bluuebunny/crossref_metadata_2025 huggingface dataset:
The Blood of the Martyrs: Erik Peterson's Theology of Martyrdom and Carl Schmitt's Political Theology of Sovereignty
Authors: Passos Eduardo Schmidt
Published: June 2018

There is a growing literature on the theological roots of Schmitt's theory, however, such interpretations depart from the same position as Schmitt: from the political into the theological. In this quarrel between politics and theology, there is a less known contender, the theologian Erik Peterson, who developed a theological critique of Schmitt and shows the impossibility of a Christian political theology. InPolitical Theology II(1970), Schmitt criticizes the apolitical nature of Peterson's theology, but he ignores Peterson's theology of martyrdom. This paper recovers the centrality of martyrdom in Peterson's theology and argues that the martyr represents a counter model to Schmitt's sovereign. For Peterson, martyrdom is not apolitical act, but a public claim in which the martyrs testify in the public sphere that the highest human good is not political but eschatological. By recovering this eschatological dimension, Peterson shows the limits of Schmitt's interpretation of the political.
On the Anti-paternalist Project of Reconciliation
Authors: PEDERSEN VIKI MØLLER LYNGBY
Published: June 2018

How should anti-paternalists deal with policies that seem to be simultaneously reasonable and paternalistic? In the literature, anti-paternalists have sought to show that many policies that prevent people from harming themselves can be justified without appeal to the good accruing to the people interfered with; that is, without appeal to paternalistic reasons. However, while perhaps identifying sufficient non-paternalistic reasons for supporting these policies under realistic circumstances, anti-paternalists often fail, I argue, to identify satisfactory reasons that adequately reflect our underlying concerns pertaining to such policies. Included in those concerns are arguably the interests and well-being of the people whose choices are restricted by the policy in question. In this way, this article reveals that the strategy of reconciling anti-paternalism with seemingly paternalistic policies is beset by serious problems.
The Number of Satisfying Assignments of Random Regulark-SAT Formulas
Authors: COJA-OGHLAN AMIN , WORMALD NICK
Published: June 2018

Let Φ be a randomk-SAT formula in which every variable occurs preciselydtimes positively anddtimes negatively. Assuming thatkis sufficiently large and thatdis slightly below the critical degree where the formula becomes unsatisfiable with high probability, we determine the limiting distribution of the number of satisfying assignments.
Out-of-pocket medical expenses in severe CHD
Authors: Elhoff Justin J. , McHugh Kimberly E. , Buckley Jason R. , Morris Shaine A. , Simpson Kit N. , Scheurer Mark A.
Published: June 2018

Introduction

Families of children born with CHD face added stress owing to uncertainty about the magnitude of the financial burden for medical costs they will face. This study seeks to assess the family responsibility for healthcare bills during the first 12 months of life for commercially insured children undergoing surgery for severe CHD.

Methods

The MarketScan® database from Truven was used to identify commercially insured infants in 39 states from 2010 to 2012 with an ICD-9 diagnosis code for transposition of the great arteries, tetralogy of Fallot, or truncus arteriosus, as well as the corresponding procedure code for complete repair. Data extraction identified payment responsibilities of the patients’ families in the form of co-payments, deductibles, and co-insurance during the 1st year of life.

Results

There were 481 infants identified who met the criteria. Average family responsibility for healthcare bills during the 1st year of life was $2928, with no difference between the three groups. The range of out-of-pocket costs was $50–$18,167. Initial hospitalisation and outpatient care accounted for the majority of these responsibilities.

Conclusions

Families of commercially insured children with severe CHD requiring corrective surgery face an average of ~$3000 in out-of-pocket costs for healthcare bills during the first 12 months of their child’s life, although the amount varied considerably. This information provides a framework to alleviate some of the uncertainty surrounding healthcare financial responsibilities, and further examination of the origination of these expenditures may be useful in informing future healthcare policy discussion.
Islamic law and international humanitarian law: An introduction to the main principles
Authors: Al-Dawoody Ahmed
Published: June 2018

This article gives an overview of the principles regulating the use of force under the Islamic law of war in the four Sunni schools of Islamic law. By way of introducing the topic, it briefly discusses the origins, sources and characteristics of the Islamic law of war. The discussion reveals the degree of compatibility between these Islamic principles and the modern principles of international humanitarian law, and offers insights into how these Islamic principles can help in limiting the devastation and suffering caused by contemporary armed conflicts in Muslim contexts, particularly those conflicts in which Islamic law is invoked as the source of reference.
Resisting the Market University: Political Challenges to the Locus of Authority in Public University Tuition Policy
Authors: Nations Jennifer M.
Published: June 2018

