bluuebunny/crossref_metadata_2025 huggingface dataset:
EDTA‐Capped Iron Oxide Core‐Corona System as Vehicle for Gene Delivery to Transform E.coli: Mimicking the Lipid Bilayer Environment
Authors: Shah Ekta , Kadam Ashlesha , Jubin Tina , Begum Rasheedunnisa , Upadhyay Pratik , Soni Hemant P.
Published: July 2019

EDTA‐capped iron oxide nanoparticles (Fe3O4/edta NPs) were synthesized by simple wet chemical method and encapsulated with amphiphilic triblock copolymer Pluronic®F127 (Fe3O4/edta/P). The resulting ‘core‐corona’ system becomes capable of condensing plasmid DNA (pDNA) and act as vehicle for cell transformation. As a proof‐of‐concept, E.coli_DH5α bacterial strain was selected. The plasmids like pBSKS and pUC18 having antibiotic resistance marker gene were eluted from the bacterial strain, purified and loaded on the synthesized nano‐assembly. Green fluorescence protein tag was attached to pTX (pTXgfp) to confirm successful transformation. The gene transformation efficiency (TE) of the developed Fe3O4/edta/P vehicle was compared with traditional CaCl2 mediated transformation as a positive control and naked pTXgfp was used as a negative control. PEGlation of Fe3O4/edta was also carried out and the TE of the resulting system was compared with as‐synthesized Fe3O4/edta/P. This study demonstrates that Pluronic® F127 polymeric surfactant can be used to form stealth surface of the nanocarrier to solve Polyethylene Glycol (PEG) dilemma. The probable mechanism to explain the bacterial cell transformation is discussed.
Distribution of Effective Ferrierite Active Sites for Skeletal Isomerization of n‐Butene to Isobutene
Authors: Liu Wen , Hu Haiqiang , Liu Yang , Zhang Lei , Xia Chengjie , Wang Qi , Ke Ming
Published: July 2019

In this study, the effective active sites of aged ferrierite(FER) were confirmed to be located in the 10‐membered ring (10‐MR) pore mouths by modification with ammonium hexafluorosilicate((NH4)2SiF6 )and long‐term experiments. Analysis of SiO2/Al2O3 ratios showed that aluminum atoms were selectively removed from the FER surface after the modification with (NH4)2SiF6. Comparison of the catalytic properties before and after modification showed that the catalytic activity of aged FER depended only on the amount of acid sites located in the 10‐MR pore mouths. Monitoring of the change in acid amount with reaction time and the difference between aged and deactivated FER showed that aged FER retained only weak acid sites, and its deactivation was caused by carbon deposition on the 10‐MR pore mouth acid sites. Therefore, the catalytic performance of FER can be improved by increasing the number of 10‐MR pore mouths.
Wetting Transition from Lotus Leaf to Rose Petal using Modified Fly Ash
Authors: Mahanta Urbashi , Khandelwal Mudrika , Deshpande Atul S.
Published: July 2019

We present a facile and scalable approach to develop lotus leaf as well rose petal like superhydrophobic surfaces using fly ash (an industrial waste obtained from the burning of coal). To achieve this, as‐obtained fly ash powder with wide particle size distribution (FA) was processed through sedimentation technique to obtain fly ash powder with narrower particle size distribution (FAS) and modified with two different concentrations of stearic acid (SA) and treated at two different temperatures – one each below and above melting point of SA. All samples showed superhydrophobicity, where, the water contact angle (WCA) increased with an increase in the amount of stearic acid and modification temperature. Interestingly, the water droplets roll‐off from the modified FA surfaces at a small tilting angle of 5° similar to the lotus leaf, whereas, the modified FAS surfaces exhibited high adhesion for water droplets even when inverted, as in case of the rose petal. It was seen that drying at temperature lower than melting temperature of stearic acid introduced additional roughness, yet the WCA decreased. This is investigated to understand the effect of topology and substrate nature on WCA in different wetting states.
MOF‐Derived Ni(OH)2 Nanocubes/GO For High‐Performance Supercapacitor
Authors: Hu Xinran , Li Jiangfeng , Wu Qingsheng , Zhang Qiwei , Wang Xu
Published: July 2019

Prussian blue analogues (Ni3[Fe(CN)6]2)) derived nanocube‐like Ni(OH)2 was grown evenly on the surface of GO via solution‐precipitation and potassium hydroxide etching process at room temperature. Due to the even dispersion of Ni(OH)2 nancubes, the obtained sample Ni(OH)2/GO exhibits a maximum specific capacitance of 1299 F g−1 at 0.5 A g−1, excellent electrochemical stability (capacity retention of 63% from 0.5 A g−1 to 10 A g−1), and long‐cycle stability (capacity retention of 78% over 2000 cycles).
An Enzymatic and Environmentally Friendly Route for the Synthesis of Chiral β‐Hydroxy Ketones
Authors: Yıldız Tülay
Published: July 2019

The present study deals with the biocatalytic enantioselective synthesis of chiral β‐hydroxy ketones. For the first time, we report that among many enzymes, the lipase AL‐AN (Amano Lipase A from Aspergillus niger) catalyzed the enzymatic hydrolysis of racemic 1,3‐keto acetates in aqueous media. Optimum reaction conditions were determined by changing the enzyme, solvent, temperature, pH and amounts of enzymes. After AL‐AN was determined to be the best enzyme in this study, we examined fifteen substrates with different structures in this reaction and obtained chiral β‐hydroxy ketones with good yield, high enantioselectivity and S configuration. This study presents an environmentally friendly and green method for the synthesis of (S)‐β‐hydroxy ketones.
Controllable Synthesis of V2O5/Mn3O4 Nanoflakes and rGO Nanosheets: To Investigate the Performance of All Solid‐State Asymmetric Supercapacitor Device
Authors: Mary Amalraj Juliet Christina , Bose Arumugam Chandra
Published: July 2019

Different nanostructured/composite materials are considered as a promising electrode material which enhances the electrochemical activity of the individual substances. V2O5/Mn3O4 composite material is synthesized using hydrothermal method at different reaction time ranging from 12 h to 24 h. Obviously, by varying the reaction time, the morphology of composite changes from individual flakes to agglomerated flakes. The change in surface morphology of the material is observed from the SEM images. Electrochemical performance of V2O5, Mn3O4, V2O5 /Mn3O4‐1, V2O5 /Mn3O4‐2 V2O5 /Mn3O4‐3, V2O5 /Mn3O4‐4 and rGO is studied using cyclic voltammetric, charge/discharge, and electrochemical impedance spectroscopic studies. At a current density of 5 A g−1, V2O5, Mn3O4, V2O5 /Mn3O4‐3, and rGO nanosheet exhibit the maximum specific capacitance of 441, 190, 1008 and 464 F g−1 respectively. Moreover, the asymmetric supercapacitor device is constructed using V2O5 /Mn3O4‐3and rGO nanomaterials. At 2 A g−1, the asymmetric V2O5 /Mn3O4‐3and rGO device obtains the highest energy density of 44.9 W h kg−1 and the corresponding power density is 1.76 kW kg−1.
Solvent Dependent Prototropic Tautomerism in a Schiff Base Derived from o‐Vanillin and 2‐Aminobenzylalcohol
Authors: Plyuta Nataliya , Kokozay Vladimir , Cauchy Thomas , Avarvari Narcis , Goreshnik Evgeny , Petrusenko Svitlana
Published: July 2019

The Schiff base H2L, namely 2‐(3‐methoxysalicylidene‐amino)‐benzyl‐alcohol, 1 and its two pseudo‐polymorphs H2L⋅CH3OH 2 and H2L⋅H2O 3, have been synthesized by the condensation reaction of 2‐aminobenzyl alcohol and o‐vanillin in different solvents. X‐ray crystallographic analysis revealed that the keto‐enol tautomerism of H2L in solid state exists as a complex system of three different enol, keto and zwitterionic forms in equilibrium, dependent on crystal packing forces and the crystallization solvent. The enol, keto and mixed enol‐zwitterionic (roughly 1:1) forms were observed in the crystal structures of 1, 2 and 3, respectively. The crystallographic results are supported by FTIR and DFT calculations. Photophysical properties were determined in acetonitrile solution and solid state and were supported by TD‐DFT studies.
Ranking open source application integration frameworks based on maintainability metrics: A review of five‐year evolution
Authors: Frantz Rafael Z. , Rehbein Matheus H. , Berlezi Rodolfo , Roos‐Frantz Fabricia
Published: July 2019

Integration frameworks are specialized software tools built and adapted to facilitate the design and implementation of integration solutions. An integration solution allows for the reuse of applications from the software ecosystem of companies to support their business processes. There are several open‐source integration frameworks available on the market designed to operate in a business context to manipulate structured data; however, increasingly, they are required to deal with unstructured and large volumes of data, thus requiring effort to adapt these frameworks to work with unstructured and large volume of data. Choosing the framework, which is the easiest to be adapted, is not a trivial task. In this article, we review the newest stable versions of four open‐source integration frameworks by analyzing how they have evolved regarding their adaptive maintainability over five years. We rank them according to their maintainability degree and compare past and current versions of each framework. To encourage and enable researchers and developers to replicate our experiments, with the aim of verifying our findings, and to experiment with new versions of the integration frameworks analyzed, we detail the experimental protocol used while also having made all the required software involved available on the Web.
The Effect of Al‐Mg Deoxidation on the Cleanliness of Steel during the Electroslag Remelting Process
Authors: Liu Weijian , Li Jing , Wang Hao , Shi Chengbin
Published: July 2019

Herein, the effect on inclusions and oxygen content of steel with Al‐Mg deoxidant addition during the electroslag remelting (ESR) process is studied. Combined with thermodynamics, the evolution mechanism of inclusions during the ESR process is analyzed. The results indicate that the inclusions in the consumable electrode are SiO2‐Al2O3‐MnO complex inclusions, where most are located in the 1873 K low‐melting‐temperature region. The inclusions in remelted ingots are mainly Al2O3 and small amounts of MnS in the Al‐Mg deoxidant‐free trials, and the inclusions are in the size of 1–3 μm. In the Al‐Mg deoxidant addition trial, the main inclusions are Al2O3, MgO‐Al2O3, CaO‐Al2O3‐MgO, and CaO‐Al2O3. The proportions of CaO‐Al2O3‐MgO and CaO‐Al2O3 inclusions increase with the increase in the deoxidant.
Phthalate plasticizer di(2‐ethyl‐hexyl) phthalate induces cyclooxygenase‐2 expression in gastric adenocarcinoma cells
Authors: Wong Jhen‐Hong , Wang Yu‐Shiuan , Nam Sean , Ho Kuo‐Hao , Chang Che‐Mai , Chen Ku‐Chung , Chen Yi‐Fan , Chang Wei‐Chiao
Published: July 2019

