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The phase behavior of symmetric polystyrene-block-poly(n-butyl-ran-n-hexyl) methacrylate copolymers (PS-b-Pn(B-r-H)MA) with various molecular weights was investigated by small-angle X-ray scatterin...

ContextWhile the world population is steadily growing, the demand for plant-based protein in general, and chickpea in particular, is rising. Heatwaves and terminal drought are the main abiotic factors limiting chickpea yield worldwide.ObjectiveDeveloping better irrigation management for the chickpea agro-system can promote higher and more sustainable yields. Supplemental irrigation at the right timing and dose may increase yield dramatically.MethodsWe studied the response of a modern Kabuli chickpea cultivar to irrigation during the pod-filling period over three growing seasons (2019-2021) in northern Negev, Israel, under semi-arid conditions. Six irrigation treatments were applied based on crop coefficients (Kc) of 0, 0.5, 0.7, 1.0, 1.25, and 1.4 of crop evapotranspiration (ETc) as measured by a meteorological station on site. Morpho-physiological parameters and above-ground biomass accumulation were monitored throughout the cropping seasons, and the final grain yield was determined at maturation. Irrigation onset was determined based on the plants’ water potential (> 15 bar).ResultsOur results indicate that optimal water status (as reflected by pressure chamber values) was in the range of 12-14 bar during the irrigation period. Irrigation according to evapotranspiration (ETc) with a crop coefficient factor (Kc) of 1.25 resulted in the highest grain yields over the three years. To ensure optimal water supply during the reproductive phase, one that is compatible with the crop water requirements, maintaining values of 25 mm node length above the Last Fully Developed Pod (LFDP) and a 90 mm distance between LFDP to the stem apex is recommended.ConclusionsIrrigation onset when the crop is already at mild drought stress, followed by sufficient irrigation while following the indicated morphology and water potential values, may help farmers optimize irrigation and maximize chickpea crop production.

Following a governmental decision to build a national earthquake early warning system (EEWS) named TRUAA, the Geological Survey of Israel has upgraded the national Israeli Seismic Network with more than 100 stations countrywide. The stations are spread mainly along the main hazardous fault systems of the Dead Sea and Carmel-Zfira, which potentially may produce Mw 7.5 earthquakes. Currently the system is shifting from the deployment phase into a testing phase in which the earthquake point-source integrated code (EPIC) EEW algorithm is used. During the deployment phase, real-time performance of the EEW algorithm has steadily improved, with alert delays (span between origin time and EEW alert time) reduced down to 3 s in some cases. We present an overview of TRUAA, the performance of EPIC during the deployment phase and during playbacks of historic events, as well as our suggested alert approach for Israel.

Following the recommendations of an international committee (Allen et al., 2012), since October 2017, the Israeli Seismic Network has been undergoing significant upgrades, with 120 stations being added or upgraded throughout the country and the addition of two new datacenters. These enhancements are the backbone of the TRUAA project, assigned to the Geological Survey of Israel (GSI) by the Israeli Government, to provide earthquake early warning (EEW) capabilities for the state of Israel. The GSI contracted Nanometrics (NMX), supported by Motorola Solutions Israel, to deliver these upgrades through a turnkey project, including detailed design, equipment supply, and deployment of the network and two datacenters. The TRUAA network was designed and tailored by the GSI, in collaboration with the NMX project team, specifically to achieve efficient and robust EEW. Several significant features comprise the pillars of this network:Coverage: Station distribution has high density (5–10 km spacing) along the two main fault systems—the Dead Sea Fault and the Carmel Fault System;Instrumentation: High-quality strong-motion accelerometers and broadband seismometers with modern three-channel and six-channel dataloggers sampling at 200 samples per second;Low latency acquisition: Data are encapsulated in small packets ( At this time, both datacenters and over 100 stations are operational. The system is currently being commissioned, with initial early warning operation targeted for early 2021.

A nitroxide (2,2,6,6-tetramethylpiperidin-1-oxyl, TEMPO) mediated polymerization method was applied to the graft polymerization of styrene (ST)/ n-butyl methacrylate (BMA) to isotactic polypropylene (PP). PP peroxides produced by γ-irradiation in air were used as macroinitiator for grafting. The molecular characteristics of grafted and free poly(ST-r-BMA) chains were analysed by gel permeation chromatography, NMR and IR measurements. The molecular weight of grafted poly(ST-r-BMA) cleaved from PP was slightly higher than that of free poly(ST-r-BMA) generated simultaneously in the reaction system. Polydispersities of these polymers were narrow, indicating that grafting proceeded in a living fashion. The incorporated amount of BMA into grafted poly(ST-r-BMA) was smaller than that of free poly(ST-r-BMA). It is considered that the local concentration of BMA around propagating ends of graft poly(ST-r-BMA) was lower than that around free poly(ST-r-BMA) because PP cannot be dissolved in BMA monomer but in ST monomer at the polymerization temperature.

Earthquake Early Warning Systems (EEWS) are often challenged when the earthquakes occur outside the seismic network or where the station density is sparse. In these situations, poor locations and large alert delays are more common because of the limited azimuthal coverage and the time required for the wavefield to reach the minimum number of seismic stations to issue an alert. Seismic arrays can be used to derive the directivity of the wavefield and obtain better location. However, they are uncommon because of the prohibitive cost of the sensors. Here, we propose the development of an array-based approach using mini-arrays of low-cost Microelectromechanical Systems (MEMS) accelerometers and show how they can be used to improve EEWS. In this paper, we demonstrate this approach using data from two MEMS Accelerometer Mini-Arrays (MAMA) deployed at University of California Berkeley and Humboldt State University. We use a new low-cost (

The seismic activity in Israel and its surrounding neighbors originates mainly from the active Dead Sea fault system. The historical and archeological records suggest a recurrence interval of approximately 102 and 103 yr for earthquakes of M 6 and 7, respectively. Despite the existing hazard, local advancements on this topic have been slow and incremental, partly due to inherent challenges, such as the limited number of significant recorded earthquakes and a limited azimuthal coverage resulting from geopolitical constraints. Annual earthquake bulletins and an earthquake catalog have been published over the years by the Geophysical Institute of Israel, which operated the network until January 2020. In this article, we summarize a joint effort aimed at standardizing the catalog and creating the first of its kind, publicly available ground-motion database for Israel, which is open to the scientific and engineering communities. The database is composed of three main components: event database, ground-motion recording database, and site database. Once compiled, we use this database to derive and calibrate the source, path, and site parameters required to execute ground-motion simulations, namely, the regional stress drop, anelastic attenuation factor Q, geometrical spreading, and the near-surface high-frequency attenuation, kappa. The parameters are optimized to fit the measurement database, and once they do, a synthetic dataset can be simulated, which will compensate for the lack of measurements in the large-magnitude range.

