Semi-classical buckling of stiff polymers

A quantitative theory of the buckling of a worm like chain based on a semi-classical approximation of the partition function is presented. The contribution of thermal fluctuations to the force-extension relation that allows to go beyond the classical Euler buckling is derived in the linear and non-linear regime as well. It is shown that the thermal fluctuations in the nonlinear buckling regime increase the end-to-end distance of the semiflexible rod if it is confined to 2 dimensions as opposed to the 3 dimensional case. Our approach allows a complete physical understanding of buckling in D=2 and in D=3 below and above the Euler transition.Comment: Revtex, 17 pages, 4 figure

Major depression, fibromyalgia and labour force participation: A population-based cross-sectional study

BACKGROUND: Previous studies have documented an elevated frequency of depressive symptoms and disorders in fibromyalgia, but have not examined the association between this comorbidity and occupational status. The purpose of this study was to describe these epidemiological associations using a national probability sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey. The prevalence of major depression in subjects reporting that they had been diagnosed with fibromyalgia by a health professional was estimated, and then stratified by demographic variables. Logistic regression models predicting labour force participation were also examined. RESULTS: The annual prevalence of major depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI 19.4 – 24.9), than in those without this condition: 7.2% (95% CI 7.0 – 7.4). The association persisted despite stratification for demographic variables. Logistic regression models predicting labour force participation indicated that both conditions had an independent (negative) effect on labour force participation. CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be related to each other at a pathophysiological level. However, each syndrome is independently and negatively associated with labour force participation. A strength of this study is that it was conducted in a large probability sample from the general population. The main limitations are its cross-sectional nature, and its reliance on self-reported diagnoses of fibromyalgia

Nucleotide Binding Switches the Information Flow in Ras GTPases

The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (SGDP and SGTP, respectively). For all the considered systems, the intrinsic flexibility of SGDP was higher than that of SGTP, suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, SGDP of Gαt, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP

Overview of medical errors and adverse events

Safety is a global concept that encompasses efficiency, security of care, reactivity of caregivers, and satisfaction of patients and relatives. Patient safety has emerged as a major target for healthcare improvement. Quality assurance is a complex task, and patients in the intensive care unit (ICU) are more likely than other hospitalized patients to experience medical errors, due to the complexity of their conditions, need for urgent interventions, and considerable workload fluctuation. Medication errors are the most common medical errors and can induce adverse events. Two approaches are available for evaluating and improving quality-of-care: the room-for-improvement model, in which problems are identified, plans are made to resolve them, and the results of the plans are measured; and the monitoring model, in which quality indicators are defined as relevant to potential problems and then monitored periodically. Indicators that reflect structures, processes, or outcomes have been developed by medical societies. Surveillance of these indicators is organized at the hospital or national level. Using a combination of methods improves the results. Errors are caused by combinations of human factors and system factors, and information must be obtained on how people make errors in the ICU environment. Preventive strategies are more likely to be effective if they rely on a system-based approach, in which organizational flaws are remedied, rather than a human-based approach of encouraging people not to make errors. The development of a safety culture in the ICU is crucial to effective prevention and should occur before the evaluation of safety programs, which are more likely to be effective when they involve bundles of measures

The Energy Landscape Analysis of Cancer Mutations in Protein Kinases

The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results of this study have shown that the energy landscape effect of oncogenic mutations may be allosteric eliciting global changes in the spatial distribution of highly frustrated residues. We have found that mutation-induced allosteric signaling may involve a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. The presented study has demonstrated that activation cancer mutations may affect the thermodynamic equilibrium between kinase states by allosterically altering the distribution of locally frustrated sites and increasing the local frustration in the inactive form, while eliminating locally frustrated sites and restoring structural rigidity of the active form. The energy landsape analysis of protein kinases and the proposed role of locally frustrated sites in activation mechanisms may have useful implications for bioinformatics-based screening and detection of functional sites critical for allosteric regulation in complex biomolecular systems

Viking Thrust Vector Control Dynamics Using Hybrid Coordinates to Model Vehicle Flexibility and Propellant Slosh

