bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced density and altered regulation of rat atrial L-type Ca2+current in heart failure
Authors: Bond Richard C. , Bryant Simon M. , Watson Judy J. , Hancox Jules C. , Orchard Clive H. , James Andrew F. 
Published: December 2016

Constitutive regulation by PKA has recently been shown to contribute to L-type Ca2+current ( ICaL) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial ICaLin heart failure. The hypothesis that downregulation of atrial ICaLin heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N=10) or equivalent sham-operation (Sham, N=12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). ICaLactivated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal ICaLconductance ( Gmax) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P < 0.0001). Norepinephrine (1 μmol/l) increased Gmax>50% more effectively in CAL than in Sham so that differences in ICaLdensity were abolished. Differences between CAL and Sham Gmaxwere not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for ICaLdownregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal ICaL. Expression of the L-type α1C-subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial ICaLin heart failure.NEW & NOTEWORTHY Whole cell recording of L-type Ca2+currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit expression and associated with altered phosphorylation independent of protein kinase A.
Modeling fast and slow gamma oscillations with interneurons of different subtype
Authors: Keeley Stephen , Fenton André A. , Rinzel John 
Published: December 2016

Experimental and theoretical studies demonstrate that neuronal gamma oscillations crucially depend on interneurons, but current models do not consider the diversity of known interneuron subtypes. Moreover, in CA1 of the hippocampus, experimental evidence indicates the presence of multiple gamma oscillators, two of which may be coordinated by differing interneuron populations. In this article, we show that models of networks with competing interneuron populations with different postsynaptic effects are sufficient to generate, within CA1, distinct oscillatory regimes. We find that strong mutual inhibition between the interneuron populations permits distinct fast and slow gamma states, whereas weak mutual inhibition generates mixed gamma states. We develop idealized firing rate models to illuminate dynamic properties of these competitive gamma networks, and reinforce these concepts with basic spiking models. The models make several explicit predictions about gamma oscillators in CA1. Specifically, interneurons of different subtype phase-lock to different gamma states, and one population of interneurons is silenced and the other active during fast and slow gamma events. Finally, mutual inhibition between interneuron populations is necessary to generate distinct gamma states. Previous experimental studies indicate that fast and slow gamma oscillations reflect different information processing modes, although it is unclear whether these rhythms are intrinsic or imposed. The models outlined demonstrate that basic architectures can locally generate these oscillations, as well as capture other features of fast and slow gamma, including theta-phase preference and spontaneous transitions between gamma states. These models may extend to describe general dynamics in networks with diverse interneuron populations. NEW & NOTEWORTHY The oscillatory coordination of neural signals is crucial to healthy brain function. We have developed an idealized neuronal model that generates distinct fast and slow gamma oscillations, a known feature of the rodent hippocampus. Our work provides a mechanism of this phenomenon, as well as a theoretical framework for future experiments concerning hippocampal gamma. It moreover offers a tractable model of competitive gamma oscillations that is generalizable across the nervous system.
Adenosine-dependent phrenic motor facilitation is inflammation resistant
Authors: Agosto-Marlin Ibis M. , Nichols Nicole L. , Mitchell Gordon S. 
Published: December 2016

Phrenic motor facilitation (pMF), a form of respiratory plasticity, can be elicited by acute intermittent hypoxia (i.e., phrenic long-term facilitation, pLTF) or direct application of drugs to the cervical spinal cord. Moderate acute intermittent hypoxia (mAIH; 3 × 5-min episodes of 35–50 mmHg arterial Po2, 5-min normoxic intervals) induces pLTF by a serotonin-dependent mechanism; mAIH-induced pLTF is abolished by mild systemic inflammation induced by a low dose of lipopolysaccharide (LPS; 100 μg/kg ip). In contrast, severe acute intermittent hypoxia (sAIH; 3 × 5-min episodes of 25–30 mmHg arterial Po2, 5-min normoxic intervals) elicits pLTF by a distinct, adenosine-dependent mechanism. Since it is not known if systemic LPS blocks the mechanism giving rise to sAIH-induced pLTF, we tested the hypothesis that sAIH-induced pLTF and adenosine 2A (A2A) receptor-induced pMF are insensitive to mild systemic inflammation elicited by the same low dose of LPS. In agreement with our hypothesis, neither sAIH-induced pLTF nor cervical intrathecal A2A receptor agonist (CGS-21680; 200 μM, 10 μl × 3)-induced pMF were affected 24 h post-LPS. Pretreatment with intrathecal A2A receptor antagonist injections (MSX-3; 10 μM, 12 μl) blocked sAIH-induced pLTF 24 h post LPS, confirming that pLTF was adenosine dependent. Our results give insights concerning the differential impact of systemic inflammation and the functional significance of multiple cascades capable of giving rise to phrenic motor plasticity. The relative resistance of adenosine-dependent pMF to inflammation suggests that it provides a “backup” system in animals lacking serotonin-dependent pMF due to ongoing inflammation associated with systemic infections and/or neural injury. NEW & NOTEWORTHY This study gives novel insights concerning how a mild systemic inflammation impacts phrenic motor plasticity (pMF), particularly adenosine-dependent pMF. We suggest that since this adenosine-dependent pathway is insensitive to systemic inflammation, it represents an alternative or “backup” mechanism of pMF when other mechanisms are suppressed.
Revealing unobserved factors underlying cortical activity with a rectified latent variable model applied to neural population recordings
Authors: Whiteway Matthew R. , Butts Daniel A. 
Published: December 2016

