bluuebunny/crossref_metadata_2025 huggingface dataset:
Enlist E3™ Soybean Sensitivity and Enlist™ Herbicide-Based Program Control of Sumatran Fleabane (Conyza sumatrensis)
Authors: Frene Rafael L. , Simpson David M. , Buchanan Marcos Baez , Vega Ernesto Teran , Ravotti Maximiliano E. , Valverde Pablo P.
Published: June 2018

Enlist E3™ soybean, resistant to 2,4-D, glufosinate, and glyphosate, provides options to control glyphosate-resistant Sumatran fleabane before planting and in crop. Twenty field trials were conducted in Argentina to determine Enlist E3 soybean sensitivity to POST applications of 2,4-D choline+glyphosate or glufosinate. Maximum injury from a single 2,4-D choline+glyphosate application at 1X (1140+1140 g ae ha−1) and 2X rate was 4% and 13%, respectively, at 3 days after treatment in the temperate Humid Pampa region. Slightly higher injury of 11 and 23% was observed in sub-tropical region of northern Argentina. Injury was transient with recovery occurring within 14 days. Injury caused by sequential applications was equivalent to that caused by single applications. Soybean yield was not affected by single nor sequential applications. In four trials, control programs containing 2,4-D choline+glyphosate applied PRE and POST provided greater GR Sumatran fleabane control and a 12 to 26% increase in yield compared to 2,4-D choline+glyphosate applied at PRE only. This research demonstrates the glyphosate-resistant control programs that include 2,4-D choline, glyphosate, and glufosinate provide excellent GR Sumatran fleabane control.
Fractures vertébrales multiples à l’arrêt du denosumab: comment les éviter?
Authors: Lamy Olivier , Gonzalez Rodriguez Elena , Stoll Delphine , Aubry-Rozier Bérengère , Livio Françoise
Published: June 2018

Zusammenfassung. Denosumab ist ein monoklonaler Antikörper gegen den RANK-Liganden, der die Reifung und Aktivität von Osteoklasten hemmt. Es verringert die Knochenresorption, erhöht die Knochendichte und reduziert das Frakturrisiko. Nach dem Abbruch der Behandlung zeigt sich jedoch ein deutlicher Rebound-Effekt, der etwa zwei Jahre anhält. Es führt zu erhöhten Markern des Knochenumbaus, einem Verlust der Knochendichte, der grösser als der Gewinn sein kann, und zu einem erhöhten Risiko für multiple Wirbelfrakturen. Diese Frakturen treten mit einer Häufigkeit von 1–10 % auf. Wegen dieses hohen Risikos sollte Denosumab eine Zweitlinientherapie sein, die auf sehr spezifische Indikationen beschränkt ist. Um den Rebound-Effekt zu begrenzen, wird derzeit empfohlen, beim Abbruch der Denosumab-Behandlung ein starkes Bisphosphonat (Alendronat, Zoledronat) zu verschreiben und die Knochenresorptionsmarker regelmässig zu prüfen.
Negative Mental States and Their Association to the Cognitive Function of Nurses
Authors: Maharaj Shamona , Lees Ty , Lal Sara
Published: June 2018

Abstract. Nurses’ inherently stressful occupation leaves them at a higher risk of developing negative mental states (stress, anxiety, and depression). However, research examining the effect of negative mental states on these health professionals’ cognitive performance is sparse. Thus, the present study aimed to assess the link between negative mental states and cognitive performance in nurses ( n = 53). Negative mental state data was obtained using the Depression Anxiety Stress Scale, brain activity was measured using electroencephalography, and finally, cognitive performance was assessed using the Cognistat and the Mini-Mental State Examination. Significant negative correlations ( p < .05) were observed between anxiety and attention, and all three negative mental states and memory performance. Electroencephalographic changes indicated that increases in anxiety were significantly associated ( p < .05) with decreases in gamma reactivity at fronto-central sites. The current study suggests that higher levels of negative mental states are associated with domain-specific cognitive impairments, and variations in gamma reactivity; possibly reflecting less optimal cortical functioning.
Children Consider Their Own Group to Be More Human Than Other Social	Groups
Authors: Chas Alexandra , Betancor Verónica , Delgado Naira , Rodríguez-Pérez Armando
Published: June 2018

Abstract. Three studies were conducted to determine whether outgroups were dehumanized through animalization since childhood. Using the Implicit Association Test (IAT), in Study 1 we found faster reaction times in the compatible condition (ingroup names and human words, outgroup names and animal words), compared with the incompatible condition (ingroup names and animal words, outgroup names and human words). In Study 2, we used a paper-and-pencil design and found that the association between animal-related words and outgroups was more prevalent in comparison to ingroups. The participants of Study 3 selected a larger number of animal-related words to describe the outgroups than their own groups. Results revealed that the tendency to animalize is a process that begins during early childhood.
Numerical Evaluation of the Modern and Future Origins of Atmospheric River Moisture Over the West Coast of the United States
Authors: Nusbaumer Jesse , Noone David
Published: June 2018

Atmospheric rivers (ARs) are one of the major causes of extreme precipitation and flooding in many regions around the world and have been found to contribute substantially to global poleward moisture transport. However, the evaporative origin of the moisture in ARs remains unclear, at least on climatological timescales. Here we use the water tracer and water isotope‐enabled Community Atmosphere Model version 5 (CAM5) model to examine the moisture sources of ARs that impact the West Coast of the United States. The climatological distribution of moisture sources is determined for both the modern era and for 2100 under a Representative Concentration Pathway (RCP) 8.5 scenario. It is found that 33 to 53% of the precipitable water over the West Coast of the United States originates from the Northeast Pacific, in particular the midlatitudes and subtropics, although in June‐July‐August more moisture is recycled from continental regions. It is also found that although ARs are at least 70% Northeast Pacific moisture, a significant amount of the moisture is derived from tropical latitudes (>15% from south of 20°N). It is found that in the warmer 2100 climate there is a 39% increase in the magnitude of ARs. In this future epoch, moisture is transported from more remote regions for all seasons and for both ARs and the average climatology. To provide future observational evidence that this model result is robust, it is shown that water isotopes provide an observational constraint on the moisture transport pathways, and thus the possibility to observe changes in moisture source.
Antenna Array Simulation and Detection Performance Analysis of Sanya Prototype Incoherent Scatter Radar
Authors: Zhao Hailong , Yao Ming , Deng Xiaohua , Yuan Kai , Ding Feng , Zeng Lingqi , Li Chen
Published: June 2018

Incoherent scatter radars have become an important means of ionospheric detection, which is the only ground instrument that can detect important plasma parameters over the entire ionosphere (60–2,000 km). In Sanya of China, the advanced high‐power phased array incoherent scatter radar is under construction. The radar has the advantages of continuous observation, full space coverage, and rapid scanning. Usually, since the plasma‐scattered signal is weak, the estimation of signal‐to‐noise ratio (SNR) and relative error is significant for radar detection performance analysis. Major factors affecting the detection performance, such as power aperture product, pulse width, daytime and nighttime, and different antenna gains (zenith angles), are investigated in the present study. Details of the impacts of these factors on the radar performance are analyzed. According to analysis, the SNR and the detection range could be enhanced significantly by increasing the power aperture product. The integration significantly reduces the relative error; for instance, the relative error could reach 5% in the range of 80–700 km by a few seconds' integration. The SNR decreases with the range resolution improving. The detection performance during nighttime is worse than that of daytime. Furthermore, the SNR decreases with the increasing zenith angle. However, the detection performance can be compensated by the integration. Once the radar becomes operational practically, the numerical simulation results will help to choose the appropriate operation parameters to achieve the best operational performance with given budget of operation cost.
Development of Probabilistic Dam Breach Model Using Bayesian Inference
Authors: Peter S. J. , Siviglia A. , Nagel J. , Marelli S. , Boes R. M. , Vetsch D. , Sudret B.
Published: June 2018

Dam breach models are commonly used to predict outflow hydrographs of potentially failing dams and are key ingredients for evaluating flood risk. In this paper a new dam breach modeling framework is introduced that shall improve the reliability of hydrograph predictions of homogeneous earthen embankment dams. Striving for a small number of parameters, the simplified physics‐based model describes the processes of failing embankment dams by breach enlargement, driven by progressive surface erosion. Therein the erosion rate of dam material is modeled by empirical sediment transport formulations. Embedding the model into a Bayesian multilevel framework allows for quantitative analysis of different categories of uncertainties. To this end, data available in literature of observed peak discharge and final breach width of historical dam failures were used to perform model inversion by applying Markov chain Monte Carlo simulation. Prior knowledge is mainly based on noninformative distribution functions. The resulting posterior distribution shows that the main source of uncertainty is a correlated subset of parameters, consisting of the residual error term and the epistemic term quantifying the breach erosion rate. The prediction intervals of peak discharge and final breach width are congruent with values known from literature. To finally predict the outflow hydrograph for real case applications, an alternative residual model was formulated that assumes perfect data and a perfect model. The fully probabilistic fashion of hydrograph prediction has the potential to improve the adequate risk management of downstream flooding.
New Hypothesis for the Final Equilibrium Stage of a River Levee Breach due to Overflow
Authors: Michelazzo Giovanni , Oumeraci Hocine , Paris Enio
Published: June 2018

Breaching of earthen embankments is a complex process that often results in disastrous inundations of the hinterland. The process has been studied during the last decades by means of physical and numerical modeling with particular reference to the dam case, while for river levees only few specific studies have been conducted. Moreover, the understanding and prediction of the breach final configuration are still scarce and not yet deeply addressed, despite their importance for mitigating flood risk in the protected areas. The paper attempts to examine the existence of a final equilibrium stage in the river‐breach system under specified conditions based on a significant data set from new laboratory experiments. Using these data, together with those of previous studies, a new hypothesis for the final equilibrium of the river‐breach system is proposed which is supported by new flow formulae and field data.
Saving Energy From Urban Water Demand Management
Authors: Escriva‐Bou A. , Lund J. R. , Pulido‐Velazquez M.
Published: June 2018

Water use directly causes a significant amount of energy use in cities. In this paper we assessed energy and carbon dioxide emissions related to each part of the urban water cycle and the consequences of some water demand management policies in terms of water, energy, and CO2 emissions in urban water users, water and energy utilities, and the environment. First, we developed an hourly model of urban water uses by customer category, including water‐related energy consumption. Next, using real data from the East Bay Municipal Utility District in California, we calibrated a model of the energy used in water supply, treatment, pumping, and wastewater treatment by the utility, obtaining also energy costs. Then, using data from the California Independent System Operator, we obtained hourly costs of energy generation and transport to the point of use for the energy utility. Finally, using average emission factors reported by energy utilities, we estimated greenhouse gas emissions for the entire urban water cycle. Results for East Bay Municipal Utility District show that water end uses account for almost 95% of all water‐related energy use; however, the remaining 5% of energy used by the utility still costs over USD12 million annually. The carbon footprint of the urban water cycle is 372 kg CO2/person/year, representing approximately 4% of the total per capita emissions in California. Several simulations analyze the consequences of different water demand management policies, resulting in significant economic impacts for water and energy utilities and environmental benefits by reducing CO2 emissions.
Direct Channel Precipitation and Storm Characteristics Influence Short‐Term Fallout Radionuclide Assessment of Sediment Source
Authors: Karwan D. L. , Pizzuto J. E. , Aalto R. , Marquard J. , Harpold A. , Skalak K. , Benthem A. , Levia D. F. , Siegert C. M. , Aufdenkampe A. K.
Published: June 2018

Fallout radionuclides (FRNs) and their ratios, such as Beryllium‐7 (7Be) and excess Lead‐210 (210Pbxs), have been used to determine suspended sediment source and age in catchments. These models are based on numerous assumptions, for example, that channel deposition of FRNs from precipitation is negligible in comparison to their delivery to the channel from land surface erosion during individual storm events. We test this assumption using a mass balance approach during eight storms from summer 2011 to fall 2012 in a mid‐Atlantic United States piedmont region watershed with mixed land use. Event peak discharge and storm type corresponded to the importance of direct channel FRN deposition from precipitation. During relatively low discharge summer thunderstorms, with minimal overland flow, less than 1% of7Be and210Pbxsflux deposited on the watershed exits the watershed associated with suspended sediment. The majority but not all deposited on the stream channel exits the watershed associated with suspended sediment (60% of7Be and 80% of210Pbxs). Here precipitation and throughfall onto the wetted channel area can be responsible for any FRN newly associated with suspended sediment, as opposed to landscape surface erosion. Furthermore, FRNs can be stored with sediments in the channel between events. Events with higher discharges, including hurricanes, show the opposite pattern—FRN flux associated with suspended sediment exported from the reach is greater than channel FRN wet deposition, suggesting net erosion from the watershed landscape and/or stored material during these types of storms.
Metamodeling for Groundwater Age Forecasting in the Lake Michigan Basin
Authors: Fienen Michael N. , Nolan B. Thomas , Kauffman Leon J. , Feinstein Daniel T.
Published: June 2018

Groundwater age is an important indicator of groundwater susceptibility to anthropogenic contamination and a key input to statistical models for forecasting water quality. Numerical models can provide estimates of groundwater age, enabling interpretation of measured age tracers. However, to extend to national‐scale groundwater systems where numerical models are not routinely available, a more efficient metamodeling approach can provide a less precise but widely applicable estimate of groundwater age, trained to make forecasts based on predictor variables that can be measured independent of numerical models. We trained gradient‐boosted regression tree statistical metamodels to MODFLOW/MODPATH‐derived groundwater age estimates in five inset models in the Lake Michigan Basin, USA. Using high‐throughput computing, we explored an exhaustive range of tuning parameters and tested metamodels through cross validation, a 20% holdout, and a round robin approach among the five inset models withholding each inset model from training and testing on the held‐out inset model. Forecast skill—measured by Nash Sutcliffe efficiency—was high for age‐related responses in the 20% hold‐out case (ranging from 0.73 to 0.84). The round robin analysis provided the opportunity to explore extending to unmodeled areas and a greater range of skill indicated the need to evaluate when it is appropriate to apply a metamodel from one region to another. We further explored the ramifications of metamodel simplification achieved through removing predictor variables based on their estimated importance. We found that similar metamodel performance was achievable with a fraction of the candidate set of predictor variables with well construction variables being most important.
Full‐Wave Seismic Tomography in the Northeastern United States: New Insights Into the Uplift Mechanism of the Adirondack Mountains
Authors: Yang Xiaotao , Gao Haiying
Published: June 2018

Studying the driving force of intracratonic uplifts is important in understanding the deformation mechanism of continental lithosphere and the role of mantle dynamics. The Adirondack Mountains are located at the eastern Laurentian margin in the northeastern United States forming a distinct domal uplift. Subsurface structural constraints on their uplift mechanism are limited. Here we construct a high‐resolution velocity model for the crust and mantle lithosphere using full‐wave ambient noise tomography. A distinct low shear velocity anomaly with a diameter of ~70–100 km is imaged beneath the Moho at the Adirondack Mountains. This anomaly is connected with the large‐scale low‐velocity volume beneath southern New England and eastern New York at greater depths. The observed low‐velocity anomalies may reflect asthenosphere upwelling induced by a combined effect of the Great Meteor hot spot and edge‐driven mantle convections. The buoyancy of upwelling asthenosphere, together with possible thermal expansion, may have uplifted the Adirondack Mountains.
Agricultural Fire Impacts on Ozone Photochemistry Over the Yangtze River Delta Region, East China
Authors: Li Mengmeng , Wang Tijian , Xie Min , Li Shu , Zhuang Bingliang , Chen Pulong , Huang Xin , Han Yong
Published: June 2018