The phthalate plasticizer, di(2‐ethyl‐hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoting inflammation has been reported by both human epidemiological and animal studies. In stomach tissue, chronic inflammation is known to accompany mucosal damage, and pave the way to gastritis, stomach ulcers, and ultimately gastric cancer. Eastern Asian populations possess the highest gastric cancer incidences in the world. Coincidentally, East Asia is one of the world's major sites for plastics manufacture and export. Thus, possible correlations between DEHP, a common plasticizer, and gastric cancer are of great interest. Our study revealed several critical findings. First, even at very low dosage, mimicking the residual plasticizer exposure, detrimental effects of DEHP on gastric cells can be detected. Second, gastric cells treated with DEHP increased cyclooxygenase‐2 (COX‐2) in a time‐dependent manner. Third, promoter deletion studies revealed a critical role of nuclear factor‐kappa B (NF‐κB) for COX‐2 gene responses. Finally, our results indicated that a low concentration of DEHP is able to trigger COX‐2 activation via the extracellular signal–regulated kinase (ERK1/2) and NF‐κB signaling pathway. Taken together, we demonstrate that very low doses of DEHP enhance the expression of the prototypical inflammatory gene, COX‐2, in gastric cancer cells via ERK1/2 and NF‐κB activation. This study provides important insights into the inflammatory process and damages associated with phthalate plasticizers exposure.
Load case reduction for offshore wind turbine support structure fatigue assessment by importance sampling with two‐stage filtering
Authors: Stieng Lars Einar S. , Muskulus Michael
Published: July 2019

A complete fatigue assessment for operational conditions for offshore wind turbines involves simulating thousands of environmental states. For applications such as optimization, where this assessment needs to be repeated many times, that presents a significant computational problem. Here, we propose a novel way of reducing the number of simulated environmental states (load cases) while maintaining an acceptable accuracy. From one full fatigue analysis of a base design, the OC3 monopile (with the NREL 5MW turbine), the distribution of fatigue damage per load case can be used to estimate the lifetime fatigue damage of a range of modified designs. Using importance sampling and a specially adapted two‐stage filtering procedure, we obtain pseudo‐optimal sets of load cases from which the fatigue damage is estimated. This is applied to seven different designs that have been modified to emulate iterations of an optimization loop. For several of these designs, sampling less than 1% of all load cases can give damage estimates with median errors of less than 2%. Even for the most severe cases, using 3% of the environmental states yields a maximum error of 10%. While further refinement is possible, the method is considered viable for applications within design optimization and preliminary design.
Spatial variability of soil organic carbon and total nitrogen in the hilly red soil region of Southern China
Authors: Yao Xiong , Yu Kunyong , Deng Yangbo , Liu Jian , Lai Zhuangjie
Published: July 2019

To obtain accurate spatial distribution maps of soil organic carbon (SOC) and total nitrogen (TN) in the Hetian Town in Fujian Province, China, soil samples from three depths (0–20, 20–40, and 40–60 cm) at 59 sampling sites were sampled by using traditional analysis and geostatistical approach. The SOC and TN ranged from 2.26 to 47.54 g kg−1, and from 0.28 to 2.71 g kg−1, respectively. The coefficient of variation for SOC and TN was moderate at 49.02–55.87% for all depths. According to the nugget-to-sill ratio values, a moderate spatial dependence of SOC content and a strong spatial dependence of TN content were found in different soil depths, demonstrating that SOC content was affected by both extrinsic and intrinsic factors while TN content was mainly influenced by intrinsic factors. Indices of cross-validation, such as mean error, mean standardized error, were close to zero, indicating that ordinary kriging interpolation is a reliable method to predict the spatial distribution of SOC and TN in different soil depths. Interpolation using ordinary kriging indicated the spatial pattern of SOC and TN were characterized by higher in the periphery and lower in the middle. To improve the accuracy of spatial interpolation for soil properties, it is necessary and important to incorporate a probabilistic and machine learning methods in the future study.
A Gutsy Move for Cell-Based Regenerative Medicine in Parkinson’s Disease: Targeting the Gut Microbiome to Sequester Inflammation and Neurotoxicity
Authors: Lee Jea-Young , Tuazon Julian P. , Corey Sydney , Bonsack Brooke , Acosta Sandra , Ehrhart Jared , Sanberg Paul R. , Borlongan Cesario V.
Published: July 2019