Most operational earthquake early warning systems (EEWS) consider earthquakes to be point-sources and have difficulty providing imminent and robust source locations and magnitudes, especially at the edge of the seismic network or where seismic stations are sparse. Mini-arrays have the potential to estimate reliable hypocentral locations by beam forming (FK-analysis) techniques. They can also characterize the rupture dimensions and account for finite-source effects, leading to more reliable estimates of ground motions for large magnitude earthquakes. In the past, the high price of multiple seismometers has made creating arrays cost- prohibitive. Here, we present a setup of two mini-arrays of a new low-cost (We will present our new 24-bit device details, benchmarks, and results from two MAMAs deployed at the UC Berkeley and Humboldt State University campuses. The new device shows lower noise levels than the currently available off-the-shelf 16-bit sensors, commonly used by several citizen-science projects (e.g. QCN, CSN, MyShake, etc.). This lower noise level enables us to record and process lower magnitude events. We show examples of back-azimuth calculations of M>=2.5 events at a range of

The performance of the Robovator (F. Poulsen Engineering ApS, Hvals⊘, Denmark), a commercial robotic intrarow cultivator, was evaluated in direct-seeded broccoli and transplanted lettuce during 2014 and 2015 in Salinas, CA, and Yuma, AZ. The main objective was to evaluate the crop stand after cultivation, crop yield, and weed control efficacy of the Robovator compared with a standard cultivator. A second objective was to compare hand weeding time after cultivation within a complete integrated weed management (IWM) system. Herbicides were included as a component of the IWM system. The Robovator did not reduce crop stand or marketable yield compared with the standard cultivator. The Robovator removed 18 to 41% more weeds at moderate to high weed densities and reduced hand-weeding times by 20 to 45% compared with the standard cultivator. At low weed densities there was little difference between the cultivators in terms of weed control and hand-weeding times. The lower-hand weeding time with the Robovator treatments suggest that robotic intrarow cultivators can reduce dependency on hand weeding compared with standard cultivators. Technological advancements and price reductions of these types of machines will likely improve their weed removal efficacy and the long-term viability of IWM programs that will use them.

We report a rationally designed nanobody activation immunotherapeutic that selectively redirects anti-dinitrophenyl (anti-DNP) antibodies to the surface of HER2-positive breast cancer cells, resulting in their targeted destruction by antibody-dependent cellular cytotoxicity. Since nanobodies are relatively easy to express, stable, can be humanized, and can be evolved to potently and selectively bind virtually any disease-relevant cell surface receptor, we anticipate broad utility of this therapeutic strategy.

Few herbicides are available for use in lettuce and hand weeding is required for commercially acceptable weed control. More effective herbicides are needed. Here field evaluations of pendimethalin andS-metolachlor for weed control in transplanted lettuce are reported. Pendimethalin was evaluated PRE at rates between 0.6 and 6.7 kg ai ha−1, and POST at 1.1 and 2.2 kg ha−1. Both pendimethalin PRE and POST applications were safe to transplanted lettuce and provided similar weed control. Pendimethalin PRE at rates of 1.1 kg ha−1and higher provided better weed control than the industry standard, pronamide at 1.3 kg ha−1.S-Metolachlor PRE was evaluated at rates between 0.6 and 5.6 kg ha−1.S-Metolachlor at rates up to 2.8 kg ha−1caused little or no crop injury or yield reduction in transplanted lettuce, andS-metolachlor at rates of 1.4 kg ha−1and higher improved weed control compared with pronamide at 1.3 kg ha−1. Pendimethalin andS-metolachlor are not labeled for transplanted lettuce, but we suggest that labeling be pursued at rates of 1.1 and 0.7 kg ha−1, respectively. Pendimethalin at 1.1 kg ha−1applied PRE or POST improved weed control by 57 and 42%, respectively compared with pronamide.S-Metolachlor PRE at 0.7 kg ha−1was less effective on weeds than pendimethalin, but maintained weed control level similar to pronamide. Pendimethalin andS-metolachlor have potential for use in transplanted lettuce production and provide alternatives to current transplanted lettuce herbicides.

Fresh market spinach has limited herbicides available and weed management in this crop is dependent on hand-weeding. Phenmedipham is a POST herbicide registered for use on spinach grown for processing or for seed, but not fresh market spinach. This study evaluates the potential use of phenmedipham alone and in combination with cycloate for weed control in fresh spinach production. Greenhouse and field studies were conducted in 2013 using two spinach varieties known to have low and high tolerance to phenmedipham. The greenhouse studies showed that phenmedipham at 270 and 550 g ai ha−1 was safe to spinach when applied at the four-leaf stage for the low- and high-tolerance varieties, respectively. Phenmedipham was evaluated alone (550 g ha−1) and applied to the four-leaf stage in two varieties. Subsequently, a second experiment evaluated cycloate (1,700 g ha−1) followed by (fb) phenmedipham at several rates (90, 180, and 270 g ha−1). Phenmedipham alone (550 g ha−1) did not result in crop injury when applied to four-leaf spinach; however, the weed control was not better than cycloate alone. When applied as a sequential treatment following cycloate, all phenmedipham rates were safe to spinach and significantly improved weed control compared to cycloate alone. Cycloate fb phenmedipham at 270 g ha−1 provided 87% weed control relative to cycloate alone. This level of weed control was similar to the cycloate plus hand-weeding treatment, which provided 98% control. Results here show that cycloate fb phenmedipham improves weed control compared to cycloate alone, and has the potential to reduce hand-weeding costs in the fresh spinach production.

