A Mathematical Model of Muscle Containing Heterogeneous Half-Sarcomeres Exhibits Residual Force Enhancement

A skeletal muscle fiber that is stimulated to contract and then stretched from L1 to L2 produces more force after the initial transient decays than if it is stimulated at L2. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half-sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement

Interfacial Tensions near Critical Endpoints: Experimental Checks of EdGF Theory

Predictions of the extended de Gennes-Fisher local-functional theory for the universal scaling functions of interfacial tensions near critical endpoints are compared with experimental data. Various observations of the binary mixture isobutyric acid $+$ water are correlated to facilitate an analysis of the experiments of Nagarajan, Webb and Widom who observed the vapor-liquid interfacial tension as a function of {\it both} temperature and density. Antonow's rule is confirmed and, with the aid of previously studied {\it universal amplitude ratios}, the crucial analytic ``background'' contribution to the surface tension near the endpoint is estimated. The residual singular behavior thus uncovered is consistent with the theoretical scaling predictions and confirms the expected lack of symmetry in $(T-T_c)$. A searching test of theory, however, demands more precise and extensive experiments; furthermore, the analysis highlights, a previously noted but surprising, three-fold discrepancy in the magnitude of the surface tension of isobutyric acid $+$ water relative to other systems.Comment: 6 figure

Supersymmetric geometries of IIA supergravity I

IIA supergravity backgrounds preserving one supersymmetry locally admit four types of Killing spinors distinguished by the orbits of $Spin(9,1)$ on the space of spinors. We solve the Killing spinor equations of IIA supergravity with and without cosmological constant for Killing spinors representing two of these orbits, with isotropy groups $Spin(7)$ and $Spin(7)\ltimes\mathbb{R}^8$. In both cases, we identify the geometry of spacetime and express the fluxes in terms of the geometry. We find that the geometric constraints of backgrounds with a $Spin(7)\ltimes\mathbb{R}^8$ invariant Killing spinor are identical to those found for heterotic backgrounds preserving one supersymmetry.Comment: 21 page

Interactions between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior in a Mathematical Model of Muscle

Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes ∼300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most ∼30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere

Social research on neglected diseases of poverty: Continuing and emerging themes

Copyright: © 2009 Manderson et al.Neglected tropical diseases (NTDs) exist and persist for social and economic reasons that enable the vectors and pathogens to take advantage of changes in the behavioral and physical environment. Persistent poverty at household, community, and national levels, and inequalities within and between sectors, contribute to the perpetuation and re-emergence of NTDs. Changes in production and habitat affect the physical environment, so that agricultural development, mining and forestry, rapid industrialization, and urbanization all result in changes in human uses of the environment, exposure to vectors, and vulnerability to infection. Concurrently, political instability and lack of resources limit the capacity of governments to manage environments, control disease transmission, and ensure an effective health system. Social, cultural, economic, and political factors interact and influence government capacity and individual willingness to reduce the risks of infection and transmission, and to recognize and treat disease. Understanding the dynamic interaction of diverse factors in varying contexts is a complex task, yet critical for successful health promotion, disease prevention, and disease control. Many of the research techniques and tools needed for this purpose are available in the applied social sciences. In this article we use this term broadly, and so include behavioral, population and economic social sciences, social and cultural epidemiology, and the multiple disciplines of public health, health services, and health policy and planning. These latter fields, informed by foundational social science theory and methods, include health promotion, health communication, and heath education

Involvement of the genicular branches in cystic adventitial disease of the popliteal artery as a possible marker of unfavourable early clinical outcome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic adventitial disease of the popliteal artery is a rare cause of non-atheromatous claudication. It usually requires surgery to improve the distance walked by patients.</p> <p>Case presentation</p> <p>We report the case of a 44-year-old Caucasian man with unilateral symptomatic popliteal cysts extending to his genicular branches and associated with multilevel stenosis of his anterior tibial artery. A surgical evacuation of the cysts successfully restored his arterial patency and led to an objective haemodynamic improvement but was associated with early recurrence of symptoms.</p> <p>Conclusion</p> <p>We suggest that the involvement of the genicular branches in cystic adventitial disease of the popliteal artery is a possible indicator of extensive adventitial degeneration and unfavourable clinical prognosis.</p

Design choices made by target users for a pay-for-performance program in primary care: an action research approach

Contains fulltext : 110832.pdf (publisher's version ) (Open Access)BACKGROUND: International interest in pay-for-performance (P4P) initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. METHODS: For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. RESULTS: Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience). The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. CONCLUSIONS: Designing a P4P program for primary care with involvement of the target users gave us an insight into their motives, which can help others who need to discuss similar programs. The resulting program is in line with target users' views and assessments of relevance and applicability. This may enhance their commitment to the program as was indicated by the growing number of voluntary participants after a successfully performed field test during the procedure. The elements of our framework can be very helpful for others who are developing or evaluating a P4P program

Large Anomalous Hall effect in a silicon-based magnetic semiconductor

Magnetic semiconductors are attracting high interest because of their potential use for spintronics, a new technology which merges electronics and manipulation of conduction electron spins. (GaMn)As and (GaMn)N have recently emerged as the most popular materials for this new technology. While Curie temperatures are rising towards room temperature, these materials can only be fabricated in thin film form, are heavily defective, and are not obviously compatible with Si. We show here that it is productive to consider transition metal monosilicides as potential alternatives. In particular, we report the discovery that the bulk metallic magnets derived from doping the narrow gap insulator FeSi with Co share the very high anomalous Hall conductance of (GaMn)As, while displaying Curie temperatures as high as 53 K. Our work opens up a new arena for spintronics, involving a bulk material based only on transition metals and Si, and which we have proven to display a variety of large magnetic field effects on easily measured electrical properties.Comment: 19 pages with 5 figure

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)