Pharmaceuticals and cell-based regenerative medicine for Parkinson’s disease (PD) offer palliative relief but do not arrest the disease progression. Cell therapy has emerged as an experimental treatment, but current cell sources such as human umbilical cord blood (hUCB) stem cells display only partial recapitulation of mature dopaminergic neuron phenotype and function. Nonetheless, stem cell grafts ameliorate PD-associated histological and behavioral deficits likely through stem cell graft-secreted therapeutic substances. We recently demonstrated the potential of hUCB-derived plasma in enhancing motor capabilities and gastrointestinal function, as well as preventing dopaminergic neuronal cell loss, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) rodent model of PD. Recognizing the translational need to test in another PD model, we now examined here the effects of an intravenously transplanted combination of hUCB and plasma into the 6-hydroxydopamine (6-OHDA) lesioned adult rats. Animals received three separate doses of 4 × 106 hUCB cells with plasma beginning at 7 days after stereotaxic 6-OHDA lesion, then behaviorally and immunohistochemically evaluated over 56 days post-lesion. Whereas vehicle-treated lesioned animals exhibited the typical 6-OHDA neurobehavioral symptoms, hUCB and plasma-treated lesioned animals showed significant attenuation of motor function, gut motility, and nigral dopaminergic neuronal survival, combined with diminished pro-inflammatory microbiomes not only in the nigra, but also in the gut. Altogether these data support a regenerative medicine approach for PD by sequestering inflammation and neurotoxicity through correction of gut dysbiosis.
Correction to: Towards Determining Kinetics of Annihilation Electrogenerated Chemiluminescence by Concentration-Dependent Luminescent Intensity
Authors: Mathwig Klaus , Sojic Neso
Published: July 2019

The article Towards Determining Kinetics of Annihilation Electrogenerated Chemiluminescence by Concentration-Dependent Luminescent Intensity.
Agent-Based Strategizing
Authors: Robertson Duncan A.
Published: July 2019

Strategic management is a system of continual disequilibrium, with firms in a continual struggle for competitive advantage and relative fitness. Models that are dynamic in nature are required if we are to really understand the complex notion of sustainable competitive advantage. New tools are required to tackle challenges of how firms should compete in environments characterized by both exogeneous shocks and intense endogenous competition. Agent-based modelling of firms' strategies offers an alternative analytical approach, where individual firm or component parts of a firm are modelled, each with their own strategy. Where traditional models can assume homogeneity of actors, agent-based models simulate each firm individually. This allows experimentation of strategic moves, which is particularly important where reactions to strategic moves are non-trivial. This Element introduces agent-based models and their use within management, reviews the influential NK suite of models, and offers an agenda for the development of agent-based models in strategic management.
Sex under Necropolitics: Waldo Frank, Jean Toomer, and Black Enfleshment
Authors: KAHAN BENJAMIN , KISHI MADOKA
Published: July 2019

Though Jean Toomer'sCane(1923) is one of the best-known texts of the Harlem Renaissance, it has rarely been discussed with the text alongside which it was initially imagined: Waldo Frank'sHoliday(1923). These works were inspired by a joint trip to Spartanburg, South Carolina and were conceptualized as a shared project, what the authors termed “Holiday + Cane.” This essay tracks their coproduction with particular attention to their parallax vision of lynching to theorize what we call, building on Achille Mbembe's work, “sex under necropolitics.” This dispensation does not take shape within a privatized notion of sexuality, but instead is “ungendered” and unindividuated in the ways that Hortense Spillers has described through the notion of the flesh. We take up her work to suggest that black bodily practices and corporeal intimacies are governed by a regime other than sexuality. In this essay, we map the contours of this regime and its effects on both sides of the color line. Our new cartography promises to reconfigure understandings of the sexuality of Toomer and Frank and of the Harlem Renaissance, and to clarify the relationship between (white) queer theory and queer-of-color critique.
Practice what you preach!
Authors: Wabnitz Pascal
Published: July 2019

Zusammenfassung. Selbsterfahrung sollte unverzichtbares Element der Aus-, Fort- und Weiterbildung psychiatrisch Pflegender sein. Dieser Artikel stellt die Grundlagen einer angeleiteten Reflexionspraxis für therapeutisch tätige Menschen vor und fokussiert die Darstellung auf psychiatrisch Pflegende.
Therapeutisches Potential
Authors: Schwartke Heike , Klippel Tanja , Helbeck Jacob , Müller Christoph , Redzinski Kerstin , Strietholt Lea
Published: July 2019

Zusammenfassung. In einem Wahlpflichtmodul haben Studierende innerhalb des Studiengangs „Psychiatrische Pflege/Psychische Gesundheit“ die Möglichkeit, sich in die Selbstreflexion und die verhaltenstherapeutische Selbsterfahrung einzuüben. Die Autorinnen und Autoren dieses Beitrags geben einen Einblick in die eigene Gefühlswelt während des Moduls, das Professor Pascal Wabnitz angeleitet hat.
Effects of Mosaic Land Use on Dynamically Downscaled WRF Simulations of the Contiguous United States
Authors: Mallard Megan S. , Spero Tanya L.
Published: July 2019

The representation of land use (LU) in meteorological modeling strongly influences the simulation of fluxes of heat, moisture, and momentum; affecting the accuracy of 2‐m temperature and precipitation. Here the Weather Research and Forecasting (WRF) model is used with the Noah land surface model to compare a mosaic approach, which accounts for subgrid scale variability of LU types, to the default option, which only considers the dominant category in each grid cell. Three‐year historical dynamically downscaled WRF simulations are generated using a 12‐km domain over the contiguous United States to assess the sensitivities to using mosaic LU and to changes to parameters associated with LU and soil categories. Compared to dominant LU, mosaic LU features decreased coverage of forest and agricultural types and increased low‐density urban LU throughout much of the eastern and central U.S. However, highly urbanized areas show the opposite trend, as mosaic LU represents partial greenspace within areas that are exclusively urban within dominant LU. Mosaic LU results in widespread increases in sensible heat fluxes and 2‐m temperatures, with reductions in latent heat flux, 2‐m mixing ratio, and monthly precipitation across the central and eastern U.S. These changes exacerbate an existing warm bias found with dominant LU but reduce overestimations of precipitation. Highly urbanized areas in the eastern U.S. tend to have cooler, more realistic temperatures with mosaic LU relative to dominant LU. A pair of runs with updated surface parameters corroborates these results. Overall, differences between the simulations are largely attributable to their representations of urban LU.
Flow Reorganization in an Anthropogenically Modified Tidal Channel Network: An Example From the Southwestern Ganges‐Brahmaputra‐Meghna Delta
Authors: Bain R. L. , Hale R. P. , Goodbred S. L.
Published: July 2019