Here we report on the structure-based optimization of antibody-recruiting molecules targeting HIV gp120 (ARM-H). These studies have leveraged a combination of medicinal chemistry, biochemical and cellular assay analysis, and computation. Our findings have afforded an optimized analog of ARM-H, which is ~1000 fold more potent in gp120-binding and MT-2 antiviral assays than our previously reported derivative. Furthermore, computational analysis, taken together with experimental data, provides evidence that azaindole- and indole-based attachment inhibitors bind gp120 at an accessory hydrophobic pocket beneath the CD4-binding site and can also adopt multiple unique binding modes in interacting with gp120. These results are likely to prove highly enabling in the development of novel HIV attachment inhibitors, and more broadly, they suggest novel applications for ARMs as probes of conformationally flexible systems.

During the past three decades, the Dead Sea (DS) water level has dropped at an average rate of ~1 m/year, resulting in the formation of thousands of sinkholes along its coastline that severely affect the economy and infrastructure of the region. The sinkholes are associated with gradual land subsidence, preceding their collapse by periods ranging from a few days to about five years. We present the results of over six years of systematic high temporal and spatial resolution interferometric synthetic aperture radar (InSAR) observations, incorporated with and refined by detailed Light Detection and Ranging (LiDAR) measurements. The combined data enable the utilization of interferometric pairs with a wide range of spatial baselines to detect minute precursory subsidence before the catastrophic collapse of the sinkholes and to map zones susceptible to future sinkhole formation. We present here four case studies that illustrate the timelines and effectiveness of our methodology as well as its limitations and complementary methodologies used for sinkhole monitoring and hazard assessment. Today, InSAR-derived subsidence maps have become fundamental for sinkhole early warning and mitigation along the DS coast in Israel and are incorporated in all sinkhole potential maps which are mandatory for the planning and licensing of new infrastructure.

The ability to profile the prevalence and functional activity of endogenous antibodies is of vast clinical and diagnostic importance. Serum antibodies are an important class of biomarkers and are also crucial elements of immune responses elicited by natural disease-causing agents as well as vaccines. In particular, materials for manipulating and/or enhancing immune responses toward disease-causing cells or viruses have exhibited significant promise for therapeutic applications. Antibody-recruiting molecules (ARMs), bifunctional organic molecules that redirect endogenous antibodies to pathological targets, thereby increasing their recognition and clearance by the immune system, have proven particularly interesting. Notably, although ARMs capable of hijacking antibodies against oligosaccharides and electron-poor aromatics have proven efficacious, systematic comparisons of the prevalence and effectiveness of natural anti-hapten antibody populations have not appeared in the literature. Herein we report head-to-head comparisons of three chemically simple antigens, which are known ligands for endogenous antibodies. Thus, we have chemically synthesized bifunctional molecules containing 2,4-dinitrophenyl (DNP), phosphorylcholine (PC), and rhamnose. We have then used a combination of ELISA, flow cytometry, and cell-viability assays to compare these antigens in terms of their abilities both to recruit natural antibody from human serum and also to direct serum-dependent cytotoxicity against target cells. These studies have revealed rhamnose to be the most efficacious of the synthetic antigens examined. Furthermore, analysis of 122 individual serum samples has afforded comprehensive insights into population-wide prevalence and isotype distributions of distinct anti-hapten antibody populations. In addition to providing a general platform for comparing and studying anti-hapten antibodies, these studies serve as a useful starting point for the optimization of antibody-recruiting molecules and other synthetic strategies for modulating human immunity.

The water level in the Dead Sea (Israel and Jordan) has been dropping at an increasing rate since the 1960s, exceeding one meter per year during the last decade. This drop has triggered the formation of sinkholes and widespread land subsidence along the Dead Sea shoreline, resulting in severe economic loss and infrastructural damage. In this study, the spatiotemporal evolution of sinkhole-related subsidence and the effect of human activities and land perturbation on sinkhole development are examined through interferometric synthetic aperture radar measurements and field surveys conducted in Israel during 2012. Interferograms are generated using COSMO-SkyMed satellite images and a high-resolution (0.5 m/pixel) elevation model obtained from LiDAR measurements. As a result of this unique combination of high-resolution data sets, millimeter-scale subsidence has been resolved in both natural and human-disturbed environments. Precursory subsidence over a period of a few months occurred before the collapse of all three sinkhole sites reported in this study. The centers of the subsiding areas migrated, possibly due to progressive dissolution and widening of the underlying cavities. Filling of newly formed sinkholes with gravel, and mud injections into drill holes, seem to enhance land subsidence, enlarge existing sinkholes, and form new sinkholes. Apart from shedding light on the mechanical process, the results of this study may pave the way for the implementation of an operational sinkhole early-warning system.

SummaryFas apoptotic signaling regulates diverse physiological processes. Acute activation of Fas signaling triggers massive apoptosis in liver. Upon Fas receptor stimulation, the BH3-only protein Bid is cleaved into the active form, tBid. Subsequent tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM), is a critical step for commitment to apoptosis via the effector proteins Bax or Bak. MOAP-1 is a Bax-binding protein enriched at the OMM. Here, we show that MOAP-1-deficient mice are resistant to Fas-induced hepatocellular apoptosis and lethality. In the absence of MOAP-1, mitochondrial accumulation of tBid is markedly impaired. MOAP-1 binds to MTCH2, and this interaction appears necessary for MTCH2 to engage tBid. These findings reveal a role for MOAP-1 in Fas signaling in the liver by promoting MTCH2-mediated tBid recruitment to mitochondria.

The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.

An earthquake swarm struck the North Tanzania Divergence, East African Rift over a 2 month period between July and September 2007. It produced approximately 70 M > 4 earthquakes (peak magnitude Mw 5.9), and extensive surface deformation, concurrent with eruptions at the nearby Oldoinyo Lengai volcano. The spatial and temporal evolution of the entire deformation event was resolved by Interferometric Synthetic Aperture Radar (InSAR) observations, owing to a particularly favorable acquisition programming of the Envisat and ALOS satellites, and was verified by detailed ground observations. Elastic modeling based on the InSAR measurements clearly distinguishes between normal faulting, which dominated during the first week of the event, and intermittent episodes of dike propagation, oblique dike opening and dike-induced faulting during the following month. A gradual decline in the intensity of deformation occurred over the final weeks. Our observations and modeling suggest that the sequence of events was initiated by pressurization of a deep-seated magma chamber below Oldoinyo Lengai which opened the way to lateral dike injection, and dike-induced faulting and seismicity. As dike intrusion terminated, silicate magma ascended the volcano conduit, reacted with the carbonatitic magma, and set off a major episode of explosive ash eruptions producing mixed silicate-carbonatitic ejecta. The rise of the silicate magma within the volcano conduit is attributed to bubble growth and buoyancy increase in the magma chamber either due to a temporary pressure drop after the termination of the diking event, or due to the dynamic effects of seismic wave passage from the earthquake swarm. Similar temporal associations between earthquake swarms and major explosive ash eruptions were observed at Oldoinyo Lengai over the past half century.

The study was done to investigate various factors that are associated with the consumption behaviour of the consumers in the Indian market. This study also tries to find out the new and emerging trends of the Indian cosmeceutical industry. The research first sought to explore how different variables influence the behaviour of the consumers regarding the usage of cosmeceutical product. Various factors such as self esteem, the decision making process while purchasing the cosmeceutical products etc were also studied in depth. However this study also tries to examine the various key determinants involved in the purchasing behaviour of consumers while purchasing their cosmeceutical product. The target sample was above 15 years. The sample size is 120 and the sampling method used is the quota sampling method. The study was conducted in six different cities of India that are Delhi, Mumbai, Kolkata, Lucknow, Jaipur and Patna. Among these six cities three are metro cities and the rest of the three are Tier-I cities. Delhi, Mumbai and Kolkata are the metro cities and luck now, Jaipur and Patna are the Tier-I cities. The instrument used to collect primary data is the questionnaire. The data is finally analyzed through analytical software named SPSS version 16. The various analytical tests used are Correlation, ANOVA, and Post Hoc Tukey and Cross tabulation. The result of the study indicates that more of the young males were becoming aware of the cosmeceutical products. The result also shows that the brand, quality, price and availability are certain factors that influence consumer behaviour.

Weed/crop classification is considered the main problem in developing precise weed-management methodologies, because both crops and weeds share similar hues. Great effort has been invested in the development of classification models, most based on expensive sensors and complicated algorithms. However, satisfactory results are not consistently obtained due to imaging conditions in the field.We report on an innovative approach that combines advances in genetic engineering and robust image-processing methods to detect weeds and distinguish them from crop plants by manipulating the crop's leaf color. We demonstrate this on genetically modified tomato (germplasm AN-113) which expresses a purple leaf color. An autonomous weed/crop classification is performed using an invariant-hue transformation that is applied to images acquired by a standard consumer camera (visible wavelength) and handles variations in illumination intensities.The integration of these methodologies is simple and effective, and classification results were accurate and stable under a wide range of imaging conditions. Using this approach, we simplify the most complicated stage in image-based weed/crop classification models.

Background: Vascular dementia affects a broad spectrum of patients with various manifestations of cognitive decline, which are attributed to cerebral or cardiovascular disease. Laboratory studies have shown that transplanted bone marrow stem cells improve neurological diseases of the central nervous system by generating neural cells or myelin-producing oligodendroglial cells and enhancing neural plasticity. But till now, there has been lack of objective data in the form of investigational findings providing evidence for clinical improvements. Method: We present a case of a 61 year old woman diagnosed with vascular dementia, who was administered autologous bone marrow derived mononuclear cells, intrathecally. Result: Even after follow up of 2 years she showed sustained significant clinical improvements recorded by MMSE and FIM along with corroborating changes in PET CT scan of brain showing significantly improved metabolic activity. Conclusion: Thus, demonstrating objective evidence showing benefits of neuroregeneration rehabilitation therapy in vascular dementia.

Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology. Parkin has been linked to multiple cellular processes including protein degradation, mitochondrial homeostasis, and autophagy; however, its precise role in pathogenesis is unclear. Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover. The precise mechanism of recruitment and the ubiquitination target are unclear. Here we show in Drosophila cells that PINK1 is required to recruit Parkin to dysfunctional mitochondria and promote their degradation. Furthermore, PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria. Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria. These findings provide a molecular mechanism by which the PINK1/Parkin pathway affects mitochondrial fission/fusion as suggested by previous genetic interaction studies. We hypothesize that Mfn ubiquitination may provide a mechanism by which terminally damaged mitochondria are labeled and sequestered for degradation by autophagy.

Stimulation of gastric motility has been supposed to accelerate the healing of gastric ulcer. The combination of the prokinetic drug cisapride and the H2 blocker ranitidine was tested in the treatment of uncomplicated gastric ulcer.Cisapride, 20 mg twice daily (Cis), and ranitidine, 150 mg twice daily (Ran), were given as monotherapies and in the combination 20 mg cisapride and 150 mg ranitidine daily (Cis + Ran) for a maximum of 8 weeks. The study was multicentre, randomized, and double-blind.A total of 197 patients were included. Healing rates in the per-protocol analysis after 4 and 8 weeks' treatment were 61%/84%, 52%/69%, and 61%/92% for the Cis + Ran (n = 56), Cis (n = 58), and Ran (n = 59) treatment groups. No statistically significant difference in healing rates was seen when comparing Cis + Ran with the monotherapies. Symptom relief at the end of treatment was significantly better in the Ran group than in the Cis + Ran group with regard to epigastric pain (p = 0.01) and vomiting (p = 0.05). Patients' global evaluation of treatment was in favour of Ran in comparison with Cis + Ran treatment (p = 0.04).Combination of cisapride and ranitidine in the treatment of gastric ulcer did not enhance the healing rate or improve symptom relief in patients treated for uncomplicated gastric ulcer when compared with the monotherapies.