Control System Design Implementation of the linear feedback control system with time varying feedback gains and command forces may be accomplished with a fairly simple analog controller. The feedback gains and command forces consist of well behaved sinusoidal functions, constants, and simple ramp functions. The difficulty caused by the gain fluctuation near the simulation final time may be overcome by cycling the control gain functions back to the beginning before the fluctuations take place. Cycling the control gain functions is not a problem because the control is in a feedback form. The effect of cycling the control gain functions may be interpreted in the analysis as restarting the nonlinear simulation with an initial state closer to the final state. Simulation of the nonlinear system within the region of operation always resulted in a stable response so the effect of restarting the simulation when the system state has moved closer to the final state is valid. A consequence of cycling the control is that the functional in Eq. Conclusions This study has shown that the dynamic instability caused by sloshing fluid stores carried in the main rigid body of a spacecraft may be controlled by use of a linear quadratic regulator with the fluid modeled as an equivalent spherical pendulum and only the first mode of fluid oscillation included. The control system presented stabilized a highly nonlinear system for a large deviation from the nominal operating point and uses easily measured state variables (only main body fixed angular rates and attitude) and was shown to be stable for a wide variation in fluid level. It was shown that sensing the dynamic state of the fluid was not necessary for the specific spacecraft under study. A pointing maneuver was also successfully accomplished by this control system and a control design based on the analysis was outlined for the specific spacecraft. Acknowledgments This study was completed under partial support of contract no. AFOSR-86-0080 and subcontract 83RIP33, U.S. Air Force. The authors wish to acknowledge the support of Iowa State University in accomplishing the lengthy digital computer simulation required in this study. References Introduction An interesting problem in robotics is cloth handling. Applications include composite lay-up and apparel and upholstery manufacturing. Rebman (1986) describes an application of a tactile sensor to assembly of a flexible diaphram and a plastic cap. Hertzanu and Tabak (1986) described an adaptive controller for an industrial sewing machine. For most applications, cloth must be held taut and unwrinkled. It was postulated that this requires multi-axis force control, and a suitable control system was designed and constructed. The system chosen is an adaptive force feedback loop with position accommodation. Non-adaptive force feedback control schemes have been described and tested by many researchers, such as Whitney (1977). An adaptive force feedback loop for coordination of two robot arms was described by Because cloth stiffness varies depending on whether the individual cloth fibers are taut or slack, a nonadaptive loop is unsuitable for cloth handling. An adaptive control loop was designed with cloth stiffness as the adaptive variable. The system design was constructed and tested using a PUMA 560 robot with a LORD 15/50 force/torque sensor mounted on its wrist. Control System Description The parameter estimator is a least mean square (LMS) estimator. Let y=KH(z)u = K a x z ' + + a"z~ -r-"u, \+b x z + ... +b"z~ where a it ..., a" and b\ b" axe found from the ordinary least squares plant identification, y is the error in the force, and u is the position command. Then the LMS estimator for A-is K* =K*^i+r{y-y*)w-l , where K* is the estimated stiffness, +a"u""), and Vf_ 1 =ff 1 «_ 1 + The position control law is where u, is the change in the position of the /th degree of freedom (DOF), y t is the force (or torque) error of the ith DOF, and K* is the stiffness of the rth DOF. end of a cloth of dimensions 36 by 36 in., the other end of which was attached to a table. Both ends of the cloth were stapled to wooden rods; proper robot end effectors would eliminate the need for these rods. Two 8086 microprocessor cards were also built. The 1st microprocessor calculated the cloth stiffness and end effector position changes; the 2nd microprocessor was used for communication with the robot and the force/torque sensor. Experimental Procedure The experiments were run with one end of the cloth fixed. The initial slack and misalignments of the cloth were as follows: Stretch (x) direction Lateral (y) direction 6 direction 6 to 10 in. of slack 2 to 4 in. of misalignment 5° to 20° of misalignment The robot straightened out the misalignments and pulled 4 lb of tension on the cloth. After it had done so the end effector was moved inward to produce 6 in. of slack in the x-direction. This movement draped the cloth over 2 boxes without wrinkling. Test Setup Experimental Results The visual results showed consistency between the experiments. In all of them, the cloth was successfully draped over the boxes without wrinkles, the motion was smooth, and the times were approximately the same. Transactions of the ASME position, the robot pulls a 4 lb tension on the cloth and adjusts the lateral (y) force and the moment to zero. This requires approximately 12 s. At 14 s the robot drapes the cloth; at this point the tension (x-force) falls to zero. This experiment was successfully repeated several times. Conclusions A force feedback control loop implemented on a robot has been used successfully to straighten and draw a tension on a cloth. Further work will include using more sophisticated end effectors to grip the cloth, and applications in upholstery and composite manufacture. Reference

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial

Background Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation. Objectives The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations. Methods This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling. Conclusion Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials