Construction and Characterization of a Frequency-Controlled, Picometer-Resolution, Displacement Encoder-Actuator

We have constructed an actuator/encoder whose generated displacement is controlled through the resonance frequency of a microwave cavity. A compact, 10-micrometer-range, digitally-controlled actuator executing frequency-coded displacement with picometer resolution is described. We consider this approach particularly suitable for metrologic-precision scanning probe microscopy.Comment: 4 pages, 4 figure

A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers

Purpose Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13–19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden. Methods Pacemakers were adjusted to optimize AF detection. Patients with AF burden \u3e1 % were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment. Results From 285 patients screened, 112 were randomized (mean age 76 years, 60 % male, 84 % hypertensive, 65 % with sick sinus syndrome, 26 % with diabetes mellitus type II, 15 % with heart failure). Baseline mean (SEM) AF burden was 8.77 % (0.16) for placebo and 10.14 % (0.17) for dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4 % (0.22) (P = 0.0009) with dronedarone and trended higher by 12.8 % (0.16) (P = 0.450) with placebo. The absolute change in burden was decreased by 5.5 % in the dronedarone group and increased by 1.1 % in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with dronedarone (P = 0.285). Adverse events were higher with dronedarone compared to placebo (65 vs 56 %). Conclusions Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50 % during the 12-week observation period

Estimation of effective connectivity via data-driven neural modeling

This research introduces a new method for functional brain imaging via a process of model inversion. By estimating parameters of a computational model, we are able to track effective connectivity and mean membrane potential dynamics that cannot be directly measured using electrophysiological measurements alone. The ability to track the hidden aspects of neurophysiology will have a profound impact on the way we understand and treat epilepsy. For example, under the assumption the model captures the key features of the cortical circuits of interest, the framework will provide insights into seizure initiation and termination on a patient-specific basis. It will enable investigation into the effect a particular drug has on specific neural populations and connectivity structures using minimally invasive measurements. The method is based on approximating brain networks using an interconnected neural population model. The neural population model is based on a neural mass model that describes the functional activity of the brain, capturing the mesoscopic biophysics and anatomical structure. The model is made subject-specific by estimating the strength of intra-cortical connections within a region and inter-cortical connections between regions using a novel Kalman filtering method. We demonstrate through simulation how the framework can be used to track the mechanisms involved in seizure initiation and termination

Actomyosin drives cancer cell nuclear dysmorphia and threatens genome stability

Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB. We detect actin filaments at nuclear envelope rupture sites and define the Rho-ROCK pathway as the driver of nuclear damage. Lamin A protects nuclei from the impact of actomyosin activity. Blocking contractility increases nuclear circularity in cultured cancer cells and suppresses deformations of xenograft nuclei in vivo. We conclude that actomyosin contractility is a major determinant of nuclear shape and that unrestrained contractility causes nuclear dysmorphia, nuclear envelope rupture and genome instability

A dynamical framework for the origin of the diagonal South Pacific and South Atlantic convergence zones

The South Pacific Convergence Zone (SPCZ) and South Atlantic Convergence Zone (SACZ) are diagonal bands of precipitation that extend from the equator southeastward into the Southern Hemisphere over the western Pacific and Atlantic Oceans, respectively. With mean precipitation rates over 5 mm day−1, they are a major component of the tropical and global climate in austral summer. However, their basic formation mechanism is not fully understood. Here, a conceptual framework for the diagonal convergence zones is developed, based on calculations of the vorticity budget from reanalysis and Rossby wave theory. Wave trains propagate eastward along the Southern Hemisphere subtropical jet, with initially quasi-circular vorticity centres. In the zonally sheared environment on the equatorward flank of the jet, these vorticity centres become elongated and develop a northwest-southeast tilt. Ray tracing diagnostics in a non-divergent, barotropic Rossby wave framework then explain the observed equatorward propagation of these diagonal vorticity structures toward the westerly ducts over the equatorial Pacific and Atlantic. The baroclinic component of these circulations leads to destabilisation and ascent ahead of the cyclonic vorticity anomaly in the wave, triggering deep convection because of the high sea surface temperatures in this region. Latent heat release then forces additional ascent and strong upper-tropospheric divergence, with an associated anticyclonic vorticity tendency. A vorticity budget shows that this cancels out the advective cyclonic vorticity tendency in the wave train over the SPCZ, and dissipates the wave within a day. The mean SPCZ is consequently comprised of the sum of these pulses of diagonal bands of precipitation. Similar mechanisms also operate in the SACZ. However, the vorticity anomalies in the wave trains are stronger, and the precipitation and negative feedback from the divergence and anticyclonic vorticity tendency are weaker, resulting in continued propagation of the wave and a more diffuse diagonal convergence zone

Changes in children’s cognitive development at the Start of School in England 2001–2008.

Since 1997, England has seen massive changes in the Early Years including the introduction of an early childhood curriculum, free pre-school education for three-year-olds and local programmes for disadvantaged communities. Many of these initiatives took time to introduce and become established. Beginning in 2001, and each year thereafter until 2008, the authors collected consistent data from thousands of children when they started school at the age of four on a range of variables, chosen because they are good predictors of later success. These included vocabulary, early reading and early mathematics. Children from the same set of 472 state primary schools in England were assessed each year. This paper contributes to the existing studies of educational trends over time by examining the extent to which children's scores on these measures changed over that period; in general, they were found to have remained stable