The devolution of tuition authority, or abdication of tuition-setting control from elected representatives to unelected university governing boards, is an instance of marketization in higher education. Except for New York and Florida, all states have moved closer to a market-priced ideal by “deregulating” tuition. In this article, I describe my analysis of these two negative cases and argue that preexisting higher education policies have lasting effects on the institutional logics to which policy makers and other stakeholders have access, leading to divergent outcomes. What policy makers deem appropriate policy in their local context is shaped by a history of education policy making that likely preceded their position in office. However, the structure of institutions and the founding ideas of those institutions—as preserved in planning documents and remembered by select institutional actors—perpetuate a commitment to a certain institutional logic. Specifically, Florida and New York policy makers were constrained in their decision making about tuition devolution at multiple points in time by a family of institutions logic that reinforced the importance of their state university systems’ lack of formal tiers and their commitment to price similarity. The state policies governing these state systems became politically consequential because policy makers invoked the system cohesiveness mandated by such policies as a principal reason for rejecting devolution proposals. This powerful narrative appears to have precluded the ideational change toward a market university despite a move in this direction in other states.
Characteristics of Turbulent Aeolian Sand Movement Over Straw Checkerboard Barriers and Formation Mechanisms of Their Internal Erosion Form
Authors: Xu Bin , Zhang Jie , Huang Ning , Gong Kang , Liu Yusheng
Published: June 2018

Straw checkerboard barrier (SCB) array is one of the most effective and widely used measures for antidesertification projects. The efficiency and durability of SCB are greatly influenced by the features of wind field and sand particle motion. Unfortunately, very few studies have explored the characteristics of turbulent flow and the internal erosional form inside the barrier cell, because of the complexity of turbulent flow and the sand particle motion around the surface of SCBs. In this paper, we simulated the wind‐sand flow around SCBs using 3‐D hybrid Reynolds‐averaged Navier‐Stokes/large eddy simulation method and Lagrangian particle tracing method to analyze the characteristics of turbulent flow, particle motion, and internal erosional form of SCBs. The results show that the vast majority of particles fall into SCB cells from their middle and posterior parts when wind‐sand flow passes SCBs, due to the impact of gravity and subsidence flow. It indicates that SCBs could effectively prevent sand flow‐induced hazards. The turbulent flow in SCBs has great instantaneous pulse velocity, resulting in retransfer of sand particles in SCBs. Analysis of the mean flow field in SCB found one huge streamwise vortex that filled the SCB cells and two spanwise vortexes in the back of SCB cells. These vortexes will drive particles inside SCBs to move toward the front and side walls, making the erosional form of SCB cells low in the middle and high near all the sides.
The Role of Atmospheric Rivers in Extratropical and Polar Hydroclimate
Authors: Nash Deanna , Waliser Duane , Guan Bin , Ye Hengchun , Ralph F. Martin
Published: June 2018

Atmospheric rivers (ARs) are narrow, long, transient, water vapor‐rich corridors of the atmosphere that are responsible for over 90% of the poleward water vapor transport in and across midlatitudes. However, the role of ARs in modulating extratropical and polar hydroclimate features (e.g., water vapor content and precipitation) has not been fully studied, even though moistening of the polar atmosphere is both a key result and amplifier of Arctic warming and sea ice melt, and precipitation is key to the surface mass balance of polar sea ice and ice sheets. This study uses the Modern‐Era Retrospective analysis for Research and Applications, Version 2 reanalysis to characterize the roles of AR water vapor transport on the column‐integrated atmospheric water vapor budget in the extratropical and polar regions of both hemispheres. Meridional water vapor transport by ARs across a given latitude (examined for 40°, 50°, 60°, and 70°) is strongly related to variations in area‐averaged (i.e., over the cap poleward of the given latitude) total water vapor storage and precipitation poleward of that latitude. For the climatological annual cycle, both AR transport (i.e., nonlocal sources) and total evaporation (i.e., local sources) are most correlated with total precipitation, although with slightly different phases. However, for monthly anomalies, the water budget at higher latitudes is largely dominated by the relationship between AR transport and precipitation. For pentad and daily anomalies, AR transport is related to both precipitation and water vapor storage variations. These results demonstrate the important role of episodic, extreme water vapor transports by ARs in modulating extratropical and polar hydroclimate.
Probabilistic Prediction and Forecast of Daily Suspended Sediment Concentration on the Upper Yangtze River
Authors: Matos José Pedro , Hassan Marwan A. , Lu Xi Xi , Franca Mário J.
Published: June 2018