Protoplanetary disks are thought to be truncated at orbital periods of around 10 days. Therefore, origin of rocky short period planets with $P < 10$ days is a puzzle. We propose that many of these planets may form through the Type-I migration of planets locked into a chain of mutual mean motion resonances. We ran N-body simulations of planetary embryos embedded in a protoplanetary disk. The embryos experienced gravitational scatterings, collisions, disk torques, and dampening of orbital eccentricity and inclination. We then modelled Kepler observations of these planets using a forward model of both the transit probability and the detection efficiency of the Kepler pipeline. We found that planets become locked into long chains of mean motion resonances that migrate in unison. When the chain reaches the edge of the disk, the inner planets are pushed past the edge due to the disk torques acting on the planets farther out in the chain. Our simulated systems successfully reproduce the observed period distribution of short period Kepler planets between 1 and 2 $R_\oplus$. However, we obtain fewer closely packed short period planets than in the Kepler sample. Our results provide valuable insight into the planet formation process, and suggests that resonance locks, migration, and dynamical instabilities play important roles the the formation and evolution of close-in small exoplanets., 12 pages, 11 figures, submitted to MNRAS

Background: Diabetic cardiomyopathy (DCM) increases the risk of heart failure. As yet, no effective therapeutic strategies exist. Recent evidence indicates that intracellular Na + concentration ([Na + ] i ) is augmented in the myocytes from diabetic hearts, where it causes oxidative stress, augments the sarcoplasmic reticulum Ca 2+ leak and contributes to electrical, structural and functional remodeling. Ranolazine (RAN), inhibiting persistent or late inward Na + current has been proposed to be a therapeutic choice for DCM. However, the role and mechanism of chronic RAN in DCM are unclear. We assessed the hypothesis that RAN improves myocyte function, [Ca 2+ ] i regulation, and β-adrenergic receptor (AR) signaling effectiveness, thus limiting DCM. Methods: We compared LV myocyte function, [Ca 2+ ] i transient ([Ca 2+ ] iT ) and responses to the stimulation of β-AR in 3 groups wild-type (WT) female mice over 10 weeks (W):1) DM (n=8), 10 W after receiving streptozotocin (STZ, 200 mg/kg, ip); 2) DM/RAN (n=6), 6 W after STZ, RAN (10 -5 M/kg/day, mini-pump) was initiated and was given for 4 W; and 3) Sham controls (C) (n=8). Results: Versus control, STZ-treated WT mice had DM with significantly elevated blood glucose levels (410 vs 128mg/dl) followed by LV myocyte dysfunction with decreases in myocyte contractility (dL/dt max ) (75.0 vs 140.1 μm/s), relengthening (dR/dt max ) (62.5 vs 116.6 μm/s) and [Ca 2+ ] iT (0.15 vs 0.22). In DM myocytes, the ability of β-AR agonist, isoproterenol (ISO, 10 -8 M) to increase cell contractility was blunted. Versus control, in DM myocytes, ISO-induced increases in dL/dt max (31% vs 60%), dR/dt max (23% vs 50%) and [Ca 2+ ] iT (15% vs 30%) were significantly reduced. By contrary, versus DM alone, DM/RAN myocytes showed normal basal cell contraction (137.8 μm/s), relaxation (117.2 μm/s) and [Ca 2+ ] iT (0.22) with preserved ISO-stimulated positive inotropic effect. Compared control, in DM/RAN, ISO caused similar increases in dL/dt max (62% vs 60%), dR/dt max (52% vs 50%) and [Ca 2+ ] iT (32% vs 30%). Conclusion: Chronic ranolazine leads to the preservation of myocyte function, [Ca 2+ ] iT and β-AR responsiveness in DCM. Thus, antagonizing myocyte [Na + ] i dysregulation might provide a new therapeutic strategy for DM-related decline in myocardial function.

Comparative data appertaining to the long-term effects of Aflibercept or Ranibizumab in newly diagnosed cases of neovascular age-related macular degeneration (nAMD) over follow-up periods exceeding 12 months in clinical routine are scarce.In this retrospective comparative analysis, a case series of patients with treatment-naïve nAMD and requiring anti-vascular endothelial growth factor (VEGF) therapy in a routine clinical setting were treated with either Aflibercept [Afl (n = 106)] or Ranibizumab [Ran (n = 47)]. During the drug-loading phase, 3 monthly injections were administered. Thereafter, a treat-and-extend protocol was pursued for a maximum of 24 months. Ran was administered predominantly in eyes with classical lesions; Afl was administered in all others. The primary outcome parameters included anatomical and functional stability after 24 months.Patients were comparable regarding age, gender distribution, and lens status. Fewer patients presented with intraretinal fluid in the Afl- than in the Ran group at diagnosis (46.2% vs. 67.4%; P = 0.02), but not after the drug-loading phase. After the drug-loading phase, visual acuity [-4.2 letters (Afl) vs. -4.5 letters (Ran); P = 0.78] and the central foveal thickness remained stable. Linked to the lesion type, the number of scheduled clinical visits during the course of 24 months was higher for the Ran- than for the Afl group [11.9 ± 4.7 visits (Ran) vs. 8.4 ± 3.1 visits (Afl); P = 0.0005]. However, the total number of injections was similar [10.5 ± 2.8 (Ran) vs. 11.7 ± 3.6 (Afl); P = 0.06].Based on tailoring according to the lesion type in cases of nAMD, the anatomical and the functional outcomes of treatment with either Afl or Ran were comparable for a maximum of 2 years.

BackgroundThe neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change.MethodsAdult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm.ResultsDuring stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity.ConclusionsAnticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

ObjectiveModels of anorexia nervosa (AN) posit that set-shifting deficits may contribute to behavioral inflexibility and extreme dietary restriction. Findings from neurocognitive studies of set-shifting in AN have been somewhat mixed, perhaps due to the use of tasks that cannot distinguish shifting from other processes (i.e., learning). To more precisely characterize cognitive flexibility and selectively assess this process independent of rule learning and feedback sensitivity, we examined task-switching ability in AN.MethodWomen ill with AN, subthreshold AN or atypical AN (IAN; n = 40), women remitted from AN (RAN; n = 24), and age-matched healthy control women (n = 42) completed a computerized cued color-shape task-switching paradigm. Groups were compared on mix costs (reflecting global cognitive control) and switch costs (reflecting transient cognitive control).ResultsAlthough mix costs were equivalent across groups, switch costs were more pronounced in the IAN group, as indicated by a group-by-trial type interaction for reaction times on stay and switch trials.DiscussionFindings indicate that IAN, but not RAN, have difficulty flexibly switching between cognitive task sets, and suggest that prior findings of set-shifting deficits in AN may reflect difficulty with cognitive flexibility independent of learning deficits. As such, task-switching may represent a promising adjunctive treatment target.