We examine variations in discharge exchange between two parallel, 1‐ to 2‐km‐wide tidal channels (the Shibsa and the Pussur) in southwestern Bangladesh over spring‐neap, and historical timescales. Our objective is to evaluate how large‐scale, interconnected tidal channel networks respond to anthropogenic perturbation. The study area spans the boundary between the pristine Sundarbans Reserved Forest, where regular inundation of the intertidal platform maintains the fluvially abandoned delta plain, and the anthropogenically modified region to the north, where earthen embankments sequester large areas of formerly intertidal landscape. Estimates of tidal response to the embankment‐driven reduction in basin volume, and hence tidal prism, predict a corresponding decrease in size of the mainstem Shibsa channel, yet the Shibsa is widening and locally scouring even as the interconnected Pussur channel faces rapid shoaling. Rather, the Shibsa has maintained or even increased its pre‐polder tidal prism by capturing a large portion of the Pussur's basin via several “transverse” channels that are themselves widening and deepening. We propose that an enhanced tidal setup in the Pussur and the elimination of an effective Shibsa‐Pussur flow barrier are driving this basin capture event. These results illustrate previously unrecognized channel interactions and emphasize the importance of flow reorganization in response to perturbations of interconnected, multichannel tidal networks that characterize several large tidal delta plains worldwide.
Elephants Boost Carbon Storage in Rain Forests
Authors: Duncombe Jenessa
Published: July 2019

Forest elephants are the “gardeners of the Congo.” How might their dwindling population affect carbon storage in the world’s second-largest tropical forest?
Forum Explores Apollo 11's Legacy, and What's Next
Authors: Showstack Randy
Published: July 2019

Scientists focus on how the Apollo 11 mission has shaped our understanding of the Moon, Earth, and planetary neighborhood.
Long‐Term Variations of June Column Atomic Oxygen Abundance in the Upper Atmosphere Inferred From Ionospheric Observations
Authors: Perrone Loredana , Mikhailov Andrey V.
Published: July 2019

For the first time, atomic oxygen column content [O]col has been inferred from June daytime monthly median foF1 and foF2 observations at Rome, Juliusruh, Sodankylä, and Boulder to analyze its long‐term variations for the period of ~6 solar cycles. The analysis is interesting in the light of possible anthropogenic impact on the upper atmosphere. After the removal of solar and geomagnetic activity effects from the inferred [O]col variations, the residual linear trends are negative and statistically insignificant at middle latitudes. It is shown that ~93% (the corresponding correlation coefficient is 0.964 ± 0.03) of the whole [O]col variability is explained by solar and geomagnetic activity long‐term variations and only ~7% may be attributed to other processes (reasons) including the anthropogenic impact. Solar and geomagnetic activity contributions to [O]col long‐term variations decrease with time, and this may be related to the low solar activity epoch, which we have entered. The main conclusion is that the long‐term variations of the atomic oxygen column content inferred from ionospheric observations are due to solar and geomagnetic activity; that is, they have a natural origin.
Intensity and Impact of the New York Railroad Superstorm of May 1921
Authors: Love Jeffrey J. , Hayakawa Hisashi , Cliver Edward W.
Published: July 2019

Analysis is made of low‐latitude ground‐based magnetometer data recording the magnetic superstorm of May 1921. By inference, the storm was driven by a series of interplanetary coronal mass ejections, one of which produced a maximum pressure on the magnetopause of ~64.5 nPa, sufficient to compress the subsolar magnetopause radius to ~5.3 Earth radii. Over the course of the storm, low‐latitude geomagnetic disturbance exhibited extreme local time (longitude) asymmetry that can be attributed to substorm disturbance extending to low latitudes. The storm attained an estimated maximum −Dston 15 May of 907 ± 132 nT, an intensity comparable to that of the Carrington event of 1859. The May 1921 storm brought spectacular aurorae to the nighttime sky. It also interfered with and damaged telephone and telegraph systems associated with railroad systems in New York City and State. These later effects were due to a combination of three factors: the localized details of geomagnetic vector disturbance, the geographic expression of the Earth's surface impedance tensor, and the configurations and physical parameters of the electrical networks of the day.
Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions
Authors: Birtley James R. , Alomary Mohammad , Zanini Elisa , Antony Jane , Maben Zachary , Weaver Grant C. , Von Arx Claudia , Mura Manuela , Marinho Aline T. , Lu Haonan , Morecroft Eloise V. N. , Karali Evdoxia , Chayen Naomi E. , Tate Edward W. , Jurewicz Mollie , Stern Lawrence J. , Recchi Chiara , Gabra Hani
Published: July 2019

