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Anisotropy in sickle hemoglobin fibers from variations in bending and twist.

We have studied the variations of twist and bend in sickle hemoglobin fibers. We find that these variations are consistent with an origin in equilibrium thermal fluctuations, which allows us to estimate the bending and torsional rigidities and effective corresponding material moduli. We measure bending by electron microscopy of frozen hydrated fibers and find that the bending persistence length, a measure of the length of fiber required before it starts to be significantly bent due to thermal fluctuations, is 130microm, somewhat shorter than that previously reported using light microscopy. The torsional persistence length, obtained by re-analysis of previously published experiments, is found to be only 2.5microm. Strikingly this means that the corresponding torsional rigidity of the fibers is only 6x10(-27)Jm, much less than their bending rigidity of 5x10(-25)Jm. For (normal) isotropic materials, one would instead expect these to be similar. Thus, we present the first quantitative evidence of a very significant material anisotropy in sickle hemoglobin fibers, as might arise from the difference between axial and lateral contacts within the fiber. We suggest that the relative softness of the fiber with respect to twist deformation contributes to the metastability of HbS fibers: HbS double strands are twisted in the fiber but not in the equilibrium crystalline state. Our measurements inform a theoretical model of the thermodynamic stability of fibers that takes account of both bending and extension/compression of hemoglobin (double) strands within the fiber.

Anisotropy↗

Evidence that negative feedback between antibody concentration and affinity regulates humoral response consolidation to a non-infectious antigen in infants.

The dynamics of human antigen-specific immunoglobulin (Ig) responses in early life are not well characterized. We have previously observed an inverse relationship between allergen-specific Ig concentration and allergen-Ig-binding affinity in allergen-sensitive atopic adults, suggesting a possible feedback relationship between these variables. We prospectively studied children (6 months to 6 years) with and without atopic sensitization to the Der p 1 major allergen. Experimental results showed the following trends. (1) In both study groups, there was little change with age in average Der p 1-specific Ig (IgG1 or IgE) concentrations or allergen-Ig-binding affinities, and concentrations and affinities were independent. (2) Among individuals, however, there was a negative correlation between Ig concentration changes and affinity changes with age. (3) The rate of increase with age of the non-atopic Der p 1-IgG1 total binding capacity (Ig concentration x Ig affinity) paralleled that for the atopic Der p 1-IgE total binding capacity, and there was a comparable 'consolidation' of responses with age reflected by a narrowing of the variance of total binding capacity values. Except for the Ig classes involved, development of a humoral response to a non-infectious allergen is similarly regulated in atopic and non-atopic children, with Ig total binding capacity as the key regulatory variable. These results also suggest that there is a time-dependent feedback relationship between Ig concentrations and affinities that establishes an optimal Ig total binding capacity for a given environmental 'antigen load'. A theoretical model is proposed to account for this relationship.

Allergens↗

Magnetically induced electric fields and currents in the circulatory system.

Blood flow in an applied magnetic field gives rise to induced voltages in the aorta and other major arteries of the central circulatory system that can be observed as superimposed electrical signals in the electrocardiogram (ECG). The largest magnetically induced voltage occurs during pulsatile blood flow into the aorta, and results in an increased signal at the location of the T-wave in the ECG. Studies involving the measurement of blood pressure, blood flow rate, heart sounds, and cardiac valve displacements have been conducted with monkeys and dogs exposed to static fields up to 1.5 tesla (T) under conditions producing maximum induced voltages in the aorta. Results of these studies gave no indication of alterations in cardiac functions or hemodynamic parameters. Cardiac activity monitored by ECG biotelemetry during continuous exposure of rats to a 1.5-T field for 10 days gave no evidence for any significant changes relative to the 10 days prior to and following exposure. Theoretical modeling of magnetic field interactions with blood flow has included a complete solution of the equation describing the flow of an electrically conductive fluid in the presence of a magnetic field (the Navier-Stokes equation) using the finite element technique. Magnetically induced voltages and current densities as a function of the applied magnetic field strength have been calculated for the aorta and surrounding tissues structures, including the sinoatrial node. Induced current densities in the region of the sinoatrial node are predicted to be >100 mA/m2 at field levels >5 T in an adult human under conditions of maximum electrodynamic coupling with aortic blood flow. Magnetohydrodynamic interactions are predicted to reduce the volume flow rate of blood in the human aorta by a maximum of 1.3%, 4.9%, and 10.4% at field levels of 5, 10, and 15 T, respectively.