Agricultural fires could affect tropospheric photochemistry by emitting trace gases, interacting with solar radiation or providing reactive surfaces for heterogeneous reactions. This study examines the effects of a typical agricultural fire event (8–13 June 2012) on ozone photochemistry over the Yangtze River Delta region, East China. The online coupled Weather Research and Forecasting‐Chemistry model is used, with the inclusion of a detailed agricultural fire emission inventory and seven heterogeneous reactions on soot surfaces. Comparisons with satellite and ground observational data indicate that the model is capable of reproducing the transport and evolution of this crop fire event. The precursor emissions from agricultural fires play a major role in modifying ozone photochemistry, with a maximal increase in ozone mixing ratio reaching 20 ppb (40%) near the fire zones in northern Anhui. The radiation feedback generates a small increase of surface NO2 levels by 2% and a decrease in surface O3 levels by 1% in the smoke plume. The effects due to heterogeneous uptake on soot are rather small, on average, changing the average O3, NO2, ˙OH, and HO2˙ concentrations by +0.8%, −0.5%, −0.7%, and +0.8%, respectively. This study highlights the complicated interactions between agricultural fire emissions and photochemistry.
North Pacific Paleotemperature and Paleoproductivity Reconstructions Based on Diatom Species
Authors: Lopes C. , Mix A. C.
Published: June 2018

Regionally developed diatom‐based transfer functions reconstruct both summer sea surface temperature and primary productivity (PP) in the North Pacific based on a calibration data set including the eastern subtropical gyre (California and Oregon), the Gulf of Alaska, the western Pacific, and Bering Sea. Factors of the floral assemblage and environment data sets, and canonical correspondence, support estimation of two essentially orthogonal variables. Validation of the summer sea surface temperature transfer function resulted in r2jack of 0.9 and a root‐mean‐square error of prediction of 1.0°C over a range of 7–17°C. The summer PP transfer function yielded r2jack of 0.7 and a root‐mean‐square error of prediction of 219 g C·m2·year over a range of 200–2,000 g C·m2·year. Application in downcore locations within the modern nearshore upwelling regime and within the California Current offshore Oregon reveals that during Holocene time higher PP (>800 g C·m2·year) was associated with cooler temperatures (<16°C) forced by upwelling. In contrast, during the Last Glacial Maximum, when subpolar conditions are present off Oregon, higher PP (>1,000 g C·m2·year) was associated with warmer SSTs (>10°C; significant in the nearshore site). This finding supports previous hypotheses that in cold regimes warming may augment biological production, perhaps by relieving metabolic constraints. This is of particular interest because of projected amplification of future warming in high latitudes and the potential for greening of the subpolar and polar oceans.
Tectonic Evolution of the Chos Malal Fold‐and‐Thrust Belt (Neuquén Basin, Argentina) From (U‐Th)/He and Fission Track Thermochronometry
Authors: Sánchez N. P. , Coutand I. , Turienzo M. , Lebinson F. , Araujo V. , Dimieri L.
Published: June 2018

In the southern central Andes at 37–38°S latitude, the Chos Malal fold‐and‐thrust belt (FTB), which results from the Late Cretaceous closure of the Neuquén Basin, has generated increasing interest because of its potential for hydrocarbon exploration. Using detailed field mapping, seismic reflection, and well data analysis, we have produced balanced cross sections, which combined with apatite and zircon (U‐Th)/He, and fission track thermochronology from samples distributed along the FTB, bring new constraints on the chronology of the structural development of the Chos Malal FTB. Fully reset samples obtained from the Early Jurassic rocks at the bottom of the sedimentary sequence exposed in the Cordillera del Viento, a major basement‐involved hinterland structure, permit to quantify its cooling rate from 5.4 ± 4.1 and 3.8 ± 3.2 °C/Ma between 70 and 55 Ma down to between 2.0 ± 1.3 and 1.3 ± 0.9 °C/Ma after 55 Ma until the present. Detrital apatite fission track ages from Late Jurassic and Early Cretaceous sandstones reveal that tectonically driven exhumation through basement‐involved thrusting has occurred at ~15–7 Ma in both the inner and outer sectors of the FTB. Finally, the cooling and exhumation of the Las Yeseras‐Pampa Tril basement‐involved anticlines at the mountain front at ~9–7 Ma, slightly younger than previously assumed, suggests a normal sequence of faulting propagation. Our proposed thermostructural model of the Chos Malal FTB contributes to a better understanding of the tectonic evolution of this segment of the Andes.
Mesozoic Development of Nonmarine Basins in the Northern Yidun Terrane: Deposition and Deformation in the Eastern Tibetan Plateau Prior to the India‐Asia Collision
Authors: Jackson W. T. , Robinson D. M. , Weislogel A. L. , Shang F. , Jian X.
Published: June 2018

To determine the timing and spatial patterns of syntectonic nonmarine deposition and deformation in the eastern Tibetan Plateau, we present field data, thin section petrology, and detrital U‐Pb zircon geochronology from the west Ganzi basin (WGB) and east Ganzi basin (EGB) in the northern Yidun terrane. The WGB and EGB contain ~800 and ~1,300–1,600 m of nonmarine strata, respectively, deposited in alluvial environments. Along the southern margins of both the WGB and EGB and the northwestern margin of the WGB, reverse faults place Triassic Ganzi Pluton and Triassic Yidun Grouprocks on top of nonmarine strata. Growth strata in the footwalls of basin‐bounding faults indicate that deposition was synchronous with fault development. The western and eastern margins of the WGB, as well as the northern margin of the EGB, exhibit uncomformable contacts with the underlying Triassic Ganzi Pluton and Triassic Yidun Grouprocks. Provenance results suggest a regionally mixed sediment source from the Yidun and Songpan‐Ganzi terranes. Maximum deposition ages from detrital U‐Pb zircon geochronology, as well as previously reported thermochronology and palynology results, indicate a Late Mesozoic depositional age for WGB and EGB strata. We interpret the spatial and temporal developments of the WGB and EGB to be associated with the Lhasa‐Qiangtang collision.
Exploring How Changing Monsoonal Dynamics and Human Pressures Challenge Multireservoir Management for Flood Protection, Hydropower Production, and Agricultural Water Supply
Authors: Quinn J. D. , Reed P. M. , Giuliani M. , Castelletti A. , Oyler J. W. , Nicholas R. E.
Published: June 2018

Multireservoir systems require robust and adaptive control policies capable of managing hydroclimatic variability and human demands across a range of time scales. This is especially true for river basins with high intraannual and interannual variability, such as monsoonal systems that need to buffer against seasonal droughts while also managing extreme floods. Moreover, the timing, intensity, duration, and frequency of these hydrologic extremes may evolve with deeply uncertain changes in socioeconomic and climatic pressures. This study contributes an innovative method for exploring how possible changes in the timing and magnitude of the monsoonal cycle impact the robustness of reservoir operating policies designed assuming stationary hydrologic and socioeconomic conditions. We illustrate this analysis on the Red River basin in Vietnam, where reservoirs and dams serve as important sources of hydropower production, multisectoral water supply, and flood protection for the capital city of Hanoi. Applying our scenario discovery approach, we find that reservoir operations designed assuming stationarity provide robust hydropower performance in the Red River but that increased mean streamflow, amplification of the within‐year monsoonal cycle, and increased interannual variability all threaten their ability to manage flood risk. Additionally, increased agricultural water demands can only be tolerated if they are accompanied by greater mean flow, exacerbating food‐flood trade‐offs in the basin. These findings highlight the importance of exploring the impacts of a wide range of deeply uncertain socioeconomic and hydrologic factors when evaluating system robustness in monsoonal river basins, considering in particular both lower‐order moments of annual streamflow and intraannual monsoonal behavior.
Phage-inducible chromosomal islands are ubiquitous within the bacterial universe
Authors: Fillol-Salom Alfred , Martínez-Rubio Roser , Abdulrahman Rezheen F , Chen John , Davies Robert , Penadés José R
Published: June 2018

Phage-inducible chromosomal islands (PICIs) are a recently discovered family of pathogenicity islands that contribute substantively to horizontal gene transfer, host adaptation and virulence in Gram-positive cocci. Here we report that similar elements also occur widely in Gram-negative bacteria. As with the PICIs from Gram-positive cocci, their uniqueness is defined by a constellation of features: unique and specific attachment sites, exclusive PICI genes, a phage-dependent mechanism of induction, conserved replication origin organization, convergent mechanisms of phage interference, and specific packaging of PICI DNA into phage-like infectious particles, resulting in very high transfer frequencies. We suggest that the PICIs represent two or more distinct lineages, have spread widely throughout the bacterial world, and have diverged much more slowly than their host organisms or their prophage cousins. Overall, these findings represent the discovery of a universal class of mobile genetic elements.
Leukemic stem cell signatures identify novel therapeutics targeting acute myeloid leukemia
Authors: Laverdière Isabelle , Boileau Meaghan , Neumann Andrea L. , Frison Héloïse , Mitchell Amanda , Ng Stanley W. K. , Wang Jean C. Y. , Minden Mark D. , Eppert Kolja
Published: June 2018

Therapy for acute myeloid leukemia (AML) involves intense cytotoxic treatment and yet approximately 70% of AML are refractory to initial therapy or eventually relapse. This is at least partially driven by the chemo-resistant nature of the leukemic stem cells (LSCs) that sustain the disease, and therefore novel anti-LSC therapies could decrease relapses and improve survival. We performed in silico analysis of highly prognostic human AML LSC gene expression signatures using existing datasets of drug–gene interactions to identify compounds predicted to target LSC gene programs. Filtering against compounds that would inhibit a hematopoietic stem cell (HSC) gene signature resulted in a list of 151 anti-LSC candidates. Using a novel in vitro LSC assay, we screened 84 candidate compounds at multiple doses and confirmed 14 drugs that effectively eliminate human AML LSCs. Three drug families presenting with multiple hits, namely antihistamines (astemizole and terfenadine), cardiac glycosides (strophanthidin, digoxin and ouabain) and glucocorticoids (budesonide, halcinonide and mometasone), were validated for their activity against human primary AML samples. Our study demonstrates the efficacy of combining computational analysis of stem cell gene expression signatures with in vitro screening to identify novel compounds that target the therapy-resistant LSC at the root of relapse in AML.
Synergetic coordination and catecholamine chemistry for catalytic generation of nitric oxide on vascular stents
Authors: Li Xiangyang , Qiu Hua , Gao Peng , Yang Ying , Yang Zhilu , Huang Nan
Published: June 2018

The unique advantages of nitric oxide (NO) in cardiovascular disease therapy have driven the development of methods to functionalize cardiovascular stents for local generation of NO. However, current NO-generating materials used for surface engineering stents have limitations such as a complex fabrication process, poor stent adhesion strength, and low control of NO release. Herein, we apply synergetic coordination and catecholamine surface chemistry to develop an adhesive NO-generating coating with a copper-catecholamine framework through a simple, one-step molecule/ion co-assembly process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in long-term, stable, adjustable NO release rates from the coating. The resulting desirable therapeutic dose and release kinetics of NO endow the vascular stent with the ability to simultaneously inhibit platelet activation and smooth muscle cell (SMC) proliferation, and enhances endothelial cell (EC) adhesion, proliferation, and migration in vitro. Vascular stent functionalized by the optimized copper-catecholic-selenocystamine coating significantly suppresses thrombosis, promotes re-endothelialization, and reduces intimal hyperplasia in vivo, and may be promising to address the clinical complications associated with restenosis and late stent thrombosis.
Publisher Correction: Probing the strongly driven spin-boson model in a superconducting quantum circuit
Authors: Magazzù L. , Forn-Díaz P. , Belyansky R. , Orgiazzi J.-L. , Yurtalan M. A. , Otto M. R. , Lupascu A. , Wilson C. M. , Grifoni M.
Published: June 2018

The original PDF and HTML versions of this Article omitted the ORCID ID of the authors L. Magazzù and P. Forn-Díaz. (L. Magazzù: 0000-0002-4377-8387; P. Forn-Diaz: 0000-0003-4365-5157).

The original PDF version of this Article contained errors in Eqs. (2), (6), (13), (14), (25), (26). These equations were missing all instances of ‘Γ’ and ‘Δ’, which are correctly displayed in the HTML version.

Similarly, the inline equation in the third sentence of the caption of Fig. 2 was missing the left hand term ‘Ω’.

The original HTML version of this Article contained errors in Table 1. The correct version of the sixth row of the first column states ‘Figure 2’ instead of the original, incorrect ‘Figure’. And the correction version of the ninth row of the first column states ‘Figure 3’ instead of the original, incorrect ‘Figure’.

This has been corrected in both the PDF and HTML versions of the Article.
α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease
Authors: Ludtmann Marthe H. R. , Angelova Plamena R. , Horrocks Mathew H. , Choi Minee L. , Rodrigues Margarida , Baev Artyom Y. , Berezhnov Alexey V. , Yao Zhi , Little Daniel , Banushi Blerida , Al-Menhali Afnan Saleh , Ranasinghe Rohan T. , Whiten Daniel R. , Yapom Ratsuda , Dolt Karamjit Singh , Devine Michael J. , Gissen Paul , Kunath Tilo , Jaganjac Morana , Pavlov Evgeny V. , Klenerman David , Abramov Andrey Y. , Gandhi Sonia
Published: June 2018

Protein aggregation causes α-synuclein to switch from its physiological role to a pathological toxic gain of function. Under physiological conditions, monomeric α-synuclein improves ATP synthase efficiency. Here, we report that aggregation of monomers generates beta sheet-rich oligomers that localise to the mitochondria in close proximity to several mitochondrial proteins including ATP synthase. Oligomeric α-synuclein impairs complex I-dependent respiration. Oligomers induce selective oxidation of the ATP synthase beta subunit and mitochondrial lipid peroxidation. These oxidation events increase the probability of permeability transition pore (PTP) opening, triggering mitochondrial swelling, and ultimately cell death. Notably, inhibition of oligomer-induced oxidation prevents the pathological induction of PTP. Inducible pluripotent stem cells (iPSC)-derived neurons bearing SNCA triplication, generate α-synuclein aggregates that interact with the ATP synthase and induce PTP opening, leading to neuronal death. This study shows how the transition of α-synuclein from its monomeric to oligomeric structure alters its functional consequences in Parkinson’s disease.
Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes
Authors: Shen Yue-xiao , Song Woochul , Barden D. Ryan , Ren Tingwei , Lang Chao , Feroz Hasin , Henderson Codey B. , Saboe Patrick O. , Tsai Daniel , Yan Hengjing , Butler Peter J. , Bazan Guillermo C. , Phillip William A. , Hickey Robert J. , Cremer Paul S. , Vashisth Harish , Kumar Manish
Published: June 2018

Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m−2 h−1 bar−1 compared with 4–7 L m−2 h−1 bar−1) over similarly rated commercial membranes.
Spatially confined lignin nanospheres for biocatalytic ester synthesis in aqueous media
Authors: Sipponen Mika Henrikki , Farooq Muhammad , Koivisto Jari , Pellis Alessandro , Seitsonen Jani , Österberg Monika
Published: June 2018