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers.
Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis
Authors: Yoshida Masahiro , Minagawa Shunsuke , Araya Jun , Sakamoto Taro , Hara Hiromichi , Tsubouchi Kazuya , Hosaka Yusuke , Ichikawa Akihiro , Saito Nayuta , Kadota Tsukasa , Sato Nahoko , Kurita Yusuke , Kobayashi Kenji , Ito Saburo , Utsumi Hirohumi , Wakui Hiroshi , Numata Takanori , Kaneko Yumi , Mori Shohei , Asano Hisatoshi , Yamashita Makoto , Odaka Makoto , Morikawa Toshiaki , Nakayama Katsutoshi , Iwamoto Takeo , Imai Hirotaka , Kuwano Kazuyoshi
Published: July 2019

Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.
NASC-seq monitors RNA synthesis in single cells
Authors: Hendriks Gert-Jan , Jung Lisa A. , Larsson Anton J. M. , Lidschreiber Michael , Andersson Forsman Oscar , Lidschreiber Katja , Cramer Patrick , Sandberg Rickard
Published: July 2019

Sequencing of newly synthesised RNA can monitor transcriptional dynamics with great sensitivity and high temporal resolution, but is currently restricted to populations of cells. Here, we develop new transcriptome alkylation-dependent single-cell RNA sequencing (NASC-seq), to monitor newly synthesised and pre-existing RNA simultaneously in single cells. We validate the method on pre-labelled RNA, and by demonstrating that more newly synthesised RNA was detected for genes with known high mRNA turnover. Monitoring RNA synthesis during Jurkat T-cell activation with NASC-seq reveals both rapidly up- and down-regulated genes, and that induced genes are almost exclusively detected as newly transcribed. Moreover, the newly synthesised and pre-existing transcriptomes after T-cell activation are distinct, confirming that NASC-seq simultaneously measures gene expression corresponding to two time points in single cells. Altogether, NASC-seq enables precise temporal monitoring of RNA synthesis at single-cell resolution during homoeostasis, perturbation responses and cellular differentiation.
SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication
Authors: Halder Swagata , Torrecilla Ignacio , Burkhalter Martin D. , Popović Marta , Fielden John , Vaz Bruno , Oehler Judith , Pilger Domenic , Lessel Davor , Wiseman Katherine , Singh Abhay Narayan , Vendrell Iolanda , Fischer Roman , Philipp Melanie , Ramadan Kristijan
Published: July 2019

The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient in SPRTN protease exhibit DPC-induced replication stress and genome instability, manifesting as premature ageing and liver cancer. Here, we provide a body of evidence suggesting that SPRTN activates the ATR-CHK1 phosphorylation signalling cascade during physiological DNA replication by proteolysis-dependent eviction of CHK1 from replicative chromatin. During this process, SPRTN proteolyses the C-terminal/inhibitory part of CHK1, liberating N-terminal CHK1 kinase active fragments. Simultaneously, CHK1 full length and its N-terminal fragments phosphorylate SPRTN at the C-terminal regulatory domain, which stimulates SPRTN recruitment to chromatin to promote unperturbed DNA replication fork progression and DPC repair. Our data suggest that a SPRTN-CHK1 cross-activation loop plays a part in DNA replication and protection from DNA replication stress. Finally, our results with purified components of this pathway further support the proposed model of a SPRTN-CHK1 cross-activation loop.
Qualitative study of practices and challenges when making a diagnosis of asthma in primary care
Authors: Akindele Adeola , Daines Luke , Cavers Debbie , Pinnock Hilary , Sheikh Aziz
Published: July 2019

Misdiagnosis (over-diagnosis and under-diagnosis) of asthma is common. Under-diagnosis can lead to avoidable morbidity and mortality, while over-diagnosis exposes patients to unnecessary side effects of treatment(s) and results in unnecessary healthcare expenditure. We explored diagnostic approaches and challenges faced by general practitioners (GPs) and practice nurses when making a diagnosis of asthma. Fifteen healthcare professionals (10 GPs and 5 nurses) of both sexes, different ages and varying years of experience who worked in NHS Lothian, Scotland were interviewed using in-depth, semi-structured qualitative interviews. Transcripts were analysed using a thematic approach. Clinical judgement of the probability of asthma was fundamental in the diagnostic process. Participants used heuristic approaches to assess the clinical probability of asthma and then decide what tests to do, selecting peak expiratory flow measurements, spirometry and/or a trial of treatment as appropriate for each patient. Challenges in the diagnostic process included time pressures, the variable nature of asthma, overlapping clinical features of asthma with other conditions such as respiratory viral illnesses in children and chronic obstructive pulmonary disease (COPD) in adults. To improve diagnostic decision-making, participants suggested regular educational opportunities and better diagnostic tools. In the future, standardising the clinical assessment made by healthcare practitioners should be supported by improved access to diagnostic services for additional investigation(s) and clarification of diagnostic uncertainty.
Quantifying two-dimensional and three-dimensional stereoscopic learning in anatomy using electroencephalography
Authors: Anderson Sarah J. , Jamniczky Heather A. , Krigolson Olave E. , Coderre Sylvain P. , Hecker Kent G.
Published: July 2019