Animals↗

Transfer of asthma management responsibility from parents to their school-age children.

This study used grounded theory to explore the process of transfer of responsibility for asthma management from parents to their school-age children. Interviews were conducted with 11 mothers, 2 fathers, 1 grandmother, and their 14 children who were between 8 and 13 years old. Responses revealed that transfer of responsibility within families is a complex, uneven process that occurs over years and involves identifiable stages and transitions. The Theoretical Model for Parent-Child Transfer of Asthma Responsibility emerged from the data. The central concept underlying the process was controlling the situation. Specific cues stimulated changes in parent-child responsibility.

Adaptation, Psychological↗

Automatic fitting to 'powder' EPR spectra of coupled paramagnetic species employing Feynman's theorem.

A previous automatic fitting procedure of EPR spectra has been extended with the purpose to characterise coupled paramagnetic complexes in powders and frozen solutions. The theoretical EPR spectra were obtained by matrix diagonalization of a general spin Hamiltonian. A least-squares fitting procedure using analytical derivatives of the calculated spectrum with respect to the spectroscopic, fine structure, nuclear quadrupole, electron-electron, and hyperfine coupling tensors was used to refine those parameters. The powder spectra of matrix isolated *CF3 and RCF2CF2* radicals, previously measured at low temperature, were reanalysed with this method. A theoretically modeled complex consisting of a Cu2+ ion, featuring an axially symmetric g-tensor and 63Cu hyperfine structure anisotropy, and a free radical located at different orientations, with respect to the symmetry axis of the Cu2+ ion, was examined in order to investigate the possibility to recover the magnetic parameters of the separate units and the magnetic couplings between them.

Copper↗

Culture and stigma: adding moral experience to stigma theory.

Definitions and theoretical models of the stigma construct have gradually progressed from an individualistic focus towards an emphasis on stigma's social aspects. Building on other theorists' notions of stigma as a social, interpretive, or cultural process, this paper introduces the notion of stigma as an essentially moral issue in which stigmatized conditions threaten what is at stake for sufferers. The concept of moral experience, or what is most at stake for actors in a local social world, provides a new interpretive lens by which to understand the behaviors of both the stigmatized and stigmatizers, for it allows an examination of both as living with regard to what really matters and what is threatened. We hypothesize that stigma exerts its core effects by threatening the loss or diminution of what is most at stake, or by actually diminishing or destroying that lived value. We utilize two case examples of stigma--mental illness in China and first-onset schizophrenia patients in the United States--to illustrate this concept. We further utilize the Chinese example of 'face' to illustrate stigma as having dimensions that are moral-somatic (where values are linked to physical experiences) and moral-emotional (values are linked to emotional states). After reviewing literature on how existing stigma theory has led to a predominance of research assessing the individual, we conclude by outlining how the concept of moral experience may inform future stigma measurement. We propose that by identifying how stigma is a moral experience, new targets can be created for anti-stigma intervention programs and their evaluation. Further, we recommend the use of transactional methodologies and multiple perspectives and methods to more fully capture the interpersonal core of stigma as framed by theories of moral experience.

Culture↗

Ultrasonic velocity in water-ethanol-sucrose mixtures during alcoholic fermentation.