Dehydration reactions proceed readily in water-filled biological cells. Development of biocatalysts that mimic such compartmentalized reactions has been cumbersome due to the lack of low-cost nanomaterials and associated technologies. Here we show that cationic lignin nanospheres function as activating anchors for hydrolases, and enable aqueous ester synthesis by forming spatially confined biocatalysts upon self-assembly and drying-driven aggregation in calcium alginate hydrogel. Spatially confined microbial cutinase and lipase retain 97% and 70% of their respective synthetic activities when the volume ratio of water to hexane increases from 1:1 to 9:1 in the reaction medium. The activity retention of industrially most frequently used acrylic resin-immobilized Candida antarctica lipase B is only 51% under similar test conditions. Overall, our findings enable fabrication of robust renewable biocatalysts for aqueous ester synthesis, and provide insight into the compartmentalization of diverse heterogeneous catalysts.
A Dual-Modality Hybrid Imaging System Harnesses Radioluminescence and Sound to Reveal Molecular Pathology of Atherosclerotic Plaques
Authors: Zaman Raiyan T. , Yousefi Siavash , Long Steven R. , Saito Toshinobu , Mandella Michael , Qiu Zhen , Chen Ruimin , Contag Christopher H. , Gambhir Sanjiv S. , Chin Frederick T. , Khuri-Yakub Butras T. , McConnell Michael V. , Shung K. Kirk , Xing Lei
Published: June 2018

Atherosclerosis is a progressive inflammatory condition caused by an unstable lesion, called thin-cap fibro atheromata (TCFA) that underlies coronary artery disease (CAD)—one of the leading causes of death worldwide. Therefore, early clinical diagnosis and effective risk stratification is important for CAD management as well as preventing progression to catastrophic events. However, early detection could be difficult due to their small size, motion, obscuring 18F-FDG uptake by adjacent myocardium, and complex morphological/biological features. To overcome these limitations, we developed a catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system that can detect vulnerable plaques in coronary arteries and characterizes them with respect to pathology and biology. Our CIRPI system combined two imaging modalities: Circumferential Radioluminescence Imaging (CRI) and PhotoAcoustic Tomography (PAT) within a novel optical probe. The probe’s CaF2:Eu based scintillating imaging window provides a 360° view of human (n = 7) and murine carotid (n = 10) arterial plaques by converting β-particles into visible photons during 18F-FDG decay. A 60× and 63× higher radioluminescent signals were detected from the human and murine plaque inflammations, respectively, compared to the control. The system’s photoacoustic imaging provided a comprehensive analysis of the plaque compositions and its morphologic information. These results were further verified with IVIS-200, immunohistochemical analysis, and autoradiography.
Author Correction: Quantitative shadow compensated optical coherence tomography of choroidal vasculature
Authors: Vupparaboina Kiran Kumar , Dansingani Kunal K. , Goud Abhilash , Rasheed Mohammed Abdul , Jawed Fayez , Jana Soumya , Richhariya Ashutosh , Freund K. Bailey , Chhablani Jay
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Holocene forest dynamics in central and western Mediterranean: periodicity, spatio-temporal patterns and climate influence
Authors: Di Rita Federico , Fletcher William J. , Aranbarri Josu , Margaritelli Giulia , Lirer Fabrizio , Magri Donatella
Published: June 2018

It is well-known that the Holocene exhibits a millennial-scale climate variability. However, its periodicity, spatio-temporal patterns and underlying processes are not fully deciphered yet. Here we focus on the central and western Mediterranean. We show that recurrent forest declines from the Gulf of Gaeta (central Tyrrhenian Sea) reveal a 1860-yr periodicity, consistent with a ca. 1800-yr climate fluctuation induced by large-scale changes in climate modes, linked to solar activity and/or AMOC intensity. We show that recurrent forest declines and dry events are also recorded in several pollen and palaeohydrological proxy-records in the south-central Mediterranean. We found coeval events also in several palaeohydrological records from the south-western Mediterranean, which however show generally wet climate conditions, indicating a spatio-temporal hydrological pattern opposite to the south-central Mediterranean and suggesting that different expressions of climate modes occurred in the two regions at the same time. We propose that these opposite hydroclimate regimes point to a complex interplay of the prevailing or predominant phases of NAO-like circulation, East Atlantic pattern, and extension and location of the North African anticyclone. At a larger geographical scale, displacements of the ITCZ, modulated by solar activity and/or AMOC intensity, may have also indirectly influenced the observed pattern.
Analysis of the Co-existence of Long-range Transport Biomass Burning and Dust in the Subtropical West Pacific Region
Authors: Dong Xinyi , Fu Joshua S. , Huang Kan , Lin Neng-Huei , Wang Sheng-Hsiang , Yang Cheng-En
Published: June 2018