Sediment transport in suspension can represent more than 90% of a river's total annual flux of sediment. In the case of the Yangtze River, more than 99% of the sediment supplied to the sea is suspended load. Suspended sediment is thus an important component of the total sediment load, with implications for channel dynamics, landscape evolution, ecology, and human‐related activities. For hydrological management of large basins such as the Yangtze River, knowledge of the processes governing suspended sediment concentration (SSC) is essential. An analysis of the temporal variation of SSC for the Upper Yangtze basin (defined at Pingshan station) is presented here. For this purpose, a database of 50 years of concurrent discharge and SSC measurements, made by the Yangtze River Commission, is used. The analysis is made using a novel probabilistic data‐driven technique, the Generalized Pareto Uncertainty (GPU). This technique allows for the testing of several strategies of prediction and forecast applied to a time series of SSC and streamflow. Changing between local or seasonal variables to feed these strategies, we inferred that although the main driver of the SSC transport is flow (as reported by previous authors), sediment storage is also a major control. Furthermore, the maximum necessary time lag for forecasts made with the data is on the order of one week, which provides one indication of the time scale of the local processes of SSC transport in the Upper Yangtze. In this paper, limitations and data requirements of the GPU methodology are also discussed.
Comment on “Large Eddy Simulation of Turbulence and Solute Transport in a Forested Headwater Stream” by Khosronejad et al.: Invalid Representation of Scalar Transport by the Act of Diffusion
Authors: Sookhak Lari Kaveh , Davis Greg B.
Published: June 2018

An invalid representation of diffusion‐based scalar transport in the advection‐diffusion equation in Khosronejad et al. (2016, https://doi.org/10.1002/2014JF003423) is discussed here. It is discussed that the error may increase diffusion‐based transport by up to 3 orders of magnitude where the turbulence intensity is low.
Pacific Plate Apparent Polar Wander, Hot Spot Fixity, and True Polar Wander During the Formation of the Hawaiian Island and Seamount Chain From an Analysis of the Skewness of Magnetic Anomaly 20r (44 Ma)
Authors: Zheng Lin , Gordon Richard G. , Woodworth Daniel
Published: June 2018

While it is well documented that the Hawaiian hot spot has shifted southward relative to the spin axis since the formation of some of the Emperor seamounts, the paleolatitude of the hot spot during the formation of the Hawaiian chain is poorly known. To better determine the latter, here we estimate the location of the 44 Ma Pacific plate paleomagnetic pole by investigating the skewness (asymmetry) of 14 airplane and 19 ship‐board crossings of magnetic anomaly 20r between the Murray and Marquesas fracture zones on the Pacific plate. The new 44 Ma paleomagnetic pole (78.0°N, 26.0°E, A95_1 = 5.4° at 101°, A95_2 = 2.0°) differs by ≈4° from its position expected if the Pacific hot spots have been fixed relative to the spin axis. This shift is independently recorded by the chron 12r (32 Ma) Pacific plate skewness paleomagnetic pole and is also confirmed by paleomagnetic poles reconstructed from the continents, indicating that global hot spots have moved in unison with respect to the spin axis, probably due to true polar wander, which may continue today as recorded by optical astronomy and geodetic very long baseline interferometry. An analysis of spreading rates recorded in the magnetic profiles indicates that spreading rates doubled between ≈50 and ≈42 Ma (confirming prior results), as expected if the bend in the Hawaiian‐Emperor chain records a change in Pacific plate motion relative to the deep mantle.
Transient Groundwater Travel Time Distributions and Age‐Ranked Storage‐Discharge Relationships of Three Lowland Catchments
Authors: Kaandorp V. P. , de Louw P. G. B. , van der Velde Y. , Broers H. P.
Published: June 2018

The contribution of groundwater to streams is controlled by temporally and spatially variable groundwater flow paths with distinctive travel times. The aggregated average travel time distribution (TTD) of all these flow paths functions as a catchment characteristic. Currently, research on TTDs is expanding towards dynamic TTDs and building on this, we present dynamic backward TTDs and residence time distributions using forward particle tracking on a high‐resolution spatially distributed groundwater flow model (25*25 m). We show that the dynamic backward TTDs of three Dutch catchments are determined by the interplay between the activation of shallow short flow paths and the intensification of fluxes through all flow paths when groundwater levels rise. In addition, the preference for young water in our lowland catchments appears strongly controlled by drainage density. Variations in catchment mixing with time and between catchments were analyzed using dynamic StorAge Selection (SAS) functions. This showed the effect of differences in geology and topography on the shape of the SAS functions. Additionally, the variability of SAS functions in time was shown to depend on the extent to which new flow paths can be activated. Time‐varying SAS functions are required for computation of dynamic TTDs, and this research showed realistic values for the variability in the SAS functions of lowland catchments. The step towards dynamic TTDs is crucial for understanding the temporal and spatial behavior of streams, their chemical composition, and their ecological value.
UAVSAR and Optical Analysis of the Thomas Fire Scar and Montecito Debris Flows: Case Study of Methods for Disaster Response Using Remote Sensing Products
Authors: Donnellan Andrea , Parker Jay , Milliner Christopher , Farr Tom G. , Glasscoe Margaret , Lou Yunling , Zheng Yang , Hawkins Brian
Published: June 2018

