and of the osteoclast-like giant cells for CD68, vimentin and leucocyte common antigen. GCRG is a benign lesion and conservative therapy is curative. As GCRG may have histological features which resemble AnBC it may be considered to be the solid variant of AnBC.

Actins↗

PubMed1995

Determination of the NMR solution structure of a specific DNA complex of the Myb DNA-binding domain.

The solution structure of a specific DNA complex of the minimum DNA-binding domain of the mouse c-Myb protein was determined by distance geometry calculations using a set of 1732 nuclear Overhauser enhancement (NOE) distance restraints. In order to determine the complex structure independent of the initial guess, we have developed two different procedures for the docking calculation using simulated annealing in four-dimensional space (4D-SA). One is a multiple-step procedure, where the protein and the DNA were first constructed independently by 4D-SA using only the individual intramolecular NOE distance restraints. Here, the initial structure of the protein was a random coil and that of the DNA was a typical B-form duplex. Then, as the starting structure for the next docking procedure, the converged protein and DNA structures were placed in random molecular orientations, separated by 50 A. The two molecules were docked by 4D-SA utilizing all the restraints, including the additional 66 intermolecular distance restraints. The second procedure comprised a single step, in which a random-cell protein and a typical B-form DNA duplex were first placed 70 A from each other. Then, using all the intramolecular and intermolecular NOE distance restraints, the complex structure was constructed by 4D-SA. Both procedures yielded the converged complex structures with similar quality and structural divergence, but the multiple-step procedure has much better convergence power than the single-step procedure. A model study of the two procedures was performed to confirm the structural quality, depending upon the number of intermolecular distance restraints, using the X-ray structure of the engrailed homeodomain-DNA complex.

Animals↗

PubMed1998

Measuring regularity by means of a corrected conditional entropy in sympathetic outflow.

A new method for measuring the regularity of a process over short data sequences is reported. This method is based on the definition of a new function (the corrected conditional entropy) and on the extraction of its minimum. This value is taken as an index in the information domain quantifying the regularity of the process. The corrected conditional entropy is designed to decrease in relation to the regularity of the process (like other estimates of the entropy rate), but it is able to increase when no robust statistic can be performed as a result of a limited amount of available samples. As a consequence of the minimisation procedure, the proposed index is obtained without an a-priori definition of the pattern length (i.e. of the embedding dimension of the reconstructed phase space). The method is validated on simulations and applied to beat-to-beat sequences of the sympathetic discharge obtained from decerebrate artificially ventilated cats. At control, regular, both quasiperiodic and periodic (locked to ventilation) dynamics are observed. During the sympathetic activation induced by inferior vena cava occlusion, the presence of phase-locked patterns and the increase in regularity of the sympathetic discharge evidence an augmented coupling between the sympathetic discharge and ventilation. The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation.

Animals↗

PubMed2005

Modeling patient flows using a queuing network with blocking.

The downsizing and closing of state mental health institutions in Philadelphia in the 1990's led to the development of a continuum care network of residential-based services. Although the diversity of care settings increased, congestion in facilities caused many patients to unnecessarily spend extra days in intensive facilities. This study applies a queuing network system with blocking to analyze such congestion processes. "Blocking" denotes situations where patients are turned away from accommodations to which they are referred, and are thus forced to remain in their present facilities until space becomes available. Both mathematical and simulation results are presented and compared. Although queuing models have been used in numerous healthcare studies, the inclusion of blocking is still rare. We found that, in Philadelphia, the shortage of a particular type of facilities may have created "upstream blocking". Thus removal of such facility-specific bottlenecks may be the most efficient way to reduce congestion in the system as a whole.

Health Facility Closure↗

PubMed1986

gamma-Aminobutyric acid stimulates chloride permeability across microdissected Deiters' neuronal membrane.

Fluxes of 36Cl- across freshly prepared Deiters' neuronal membranes have been studied in a two-compartment microchamber simulating the extra- and the intracellular space. The rate of 36Cl- influx was enhanced by gamma-aminobutyric acid (GABA) (10(-4) M), the effect being reversed by picrotoxin (10(-4) M) and by bicuculline (10(-5) M). Diazepam (10(-8)-10(-7) M) did not potentiate the response to GABA and rather depressed it. However, a barbiturate site is most probably present in the GABA receptor complexes since pentobarbitone (10(-4) M) was able to stimulate 36Cl- permeability to the same extent as GABA itself.

Animals↗

PubMed1979

A computer program for topographic analysis of biomolecular systems.

