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Reactivity to superficial and deep stimuli in patients with chronic musculoskeletal pain.

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire to provide information about fatigue, stiffness, sleep, the intensity of pain (VAS 0-100) and its extent both at onset and at present. Algometry was performed at all American College of Rheumatology (ACR) tender points and at ten control points. Patients were divided into five main groups: fibromyalgia (FS) patients, secondary-concomitant fibromyalgia (SCFS) patients, patients with widespread pain (WP) but not reaching the ACR criterion of 11 tender points, patients with diffuse multiregional pain (MP) not reaching the ACR criteria (widespread pain, tender point counts), and patients with multiregional pain associated with at least 11 tender points (MPTE). von Frey monofilaments were used to assess superficial punctate pressure pain thresholds. Heat and cold pain thresholds were determined with a thermal stimulator. Ischemic pain was assessed by the cold pressure test and the submaximal effort tourniquet test. The scores for stiffness and present pain intensity gradually increased concomitantly with the increase in tender point count and pain extent. The pressure pain thresholds for positive tender and positive control points were significantly lower in the SCFS, FS and MPTE groups than in HS, MP and WP groups, the latter three groups displaying similar values. In all groups, there were no differences in pain thresholds between positive tender and positive control points. The heat pain threshold and the pain threshold in the cold pressure test were lower in the FS and SCFS groups than in HS. The cold pressure tolerance was lower in patients with widespread pain than in HS. In the von Frey test, all patient groups except MP had similar values, which were significantly lower than in HS. Finally, all patient groups displayed lower tourniquet tolerance than HS. In each psychophysical test, patients with widespread pain and patients with multiregional pain showed similar thresholds; however, the thresholds in the MP or MPTE groups differed from those in the FS and SCFS groups. In the FS group, pain thresholds and pain tolerance did not differ according to the presence of ongoing pain at the stimulated site and were not correlated to ongoing pain. The results indicate that dysfunction in the nociceptive system is already present in patients with multiregional pain with a low tender point count; it becomes more and more severe as the positive tender point count and pain extent increase and it is maximal in fibromyalgia patients.

Adult↗

Molecular recognition of oxygen by protein mimics: dynamics on the femtosecond to microsecond time scale.

Molecular recognition by biological macromolecules involves many elementary steps, usually convoluted by diffusion processes. Here we report studies of the dynamics, from the femtosecond to the microsecond time scale, of the different elementary processes involved in the bimolecular recognition of a protein mimic, cobalt picket-fence porphyrin, with varying oxygen concentration at controlled temperatures. Electron transfer, bond breakage, and thermal "on" (recombination) and "off" (dissociation) reactions are the different processes involved. The reaction on-rate is 30 to 60 times smaller than that calculated from standard Smoluchowski theory. Introducing a two-step recognition model, with reversibility being part of both steps, removes the discrepancy and provides consistency for the reported thermodynamics, kinetics, and dynamics. The transient intermediates are configurations defined by the contact between oxygen (diatomic) and the picket-fence porphyrin (macromolecule). This intermediate is critical in the description of the potential energy landscape but, as shown here, both enthalpic and entropic contributions to the free energy are important. In the recognition process, the net entropy decrease is -33 cal mol(-1) K(-1); Delta H is -13.4 kcal mol(-1).

Kinetics↗

Imaging of intermittency in ripple-wave turbulence

The dynamics of a fluid surface filled with high-amplitude ripples were studied with a technique (diffusing light photography) that resolves the height at all locations instantaneously. Even when nonlinearities are strong enough to generate a (Kolmogorov) cascade from long wavelength (where energy is input) to shorter wavelength, the resulting turbulent state contains large coherent spatial structures. The appearance of these structures in a thermal equilibrium state (with the same average energy) would be highly improbable.

Journal Article↗

Real-time sonography of the brain through the anterior fontanelle.

Noninvasive, rapid evaluation of the neonate and young infants with reproducible results is feasible with real-time cranial sonography through the anterior fontanelle. Cerebral anatomy in coronal and sagittal planes is visualized, and the entire ventricular system and adjacent brain parenchyma are identified. This rapid (5-10 min) procedure can be done at/in the incubator making transport of sick neonates unnecessary, thus preserving their thermal stability. Images are recorded on videotape and "hard copy" is obtained afterward. Ventricular size, intracranial hemorrhage (both intraventricular and parenchymal), abnormalities of the the ventricular system, subdural effusion, and fluid-filled lesions are recognized by the usual sonographic criteria. In addition, "solid" parenchymal lesions such as diffuse hemangiomas and brain tumors are depicted as changes in sonographic parenchymal architecture.