We use the 2017 Thomas fire and ensuing Montecito debris flow as a case study to demonstrate how application of various interferometric synthetic aperture radar postprocessing techniques can be used to highlight the fire scar and major damage areas from the debris flows. We use National Aeronautics and Space Administration's airborne Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) L‐band polarimetric interferometric synthetic aperture radar (InSAR) for this study. Results demonstrate that a single polarimetric radar image highlights burn areas. Coherence and interferometric radar pairs show the fire scar and debris flow. An unwrapped interferogram shows the location of the debris flow over the 101 Freeway in greater detail than a raw interferogram. We enhanced the interferogram and coherence product of a pair of images acquired before and after the fire and debris flows, which highlights areas of destroyed structures and major damage. We first despeckled the images and then converted the interferogram to four colors and the coherence map to two colors. Analysis of optical imagery between before and after images shows that the debris flows are best identified using visible bands and that near‐infrared better highlights the lower part of the flows where more mud was deposited. These simplified products provide more actionable products for disaster responders; the products were downloaded for use by the State of California.
Modeling of Stick‐Slip Behavior in Sheared Granular Fault Gouge Using the Combined Finite‐Discrete Element Method
Authors: Gao Ke , Euser Bryan J. , Rougier Esteban , Guyer Robert A. , Lei Zhou , Knight Earl E. , Carmeliet Jan , Johnson Paul A.
Published: June 2018

Sheared granular layers undergoing stick‐slip behavior are broadly employed to study the physics and dynamics of earthquakes. Here a two‐dimensional implementation of the combined finite‐discrete element method (FDEM), which merges the finite element method (FEM) and the discrete element method (DEM), is used to explicitly simulate a sheared granular fault system including both gouge and plate, and to investigate the influence of different normal loads on seismic moment, macroscopic friction coefficient, kinetic energy, gouge layer thickness, and recurrence time between slips. In the FDEM model, the deformation of plates and particles is simulated using the FEM formulation while particle‐particle and particle‐plate interactions are modeled using DEM‐derived techniques. The simulated seismic moment distributions are generally consistent with those obtained from the laboratory experiments. In addition, the simulation results demonstrate that with increasing normal load, (i) the kinetic energy of the granular fault system increases, (ii) the gouge layer thickness shows a decreasing trend, and (iii) the macroscopic friction coefficient does not experience much change. Analyses of the slip events reveal that, as the normal load increases, more slip events with large kinetic energy release and longer recurrence time occur, and the magnitude of gouge layer thickness decrease also tends to be larger; while the macroscopic friction coefficient drop decreases. The simulations not only reveal the influence of normal loads on the dynamics of sheared granular fault gouge but also demonstrate the capabilities of FDEM for studying stick‐slip dynamic behavior of granular fault systems.
Partitioning of Kinetic Energy in the Arctic Ocean's Beaufort Gyre
Authors: Zhao Mengnan , Timmermans Mary‐Louise , Krishfield Richard , Manucharyan Georgy
Published: June 2018

Kinetic energy (KE) in the Arctic Ocean's Beaufort Gyre is dominated by the mesoscale eddy field that plays a central role in the transport of freshwater, heat, and biogeochemical tracers. Understanding Beaufort Gyre KE variability sheds light on how this freshwater reservoir responds to wind forcing and sea ice and ocean changes. The evolution and fate of mesoscale eddies relate to energy pathways in the ocean (e.g., the exchange of energy between barotropic and baroclinic modes). Mooring measurements of horizontal velocities in the Beaufort Gyre are analyzed to partition KE into barotropic and baroclinic modes and explore their evolution. We find that a significant fraction of water column KE is in the barotropic and the first two baroclinic modes. We explain this energy partitioning by quantifying the energy transfer coefficients between the vertical modes using the quasi‐geostrophic potential vorticity conservation equations with a specific background stratification observed in the Beaufort Gyre. We find that the quasi‐geostrophic vertical mode interactions uphold the persistence of KE in the first two baroclinic modes, consistent with observations. Our results explain the specific role of halocline structure on KE evolution in the gyre and suggest depressed transfer to the barotropic mode. This limits the capacity for frictional dissipation at the sea floor and suggests that energy dissipation via sea ice‐ocean drag may be prominent.
Vertical Distributions of Soil Organic Carbon and its Influencing Factors Under Different Land Use Types in the Desert Riparian Zone of Downstream Heihe River Basin, China
Authors: Fan Hao , Zhao Wenwu , Daryanto Stefani , Fu Bojie , Wang Shuai , Wang Yaping
Published: June 2018