Advances in computer visualization enabling both 2D and 3D representation have generated tools to aid perception of spatial relationships and provide a new forum for instructional design. A key knowledge gap is the lack of understanding of how the brain neurobiologically processes and learns from spatially presented content, and new quantitative variables are required to address this gap. The objective of this study was to apply quantitative neural measures derived from electroencephalography (EEG) to examine stereopsis in anatomy learning by comparing mean amplitude changes in N250 (related to object recognition) and reward positivity (related to responding to feedback) event related to potential components using a reinforcement-based learning paradigm. Health sciences students (n = 61) learned to identify and localize neuroanatomical structures using 2D, 3D, or a combination of models while EEG and behavioral (accuracy) data were recorded. Participants learning using 3D models had a greater object recognition (N250 amplitude) compared to those who learned from 2D models. Based on neurological results, interleaved learning incorporating both 2D and 3D models provided an advantage in learning, retention, and transfer activities represented by decreased reward positivity amplitude. Behavioral data did not have the same sensitivity as neural data for distinguishing differences in learning with and without stereopsis in these learning activities. Measuring neural activity reveals new insights in applied settings for educators to consider when incorporating stereoscopic models in the design of learning interventions.
Insights into the transcriptomic response of the plant engineering bacterium Ensifer adhaerens OV14 during transformation
Authors: Zuniga-Soto Evelyn , Fitzpatrick David A. , Doohan Fiona M. , Mullins Ewen
Published: July 2019

The ability to engineer plant genomes has been primarily driven by the soil bacterium Agrobacterium tumefaciens but recently the potential of alternative rhizobia such as Rhizobium etli and Ensifer adhaerens OV14, the latter of which supports Ensifer Mediated Transformation (EMT) has been reported. Surprisingly, a knowledge deficit exists in regards to understanding the whole genome processes underway in plant transforming bacteria, irrespective of the species. To begin to address the issue, we undertook a temporal RNAseq-based profiling study of E. adhaerens OV14 in the presence/absence of Arabidopsis thaliana tissues. Following co-cultivation with root tissues, 2333 differentially expressed genes (DEGs) were noted. Meta-analysis of the RNAseq data sets identified a clear shift from plasmid-derived gene expression to chromosomal-based transcription within the early stages of bacterium-plant co-cultivation. During this time, the number of differentially expressed prokaryotic genes increased steadily out to 7 days co-cultivation, a time at which optimum rates of transformation were observed. Gene ontology evaluations indicated a role for both chromosomal and plasmid-based gene families linked specifically with quorum sensing, flagellin production and biofilm formation in the process of EMT. Transcriptional evaluation of vir genes, housed on the pCAMBIA 5105 plasmid in E. adhaerens OV14 confirmed the ability of E. adhaerens OV14 to perceive and activate its transcriptome in response to the presence of 200 µM of acetosyringone. Significantly, this is the first study to characterise the whole transcriptomic response of a plant engineering bacterium in the presence of plant tissues and provides a novel insight into prokaryotic genetic processes that support T-DNA transfer.
Cloud-driven modulations of Greenland ice sheet surface melt
Authors: Niwano Masashi , Hashimoto Akihiro , Aoki Teruo
Published: July 2019

Clouds have been recognized to enhance surface melt on the Greenland Ice Sheet (GrIS). However, quantitative estimates of the effects of clouds on the GrIS melt area and ice-sheet-wide surface mass balance are still lacking. Here we assess the effects of clouds with a state-of-the-art regional climate model, conducting a numerical sensitivity test in which adiabatic atmospheric conditions as well as zero cloud water/ice amounts are assumed (i.e., clear-sky conditions), although the precipitation rate is the same as in the control all-sky simulation. By including or excluding clouds, we quantify time-integrated feedbacks for the first time. We find that clouds were responsible for a 3.1%, 0.3%, and 0.7% increase in surface melt extent (of the total GrIS area) in 2012, 2013, and 2014, respectively. During the same periods, clouds reduced solar heating and thus daily runoff by 1.6, 0.8, and 1.0 Gt day−1, respectively: clouds did not enhance surface mass loss. In the ablation areas, the presence of clouds results in a reduction of downward latent heat flux at the snow/ice surface so that much less energy is available for surface melt, which highlights the importance of indirect time-integrated feedbacks of cloud radiative effects.
Author Correction: Development of new method to enrich human iPSC-derived renal progenitors using cell surface markers
Authors: Hoshina Azusa , Kawamoto Tatsuya , Sueta Shin-Ichi , Mae Shin-Ichi , Araoka Toshikazu , Tanaka Hiromi , Sato Yasunori , Yamagishi Yukiko , Osafune Kenji
Published: July 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Molecular contrast on phase-contrast microscope
Authors: Toda Keiichiro , Tamamitsu Miu , Nagashima Yu , Horisaki Ryoichi , Ideguchi Takuro
Published: July 2019

An optical microscope enables image-based findings and diagnosis on microscopic targets, which is indispensable in many scientific, industrial and medical settings. A standard benchtop microscope platform, equipped with e.g., bright-field and phase-contrast modes, is of importance and convenience for various users because the wide-field and label-free properties allow for morphological imaging without the need for specific sample preparation. However, these microscopes never have capability of acquiring molecular contrast in a label-free manner. Here, we develop a simple add-on optical unit, comprising of an amplitude-modulated mid-infrared semiconductor laser, that is attached to a standard microscope platform to deliver the additional molecular contrast of the specimen on top of its conventional microscopic image, based on the principle of photothermal effect. We attach this unit, termed molecular-contrast unit, to a standard phase-contrast microscope, and demonstrate high-speed label-free molecular-contrast phase-contrast imaging of silica-polystyrene microbeads mixture and molecular-vibrational spectroscopic imaging of HeLa cells. Our simple molecular-contrast unit can empower existing standard microscopes and deliver a convenient accessibility to the molecular world.
Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation
Authors: Kim Kyeoung-Hwa , Kim Eun-Young , Ko Jung-Jae , Lee Kyung-Ah
Published: July 2019