OBJECTIVE: Models of anorexia nervosa (AN) posit that set-shifting deficits may contribute to behavioral inflexibility and extreme dietary restriction. Findings from neurocognitive studies of set-shifting in AN have been somewhat mixed, perhaps due to the use of tasks that cannot distinguish shifting from other processes (i.e., learning). To more precisely characterize cognitive flexibility and selectively assess this process independent of rule learning and feedback sensitivity, we examined task-switching ability in AN. METHOD: Women ill with AN, subthreshold AN, or atypical AN (IAN; n = 40), women remitted from AN (RAN; n = 24), and age-matched healthy control women (CW; n = 42) completed a computerized cued color-shape task-switching paradigm. Groups were compared on mix costs (reflecting global cognitive control) and switch costs (reflecting transient cognitive control). RESULTS: Although mix costs were equivalent across groups, switch costs were more pronounced in the IAN group, as indicated by a group-by-trial type interaction for reaction times on stay and switch trials. DISCUSSION: Findings indicate that IAN, but not RAN, have difficulty flexibly switching between cognitive task sets, and suggest that prior findings of set-shifting deficits in AN may reflect difficulty with cognitive flexibility independent of learning deficits. As such, task-switching may represent a promising adjunctive treatment target.

Made available in DSpace on 2022-04-29T07:55:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01 The high cost and the low efficiency of fertilizers, especially nitrogen (N), are of major concerns in agriculture. This study aimed to evaluate the effect of N fertilizers sources in Urochloa brizantha cv. Marandu (palisade grass). The study was conducted in Cerrado of Brazil to evaluate dry-matter yield (DMY), recovery of applied N (RAN), N use efficiency (NUE), and chemical composition of palisade grass in response to sources of N (ammonium nitrate, ammonium sulfate, ammonium sulfate-nitrate, urea, urea with urease inhibitor, polymer-coated urea, and control) in seven harvests (100 kg ha-1 N were applied after each harvest). The N fertilization increased DMY and growth of palisade grass compared to control (without N fertilization). However, there was not any difference in DMY due to N sources. Application of ammonium sulfate-nitrate increased RAN. The urea, urea with urease inhibitor, and polymer-coated urea improved NUE. Concentration of neutral detergent fiber (NDF) was decreased, while concentrations of acid detergent fiber (ADF) and cellulose were not affected by the fertilizers. Crude protein (CP) content was increased with N supply, but CP fractions A and B were not changed, except in the fifth period of growth. The results indicated protected fertilizers (ammonium sulfate-nitrate, urea with urease inhibitor, and polymer-coated urea) are more recommended for the cultivation of palisade grass in the Cerrado biome of Brazil. Department of Plant Health Rural Engineering and Soils Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista Júlio de Mesquita Filho Laboratory of Plant Mineral Nutrition Centro de Energia Nuclear na Agricultura Universidade de São Paulo André Luis Sarto ME - Serviços Agrícolas Ivinhema Mato Grosso do Sul State Luiz de Queiroz College of Agriculture Department of Soil and Plant Nutrition Department of Plant Health Rural Engineering and Soils Faculdade de Engenharia de Ilha Solteira Universidade Estadual Paulista Júlio de Mesquita Filho

Novel photo-reactive phospholipid polymers were synthesized for use in the preparation of nonfouling surfaces with protein conjugation capacity. Poly[2-methacryloyloxyethyl phosphorylcholine (MPC)- ran - N -methacryloyl-( l )-tyrosinemethylester (MAT)] (P(MPC/MAT)) was synthesized by conventional radical polymerization, with the MAT units capable of being oxidized by 254 nm UV irradiation. Because of this photo-oxidation, active species such as catechol and quinone were alternately generated in the copolymer. A silicon wafer was subjected to surface modification through spin coating of P(MPC/MAT) from an aqueous solution for use as a model substrate. The surface was then irradiated several times with UV light. The thickness of the polymer layers formed on the Si wafers was influenced by various parameters such as polymer concentration, UV irradiation time, and composition of the MAT units in P(MPC/MAT). Oxidized MAT units were advantageous not only for polymer adhesion to a solid surface but also for protein conjugation with the adhered polymers. The amount of protein immobilized on UV-irradiated P(MPC/MAT) was dependent on the composition of the MAT units in the polymer. Furthermore, it was confirmed that protein immobilization on the polymer occurred through the oxidized MAT units because the protein adsorption was significantly reduced upon blocking these units through pretreatment with glycine. Conjugation of regiospecific protein could also be achieved through the use of a photomask. In addition, nonspecific protein adsorption was reduced on the non-irradiated regions whose surface was covered with physisorbed P(MPC/MAT). Therefore, P(MPC/MAT) can be used in the preparation of nonfouling substrates, which enable micrometer-sized manipulation of proteins through photo-irradiation. Function of proteins immobilized on MPC copolymers was also confirmed by cell adhesion test. As such, photo-reactive MPC copolymers are suitable for performing controlled protein conjugation and preparing polymer–protein hybrid platforms for use in biomedical and diagnostic devices. Statement of Significance Novel photo-reactive phospholipid polymers have been synthesized for immobilization on solid surfaces and regiospecific protein conjugation. Tyrosine residues embedded in 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers could be photo-oxidized, resulting in polymers able to form layers on a solid surface and conjugate with proteins. Moreover, nonspecific biofouling on the surface significantly reduced when the oxidized tyrosine units in the polymer layers were blocked. Upon UV irradiation through a photomask, the UV-exposed tyrosine units were selectively oxidized, forming the only specific regions in which protein conjugation could occur.

