Maximal acceleration of calcium release refractoriness by β-adrenergic stimulation requires dual activation of protein kinase A and CaMKII in mouse ventricular myocytes

Time-dependent refractoriness of calcium (Ca2+) release in cardiac myocytes is an important factor in determining whether pro-arrhythmic release patterns develop. At the subcellular level of the Ca2+ spark, recent studies have suggested that recovery of spark amplitude is controlled by local sarcoplasmic reticulum (SR) refilling whereas refractoriness of spark triggering depends on both refilling and the sensitivity of the ryanodine receptor (RyR) release channels that produce sparks. Here we studied regulation of Ca2+ spark refractoriness in mouse ventricular myocytes by examining how β-adrenergic stimulation influenced sequences of Ca2+ sparks originating from individual RyR clusters. Our protocol allowed us to separately measure recovery of spark amplitude and delays between successive sparks, and data were interpreted quantitatively through simulations with a stochastic mathematical model. We found that, compared with spark sequences measured under control conditions: (1) β-adrenergic stimulation with isoproterenol accelerated spark amplitude recovery and decreased spark-to-spark delays; (2) activating protein kinase A (PKA) with forskolin accelerated amplitude recovery but did not affect spark-to-spark delays; (3) inhibiting PKA with H89 retarded amplitude recovery and increased spark- to-spark delays; (4) preventing phosphorylation of the RyR at serine 2808 with a knock-in mouse prevented the decrease in spark-to-spark delays seen with β-adrenergic stimulation; (5) inhibiting either PKA or Ca2+/calmodulin-dependent protein kinase II (CaMKII) during β-adrenergic stimulation prevented the decrease in spark-to-spark delays seen) without inhibition. The results suggest that activation of either PKA or CaMKII is sufficient to speed SR refilling, but activation of both kinases appears necessary to observe increased RyR sensitivity. The data provide novel insight into β-adrenergic regulation of Ca2+ release refractoriness in mouse myocytes.

Evaluation of aeolian dust records obtained from Polar Ice Cores

When an ice core sample is analysed for its aeolian dust content, it is melted and the particles detected are suspended in water. Consequently, dust measurement techniques employed in the ice core community differ from those used for in-situ studies of airborne dust. Methods commonly used to classify insolubles suspended in a liquid are either based on the particles’ interaction with light or on the detection of resistive pulses by means of Coulter counting. Data sets obtained with Coulter counters are widely accepted as references and other techniques are judged against their ability to reproduce these. Unfortunately, optically acquired ice core dust records were found to differ. By analyzing two sections of the NEEM dust record, two different evaluation procedures are discussed before a third protocol is proposed. It is found that relative changes in the archived dust load can be reproduced, while the simultaneous attainment of absolute concentrations or changes in the grain size frequency histograms in high resolution remains difficult.

Multiple sources of Greenland dust throughout the Holocene

It is contested that the mineral dust found in Greenlandic ice cores during the Holocene stems from multiple source areas. Particles entrained above a more productive, primary source dominate the signal’s multi-seasonal average. Data in sub-annual resolution, however, reveal at least one further source. Whereas distinct inputs from the primary source are visible in elevated concentration levels, various inputs of the secondary source(s) are reflected by multiple maxima in the coarse particle percentage. As long as the dust sources’ respective seasonal cycles are preserved, primary and secondary source can be distinguished. Since the two source’s ejecta eventually detected differ in size, which can be attributed to a change in atmospheric residence times, it is suggested that the secondary source is located in closer proximity to the drilling site than the primary one.

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

OBJECTIVE We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. MATERIALS AND METHODS k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). RESULTS Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). CONCLUSION k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.

The AEgIS experiment at CERN for the measurement of antihydrogen gravity acceleration

The Antihydrogen Experiment: Gravity, Interferometry, Spectroscopy (AEgIS) experiment is conducted by an international collaboration based at CERN whose aim is to perform the first direct measurement of the gravitational acceleration of antihydrogen in the local field of the Earth, with Δg/g = 1% precision as a first achievement. The idea is to produce cold (100 mK) antihydrogen ( ¯H) through a pulsed charge exchange reaction by overlapping clouds of antiprotons, from the Antiproton Decelerator (AD) and positronium atoms inside a Penning trap. The antihydrogen has to be produced in an excited Rydberg state to be subsequently accelerated to form a beam. The deflection of the antihydrogen beam can then be measured by using a moir´e deflectometer coupled to a position sensitive detector to register the impact point of the anti-atoms through the vertex reconstruction of their annihilation products. After being approved in late 2008, AEgIS started taking data in a commissioning phase in 2012. This paper presents an outline of the experiment with a brief overview of its physics motivation and of the state-of-the-art of the g measurement on antimatter. Particular attention is given to the current status of the emulsion-based position detector needed to measure the ¯H sag in AEgIS.

The influence of absorbed solar radiation by Saharan dust on hurricane genesis

To date, the radiative impact of dust and the Sahar an air layer (SAL) on North Atlantic hurricane activity is not yet known. According to previous studies, dust stabilizes the atmosphere due to absorption of solar radiation but thus shifts convection to regions more conducive for hurricane genesis. Here we analyze differences in hurricane genesis and frequency from ensemble sensitivity simulations with radiatively active and inactive dust in the aerosol-climate model ECHAM6-HAM. We investigate dust burden and other hurricane-related variables and determine their influence on disturbances which develop into hurricanes (developing disturbances, DDs) and those which do not (nondeveloping disturbances, NDDs). Dust and the SAL are found to potentially have both inhibiting and supporting influences on background conditions for hurricane genesis. A slight southward shift of DDs is determined when dust is active as well as a significant warming of the SAL, which leads to a strengthening of the vertical circulation associated with the SAL. The dust burden of DDs is smaller in active dust simulations compared to DDs in simulations with inactive dust, while NDDs contain more dust in active dust simulations. However, no significant influence of radiatively active dust on other variables in DDs and NDDs is found. Furthermore, no substantial change in the DD and NDD frequency due to the radiative effects of dust can be detected.