The amount of soil organic carbon (SOC) reflects the ability of ecosystem to sequester carbon (C). In the desert riparian zone of Heihe River basin, northwest China, that has been the subject of an ecological water conveyance since 2000, studies on SOC under different land use types remain scarce. Yet analyzing soil organic carbon content (SOCC) and its spatial distribution in the area is a key component when studying C cycle in this desert ecosystem. We therefore investigated the vertical distribution of SOC and its influencing factors using field study, and we found significant differences among different land use types and soil depths. The average SOCC and soil organic carbon density in the 0–100 cm soil layers were 23.31 g kg−1 and 6.08 kg m−2, respectively. SOCC and soil organic carbon density decreased in the following order: grassland (5.73 g kg−1) > forestland (5.03 g kg−1) > shrubland (4.79 g kg−1) > cropland (4.28 g kg−1) > Gobi desert (2.10 g kg−1). We also found that vegetation and soil properties jointly affected SOCC in this riparian arid zone, in addition to human disturbance, as indicated by a low stratification ratio in the grassland (1.575) and cropland (1.366). When natural vegetation was transformed into cropland, SOCC decreased with the removal of plant biomass and the increase of wind erosion. Consequently, conservation agricultural practices that consider preservation of soil organic matter (e.g., no‐tillage and intercropping with deep‐rooted leguminous perennial plants) should be introduced in order to prevent further degradation.
Initiation of Streamers Due to Hydrometeor Collisions in Thunderclouds
Authors: Cai Qiheng , Jánský Jaroslav , Pasko Victor P.
Published: June 2018

In order to initiate streamers and leaders under thunderstorm conditions the electric field should reach values higher than the critical breakdown field Ek (i.e., ∼30 kV·cm−1·atm−1). However, the maximum electric field in thunderstorms measured by balloons is ∼6–9 kV·cm−1·atm−1. In present work, to achieve the electric field amplification required for streamer initiation, a system of two approaching spherical hydrometeors is investigated. Streamer initiation is determined from a Meek number, describing electron multiplication in fields above Ek. We have found the relationships between radii of particles for successful streamer initiation in the gap between these two particles and also on the outside periphery of the two particle system when the particles are connected by a discharge channel. Furthermore, we estimated the frequency of streamer initiation using three realistic hydrometeor size model distributions available in the literature and found that the scenario of streamer initiation on the outside periphery is only possible for relatively high electric fields ≥0.5Ek at altitudes of 3 and 6 km.
Crop Residue Burning in Northern India: Increasing Threat to Greater India
Authors: Sarkar S. , Singh R. P. , Chauhan A.
Published: June 2018

Crop residue burning (CRB) is a recurring problem, during October–November, in the northwestern regions (Punjab, Haryana, and western Uttar Pradesh) of India. The emissions from the CRB source regions spread in all directions through long‐range transport mechanisms, depending upon the meteorological conditions. In recent years, numerous studies have been carried out dealing with the impact of CRB on the air quality of Delhi and surrounding areas, especially in the Indo‐Gangetic Basin (also referred to as Indo‐Gangetic Plain). In this paper, we present detailed analysis using both satellite‐ and ground‐based sources, which show an increasing impact of CRB over the eastern parts of the Indo‐Gangetic Basin and also over parts of central and southern India. The increasing trends of finer black carbon particles and greenhouse gases have accelerated since the year 2010 onward, which is confirmed by the observation of different wavelength dependent aerosol properties. Our study shows an increased risk to ambient air quality and an increased spatiotemporal extent of pollutants in recent years, from CRB, which could be a severe health threat to the population of these regions.
Development of Multivariable Dynamic System Response Curve Method for Real‐Time Flood Forecasting Correction
Authors: Sun Y. , Bao W. , Jiang P. , Ji X. , Gao S. , Xu Y. , Zhang Q. , Si W.
Published: June 2018

Error correction method is widely used to improve the performance of flood forecasting. The Dynamic System Response Curve method (DSRC) has been proposed as an error correction method to improve the performance of hydrological modeling. One of the critical problems is the unstable performance caused by the ill‐posed property of the model structure and the inability of estimating multiple variables. To address this problem, the original structure of DSRC was modified to enable the capability of estimating multiple variables. Using the variable forgetting factor recursive least squares algorithm (VFF‐RLS), we proposed an improved version of DSRC (VFF‐RLS‐MDSRC). The proposed method was tested in a synthetic case to examine the ability to correct state variables of a hydrological model. In addition, it was compared with the autoregressive technique in a real case study to evaluate the effects on the improvement of model performance. The results of the synthetic study indicate that the proposed method can significantly improve the performance of both the model output and the state variables. The results of the real case study indicate that the performance obtained by the proposed method tends to have a slower decline trend when increasing the lead time compared with autoregressive technique.
Inverse Modeling of Hydrologic Systems with Adaptive Multifidelity Markov Chain Monte Carlo Simulations
Authors: Zhang Jiangjiang , Man Jun , Lin Guang , Wu Laosheng , Zeng Lingzao
Published: June 2018