During alcoholic fermentation, sucrose and water are transformed into ethanol and carbon dioxide by the action of yeast enzymes. The measurement of the velocity of an ultrasonic pulse travelling through a fermentation tank can be used to characterize the state of the process. In this work, an experimental study of the density and ultrasonic velocity in the ternary mixture (water-ethanol-saccharose) is presented. Experimental results were compared to ideal density and to commonly used expressions of the sound velocity in liquid mixtures (Urick, Natta-Baccaredda and Nomoto). A semiempirical approach was proposed to improve the efficiency of theoretical models when dealing with mixtures of associated liquids.

Alcohols↗

Origins of the edge shadowing artefact in medical ultrasound imaging.

Ultrasound (US) B-mode images distal to smooth, rounded cavities, such as cysts, containing a fluid with a speed of sound mismatch to the surrounding tissue, often exhibit a "refractile" edge shadowing artefact. This usually appears as narrow, hypoechoic, shadow lines extending a significant distance distal to the lateral edges of the fluid cavity and parallel to the US beam. The true reasons for this artefact are likely to be complex and to vary from case to case, with many different explanations found in the literature. However, we present a simplified theoretical model for the phenomenon based on a pulsed, finite-beam solution of US scattering from circular fluid-filled cylinders that suggests that "edge" shadows can occur distal not only to edges but also to points where the incident beam intersects the cavity near to the critical angle. Both mechanisms support the view that edge shadows can arise from the combination of unusually high wavefront spreading and the speckle-generating nature of the surrounding tissue. In vitro data from a tissue-mimicking phantom confirms that the edge shadow structure depends on the sign of the speed of sound contrast between the cylinder fluid and the surrounding medium.

Artifacts↗

Effects of emergent vegetation on lateral diffusion in wetlands.

Constructed wetlands are widely used for a variety of environmental applications, such as wastewater treatment and recharge, and their efficacy is largely determined by the hydrodynamic characteristics of the flow system. An experimental study was carried out to quantify the lateral dispersion of passive substances in shallow zones of a constructed wetland wherein water flows though the interstices of the distributed vegetation. The experimental set up was designed to mimic the Tres Rios constructed wetland located in Phoenix, Arizona. The major emphasis was on the lateral diffusivity K(t) of a shallow zone with randomly distributed vegetation. The results are presented in the context of a simple theoretical model where K(t) is expressed in terms of the diameter of the plant stalk D(v), the characteristic distance between the plants d(v), the flow velocity U and the drag coefficient C(D) as (K(t)/UD(v))(d(v)/D(v))=betaC(D), where beta is a dimensionless constant. Fitting of data to the above model indicate that C(D), in general, is a function of the Reynolds number (Re). The data are also compared with a model proposed by Nepf et al. (Water Res 35 (1999) 479).

Diffusion↗

A Notch feeling of somite segmentation and beyond.

Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and dermis. Many theoretical models including the "clock and wavefront" model have been proposed. There is compelling genetic evidence showing that Notch-Delta signaling is indispensable for somitogenesis. Notch receptor and its target genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish, an oscillator operated by cyclical transcriptional activation and delayed negative feedback regulation is emerging as the fundamental mechanism underlying the segmentation clock. Ubiquitin-dependent protein degradation and probably other posttranslational regulations are also required. Fgf8 and Wnt3a gradients are important in positioning somite boundaries and, probably, in coordinating tail growth and segmentation. The circadian clock is another biochemical oscillator, which, similar to the segmentation clock, is operated with a negative transcription-regulated feedback mechanism. While the circadian clock uses a more complicated network of pathways to achieve homeostasis, it appears that the segmentation clock exploits the Notch pathway to achieve both signal generation and synchronization. We also discuss mathematical modeling and future directions in the end.

Animals↗

Preoperative teaching and hysterectomy outcomes.