Objective Eating disorders are complex psychiatric disorders, associated with alterations in neural and cognitive functioning. Research suggests inhibition and set-shifting deficits in anorexia nervosa (AN), but less is known about the persistence of these deficits after recovery, or their relationship to comorbid psychiatric symptoms. Method Women aged 19–45 remitted from AN (RAN, N = 47) and controls (CW, N = 24) completed the Delis–Kaplan Executive Function System Color-Word Interference Test. It was hypothesized that RAN, and those with higher anxiety or depression, would demonstrate worse Inhibition and Switching task performance than CW. Results Differences in performance between groups trended toward significance on Inhibition Ratio (p = 0.08) but were nonsignificant on Inhibition/Switching Ratio (p = 0.93). A model including State Anxiety and diagnosis revealed a significant independent effect of State Anxiety (p = 0.026), but not of diagnosis nor their interaction. Regressing State Anxiety on Color-Word Interference Test Inhibition among just the RAN group was significant [β = 0.37, t(46) = 2.63, p = 0.012] but among just CW was not (p = 0.54). Discussion Interference control for neutral stimuli is influenced by anxiety in women with a history of AN. Anxiety is linked with greater symptom severity among AN individuals, and state anxiety may account for larger deficits seen on tasks using disorder-specific stimuli. Future research is warranted to elucidate the nature of neuropsychological deficits in eating disorders. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association

Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not.

Interoception, or the sensing and integration of bodily state signals, has been implicated in anorexia nervosa (AN), given that the hallmark symptoms involve food restriction and body image disturbance. Here we focus on brain response to the anticipation and experience of affective interoceptive stimuli. Women remitted from AN (RAN; N = 18) and healthy comparison women (CW; N = 26) underwent a pleasant affective touch paradigm consisting of gentle strokes with a soft brush administered to the forearm or palm during functional neuroimaging. RAN had a lower brain response relative to CW during anticipation of touch, but a greater response when experiencing touch in the right ventral mid-insula. In RAN, this reduced anticipatory response was associated with higher levels of harm avoidance. Exploratory analyses in RAN also suggested that lower response during touch anticipation was associated with greater body dissatisfaction and higher perceived touch intensity ratings. This reduced responsivity to the anticipation of pleasant affective interoceptive stimuli in association with higher harm avoidance, along with an elevated response to the experience of touch, suggests an impaired ability in AN to predict and interpret incoming physiological stimuli. Impaired interoception may thus impact one’s sense of self, thereby supporting observations of disturbed body image and avoidance of affective and social stimuli. Therapeutic approaches that help AN to better anticipate and interpret salient affective stimuli or improve tolerance of interoceptive experiences may be an important addition to current interventions.

Poly(methylmethacrylat) (PMMA), Poly-n-(butylmethacrylat) (PnBMA) sowie Poly(methylmethacrylat-ran-n-butylmethacrylat) sind mischbar mit Poly(vinylchlorid) (PVC). Die Dreikomponentenmischungen liegen jedoch in zweiphasigen Systemen vor. Jede dieser Phasen besteht aus PVC und entsprechenden Methacrylatpolymeren. Die Abhangigkeit der Glastemperatur von der Mischungszusammensetzung fur PVC/PnBMA last sich durch Einfuhren eines zusatzlichen Terms in der Gordon-Taylor-Gleichung beschreiben. Poly(methylmethacrylate) (PMMA), Poly-n-(butylmethacrylate) (PnBMA), and Poly(methylmethacrylate-ran-n-butylmethacrylate) are miscible with Poly(vinylchloride) (PVC). The three-component mixtures, however, represent two-phase systems. Both the phases are composed of PVC and one of the two polymethacrylates. The glass-transition-composition curve for PVC/PnBMA can be reproduced by introducing an additional quadratic term into the Gordon-Taylor equation.

LaTurquie est enfrée en l'an 2000 avec un programme de stabilisation tresambitieux. Malgré les développements extérieures défavorables, l'économieturque a enrégistré, particulierement dans le premier de l'annéedes succes non négligéables, meme s'ils étaient partiels.Mais unecrise du systeme bancaire qui a éclaté vers la fin de ran_n£ interrompantla tendance a la stabilisation, a mis toute l'économie dans une grandeIncertitude. La structure du systeme bancaire, en plus des raisons d'ordremacroéconomiques était la source principaie de la crise financiere.Bienque le soutien du Fonds Monétaire international a contribué a élever lesréserves de la Banque cenfrale, la crise a engendré sans aucun doute des effetsnégatifs pour l'ensemble de l'économie et particulierement pour le secteurbancaire.

In this study, we propose a new polymer substrate that is able to covalently couple intended proteins and reduce nonspecific protein fouling. Poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-ran-N-methacryloyl-(L)-tyrosinemethylester (MAT)] [P(MPC/MAT)] was synthesized by free-radical polymerization. The photooxidation of the MAT unit in the copolymer was observed under ultraviolet (UV) light at 254 nm. P(MPC/MAT) was spin-coated on silicon (Si) and gold substrates. Without UV irradiation of the polymer-coated surface, P(MPC/MAT) physisorbed on the substrates, and the thickness of the polymer layer was less than 10 nm, regardless of the polymer concentration in the coating solution. In contrast, when the polymer-coated surface was irradiated with UV light, the thickness of the polymer layer could be controlled by changing the polymer concentration of the coating solution. Competitive protein adsorption on P(MPC/MAT) was studied. Bovine serum albumin was first contacted with the surface and later challenged with bovine fibrinogen. On bare gold and Si substrates, a large amount of albumin was adsorbed, and the competitive adsorption of albumin and fibronectin was observed. In contrast, the non-UV-irradiated P(MPC/MAT) surface effectively reduced protein adsorption. Interestingly, on the UV-irradiated P(MPC/MAT) surface, the primary protein preferably bonded, and significantly less secondary protein was adsorbed compared to primary protein. Cell adhesion was also tested on the substrate to clarify the effects of proteins existing on the substrates. On the bare Si surface, many adherent cells were observed, regardless of the protein pretreatment. On the non-UV-irradiated P(MPC/MAT) surface, cell adhesion was effectively reduced along with protein adsorption. Cell adhesion on the UV-irradiated P(MPC/MAT) surface depended strongly on the type of protein that was initially in contact with the surface. We concluded that the desired proteins could be immobilized on the photo-activated P(MPC/MAT) surface while preserving their function. Moreover, competitive protein exchange and multilayer adsorption hardly occurred on the surface.