The activity of sensory cortical neurons is not only driven by external stimuli but also shaped by other sources of input to the cortex. Unlike external stimuli, these other sources of input are challenging to experimentally control, or even observe, and as a result contribute to variability of neural responses to sensory stimuli. However, such sources of input are likely not “noise” and may play an integral role in sensory cortex function. Here we introduce the rectified latent variable model (RLVM) in order to identify these sources of input using simultaneously recorded cortical neuron populations. The RLVM is novel in that it employs nonnegative (rectified) latent variables and is much less restrictive in the mathematical constraints on solutions because of the use of an autoencoder neural network to initialize model parameters. We show that the RLVM outperforms principal component analysis, factor analysis, and independent component analysis, using simulated data across a range of conditions. We then apply this model to two-photon imaging of hundreds of simultaneously recorded neurons in mouse primary somatosensory cortex during a tactile discrimination task. Across many experiments, the RLVM identifies latent variables related to both the tactile stimulation as well as nonstimulus aspects of the behavioral task, with a majority of activity explained by the latter. These results suggest that properly identifying such latent variables is necessary for a full understanding of sensory cortical function and demonstrate novel methods for leveraging large population recordings to this end. NEW & NOTEWORTHY The rapid development of neural recording technologies presents new opportunities for understanding patterns of activity across neural populations. Here we show how a latent variable model with appropriate nonlinear form can be used to identify sources of input to a neural population and infer their time courses. Furthermore, we demonstrate how these sources are related to behavioral contexts outside of direct experimental control.
Xanthohumol Prevents DNA Damage by Dietary Carcinogens: Results of a Human Intervention Trial
Authors: Pichler Christoph , Ferk Franziska , Al-Serori Halh , Huber Wolfgang , Jäger Walter , Waldherr Monika , Mišík Miroslav , Kundi Michael , Nersesyan Armen , Herbacek Irene , Knasmueller Siegfried 
Published: December 2016

Abstract
Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and after the intervention and incubated with the carcinogens and with human liver homogenate (S9). We found substantial reduction of B(a)P and IQ (P &lt; 0.001 for both substances) induced DNA damage after consumption of the beverage; also, with the nitrosamine a moderate, but significant protective effect was found. The results of a follow-up trial (n = 10) with XN pills showed that the effects are caused by the flavonoid and were confirmed in γH2AX experiments. To elucidate the underlying mechanisms we measured several parameters of glutathione related detoxification. We found clear induction of α-GST (by 42.8%, P &lt; 0.05), but no alteration of π-GST. This observation provides a partial explanation for the DNA protective effects and indicates that the flavonoid also protects against other carcinogens that are detoxified by α-GST. Taken together, our findings support the assumption that XN has anticarcinogenic properties in humans. Cancer Prev Res; 10(2); 153–60. ©2016 AACR.
Timing of Carotid Revascularization Procedures After Ischemic Stroke
Authors: Reznik Michael , Kamel Hooman , Gialdini Gino , Pandya Ankur , Navi Babak B. , Gupta Ajay 
Published: December 2016

Background and Purpose—
In 2006, the American Heart Association recommended that carotid revascularization generally occurs within 2 weeks of stroke based on data from 2 trials of carotid endarterectomy (CEA). We aimed to determine whether the time between stroke and CEA or carotid artery stenting (CAS) has decreased and whether the proportion of procedures occurring within 14 days has increased.

Methods—

Using validated International Classification of Diseases, Ninth Revision, Clinical Modification codes and administrative claims data from nonfederal hospitals in CA, FL, and NY, we identified patients with ischemic stroke who underwent CEA or CAS within 90 days of an ischemic stroke from 2005 to 2013. Our outcomes were the number of days between stroke and CEA/CAS and the proportion of patients undergoing CEA/CAS within the recommended 14-day period. We assessed temporal trends using nonparametric correlation, the χ
2
test for trend, and logistic regression.