This study used a theoretical model to determine whether an efficacy-enhancing teaching protocol was effective in improving immediate postoperative behaviors and selected short- and long-term health outcomes in women who underwent abdominal hysterectomies. The model used was the self-efficacy theory of Albert Bandura, PhD. One hundred eight patients in a 486-bed teaching hospital in the Midwest who underwent hysterectomies participated. The participation rate was 85%, and the attrition rate was 17% during the six-month study. The major finding was that participants in the efficacy-enhancing teaching group ambulated significantly longer than participants in the usual care group. This is an important finding because the most prevalent postoperative complications after hysterectomy are atelectasis, pneumonia, paralytic ileus, and deep vein thrombosis, and postoperative ambulation has been shown to decrease or prevent all of these complications. This finding could affect the overall health status of women undergoing hysterectomies.

Adult↗

Neck injuries in car collisions--a review covering a possible injury mechanism and the development of a new rear-impact dummy.

A review of a few Swedish research projects on soft tissue neck injuries in car collisions is presented together with some new results. Efforts to determine neck injury mechanisms was based on a hypothesis stating that injuries to the nerve root region in the cervical spine are a result of transient pressure gradients in the spinal canal during rapid neck bending. In experimental neck trauma research on animals, pressure gradients were observed and indications of nerve cell membrane dysfunction were found in the cervical spinal ganglia. The experiments covered neck extension, flexion and lateral bending. A theoretical model in which fluid flow was predicted to cause the transient pressure gradients was developed and a neck injury criterion based on Navier-Stokes Equations was applied on the flow model. The theory behind the Neck Injury Criterion indicates that the neck injury occurs early on in the rearward motion of the head relative to the torso in a rear-end collision. Thus the relative horizontal acceleration and velocity between the head and the torso should be restricted during the early head-neck motion to avoid neck injury. A Bio-fidelic Rear Impact Dummy (BioRID) was developed in several steps and validated against volunteer test results. The new dummy was partly based on the Hybrid III dummy. It had a new articulated spine with curvature and range of motion resembling that of a human being. A new crash dummy and a neck injury criterion will be very important components in a future rear-impact crash test procedure.

Accidents, Traffic↗

Theory and practice for the implementation of 'in-house', continuous improvement participatory ergonomic programs.

This paper presents a case study of an implementation of a participatory ergonomics program in a public service agency. The objective of the study was to develop a theoretical model and related design principles for the implementation of 'in-house', continuous improvement participatory programs. The proposed model is based on the behavioral cybernetic theory of learning (Smith and Smith, 1966, Cybernetic Principles of Learning and Educational Design held, Rhinehart and Winsten, New York) and emphasizes the concepts of action, feedback, feedback control, and individual learning as essential for a progression from external regulation (by outside experts) to internal regulation (by organizational members) of participatory programs. Results support the proposed model, but do suggest an expansion of the model to include macro-level organizational variables as additional factors necessary for developing internally regulated participatory programs. Results have led to the specification of several design principles for implementing 'in-house', continuous improvement participatory programs.

Ergonomics↗

The binding dynamics of tropomyosin on actin.

We discuss a theoretical model for the cooperative binding dynamics of tropomyosin to actin filaments. Tropomyosin binds to actin by occupying seven consecutive monomers. The model includes a strong attraction between attached tropomyosin molecules. We start with an empty lattice and show that the binding goes through several stages. The first stage represents fast initial binding and leaves many small vacancies between blocks of bound molecules. In the second stage the vacancies annihilate slowly as tropomyosin molecules detach and reattach. Finally, the system approaches equilibrium. Using a grain-growth model and a diffusion-coagulation model we give analytical approximations for the vacancy density in all regimes.

Actins↗

A Monte Carlo study of peptide insertion into lipid bilayers: equilibrium conformations and insertion mechanisms.