Brain↗

Gravity-dependent phenomena at the scale of the single cell.

Progress in gravitational cell biology research will depend on the continuing evaluation of a wide variety of physical phenomena affected by gravity and their roles in extracellular, intercellular, and intracellular processes. This paper examines those responses of organisms to gravity which depend on functions at the single cell level. Single cell functions are affected by perturbations in their internal and external environment by a variety of factors, one of which is the effect of gravity. Physical phenomena that could influence cell function include sedimentation, buoyancy-driven convection, streaming potential, hydrostatic pressure, and interactions among physical transport processes. Thermal motion and fluid viscosity play a significant role in all transport processes at the cellular level. The sedimentation of intracellular organelles tends to be counteracted by the cytoskeleton. Intracellular convective transport may be possible in large cells. In a microgravity environment extracellular solutes must be transported by diffusion or active circulatory processes in the absence of density gradient-driven convection, and flocculation and coalescence are reduced by the lack of motion of aggregates.

Animals↗

Kinetics of the receptor current in bullfrog saccular hair cells.

The receptor current of hair cells from the bullfrog's sacculus was measured by voltage clamp recording across the isolated sensory epithelium. Several hundred hair cells were stimulated en masse by moving the overlying otolithic membrane with a piezoelectrically activated probe. As measured by optical recording of otolithic membrane motion, the step displacement stimuli reached their final amplitudes of up to 1 micrometer within 100 microseconds. The relationship between displacement and steady-state receptor current is an asymmetric, sigmoidal curve about 0.5 micrometer in extent. The time constant of the approach to steady state depends upon the magnitude of the hair bundle displacement and ranges from 100 to 500 microseconds at 4 degrees C; the time course is faster with larger displacements or at higher temperatures. Both the displacement-response curve and the kinetics of the response are changed by alterations in the Ca2+ concentration at the apical surface of the cells. The characteristics of the response are not consistent with simple models for the transduction process that involve enzymatic regulation of channel proteins or diffusible second messengers. Mechanical stimulation is instead posited to act directly by altering the free energy difference between the open and closed forms of the transduction channel, thereby inducing a redistribution between these states. The dependences of the response kinetics on displacement and on temperature suggest that the thermal interconversion between open and closed transduction channels is limited by an enthalpy of activation of about 12 kcal/mol.

Acoustic Stimulation↗

Interstitial laser hyperthermia model development for minimally invasive therapy of breast carcinoma.

BACKGROUND: This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable superficial change, reduced patient trauma, and lowered overall treatment costs. STUDY DESIGN: Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue. RESULTS: Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin. CONCLUSIONS: Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.

Adipose Tissue↗

[Thermal behavior of gypsum bonded investments. (Part 3) Sintering kinetics of insoluble anhydrite (author's transl)].

The sintering kinetics of insoluble anhydrite were studied by measuring the isothermal shrinkage of compacts of insoluble anhydrite powders in air. The sintering process of insoluble anhydrite powders consisted of two stages for the temperature range from 630 degrees C to 720 degrees C. The first shrinkage could be described as a bulk diffusion model and followed the equation delta L/Lo infinity t 0.5l +/- 0.08, where delta L/Lo is fractional shrinkage and t is the sintering time. The apparent activation energy of the shringage was 130 kcal/mole. The second shrinkage followed the equation delta L/Lo infinity t 1.83 +/- 0.30, but could not be explained with reasonable model. However, the SEM observations of the fractured surface of compacts suggested that the second shrinkage corresponded to the grain growth of insoluble anhydrite.

Anhydrides↗

Partially condensed DNA conformations observed by single molecule fluorescence microscopy.

