bluuebunny/crossref_metadata_2025 huggingface dataset:
Southern Ocean Phytoplankton Blooms Observed by Biogeochemical Floats
Authors: Uchida Takaya , Balwada Dhruv , Abernathey Ryan , Prend Channing J. , Boss Emmanuel , Gille Sarah T.
Published: October 2019

The spring bloom in the Southern Ocean is the rapid‐growth phase of the seasonal cycle in phytoplankton. Many previous studies have characterized the spring bloom using chlorophyll estimates from satellite ocean color observations. Assumptions regarding the chlorophyll‐to‐carbon ratio within phytoplankton and vertical structure of biogeochemical variables lead to uncertainty in satellite‐based estimates of phytoplankton carbon biomass. Here, we revisit the characterizations of the bloom using optical backscatter from biogeochemical floats deployed by the Southern Ocean Carbon and Climate Observations and Modeling and Southern Ocean and Climate Field Studies with Innovative Tools projects. In particular, by providing a three‐dimensional view of the seasonal cycle, we are able to identify basin‐wide bloom characteristics corresponding to physical features; biomass is low in Ekman downwelling regions north of the Antarctic Circumpolar Current region and high within and south of the Antarctic Circumpolar Current.
De novo compartment deconvolution and weight estimation of tumor samples using DECODER
Authors: Peng Xianlu Laura , Moffitt Richard A. , Torphy Robert J. , Volmar Keith E. , Yeh Jen Jen
Published: October 2019

Tumors are mixtures of different compartments. While global gene expression analysis profiles the average expression of all compartments in a sample, identifying the specific contribution of each compartment remains a challenge. With the increasing recognition of the importance of non-neoplastic components, the ability to breakdown the gene expression contribution of each is critical. Here, we develop DECODER, an integrated framework which performs de novo deconvolution and single-sample compartment weight estimation. We use DECODER to deconvolve 33 TCGA tumor RNA-seq data sets and show that it may be applied to other data types including ATAC-seq. We demonstrate that it can be utilized to reproducibly estimate cellular compartment weights in pancreatic cancer that are clinically meaningful. Application of DECODER across cancer types advances the capability of identifying cellular compartments in an unknown sample and may have implications for identifying the tumor of origin for cancers of unknown primary.
Superresolution architecture of cornerstone focal adhesions in human pluripotent stem cells
Authors: Stubb Aki , Guzmán Camilo , Närvä Elisa , Aaron Jesse , Chew Teng-Leong , Saari Markku , Miihkinen Mitro , Jacquemet Guillaume , Ivaska Johanna
Published: October 2019

While it is clear that key transcriptional programmes are important for maintaining pluripotency, the requirement for cell adhesion to the extracellular matrix remains poorly defined. Human pluripotent stem cells (hPSCs) form colonies encircled by an actin ring and large stable cornerstone focal adhesions (FA). Using superresolution two-colour interferometric photo-activated localisation microscopy, we examine the three-dimensional architecture of cornerstone adhesions and report vertical lamination of FA proteins with three main structural features distinct from previously studied focal adhesions: 1) integrin β5 and talin are present at high density, at the edges of cornerstone FA, adjacent to a vertical kank-rich protein wall, 2) vinculin localises higher than previously reported, displaying a head-above-tail orientation, and 3) surprisingly, actin and α-actinin are present in two discrete z-layers. Finally, we report that depletion of kanks diminishes FA patterning, and actin organisation within the colony, indicating a role for kanks in hPSC colony architecture.
A kinase-independent role for CDK8 in BCR-ABL1+ leukemia
Authors: Menzl Ingeborg , Zhang Tinghu , Berger-Becvar Angelika , Grausenburger Reinhard , Heller Gerwin , Prchal-Murphy Michaela , Edlinger Leo , Knab Vanessa M. , Uras Iris Z. , Grundschober Eva , Bauer Karin , Roth Mareike , Skucha Anna , Liu Yao , Hatcher John M. , Liang Yanke , Kwiatkowski Nicholas P. , Fux Daniela , Hoelbl-Kovacic Andrea , Kubicek Stefan , Melo Junia V. , Valent Peter , Weichhart Thomas , Grebien Florian , Zuber Johannes , Gray Nathanael S. , Sexl Veronika
Published: October 2019