Markov chain Monte Carlo (MCMC) simulation methods are widely used to assess parametric uncertainties of hydrologic models conditioned on measurements of observable state variables. However, when the model is CPU‐intensive and high dimensional, the computational cost of MCMC simulation will be prohibitive. In this situation, a CPU‐efficient while less accurate low‐fidelity model (e.g., a numerical model with a coarser discretization or a data‐driven surrogate) is usually adopted. Nowadays, multifidelity simulation methods that can take advantage of both the efficiency of the low‐fidelity model and the accuracy of the high‐fidelity model are gaining popularity. In the MCMC simulation, as the posterior distribution of the unknown model parameters is the region of interest, it is wise to distribute most of the computational budget (i.e., the high‐fidelity model evaluations) therein. Based on this idea, in this paper we propose an adaptive multifidelity MCMC algorithm for efficient inverse modeling of hydrologic systems. In this method, we evaluate the high‐fidelity model mainly in the posterior region through iteratively running MCMC based on a Gaussian process system that is adaptively constructed with multifidelity simulation. The error of the Gaussian process system is rigorously considered in the MCMC simulation and gradually reduced to a negligible level in the posterior region. Thus, the proposed method can obtain an accurate estimate of the posterior distribution with a small number of the high‐fidelity model evaluations. The performance of the proposed method is demonstrated by three numerical case studies in inverse modeling of hydrologic systems.
A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer
Authors: Han Weidong , Shi Linlin , Ren Lulu , Zhou Liqian , Li Tongyu , Qiao Yiting , Wang Hangxiang
Published: June 2018

Drug resistance, accounting for therapeutic failure in the clinic, remains a major challenge to effectively manage cancer. Cyclosporin A (CsA) can reverse multidrug resistance (MDR), especially resistance to epidermal growth factor receptor tyrosine kinase inhibitors. However, the application of both drugs in cancer therapies is hampered by their poor aqueous solubility and low bioavailability due to oral administration. CsA augments the potency of gefitinib (Gef) in both Gef-sensitive and Gef-resistant cell lines. Here, we show that the simultaneous encapsulation of CsA and Gef within polyethylene glycol-block-poly(D, L-lactic acid) (PEG-PLA) produced a stable and systemically injectable nanomedicine, which exhibited a sub-50-nm diameter and spherical structures. Impressively, the co-delivery of therapeutics via single nanoparticles (NPs) outperformed the oral administration of the free drug combination at suppressing tumor growth. Furthermore, in vivo results indicated that CsA formulated in NPs sensitized Gef-resistant cells and Gef-resistant tumors to Gef treatment by inactivating the STAT3/Bcl-2 signaling pathway. Collectively, our nanomedicine approach not only provides an alternative administration route for the drugs of choice but also effectively reverses MDR, facilitating the development of effective therapeutic modalities for cancer.
Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis
Authors: Zhao Dajun , Feng Pan , Sun Yang , Qin Zhigang , Zhang Zhengbin , Tan Yanzhen , Gao Erhe , Lau Wayne Bond , Ma Xinliang , Yang Jian , Yu Shiqiang , Xu Xuezeng , Yi Dinghua , Yi Wei
Published: June 2018

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9–CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9’s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis.
Reciprocity of social influence
Authors: Mahmoodi Ali , Bahrami Bahador , Mehring Carsten
Published: June 2018

Humans seek advice, via social interaction, to improve their decisions. While social interaction is often reciprocal, the role of reciprocity in social influence is unknown. Here, we tested the hypothesis that our influence on others affects how much we are influenced by them. Participants first made a visual perceptual estimate and then shared their estimate with an alleged partner. Then, in alternating trials, the participant either revised their decisions or observed how the partner revised theirs. We systematically manipulated the partner’s susceptibility to influence from the participant. We show that participants reciprocated influence with their partner by gravitating toward the susceptible (but not insusceptible) partner’s opinion. In further experiments, we showed that reciprocity is both a dynamic process and is abolished when people believed that they interacted with a computer. Reciprocal social influence is a signaling medium for human-to-human communication that goes beyond aggregation of evidence for decision improvement.
Spectroscopic ellipsometry study of thickness and porosity of the alteration layer formed on international simple glass surface in aqueous corrosion conditions
Authors: Ngo Dien , Liu Hongshen , Sheth Nisha , Lopez-Hallman Raymond , Podraza Nikolas J. , Collin Marie , Gin Stéphane , Kim Seong H.
Published: June 2018