To detect partially condensed conformations of a double-stranded DNA molecule, single molecule fluorescence microscopy is performed here. The single DNA molecules are ethidium stained, 670 kilobase pair bacteriophage G genomes that are observed both during and after expulsion from capsids. Expulsion occurs in an agarose gel. Just after expulsion, the entire G DNA molecule typically has a partially condensed conformation not previously described (called a balloon). A balloon subsequently extrudes a filamentous segment of DNA. The filamentous segment becomes gently elongated via diffusion into the network that forms the agarose gel. The elongated DNA molecule usually has bright spots that undergo both appearance/disappearance and apparent motion. These spots are called dynamic spots. A dynamic spot is assumed to be the image of a zone of partially condensed DNA segments (globule). The positions of globules along an elongated DNA molecule 1) are restricted primarily to time-stable regions with comparatively high thermal motion-induced, micrometer-scale bending of the DNA molecule and 2) move within a given region on a time scale smaller than the time scale of recording. Less mobile globules are observed when either magnesium cation or ethanol is added before gel-embedding DNA molecules. These observations are explained by globules induced at equilibrium by a bending-dependent, inter-DNA segment force. Theory has previously predicted that globules are induced by electrostatic forces along an electrically charged polymer at equilibrium. The hypothesis is proposed that intracellular DNA globules assist action-at-a-distance during DNA metabolism.

Bacteriophages↗

Kappa-carrageenan/gelatin gel beads for the co-immobilization of aerobic and anaerobic microbial communities degrading 2,4,6-trichlorophenol under air-limited conditions.

Alginate and kappa-carrageenan gels were tested as bead materials for the co-immobilization of anaerobic and aerobic microorganisms for the mineralization of 2,4,6-trichlorophenol under air-limited conditions. Chemical, mechanical and thermal culture constraints were pre-defined and the gel resistances were established. Alginate was quickly eliminated because of its chemical instability in the culture media. In anaerobic conditions, the microorganisms transformed the substrates into CH4 and CO2. The kappa-carrageenan gel did not enable these gases to diffuse. They remained as bubbles in the core of the beads and made the beads float. Gelatin was added to kappa-carrageenan in order to change the carrier properties. No biogas bubbles appeared in the bead core during the cultures in anaerobic conditions and the beads reacted well to the culture conditions in the reactor. The co-immobilization of the anaerobic and aerobic microbial communities was successfully performed with the kappa-carrageenan/gelatin gel (2% (w/w) of each polymer). The biological activities, measured by the impedancemetry technique, were preserved in the beads.

Alginates↗

Environmental conditions for treatment of burned patients by the exposure method.

The influence of the thermal environment on evaporation and heat loss from patients with severe burns treated by exposure has been studied. Simple heat transfer equations can be used to predict changes resulting from alterations in environmental conditions and these have been tested using phantoms. The method relies upon the derivation of surface diffusion resistances to describe the moisture properties of burn wounds. Clinical measurements revealed wide variations in evaporation rates and diffusion resistances for different wounds. Evaporation rates changed by less than 30 per cent during the first 5-6 days following injury, after which evaporation from partial skin thickness wounds gradually fell whereas that from full skin thickness wounds tended to remain higher. Raising ambient temperature can compensate for increased evaporation heat losses. Patients can be treated at ambient temperatures of 32-35 degrees C in the intensive care room with a specially designed airflow system. However, raising the temperatures of standard wards with no special airflow or temperature control facilities often caused patients to sweat, further increasing heat loss.

Adolescent↗

Temperature-reversible eruptions of vesicles in model membranes studied by NMR.

Deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) and freeze-fracture electron microscopy were used to study spontaneous vesiculation in model membranes composed of POPC:POPS with or without cholesterol. The NMR spectra indicated the presence of a central isotropic line, the intensity of which is reversibly and linearly dependent upon temperature in the L alpha phase, with no hysteresis when cycling between higher and lower temperatures. Freeze-fracture microscopy showed small, apparently connected vesicles that were only present when the samples were frozen (for freeze-fracture) from an initial temperature of 40-60 degrees C, and absent when the samples are frozen from an initial temperature of 20 degrees C. Analysis of motional narrowing was consistent with the isotropic lines being due to lateral diffusion in (and tumbling of) small vesicles (diameters approximately 50 nm). These results were interpreted in terms of current theories of shape fluctuations in large unilamellar vesicles which predict that small daughter vesicles may spontaneously "erupt" from larger parent vesicles in order to expel the excess area created by thermal expansion of the bilayer surface at constant volume. Assuming that all the increased area due to increasing temperature is associated with the isotropic lines, the NMR results allowed a novel estimate of the coefficient of area expansion alpha A in multilamellar vesicles (MLVs) which is in good agreement with micromechanical measurements upon giant unilamellar vesicles of similar composition. Experiments performed on unilamellar vesicles, which had been placed upon glass beads, confirmed that alpha A determined in this way is unchanged compared with the MLV case. Addition of the highly positively charged (extrinsic) myelin basic protein (MBP) to a POPC:POPS system showed that membrane eruptions of the type described here occur in response to the presence of this protein.