This program essentially generates a picture of a space filling molecular model. By precise simulation of the intersections between atoms, leaving out the 'hidden line', a good perspective is produced. Additional three dimensional information is provided by simulating reflection spots on the surface. This program has been used to visualise three dimensional surface features of biologically important molecules (e.g., valinomycin). With slight modification the program can be used to visualise enzyme active sites and receptor surfaces. It can also be used to create animated motion pictures of molecular dynamics.

Chemical Phenomena↗

PubMed1995

Analytic solution of the Variable-Volume Double-Pool urea kinetics model applied to parameter estimation in hemodialysis.

An analytic solution of the Variable-Volume Double-Pool urea kinetics model and its application to the estimation of clinically relevant parameters of the patient-machine system, are presented. These include the urea distribution volume and generation rate and the mean dialyzer clearance. The estimation of these parameters is based on the assumption of constant values for the diffusion coefficient between the two pools and the intra-extracellular volume ratio. Results obtained by computer simulations show that the effect of a +/- 50% variation of these parameters influences the estimates less than standard measurement errors. Starting from these results, four methods to in vivo estimate the urea distribution volume and generation rate from blood samples are compared. Two methods are based on the analytic solution of the double-pool model using seven samples (reference method) or three samples (new clinical method). The remaining methods are based on urea mass-balance and are largely used in the clinical practice. These last techniques differ from each other for the blood sample taken at the end of the treatment or 30 min later. The results obtained from hemofiltration sessions show that the urea generation rate is accurately estimated by all methods. The total distribution volume is still accurately estimated by the new clinical method while it is systematically underestimated by the urea mass-balance when the blood sample at the end of dialysis is used. Instead, a high overcompensation results using the blood sample taken 30 min after the end of dialysis. Finally, the new clinical method also provides reliable estimates for the dialyzer clearance starting from only three blood samples all taken during dialysis.

Algorithms↗

PubMed1993

Models for computer simulation studies of input functions for tracer kinetic modeling with positron emission tomography.

In tracer kinetic modeling with Positron Emission Tomography (PET), the direct measurement (piecewise linear approximation) of plasma time-activity curve of tracer (PTAC) is often used as the input function to estimate regional physiological parameters. However, no explicit general model is available for PTAC itself, which limits the further study of the effects of PTAC, such as PTAC measurement noise or PTAC sampling schedules, on the physiological parameters estimation. A PTAC model is proposed in this paper and compared with other four possible candidates. Eight sets of [18F]-fluoro-2-deoxy-D-glucose (FDG) experimental data were used to test the models and several statistical criteria were used to validate their adequacy. An application of the model to improve the estimation of local cerebral metabolic rate of glucose (LCMRGlc) is presented. This model is also expected to be useful for generating realistic PTAC curves in computer simulation studies of other tracers and their kinetic modeling characteristics.

Animals↗

PubMedDate not supplied

Estimation of muscle forces about the wrist joint during isometric tasks using an EMG coefficient method.

A technique for estimating isometric muscle forces based on EMGs and anatomical parameters is presented. In the present study, we record EMGs from five muscles acting at the wrist, during a series of isometric contractions in flexion, extension, ulnar deviation and radial deviation. The method then uses these EMG signals and the necessary anatomical data to estimate individual muscle forces. For one subject, complete anatomical parameters were estimated by MRI reconstruction of muscle moment arms and lines of muscle action. In all subjects, the errors associated with variability in the EMG signals were reduced through the use of signal processing techniques and intensive subject training. These EMG-based force estimates were then validated by evaluations at torque directions in which no mechanical redundancy existed. The stability of the solution space was examined using Monte Carlo simulations. The results of our study show that individual muscle forces at the wrist can be estimated with considerable accuracy, without assuming any control strategy (as is done with optimization theories). However, due to the limited mechanical redundancy of the wrist, it is uncertain whether the method can be used to estimate muscle forces in more highly redundant systems.

Adult↗

PubMed1995

Lateralization of predator-evasion response in a teleost fish (Girardinus falcatus).

Evidence of lateral asymmetries in the direction of turning during escape behaviour in a species of poeciliid fish, Girardinus falcatus, is reported. When repeatedly faced with a simulated predator (in five successive sessions, spaced 7 days apart), immature Girardinus falcatus exhibited a significant population bias to turn right on the first session and a progressive bias to turn left in subsequent sessions. Mature Girardinus were then tested to check whether the shift in the direction of turn with repeated sessions depended on maturation or habituation. It was found that adult Girardinus showed a slight population bias to turn right in the first session and a strong subsequent bias to turn left after repeated sessions. The implications of these findings to our current understanding of the evolution of brain lateralization are discussed.