Previously, we found that the silencing of growth arrest-specific gene 6 (Gas6) expression in oocytes impairs cytoplasmic maturation through mitochondrial overactivation with concurrent failure of pronuclear formation after fertilization. In this study, we report that Gas6 regulates mitophagy and safeguards mitochondrial activity by regulating mitophagy-related genes essential to the complete competency of oocytes. Based on RNA-Seq and RT-PCR analysis, in Gas6-silenced MII oocytes, expressions of mitophagy-related genes were decreased in Gas6-silenced MII oocytes, while mitochondrial proteins and Ptpn11, the downstream target of Gas6, was increased. Interestingly, GAS6 depletion induced remarkable MTOR activation. Gas6-depleted MII oocytes exhibited mitochondrial accumulation and aggregation caused by mitophagy inhibition. Gas6-depleted MII oocytes had a markedly lower mtDNA copy number. Rapamycin treatment rescued mitophagy, blocked the increase in MTOR and phosphorylated-MTOR, and increased the mitophagy-related gene expression in Gas6-depleted MII oocytes. After treatment with Mdivi-1, a mitochondrial division/mitophagy inhibitor, all oocytes matured and these MII oocytes showed mitochondrial accumulation but reduced Gas6 expression and failure of fertilization, showing phenomena very similar to the direct targeting of Gas6 by RNAi. Taken together, we conclude that the Gas6 signaling plays a crucial role in control of oocytes cytoplasmic maturation by modulating the dynamics and activity of oocyte mitochondria.
Intrinsic dynamic behavior of enzyme:substrate complexes govern the catalytic action of β-galactosidases across clan GH-A
Authors: Kumar Rajender , Henrissat Bernard , Coutinho Pedro M.
Published: July 2019

The conformational itineraries taken by carbohydrate residues in the catalytic subsite of retaining glycoside hydrolases (GHs), harness the link between substrate conformation and reactivity. GHs’ active sites may be described as a combination of subsites dedicated to the binding of individual sugar residues and to catalysis. The three-dimensional structure of GH:carbohydrate complexes has demonstrated that carbohydrate ring conformation changes in an ordered manner during catalysis. Here we demonstratein silicothat a link exists between subsite binding dynamics and substrate specificity for β-galactosidases from clan GH-A families GH1, GH2, GH35, GH42 and GH59. Different oligosaccharides were docked in the active site of reference β-galactosidase structures using Vina-Carb. Subsequent molecular dynamics (MD) simulations revealed that these enzymes favor a high degree of flexibility and ring distortion of the substrate the lytic subsite −1. Although the β-galactosidase families examined are structurally and mechanistically related, distinct patterns of ring distortion were unveiled for the different families. For β-galactosidases, three different family-dependent reaction itineraries (1S3 → 4H3‡ → 4C1,1,4B → 4H3/ 4E‡ → 4C1, and1S5 → 4E/ 4H5‡ → 4C1) were identified, all compatible with the antiperiplanar lone pair hypothesis (ALPH) for the hydrolysis of β-glycosides. This comparative study reveals the fuzzy character of the changes in carbohydrate ring geometry prior to carbohydrate hydrolysis.
SerpinA3 in the Early Recognition of Acute Kidney Injury to Chronic Kidney Disease (CKD) transition in the rat and its Potentiality in the Recognition of Patients with CKD
Authors: Sánchez-Navarro Andrea , Mejía-Vilet Juan M. , Pérez-Villalva Rosalba , Carrillo-Pérez Diego L. , Marquina-Castillo Brenda , Gamba Gerardo , Bobadilla Norma A.
Published: July 2019

Recognizing patients at early phases of chronic kidney disease (CKD) is difficult, and it is even more challenging to predict acute kidney injury (AKI) and its transition to CKD. The gold standard to timely identify renal fibrosis is the kidney biopsy, an invasive procedure not usually performed for this purpose in clinical practice. SerpinA3 was identified by high-resolution-mass-spectrometry in urines from animals with CKD. An early and progressive elevation of urinary SerpinA3 (uSerpinA3) was observed during the AKI to CKD transition together with SerpinA3 relocation from the cytoplasm to the apical tubular membrane in the rat kidney. uSerpinA3/alpha-1-antichymotrypsin was significantly increased in patients with CKD secondary to focal and segmental glomerulosclerosis (FSGS), ANCA associated vasculitis (AAV) and proliferative class III and IV lupus nephritis (LN). uSerpinA3 levels were independently and positively associated with renal fibrosis. In patients with class V LN, uSerpinA3 levels were not different from healthy volunteers. uSerpinA3 was not found in patients with systemic inflammatory diseases without renal dysfunction. Our observations suggest that uSerpinA3 can detect renal fibrosis and inflammation, with a particular potential for the early detection of AKI to CKD transition and for the differentiation among lupus nephritis classes III/IV and V.