Biophysical Phenomena↗

Intramolecular electrocatalysis of 8-oxo-guanine oxidation: secondary structure control of electron transfer in osmium-labeled oligonucleotides.

A phosphoramidite containing Os(bpy)(3)(2+) (Os; bpy, 2,2'-bipyridine) with a three-carbon linker was synthesized and used to prepare oligonucleotides with the Os redox catalyst appended to the 5'-end. The electrogenerated Os(III) is capable of oxidizing 7,8-dihydro-8-oxo-guanine (8G), but 8G is not electrochemically reactive at indium tin oxide electrodes because of poor electrode kinetics for the direct reaction. The hairpin-forming oligonucleotide Os-5'-ATG TCA GAT TAG CAG GCC TGA CAT 8G was synthesized and characterized by thermal denaturation and native gel electrophoresis both in the hairpin form and when hybridized to its Watson-Crick complement. The redox potential in both forms of the appended Os(III/II) couple was 0.63 V (all potentials vs Ag/AgCl), which is identical to that for the free complex. The diffusion coefficients of the hairpin form (10.2 x 10(-)(7) cm(2)/s) and the duplex form (8.7 x 10(-)(7) cm(2)/s) were consistent with values expected from studies of noncovalently bound redox labels, which suggest that the measured diffusion coefficient should be that of the appended DNA molecule. The oligonucleotide was designed such that in the duplex form, the 8G is far from the Os(III/II) couple, but in the hairpin form, the 8G is situated close to the redox center. For the duplex form, cyclic voltammetry studies showed that mediated oxidation of the 8G nucleobase occurred only through bimolecular reaction of the electrogenerated Os(III) of one duplex with the 8G of another duplex. However, in the hairpin form, intramolecular electron transfer from 8G to Os(III) in the same molecule was apparent in both chronoamperometry and cyclic voltammetry.

Catalysis↗

Thermal aggregation of patatin studied in situ.

In this work dynamic light scattering was used to study the thermal aggregation of patatin in situ, to elucidate the physical aggregation mechanism of the protein and to be able to relate the aggregation behavior to its structural properties. The dependence of the aggregation rates on the temperature and the ionic strength suggested a mechanism of slow coagulation, being both diffusion and chemically limited. The aggregation rate dependence on the protein concentration was in accordance with the mechanism proposed. The aggregation rates as obtained at temperatures ranging from 40 to 65 degrees C correlated well with unfolding of the protein at a secondary level. Small-angle neutron scattering and dynamic light scattering results were in good accordance; they revealed that native patatin has a cylindrical shape with a diameter and length of 5 and 9.8 nm, respectively.

Carboxylic Ester Hydrolases↗

Dipolar-interaction-induced fractal pattern formation in magnetic multilayers.

Models concerning particle diffusion and aggregation have been proposed for decades, and the aggregations with long-range dipolar interaction are simulated and analyzed numerically. In this paper, fractal clusters composed of particles diffusing with dipolar interaction are observed, and a model taking both magnetic force and diffusion activation energy into account is presented. The computer-simulation results generate clusters similar to those observed. And the measured sizes and dimensions of the experimental results are close to that of simulation. Further investigations on the magnetic energy and cluster size reveal that the dipolar interaction and thermal disruption play significant roles in the aggregation of nanosize magnetic particles and the interaction energy is the main driving force of the formation of the ordered structure.

Journal Article↗

Computational fluid dynamics and room air movement.

UNLABELLED: Computational Fluid Dynamics (CFD) and new developments of CFD in the indoor environment as well as quality considerations are important elements in the study of energy consumption, thermal comfort and indoor air quality in buildings. The paper discusses the quality level of Computational Fluid Dynamics and the involved schemes (first, second and third order schemes) by the use of the Smith and Hutton problem on the mass fraction transport equation. The importance of "false" or numerical diffusion is also addressed in connection with the simple description of a supply opening. The different aspects of boundary conditions in the indoor environment as, e.g., the simulation of Air Terminal Devices and the simulation of furnishings and occupants are discussed. The prediction of the flow in a room with a three-dimensional wall jet by the use of different turbulence models such as the k-epsilon model, the V2-f model and the Reynolds Stress model is addressed in the last chapter of the paper. PRACTICAL IMPLICATIONS: The use of computational Fluid Dynamics as a practical design method for room air distribution is widespread. It is important to consider the quality of the predictions in order to obtain a sufficient level of accuracy. It is also important to work with a practical description of supply openings as well as with the right level of details in the occupied zone and the right turbulence model. All these aspects are addressed in the article.