Animals↗

PubMed1975

Transport of H2 and SF6 in the lung.

The dead spaces for hydrogen and sulfur hexafluoride are predicted from the solution of a partial differential equation, applied to Weibel's morphometric data of the lung, and including longitudinal convection and diffusion coupled with instantaneous radial diffusion. Traces of H2 and SF6 were washed in and out of the lungs of two normal subjects. Dead spaces for both gases were calculated from the wash-out curves by a least squares analysis. Prediction and experiment agree in the case of H2. The model overestimates the dead space for SF6 particularly for large tidal volumes and for high breathing frequencies. Several factors which can contribute to this disagreement are considered. From simulation experiments it is evident, that the dead space for SF6 is highly sensitive to factors which influence molecular dispersion in the region of respiratory bronchioles. Cardiogenic mixing and some sort of flow-dependent mixing in this zone cannot be ruled out. However, the experimental data can also be explained by choosing another set of morphometric data for the alveolated airways.

Adult↗

PubMed1994

Effect of space flight on cytokine production.

Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines. Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

Animals↗

PubMed1994

Systematic analysis of errors in target localization and treatment delivery in stereotactic radiosurgery (SRS).

PURPOSE: To systematically analyze the spatial uncertainties associated with each step of the stereotactic radiosurgery (SRS) procedure and the overall spatial accuracy in the treatment delivery. METHODS AND MATERIALS: A special test device has been designed and fabricated to permit accurate simulation, localization and treatment portal verification of a SRS target. This device with simulated targets dispersed in 3-D space can be rigidly attached to the BRW CT or angio frame for localization, to the BRW phantom base for target coordinate determination, and to the floor stand for portal verification. The setup allows evaluation of the accuracy of each procedure separately as well as the overall accuracy in the delivery of SRS treatment. RESULTS: Biplanar film localizations reveal a systematic error in the phantom base pointer of the order of 0.1 mm that is applied as a correction to the measured target coordinates. Targets localized by planar film angiography had a mean positional error of 0.38 +/- 0.1 mm compared to 1.0 +/- 0.7 mm for digital angiographic localization. The positional accuracy associated with CT localization was superior when a 2 mm vs. 4 mm slice thickness was used (0.9 +/- 0.3 mm vs. 1.6 +/- 0.5 mm error). Cumulative mean errors, including inaccuracies associated with treatment setup, were 1.0 +/- 0.4 mm for radiographic localization, 1.2 +/- 0.5 mm for CT with a 512 x 512 matrix and 2 mm slice thickness, and 2.0 +/- 0.6 mm for CT at a 4 mm slice thickness (256 x 256 matrix). Larger errors would be expected in the clinical setting. CONCLUSION: Spatial errors in stereotactic radiosurgery are best estimated using a systematic approach to isolate independent contributing factors. The accuracy in target localization determines the overall accuracy of SRS procedure, provided the mechanical accuracy of the treatment apparatus is assured. Biplanar treatment portal verification with a fiducial localization frame is an accurate method of verifying the target coordinates before delivering treatment.

Humans↗

PubMed1986

Directional hearing in the grassfrog (Rana temporaria L.). II. Acoustics and modelling of the auditory periphery.

In an earlier paper (Vlaming et al., 1984) we reported on optical measurements (laser-doppler interferometry) of the vibrations characteristics of the grassfrog's tympanic membrane. In the present paper these measurements were extended to include acoustic measurements concerning the functional role of the mouth cavity in frog hearing. Based on these measurements a model of the frog's acoustic periphery, consisting of three coupled linear oscillators with three entrance ports for sound, was developed and analyzed mathematically to give the various relevant transfer functions. The model is characterized by six parameters, all of which could be estimated from the available experimental data. For frequencies up to some 1500 Hz the model adequately describes the experimental data, both our own and earlier, seemingly conflicting data in the literature. For higher frequencies deviations occur, possibly due to nonuniform vibrations of the membranes. The model was used to evaluate the monaural directional sensitivity of the frog under free-field stimulation. Essentially it behaves as a combined pressure-gradient receiver, with highly frequency-dependent directional sensitivity. Directional sensitivity of the tympanic membrane could be modulated drastically by changing the resonance properties of the mouth cavity, without affecting the intrinsic membrane properties. This, theoretically, allows the frog to manipulate its direction sensitivity by actively tuning the volume of its mouth cavity. In order to account for discrepancies with known properties of low-frequency auditory nerve fibers an additional, extra-tympanic channel was included into the model. The extended model, the second-channel possibly involving the opercularis complex, provides a good quantitative fit to the available data on tympanic membrane movement as well as auditory nerve activity. Finally, the model enables to simulate a (moving) sound source in space, while stimulating the frog via closed couplers.