The role of seasonality of mineral dust concentration and size on glacial/interglacial dust changes in the EPICA Dronning Maud Land ice core

We present a record of particulate dust concentration and size distribution in subannual resolution measured on the European Project for Ice Coring in Antarctica (EPICA) Dronning Maud Land (EDML) ice core drilled in the Atlantic sector of the East Antarctic plateau. The record reaches from present day back to the penultimate glacial until 145,000 years B.P. with subannual resolution from 60,000 years B.P. to the present. Mean dust concentrations are a factor of 46 higher during the glacial (~850–4600 ng/mL) compared to the Holocene (~16–112 ng/mL) with slightly smaller dust particles during the glacial comparedto the Holocene and with an absolute minimum in the dust size at 16,000 years B.P. The changes in dust concentration are mainly attributed to changes in source conditions in southern South America. An increase in the modal value of the dust size suggests that at 16,000 years B.P. a major change in atmospheric circulation apparently allowed more direct transport of dust particles to the EDML drill site. We find a clear in-phase relation of the seasonal variation in dust mass concentration and dust size during the glacial (r(conc,size) = 0.8) but no clear phase relationship during the Holocene (0 dust to the ice sheet using the size as an indicator for transport intensity, we find that the effect of the changes in the seasonality of the source emission strength and the transport intensity on the dust decrease over Transition 1 can significantly contribute to the large decrease of dust concentration from the glacial to the Holocene.

Kinetic simulation of neutral∕ionized gas and electrically charged dust in the coma of comet 67P∕Churyumov-Gerasimenko

The cometary coma is a unique phenomenon in the solar system being a planetary atmosphere influenced by little or no gravity. As a comet approaches the sun, the water vapor with some fraction of other gases sublimate, generating a cloud of gas, ice and other refractory materials (rocky and organic dust) ejected from the surface of the nucleus. Sublimating gas molecules undergo frequent collisions and photochemical processes in the near‐nucleus region. Owing to its negligible gravity, comets produce a large and highly variable extensive dusty coma with a size much larger than the characteristic size of the cometary nucleus. The Rosetta spacecraft is en route to comet 67P/Churyumov‐Gerasimenko for a rendezvous, landing, and extensive orbital phase beginning in 2014. Both, interpretation of measurements and safety consideration of the spacecraft require modeling of the comet’s dusty gas environment. In this work we present results of a numerical study of multispecies gaseous and electrically charged dust environment of comet Chyuryumov‐Gerasimenko. Both, gas and dust phases of the coma are simulated kinetically. Photolytic reactions are taken into account. Parameters of the ambient plasma as well as the distribution of electric/magnetic fields are obtained from an MHD simulation [1] of the coma connected to the solar wind. Trajectories of ions and electrically charged dust grains are simulated by accounting for the Lorentz force and the nucleus gravity.

Narrow dust jets in a diffuse gas coma: a natural product of small active regions on comets

Comets often display narrow dust jets but more diffuse gas comae when their eccentric orbits bring them into the inner solar system and sunlight sublimates the ice on the nucleus. Comets are also understood to have one or more active areas covering only a fraction of the total surface active with sublimating volatile ices. Calculations of the gas and dust distribution from a small active area on a comet’s nucleus show that as the gas moves out radially into the vacuum of space it expands tangentially, filling much of the hemisphere centered on the active region. The dust dragged by the gas remains more concentrated over the active area. This explains some puzzling appearances of comets having collimated dust jets but more diffuse gaseous atmospheres. Our test case is 67P/Churyumov–Gerasimenko, the Rosetta mission target comet, whose activity is dominated by a single area covering only 4% of its surface.

A New Approach for Automatic Removal of Movement Artifacts in Near-Infrared Spectroscopy Time Series by Means of Acceleration Data

Abstract: Near-infrared spectroscopy (NIRS) enables the non-invasive measurement of changes in hemodynamics and oxygenation in tissue. Changes in light-coupling due to movement of the subject can cause movement artifacts (MAs) in the recorded signals. Several methods have been developed so far that facilitate the detection and reduction of MAs in the data. However, due to fixed parameter values (e.g., global threshold) none of these methods are perfectly suitable for long-term (i.e., hours) recordings or were not time-effective when applied to large datasets. We aimed to overcome these limitations by automation, i.e., data adaptive thresholding specifically designed for long-term measurements, and by introducing a stable long-term signal reconstruction. Our new technique (“acceleration-based movement artifact reduction algorithm”, AMARA) is based on combining two methods: the “movement artifact reduction algorithm” (MARA, Scholkmann et al. Phys. Meas. 2010, 31, 649–662), and the “accelerometer-based motion artifact removal” (ABAMAR, Virtanen et al. J. Biomed. Opt. 2011, 16, 087005). We describe AMARA in detail and report about successful validation of the algorithm using empirical NIRS data, measured over the prefrontal cortex in adolescents during sleep. In addition, we compared the performance of AMARA to that of MARA and ABAMAR based on validation data.