234 research outputs found
Counterion density profiles at charged flexible membranes
Counterion distributions at charged soft membranes are studied using
perturbative analytical and simulation methods in both weak coupling
(mean-field or Poisson-Boltzmann) and strong coupling limits. The softer the
membrane, the more smeared out the counterion density profile becomes and
counterions pentrate through the mean-membrane surface location, in agreement
with anomalous scattering results. Membrane-charge repulsion leads to a
short-scale roughening of the membrane.Comment: 4 pages, 4 figure
A voice for change? Trust relationships between ombudsmen, individuals and public service providers
There has been a debate for years about what the role of the ombudsman is. This article examines a key component of the role, to promote trust in public services and government. To be able to do this, however, an ombudsman needs to be perceived as legitimate and be trusted by a range of stakeholders, including the user. This article argues that three key relationships in a person’s complaint journey can build trust in an institution, and must therefore be understood as a system. The restorative justice framework is adapted to conceptualize this trust model as a novel approach to understanding the institution from the perspective of its users. Taking two public sector ombudsmen as examples, the article finds that voice and trust need to be reinforced through the relationships in a consumer journey to manage individual expectations, prevent disengagement, and thereby promote trust in the institution, in public service providers, and in government
Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions
Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huët anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed shape of the neutrophil nucleus is less essential
The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week
Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke
A large displacement, high frequency, underwater microelectromechanical systems actuator
Here, we demonstrate an in situ electrostatic actuator that can operate underwater across a wide range of displacements and frequencies, achieving a displacement of approximately 10-μm at 500-Hz and 1-μm at 5-kHz; this performance surpasses that of existing underwater physical actuators. To attain these large displacements at such high speeds, we optimized critical design parameters using a computationally efficient description of the physics of low quality (Q) factor underwater electrostatic actuators. Our theoretical model accurately predicts actuator motion profiles as well as limits of bandwidth and displacement
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States
The phenomena that emerge from the interaction of the stochastic opening and
closing of ion channels (channel noise) with the non-linear neural dynamics are
essential to our understanding of the operation of the nervous system. The
effects that channel noise can have on neural dynamics are generally studied
using numerical simulations of stochastic models. Algorithms based on discrete
Markov Chains (MC) seem to be the most reliable and trustworthy, but even
optimized algorithms come with a non-negligible computational cost. Diffusion
Approximation (DA) methods use Stochastic Differential Equations (SDE) to
approximate the behavior of a number of MCs, considerably speeding up
simulation times. However, model comparisons have suggested that DA methods did
not lead to the same results as in MC modeling in terms of channel noise
statistics and effects on excitability. Recently, it was shown that the
difference arose because MCs were modeled with coupled activation subunits,
while the DA was modeled using uncoupled activation subunits. Implementations
of DA with coupled subunits, in the context of a specific kinetic scheme,
yielded similar results to MC. However, it remained unclear how to generalize
these implementations to different kinetic schemes, or whether they were faster
than MC algorithms. Additionally, a steady state approximation was used for the
stochastic terms, which, as we show here, can introduce significant
inaccuracies. We derived the SDE explicitly for any given ion channel kinetic
scheme. The resulting generic equations were surprisingly simple and
interpretable - allowing an easy and efficient DA implementation. The algorithm
was tested in a voltage clamp simulation and in two different current clamp
simulations, yielding the same results as MC modeling. Also, the simulation
efficiency of this DA method demonstrated considerable superiority over MC
methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur
Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial
Background
Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke.
Methods/Design
We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period.
Discussion
HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke.
Trial registration
ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014
Farnesylated Nuclear Proteins Kugelkern and Lamin Dm0 Affect Nuclear Morphology by Directly Interacting with the Nuclear Membrane
Nuclear shape changes are observed during a variety of developmental processes, pathological conditions and ageing. Here, the molecular mechanism is analyzed how the farnesylated nuclear proteins interact with the nuclear envelope and deform the phospholipid bilayer
Managerial delegation in a dynamic renewable resource oligopoly
I propose a differential oligopoly game of resource extraction under (quasi-static) open-loop and nonlinear feedback strategies, where firms are managerial and two alternative types of delegation contract are considered. Under open-loop information, delegation expands the residual steady state resource stock. Conversely, under nonlinear feedback information the outcome depends on the structure of managerial incentives. If sales are used, once again delegation favours resource preservation. On the contrary, if market shares are included in the delegation contract, this combines with an underlying voracity effect in shrinking the steady state volume of the resource
- …