Interpersonal difficulties are proposed to maintain eating disorders (EDs). This study explored whether social anhedonia (SA) was an additional social emotional maintenance factor which might also explain work/social problems in EDs. Additionally, the study explored SA and work and social adjustment in recovered participants. Women with anorexia nervosa (AN; n=105), bulimia nervosa (BN; n=46), recovered from AN (RAN; n=30) and non-ED controls (n=136) completed the Work and Social Adjustment Scale (WSAS) and the Revised Social Anhedonia Scale. ED participants reported greater SA and WSAS scores than non-ED controls; the RAN group reported an intermediate profile. AN participants had poorer work/social adjustment than BN participants. SA was associated with longer illness duration. SA, current severity (BMI) and lifetime severity (lowest adult BMI) significantly predicted work/social difficulties. Recovered participants scoring in the clinical range for SA experienced significantly greater work/social difficulties than recovered participants scoring outside the clinical range for SA. EDs are associated with clinical levels of SA and poor work/social functioning which reduce in recovery. SA may maintain the interpersonal functioning difficulties.

BACKGROUND: The literature reflects contradictory evidence on the ability of persons with anorexia nervosa (AN) to accurately report body weight and height. Furthermore, it is currently unknown if individuals are able to correctly report their weight and height following weight recovery from AN. OBJECTIVE: This study examined the accuracy of self-reported body weight and height following remission from anorexia nervosa (RAN). DESIGN: Individuals included women with RAN ( n = 45), anorexia nervosa (AN; n = 23), and controls (CON; n = 71). Subjective body mass index (BMI; kg/m2) was calculated from self-reported weight and height; objective BMI was calculated using values obtained with standard measures. RESULTS: Subjective weights were significantly less than objective weights for the RAN and CON groups ( p < .005). These groups reported being taller resulting in lower subjective BMIs ( p < .001). The AN group did not significantly differ on subjective and objective weight, height, or BMI. CONCLUSIONS: Results highlight the importance of objective measures for early identification/relapse prevention.

ObjectiveEating disorders are complex psychiatric disorders, associated with alterations in neural and cognitive functioning. Research suggests inhibition and set-shifting deficits in anorexia nervosa (AN), but less is known about the persistence of these deficits after recovery, or their relationship to comorbid psychiatric symptoms.MethodWomen aged 19-45 remitted from AN (RAN, N = 47) and controls (CW, N = 24) completed the Delis-Kaplan Executive Function System Color-Word Interference Test. It was hypothesized that RAN, and those with higher anxiety or depression, would demonstrate worse Inhibition and Switching task performance than CW.ResultsDifferences in performance between groups trended toward significance on Inhibition Ratio (p = 0.08) but were nonsignificant on Inhibition/Switching Ratio (p = 0.93). A model including State Anxiety and diagnosis revealed a significant independent effect of State Anxiety (p = 0.026), but not of diagnosis nor their interaction. Regressing State Anxiety on Color-Word Interference Test Inhibition among just the RAN group was significant [β = 0.37, t(46) = 2.63, p = 0.012] but among just CW was not (p = 0.54).DiscussionInterference control for neutral stimuli is influenced by anxiety in women with a history of AN. Anxiety is linked with greater symptom severity among AN individuals, and state anxiety may account for larger deficits seen on tasks using disorder-specific stimuli. Future research is warranted to elucidate the nature of neuropsychological deficits in eating disorders. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The Andromeda galaxy is observed to have a system of two large dwarf ellipticals and ~13 smaller satellite galaxies that are currently co-rotating in a thin plane, in addition to 2 counter-rotating satellite galaxies. We explored the consistency of those observations with a scenario where the majority of the co-rotating satellite galaxies originated from a subhalo group, where NGC 205 was the host and the satellite galaxies occupied dark matter sub-subhalos. We ran N-body simulations of a close encounter between NGC 205 and M31. In the simulations, NGC 205 was surrounded by massless particles to statistically sample the distribution of the sub-subhalos expected in a subhalo that has a mass similar to NGC 205. We made Monte Carlo samplings and found that, using a set of reference parameters, the probability of producing a thinner distribution of sub-subhalos than the observed NGC 205 + 15 smaller satellites (thus including the 2 counter-rotators, but excluding M32) increased from, 19 pages, 15 figures, to be published in MNRAS

Background Vernakalant (VER) is a relatively atrial-selective antiarrhythmic drug capable of blocking potassium and sodium currents in a frequency- and voltage-dependent manner. Ranolazine (RAN) is a sodium-channel blocker shown to exert antiarrhythmic effects in pulmonary vein (PV) sleeves. dl-Sotalol (SOT) is a β-blocker commonly used in the rhythm-control treatment of atrial fibrillation. This study evaluated the electrophysiological and antiarrhythmic effects of VER, RAN, and SOT in canine PV sleeve preparations in a blinded fashion. Methods Transmembrane action potentials were recorded from canine superfused PV sleeve preparations exposed to VER (n = 6), RAN (n = 6), and SOT (n = 6). Delayed afterdepolarizations were induced in the presence of isoproterenol and high-calcium concentrations by periods of rapid pacing. Results In PV sleeves, VER, RAN, and SOT (3–30 μM) produced small (10–15 ms) increases in action potential duration. The effective refractory period, diastolic threshold of excitation, and the shortest S 1 –S 1 cycle length permitting 1:1 activation were significantly increased by VER and RAN in a rate- and concentration-dependent manner. VER and RAN significantly reduced V max in a concentration- and rate-dependent manner. SOT did not significantly affect the effective refractory period, V max , diastolic threshold of excitation, or the shortest S 1 –S 1 cycle length permitting 1:1 activation. All 3 agents (3–30 μM) suppressed delayed afterdepolarization–mediated triggered activity induced by isoproterenol and high calcium. Conclusions In canine PV sleeves, the effects of VER and RAN were similar and largely characterized by concentration- and rate-dependent depression of sodium-channel–mediated parameters, which were largely unaffected by SOT. All 3 agents demonstrated an ability to effectively suppress delayed afterdepolarization–induced triggers of atrial arrhythmia.

© 2015. Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not.