Results—

We identified 16 298 patients with ischemic stroke who underwent CEA/CAS within 90 days. The time from stroke to CEA/CAS decreased from 25 days (interquartile range, 5–48 days) in 2005 to 6 days (interquartile range, 3–17 days) in 2013 (
P
<0.001). The proportion of patients who underwent CEA/CAS within 14 days of stroke increased from 40% (95% confidence interval, 37%–43%) in 2005 to 73% (95% confidence interval, 71%–76%) in 2013 (
P
<0.001). These temporal trends remained significant after adjustment for patient demographics and comorbidities.

Conclusions—
Since 2005, revascularization for symptomatic carotid disease has been occurring progressively sooner after ischemic stroke.
The Importance of the Shape of Cloud Droplet Size Distributions in Shallow Cumulus Clouds. Part II: Bulk Microphysics Simulations
Authors: Igel Adele L. , van den Heever Susan C. 
Published: December 2016

Abstract
In this two-part study, relationships between the cloud gamma size distribution shape parameter, microphysical processes, and cloud characteristics of nonprecipitating shallow cumulus clouds are investigated using large-eddy simulations. In Part I, the dependence of the shape parameter (which is closely related to the distribution width) on cloud properties and processes was investigated. However, the distribution width also impacts cloud process rates and in turn cloud properties, and it is this aspect of the relationship that is explored in Part II and is discussed in the context of aerosol–cloud interactions. In simulations with a bulk microphysics scheme, it is found that the evaporation rates are much more sensitive to the value of the shape parameter than to the condensation rates. This is due to changes in both the rate of removal of mass and the rate of removal of fully evaporated droplets. As a result, cloud properties such as droplet number concentration, mean droplet diameter, and cloud fraction are strongly impacted by the value of the shape parameter, particularly in the subsaturated regions of the clouds. These changes can be on the same order of magnitude as changes due to increasing or decreasing the aerosol concentration by a factor of 16. Particular attention is paid to the impact of the shape parameter on cloud albedo. The cloud albedo increases as the shape parameter is increased as a result of the changes in evaporation. The magnitude of the increase is about 4 times larger than previous estimates. However, this increase in cloud albedo is largely offset by a decrease in the cloud fraction, which results in only small increases to the domain-average albedo. Implications for the aerosol relative dispersion effect are discussed.
Effects of Rotation Rate and Seasonal Forcing on the ITCZ Extent in Planetary Atmospheres
Authors: Faulk Sean , Mitchell Jonathan , Bordoni Simona 
Published: December 2016

Abstract
The authors study a wide range of atmospheric circulations with an idealized moist general circulation model to evaluate the mechanisms controlling intertropical convergence zone (ITCZ) migrations. They employ a zonally symmetric aquaplanet slab ocean of fixed depth and force top-of-atmosphere insolation to remain fixed at the pole for an “eternal solstice” simulation and also vary seasonally for a range of rotation rates, keeping all other parameters Earth-like. For rotation rates ΩE/8 and slower, a transient maximum in zonal-mean precipitation appears at the summer pole; however, the ITCZ associated with the ascending branch of the Hadley circulation lies at ~60°. The authors assess how widely used predictors of the ITCZ position perform in this wide parameter space. Standard predictors based on different estimates of the Hadley cell’s poleward extent are correlated with but overestimate off-equatorial ITCZ locations. Interestingly, in the eternal-solstice case for Earth’s rotation rate, the ITCZ remains at subtropical latitudes even though the lower-level moist static energy maximizes at the summer pole. While seemingly at odds with convective quasi-equilibrium arguments, this can happen because at Earth’s rotation rates, the thermal stratification set in convective regions can only be communicated within the tropics, where temperature gradients are constrained to be weak. The authors therefore develop an understanding of the ITCZ’s position based on top-of-atmosphere energetics and the boundary layer momentum budget and argue that friction and pressure gradient forces determine the region of maximum convergence, offering a modified dynamical perspective on the monsoon-like seasonal weather patterns of terrestrial planets.
Indian Ocean Dipole Modes Associated with Different Types of ENSO Development
Authors: Fan Lei , Liu Qinyu , Wang Chunzai , Guo Feiyan 
Published: December 2016