Acoustics↗

PubMed2004

Experimental concept for examination of biological effects of magnetic field concealed by gravity.

Space is not only a place to study biological effects of gravity, but also provides unique opportunities to examine other environmental factors, where the biological actions are masked by gravity on the ground. Even the earth's magnetic field is steadily acting on living systems, and is known to influence many biological processes. A systematic survey and assessment of its action are difficult to conduct in the presence of dominant factors, such as gravity. Investigation of responses of biological systems against the combined environment of zero-gravity and zero-magnetic field might establish the baseline for the analysis of biological effects of magnetic factors. We propose, in this paper, an experimental concept in this context, together with a practical approach of the experiments, both in orbit and on the ground, with a thin magnetic shielding film. Plant epicotyl growth was taken as an exemplar index to evaluate technical and scientific feasibility of the proposed system concept.

Cotyledon↗

PubMed2003

Structure of the human NK cell triggering receptor NKp46 ectodomain.

NKp46, a natural killer (NK) cell-specific receptor, has been recently identified as one of the triggering receptors involved in NK cell activation mediated by non-HLA class I ligands. The structure of the NKp46 extracellular receptor region, here reported, consists of two Ig-like domains assembled similarly to leukocyte immunoglobulin-like receptors (LIRs) and killer inhibitory receptors (KIRs). The extensive NKp46 residue substitutions at sites structurally related to those mediating interaction with HLA antigens in LIRs and KIRs indicate that NKp46 recognition processes in vivo should involve non-HLA ligands. NKP46 is shown to stem from an ancestral KIR/LIR family. However, the absence of close paralogues, such as those found for LIR and KIR, indicates that NKp46 is the unique member of a distinct Ig-like subfamily and suggests a specific role, which appears to be maintained across primates and rodents.

Amino Acid Sequence↗

PubMed2004

Structure analysis of intercalated layer silicates: combination of molecular simulations and experiment.

Na(+)-montmorillonite type Wyoming, cloisite Na(+) from Southern Clay Products, Inc., was intercalated (i) with octadecylammonium cations and subsequently intercalated with octadecylamine molecules, (ii) with dodecylamine molecules, and (iii) with octylamine molecules to determine the applicability of these intercalates for nanocomposite materials on the base of polymer/clay. The structures were determined on the basis of a combination of results from X-ray diffraction and molecular simulations. The calculated values of basal spacings are in good agreement with experimental basal spacings when experimental samples were prepared. The interlayer space of intercalated montmorillonite shows a monolayer or bilayer arrangement of alkyl chains in dependence on the concentration of the intercalation solution. The values of the total sublimation energy, interaction energy, and exfoliation energy were calculated for all investigated samples. Low values of exfoliation energies lead to better exfoliation of intercalated silicate layers and this material appears suitable for use as a precursor for polymer/clay nanocomposites. The values of exfoliation energy for the investigated samples show that montmorillonite intercalated with dodecylamine or octadecylamine molecules is suitable for exfoliation of silicate layers.

Models, Chemical↗

PubMed2001

Influence of a lipid interface on protein dynamics in a fungal lipase.

Lipases catalyze lipolytic reactions and for optimal activity they require a lipid interface. To study the effect of a lipid aggregate on the behavior of the enzyme at the interfacial plane and how the aggregate influences an attached substrate or product molecule in time and space, we have performed molecular dynamics simulations. The simulations were performed over 1 to 2 ns using explicit SPC water. The interaction energies between protein and lipid are mainly due to van der Waals contributions reflecting the hydrophobic nature of the lipid molecules. Estimations of the protonation state of titratable residues indicated that the negative charge on the fatty acid is stabilized by interactions with the titratable residues Tyr-28, His-143, and His-257. In the presence of a lipid patch, the active site lid opens wider than observed in the corresponding simulations in an aqueous environment. In that lid conformation, the hydrophobic residues Ile-85, Ile-89, and Leu-92 are embedded in the lipid patch. The behavior of the substrate or product molecule is sensitive to the environment. Entering and leaving of substrate molecules could be observed in presence of the lipid patch, whereas the product forms strong hydrogen bonds with Ser-82, Ser-144, and Trp-88, suggesting that the formation of hydrogen bonds may be an important contribution to the mechanism by which product inhibition might take place.

Binding Sites↗