The porosity and pore-size distribution in the glass play an important role in glass corrosion; however, such information is difficult to be obtained non-destructively. Here we report the use of spectroscopic ellipsometry (SE) under controlled humidity environments to determine those structural parameters in the alteration layers formed on international simple glass (ISG), a model nuclear waste glass, in aqueous corrosion conditions. The SE results show that the ISG sample corroded for nearly 4.5 years develops pores larger than 2 nm in diameter, while the alteration layers formed initially in less than 1 month do not have such large pores. The development of larger pores over a long period of corrosion time, while the overall thickness remains relatively constant, implies structural rearrangements of the silicate network occurring within the alteration layer, which could eventually affect the transport of reactants and products as well as the structural stability.
Cognitive impairment in Parkinson’s disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health
Authors: Goldman Jennifer G. , Vernaleo Beth A. , Camicioli Richard , Dahodwala Nabila , Dobkin Roseanne D. , Ellis Terry , Galvin James E. , Marras Connie , Edwards Jerri , Fields Julie , Golden Robyn , Karlawish Jason , Levin Bonnie , Shulman Lisa , Smith Glenn , Tangney Christine , Thomas Cathi A. , Tröster Alexander I. , Uc Ergun Y. , Coyan Noreen , Ellman Crystal , Ellman Mike , Hoffman Charlie , Hoffman Susan , Simmonds Don
Published: June 2018

People with Parkinson’s disease (PD) and their care partners frequently report cognitive decline as one of their greatest concerns. Mild cognitive impairment affects approximately 20–50% of people with PD, and longitudinal studies reveal dementia in up to 80% of PD. Through the Parkinson’s Disease Foundation Community Choice Research Award Program, the PD community identified maintaining cognitive function as one of their major unmet needs. In response, a working group of experts across multiple disciplines was organized to evaluate the unmet needs, current challenges, and future opportunities related to cognitive impairment in PD. Specific conference goals included defining the current state in the field and gaps regarding cognitive issues in PD from patient, care partner, and healthcare professional viewpoints; discussing non-pharmacological interventions to help maintain cognitive function; forming recommendations for what people with PD can do at all disease stages to maintain cognitive health; and proposing ideas for how healthcare professionals can approach cognitive changes in PD. This paper summarizes the discussions of the conference, first by addressing what is currently known about cognitive dysfunction in PD and discussing several non-pharmacological interventions that are often suggested to people with PD. Second, based on the conference discussions, we provide considerations for people with PD for maintaining cognitive health and for healthcare professionals and care partners when working with people with PD experiencing cognitive impairment. Furthermore, we highlight key issues and knowledge gaps that need to be addressed in order to advance research in cognition in PD and improve clinical care.
“A palliative end-stage COPD patient does not exist”: a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD
Authors: Scheerens Charlotte , Deliens Luc , Van Belle Simon , Joos Guy , Pype Peter , Chambaere Kenneth
Published: June 2018

Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers’ education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0–2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients’ disease insight and training PHC nurses in care for end-stage COPD.
From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn’s disease
Authors: Bauer Eugen , Thiele Ines
Published: June 2018

Crohn’s disease (CD) is associated with an ecological imbalance of the intestinal microbiota, consisting of hundreds of species. The underlying complexity as well as individual differences between patients contributes to the difficulty to define a standardized treatment. Computational modeling can systematically investigate metabolic interactions between gut microbes to unravel mechanistic insights. In this study, we integrated metagenomic data of CD patients and healthy controls with genome-scale metabolic models into personalized in silico microbiotas. We predicted short chain fatty acid (SFCA) levels for patients and controls, which were overall congruent with experimental findings. As an emergent property, low concentrations of SCFA were predicted for CD patients and the SCFA signatures were unique to each patient. Consequently, we suggest personalized dietary treatments that could improve each patient’s SCFA levels. The underlying modeling approach could aid clinical practice to find dietary treatment and guide recovery by rationally proposing food aliments.
Simultaneous hyperaccumulation of nickel and cobalt in the tree Glochidion cf. sericeum (Phyllanthaceae): elemental distribution and chemical speciation
Authors: van der Ent Antony , Mak Rachel , de Jonge Martin D. , Harris Hugh H.
Published: June 2018

Hyperaccumulation is generally highly specific for a single element, for example nickel (Ni). The recently-discovered hyperaccumulator Glochidion cf. sericeum (Phyllanthaceae) from Malaysia is unusual in that it simultaneously accumulates nickel and cobalt (Co) with up to 1500 μg g−1 foliar of both elements. We set out to determine whether distribution and associated ligands for Ni and Co complexation differ in this species. We postulated that Co hyperaccumulation coincides with Ni hyperaccumulation operating on similar physiological pathways. However, the ostensibly lower tolerance for Co at the cellular level results in the exudation of Co on the leaf surface in the form of lesions. The formation of such lesions is akin to phytotoxicity responses described for manganese (Mn). Hence, in contrast to Ni, which is stored principally inside the foliar epidermal cells, the accumulation response to Co consists of an extracellular mechanism. The chemical speciation of Ni and Co, in terms of the coordinating ligands involved and principal oxidation state, is similar and associated with carboxylic acids (citrate for Ni and tartrate or malate for Co) and the hydrated metal ion. Some oxidation to Co3+, presumably on the surface of leaves after exudation, was observed.
Betamethasone prevents human rhinovirus- and cigarette smoke- induced loss of respiratory epithelial barrier function
Authors: Waltl Eva E. , Selb Regina , Eckl-Dorna Julia , Mueller Christian A. , Cabauatan Clarissa R. , Eiwegger Thomas , Resch-Marat Yvonne , Niespodziana Katarzyna , Vrtala Susanne , Valenta Rudolf , Niederberger Verena
Published: June 2018