Abstract
This study identifies several modes of coevolution of various types of El Niño–Southern Oscillation (ENSO) and Indian Ocean dipole (IOD) by performing rotated season-reliant empirical orthogonal function (S-EOF) analysis with consideration of ENSO asymmetry. The first two modes reveal that early-onset ENSO is associated with subsequent strong IOD development, whereas late-onset ENSO forces an obscure IOD pattern with marginal SST anomalies in the western Indian Ocean. Further studies show that El Niño starting before early summer can more easily force an IOD event than that starting in late summer or fall, even when they are of equivalent magnitudes. This is because the atmospheric responses over the Indian Ocean to the eastern Pacific warming are in sharp contrast between early and late summer. Early-onset (late onset) El Niño can (cannot) cause favorable atmospheric circulation conditions over the Indian Ocean for inducing the western Indian Ocean warming, which facilitates the subsequent IOD development. In addition, the different propagations of ocean dynamic Rossby waves during the early- or late-onset types of ENSO are also accountable for the different IOD development. For the higher-order modes, the rotated S-EOF of “Niño only” cases shows a coevolution between a negative IOD mode and a date line Pacific El Niño, with warm sea surface temperature anomalies originating from the northern Pacific meridional mode.
Impact of Atmospheric Blocking on South America in Austral Summer
Authors: Rodrigues Regina R. , Woollings Tim 
Published: December 2016

Abstract
This study investigates atmospheric blocking over eastern South America in austral summer for the period of 1979–2014. The results show that blocking over this area is a consequence of propagating Rossby waves that grow to large amplitudes and eventually break anticyclonically over subtropical South America (SSA). The SSA blocking can prevent the establishment of the South Atlantic convergence zone (SACZ). As such, years with more blocking days coincide with years with fewer SACZ days and reduced precipitation. Convection mainly over the Indian Ocean associated with Madden–Julian oscillation (MJO) phases 1 and 2 can trigger the wave train that leads to SSA blocking whereas convection over the western/central Pacific associated with phases 6 and 7 is more likely to lead to SACZ events. It is found that the MJO is a key source of long-term variability in SSA blocking frequency. The wave packets associated with SSA blocking and SACZ episodes differ not only in their origin but also in their phase and refraction pattern. The tropopause-based methodology used here is proven to reliably identify events that lead to extremes of surface temperature and precipitation over SSA. Up to 80% of warm surface air temperature extremes occur simultaneously with SSA blocking events. The frequency of SSA blocking days is highly anticorrelated with the rainfall over southeast Brazil. The worst droughts in this area, during the summers of 1984, 2001, and 2014, are linked to record high numbers of SSA blocking days. The persistence of these events is also important in generating the extreme impacts.
Impacts of Land-Use/Land-Cover Change on Afternoon Precipitation over North America
Authors: Chen Liang , Dirmeyer Paul A. 
Published: December 2016

Abstract
This study investigates the impacts of historical land-cover change on summer afternoon precipitation over North America using the Community Earth System Model. Using land–atmosphere coupling metrics, this study examines the sensitivity of afternoon atmospheric conditions to morning land surface states and fluxes that are altered by land-cover changes before and since 1850. The deforestation in the eastern United States prior to 1850 leads to increased latent but decreased sensible heat flux during the morning and a reduction in afternoon precipitation over the southern regions of the U.S. East Coast. The agricultural expansion over the Great Plains since preindustrial times shows similar effects on surface fluxes but results in a significant widespread increase in precipitation over the crop area. The coupling metrics exhibit a strong positive soil moisture–precipitation relationship over the Great Plains. Impacts of land-cover change on precipitation manifest through changes in rainfall frequency, rather than intensity, that are largely controlled by the distribution of CAPE as the trigger of convective precipitation. However, deforestation and later reforestation over the eastern United States, where coupling properties are different than the Great Plains, do not have as dominant an effect on afternoon precipitation. Additionally, precipitation over parts of the U.S. Southwest decreases in this model during the earlier period of East Coast deforestation, owing to changes in the large-scale circulation over North America driven by land-use changes prior to 1850.
Global Optimization of an Analog Method by Means of Genetic Algorithms
Authors: Horton Pascal , Jaboyedoff Michel , Obled Charles 
Published: December 2016

Abstract
Analog methods are based on a statistical relationship between synoptic meteorological variables (predictors) and local weather (predictand, to be predicted). This relationship is defined by several parameters, which are often calibrated by means of a semiautomatic sequential procedure. This calibration approach is fast, but has strong limitations. It proceeds through successive steps, and thus cannot handle all parameter dependencies. Furthermore, it cannot automatically optimize some parameters, such as the selection of pressure levels and temporal windows (hours of the day) at which the predictors are compared. To overcome these limitations, the global optimization technique of genetic algorithms is considered, which can jointly optimize all parameters of the method, and get closer to a global optimum, by taking into account the dependencies of the parameters. Moreover, it can objectively calibrate parameters that were previously assessed manually and can take into account new degrees of freedom. However, genetic algorithms must be tailored to the problem under consideration. Multiple combinations of algorithms were assessed, and new algorithms were developed (e.g., the chromosome of adaptive search radius, which is found to be very robust), in order to provide recommendations regarding the use of genetic algorithms for optimizing several variants of analog methods. A global optimization approach provides new perspectives for the improvement of analog methods, and for their application to new regions or new predictands.