Air Movements↗

Joule heating in packed capillaries used in capillary electrochromatography.

Effective heat dissipation is critical for reproducible and efficient separations in electrically driven separation systems. Flow rate, retention kinetics, and analyte diffusion rates are some of the characteristics that are affected by variation in the temperature of the mobile phase inside the column. In this study, we examine the issue of Joule heating in packed capillary columns used in capillary electrochromatography (CEC). As almost all commonly used CEC packings are poor thermal conductors, it is assumed that the packing particles do not conduct heat and heat transfer is solely through the mobile phase flowing through the system. The electrical conductivity of various mobile phases was measured at different temperatures by a conductivity meter and the temperature coefficient for each mobile phase was calculated. This was followed by measurement of the electrical current at several applied voltages to calculate the conductivity of the solution within the column as a function of the applied voltage. An overall increase in the conductivity is attributed to Joule heating within the column, while a constant conductivity means good heat dissipation. A plot of conductivity versus applied voltage was used as the indicator of poor heat dissipation. Using theories that have been proposed earlier for modeling of Joule heating effects in capillary electrophoresis (CE), we estimated the temperature within CEC columns. Under mobile and stationary phase conditions typically used in CEC, heat dissipation was found to be not always efficient. Elevated temperatures within the columns in excess of 23 degrees C above ambient temperature were calculated for packed columns, and about 35 degrees C for an open column, under a given set of conditions. The results agree with recently published experimental findings with nuclear magnetic resonance (NMR) thermometry, and Raman spectroscopic measurements.

Buffers↗

Photoreceptor processes: some problems and perspectives.

Visual photoreceptors from both vertebrates and invertebrates are characterized by extensive elaboration of membrane which contains visual pigment (rhodopsin). Visual pigments in all phyla examined are chemically similar: the chromophore is 11-cis retinaldehyde attached by an aldimine linkage (Schiff base) to a membrane protein, opsin. The effect of light is to isomerize the chromophore to the all-trans configuration. Beyond these fundamental similarities, several specific areas are discussed in which variations and differences appear. (1) Light causes vertebrate visual pigments to bleach, liberating the chromophore. Most invertebrate visual pigments do not bleach in the light, but instead form a thermally stable metarhodopsin, with the chromophore in the all-trans configuration still attached to the opsin. (2) In the disk membranes of vertebrate rod and cone outer segments, the rhodopsin molecules are oriented with their chromophores nearly coplanar with the disks. Within this plane, however, both rotational and translational diffusion are possible. In the microvillar membranes of arthropod and cephalopod rhabdoms, on the other hand, the situation is less clear. There is evidence for some preferential orientation of chromophores that implies restrictions on Brownian rotation. (3) In the outer segments of vertebrate receptors, absorption of light by rhodopsin causes the plasma membrane to hyperpolarize due to a decrease in sodium conductance, possibly mediated by calcium ions. In most invertebrate photoreceptors, light causes a depolarization due to an increase in conductance, principally to sodium ions. A subsequent entry of calcium causes a partial repolarization of the membrane, due to a decrease in sodium conductance. (4) For vertebrate receptors, log threshold is directly proportional to the fraction of rhodopsin bleached (Dowling-Rushton relationship). The proportionality constant varies in different preparations from less than four to more than 30, and the physical basis for the relationship is unknown. For invertebrates, by contrast, the dependence of sensitivity on rhodopsin concentration is much less dramatic and may well depend simply on the probability of quantum catch. (5) In most species, vertebrate and invertebrate, the accumulation of photoproduct probably has no effect on membrane conductance, but several possible exceptions exist. (6) Photoregeneration of rhodopsin from metarhodopsin is likely an important mechanism of recovery in certain arthropods such as diurnal insects, but dark mechanisms of recovery also exist in all phyla. In no single case are they adequately understood.

Adaptation, Ocular↗