The respiratory epithelium is a barrier against pathogens and allergens and a target for therapy in respiratory allergy, asthma and chronic obstructive pulmonary disease (COPD). We investigated barrier-damaging factors and protective factors by real-time measurement of respiratory cell barrier integrity. Barrier integrity to cigarette smoke extract (CSE), house dust mite (HDM) extract, interferon-γ (IFN-γ) or human rhinovirus (HRV) infection alone or in combination was assessed. Corticosteroids, lipopolysaccharide (LPS), and nasal mucus proteins were tested for their ability to prevent loss of barrier integrity. Real-time impedance-based measurement revealed different patterns of CSE-, HDM-, IFN-γ- and HRV-induced damage. When per se non-damaging concentrations of harmful factors were combined, a synergetic effect was observed only for CSE and HDM. Betamethasone prevented the damaging effect of HRV and CSE, but not damage caused by HDM or IFN-γ. Real-time impedance-based measurement of respiratory epithelial barrier function is useful to study factors, which are harmful or protective. The identification of a synergetic damaging effect of CSE and HDM as well as the finding that Betamethasone protects against HRV- and CSE-induced damage may be important for asthma and COPD.
Pulmonary Arterial Hypertension Affects the Rat Gut Microbiome
Authors: Callejo María , Mondejar-Parreño Gema , Barreira Bianca , Izquierdo-Garcia José L. , Morales-Cano Daniel , Esquivel-Ruiz Sergio , Moreno Laura , Cogolludo Ángel , Duarte Juan , Perez-Vizcaino Francisco
Published: June 2018

We have analysed whether pulmonary arterial hypertension (PAH) alters the rat faecal microbiota. Wistar rats were injected with the VEGF receptor antagonist SU5416 (20 mg/kg s.c.) and followed for 2 weeks kept in hypoxia (10% O2, PAH) or injected with vehicle and kept in normoxia (controls). Faecal samples were obtained and microbiome composition was determined by 16S rRNA gene sequencing and bioinformatic analysis. No effect of PAH on the global microbiome was found (α- or β-diversity). However, PAH-exposed rats showed gut dysbiosis as indicated by a taxonomy-based analysis. Specifically, PAH rats had a three-fold increase in Firmicutes-to-Bacteroidetes ratio. Within the Firmicutes phylum, there were no large changes in the relative abundance of the bacterial families in PAH. Among Bacteroidetes, all families were less abundant in PAH. A clear separation was observed between the control and PAH clusters based on short chain fatty acid producing bacterial genera. Moreover, acetate was reduced in the serum of PAH rats. In conclusion, faecal microbiota composition is altered as a result of PAH. This misbalanced bacterial ecosystem might in turn play a pathophysiological role in PAH by altering the immunologic, hormonal and metabolic homeostasis.
Synthesis of Pure Enantiomers of Titanium(IV) Complexes with Chiral Diaminobis(phenolato) Ligands and Their Biological Reactivity
Authors: Miller Maya , Tshuva Edit Y.
Published: June 2018

Racemic and enantiomerically pure titanium(IV) complexes with ortho-brominated or para-nitrated chiral diaminobis(phenolato) ligands were prepared with NH and NMe cyclohexyldiamino bridges through ligand to metal chiral induction. The hydrolytic behavior of the complexes was evaluated, identifying the N-methylated complex as the most stable. A representative NH complex hydrolyzed to first give a dimeric structure in solution as deduced by NMR diffusion measurements, followed by formation of clusters with higher nuclearity, as was supported by X-ray characterization of a tetranuclear cluster obtained in trace amounts following 30 days in water solutions. The cytotoxicity of the enantiomerically pure and racemic complexes was measured on HT-29 human colon cancer cell line based on the MTT assay; all stereochemical configurations of the N-methylated complex were inactive, whereas for the NH complexes, the racemic mixtures were mostly inactive but the pure enantiomers exhibited similarly high cytotoxicity, supporting a polynuclear active species. Analysis of the two enantiomers of the most active brominated complex for their cytotoxicity on human ovarian A2780, cisplatin resistant A2780cp and multi-drug-resistant A2780adr cell lines as well as for their apoptosis induction on the A2780 line revealed similar reactivity, supporting a similar mechanism for the two enantiomers.