Biomass burning and wind-blown dust has been well investigated during the past decade regarding their impacts on environment, but their co-existence hasn’t been recognized because they usually occur in different locations and episodes. In this study we reveal the unique co-existence condition that dust from the Taklamakan and Gobi Desert (TGD) and biomass burning from Peninsular Southeast Asia (PSEA) can reach to the west Pacific region simultaneously in boreal spring (March and April). The upper level trough at 700hPa along east coast of China favors the large scale subsidence of TGD dust while it travels southeastwards, and drives the PSEA biomass burning plume carried by the westerlies at 3–5 km to descend rapidly to around 1.5 km and mix with dust around southeast China and Taiwan. As compared to the monthly averages in March and April, surface observations suggested that concentrations of PM10, PM2.5, O3, and CO were 69%, 37%, 20%, and 18% higher respectively during the 10 identified co-existence events which usually lasted for 2–3 days. Co-existence also lowers the surface O3, NOx, and SO2 by 4–5% due to the heterogeneous chemistry between biomass burning and mineral dust as indicated by model simulations.
Evaluation of an artificial vertebral body fabricated by a tantalum-coated porous titanium scaffold for lumbar vertebral defect repair in rabbits
Authors: Wang Faqi , Wang Lin , Feng Yafei , Yang Xiaojiang , Ma Zhensheng , Shi Lei , Ma Xiangyu , Wang Jian , Ma Tiancheng , Yang Zhao , Wen Xinxin , Zhang Yang , Lei Wei
Published: June 2018

Tantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated the healing and fusion efficacy of this scaffold in lumbar vertebral defects after corpectomy in rabbits. The results showed that BMSCs on the surface of the Ta-coated Ti scaffolds proliferated better than BMSCs on Ti scaffolds. Histomorphometry showed better bone formation when using Ta-coated TEAVBs than that with Ti TEAVBs at both 8 and 12 weeks after implantation. In addition, the vertical and rotational stiffness results showed that, compared with uncoated TEAVBs, Ta-coated TEAVBs enhanced rabbit lumbar vertebral defect repair. Our findings demonstrate that Ta-coated TEAVBs have better healing and fusion efficacy than Ti TEAVBs in rabbit lumbar vertebral defects, which indicates their good prospects for clinical application.
Human influence on sub-regional surface air temperature change over India
Authors: Dileepkumar R. , AchutaRao Krishna , Arulalan T.
Published: June 2018

Human activities have been implicated in the observed increase in Global Mean Surface Temperature. Over regional scales where climatic changes determine societal impacts and drive adaptation related decisions, detection and attribution (D&A) of climate change can be challenging due to the greater contribution of internal variability, greater uncertainty in regionally important forcings, greater errors in climate models, and larger observational uncertainty in many regions of the world. We examine the causes of annual and seasonal surface air temperature (TAS) changes over sub-regions (based on a demarcation of homogeneous temperature zones) of India using two observational datasets together with results from a multimodel archive of forced and unforced simulations. Our D&A analysis examines sensitivity of the results to a variety of optimal fingerprint methods and temporal-averaging choices. We can robustly attribute TAS changes over India between 1956–2005 to anthropogenic forcing mostly by greenhouse gases and partially offset by other anthropogenic forcings including aerosols and land use land cover change.
Finite Element Stress Analysis of Keyhole Plate System in Sagittal Split Ramus Osteotomy
Authors: Kim Ju-Won , Park Kang-Nam , Lee Chang-Hyeon , Kim Yong-Su , Kim Young-Hee , Yang Byoung-Eun
Published: June 2018

A new miniplate applied differently from conventional application method for bone fixation has been developed. The novel approach is the insertion of the screw into the bone before miniplate installation. This study aimed to assess the stress distribution of a newly designed Yang’s Keyhole (YK)- plate for segmental-bone fixation during sagittal split ramus osteotomy (SSO). Moreover, the effectiveness of the YK-plate system based on the clinical results was determined. The YK-plate system has a widened hole in the anterior region to permit a screw-head to be screwed through the system. The stress distribution using the finite-element analysis method was compared between in the case of the YK-plate system and the case of existing mini-plate fixation technique. Moreover, the clinical results of patients were evaluated during the follow-up examination periods. No critical complications in any of the six patients were reported during the four-month follow-up period. The result of the stress distribution using finite-element analysis showed a similar trend in all four fixation methods. The YK-plate system can be applied to fixation during SSO and allow for mechanically stable and convenient application.
Dropping anchor: attachment of peptidylarginine deiminase via A-LPS to secreted outer membrane vesicles of Porphyromonas gingivalis
Authors: Gabarrini Giorgio , Heida Rick , van Ieperen Nienke , Curtis Mike A. , van Winkelhoff Arie Jan , van Dijl Jan Maarten
Published: June 2018

The periodontal pathogen Porphyromonas gingivalis has been invoked in the autoimmune disease rheumatoid arthritis (RA). This association relates to the peptidylarginine deiminase of P. gingivalis (PPAD), an enzyme capable of citrullinating human proteins and potentially contributing to loss of tolerance to citrullinated proteins in RA. PPAD is both retained in the outer membrane (OM) of P. gingivalis cells and secreted into the extracellular milieu, where it is detected in a soluble form and in association with outer membrane vesicles (OMVs). Recent studies showed that certain P. gingivalis proteins are retained in the OM through modification with an A-type lipopolysaccharide (A-LPS). Here, we investigated the possible involvement of A-LPS modification in the association of PPAD to the OM and OMVs. The results indicate that the OM- and OMV-associated PPAD is A-LPS-modified. The modified PPAD species is of low abundance in particular clinical isolates of P. gingivalis, which is not due to defects in the overall synthesis of A-LPS-modified proteins but, rather, to particular traits of the respective PPAD proteins. Lastly, we show that OMV association protects the A-LPS-modified PPAD from proteolytic degradation. Altogether, our observations show that A-LPS modification contributes to OM(V) sorting and ‘protective secretion’ of PPAD.