The membrane insertion behavior of two peptides, Magainin2 and M2 delta, was investigated by applying the Monte Carlo simulation technique to a theoretical model. The model included many novel aspects, such as a new semi-empirical lipid bilayer model and a new set of semi-empirical transfer energies, which reproduced the experimental insertion behavior of Magainin2 and M2 delta without parameter fitting. Additionally, we have taken into account diminished internal (intramolecular) hydrogen bonding at the N- and C-termini of helical peptides. All simulations were carried out at 305 K, above the membrane thermal phase transition temperature, and at pH 7.0. The peptide equilibrium conformations are discussed for a range of bilayers with tail polarities varying from octanol-like to alkane-like. Probability distributions of the individual amino-acid-residue positions show the dynamic nature of these equilibrium conformations. Two different insertion mechanisms for M2 delta, and a translocation mechanism for Magainin2, are described. A study of the effect of bilayer thickness on M2 delta insertion suggests a critical thickness above which insertion is unfavorable. Additionally, we did not need to use an orientational potential or array of hard cylinders to persuade M2 delta to insert perpendicular to the membrane surface. Instead, we found that diminished internal hydrogen bonding in the helical conformation anchored the termini in the headgroups and resulted in a nearly perpendicular orientation.

Amino Acid Sequence↗

Kinetics and mechanism of intercellular ice propagation in a micropatterned tissue construct.

Understanding the effects of cell-cell interaction on intracellular ice formation (IIF) is required to design optimized protocols for cryopreservation of tissue. To determine the effects of cell-cell interactions during tissue freezing, without confounding effects from uncontrolled factors (such as time in culture, cell geometry, and cell-substrate interactions), HepG2 cells were cultured in pairs on glass coverslips micropatterned with polyethylene glycol disilane, such that each cell interacted with exactly one adjacent cell. Assuming the cell pair to be a finite state system, being either in an unfrozen state (no ice in either cell), a singlet state (IIF in one cell only), or a doublet state (IIF in both cells), the kinetics of state transitions were theoretically modeled and cryomicroscopically measured. The rate of intercellular ice propagation, estimated from the measured singlet state probability, increased in the first 24 h of culture and remained steady thereafter. In cell pairs cultured for 24 h and treated with the gap junction blocker 18beta-glycyrrhetinic acid before freezing, the intercellular ice propagation rate was lower than in untreated controls (p < 0.001), but significantly greater than zero (p < 0.0001). These results suggest that gap junctions mediate some, but not all, mechanisms of ice propagation in tissue.

Biophysical Phenomena↗

Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: the consequence of cell structure.

Excitation signals spread along photoreceptor outer segments away from the site of photon capture because of longitudinal diffusion of cGMP, a cytoplasmic second messenger. The quantitative features of longitudinal diffusion reflect the anatomical structure of the outer segment, known to be profoundly different in rod and cone photoreceptors. To explore how structural differences affect cytoplasmic diffusion and to assess whether longitudinal diffusion may contribute to the difference in signal transduction between photoreceptor types, we investigated, both theoretically and experimentally, the longitudinal diffusion of small, hydrophilic molecules in outer segments. We developed a new theoretical analysis to explicitly compute the longitudinal diffusion constant, Dl, in terms of outer segment structure. Using time-resolved fluorescence imaging we measured Dl of Alexa488 and lucifer yellow in intact, single cones and validated the theoretical analysis. We used numerical simulations of the theoretical model to investigate cGMP diffusion in outer segments of various species. At a given time interval, cGMP spreads further in rod than in cone outer segments of the same dimensions. Across all species, the spatial spread of cGMP at the peak of the dim light photocurrent is 3-5 microm in rod outer segments, regardless of their absolute size. Similarly the cGMP spatial spread is 0.7-1 microm in cone outer segments, independently of their dimensions.

Animals↗

The diffraction pattern of dry blood smears.

A theoretical model for dry blood smears is investigated. Circular elements with normally distributed radii and ellipses are considered. The differences in diffraction pattern of sparse and dense smears are explained. The theory is supported by some recordings by means of a simple photoelectric device. A method for calculation of a distribution measure of the radii is suggested.

Biophysical Phenomena↗