Cyclin-dependent kinases (CDKs) are frequently deregulated in cancer and represent promising drug targets. We provide evidence that CDK8 has a key role in B-ALL. Loss of CDK8 in leukemia mouse models significantly enhances disease latency and prevents disease maintenance. Loss of CDK8 is associated with pronounced transcriptional changes, whereas inhibiting CDK8 kinase activity has minimal effects. Gene set enrichment analysis suggests that the mTOR signaling pathway is deregulated in CDK8-deficient cells and, accordingly, these cells are highly sensitive to mTOR inhibitors. Analysis of large cohorts of human ALL and AML patients reveals a significant correlation between the level of CDK8 and of mTOR pathway members. We have synthesized a small molecule YKL-06-101 that combines mTOR inhibition and degradation of CDK8, and induces cell death in human leukemic cells. We propose that simultaneous CDK8 degradation and mTOR inhibition might represent a potential therapeutic strategy for the treatment of ALL patients.
The importance of Antarctic krill in biogeochemical cycles
Authors: Cavan E. L. , Belcher A. , Atkinson A. , Hill S. L. , Kawaguchi S. , McCormack S. , Meyer B. , Nicol S. , Ratnarajah L. , Schmidt K. , Steinberg D. K. , Tarling G. A. , Boyd P. W.
Published: October 2019

Antarctic krill (Euphausia superba) are swarming, oceanic crustaceans, up to two inches long, and best known as prey for whales and penguins – but they have another important role. With their large size, high biomass and daily vertical migrations they transport and transform essential nutrients, stimulate primary productivity and influence the carbon sink. Antarctic krill are also fished by the Southern Ocean’s largest fishery. Yet how krill fishing impacts nutrient fertilisation and the carbon sink in the Southern Ocean is poorly understood. Our synthesis shows fishery management should consider the influential biogeochemical role of both adult and larval Antarctic krill.
Revealing neural correlates of behavior without behavioral measurements
Authors: Rubin Alon , Sheintuch Liron , Brande-Eilat Noa , Pinchasof Or , Rechavi Yoav , Geva Nitzan , Ziv Yaniv
Published: October 2019

Measuring neuronal tuning curves has been instrumental for many discoveries in neuroscience but requires a priori assumptions regarding the identity of the encoded variables. We applied unsupervised learning to large-scale neuronal recordings in behaving mice from circuits involved in spatial cognition and uncovered a highly-organized internal structure of ensemble activity patterns. This emergent structure allowed defining for each neuron an ‘internal tuning-curve’ that characterizes its activity relative to the network activity, rather than relative to any predefined external variable, revealing place-tuning and head-direction tuning without relying on measurements of place or head-direction. Similar investigation in prefrontal cortex revealed schematic representations of distances and actions, and exposed a previously unknown variable, the ‘trajectory-phase’. The internal structure was conserved across mice, allowing using one animal’s data to decode another animal’s behavior. Thus, the internal structure of neuronal activity itself enables reconstructing internal representations and discovering new behavioral variables hidden within a neural code.
Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors
Authors: Powers Rani K. , Culp-Hill Rachel , Ludwig Michael P. , Smith Keith P. , Waugh Katherine A. , Minter Ross , Tuttle Kathryn D. , Lewis Hannah C. , Rachubinski Angela L. , Granrath Ross E. , Carmona-Iragui María , Wilkerson Rebecca B. , Kahn Darcy E. , Joshi Molishree , Lleó Alberto , Blesa Rafael , Fortea Juan , D’Alessandro Angelo , Costello James C. , Sullivan Kelly D. , Espinosa Joaquin M.
Published: October 2019

Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpressIDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression ofIFNreceptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causingIDO1overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS.
Green oxidation of indoles using halide catalysis
Authors: Xu Jun , Liang Lixin , Zheng Haohao , Chi Yonggui Robin , Tong Rongbiao
Published: October 2019

Oxidation of indoles is a fundamental organic transformation to deliver a variety of synthetically and pharmaceutically valuable nitrogen-containing compounds. Prior methods require the use of either organic oxidants (meta-chloroperoxybenzoic acid, N-bromosuccinimide,t-BuOCl) or stoichiometric toxic transition metals [Pb(OAc)4, OsO4, CrO3], which produced oxidant-derived by-products that are harmful to human health, pollute the environment and entail immediate purification. A general catalysis protocol using safer oxidants (H2O2, oxone, O2) is highly desirable. Herein, we report a unified, efficient halide catalysis for three oxidation reactions of indoles using oxone as the terminal oxidant, namely oxidative rearrangement of tetrahydro-β-carbolines, indole oxidation to 2-oxindoles, and Witkop oxidation. This halide catalysis protocol represents a general, green oxidation method and is expected to be used widely due to several advantageous aspects including waste prevention, less hazardous chemical synthesis, and sustainable halide catalysis.
Multidecade Mortality and a Homolog of Hepatitis C Virus in Bald Eagles (Haliaeetus leucocephalus), the National Bird of the USA
Authors: Goldberg Tony L. , Sibley Samuel D. , Pinkerton Marie E. , Dunn Christopher D. , Long Lindsey J. , White LeAnn C. , Strom Sean M.
Published: October 2019

The bald eagle (Haliaeetus leucocephalus) once experienced near-extinction but has since rebounded. For decades, bald eagles near the Wisconsin River, USA, have experienced a lethal syndrome with characteristic clinical and pathological features but unknown etiology. Here, we describe a novel hepacivirus-like virus (Flaviviridae: Hepacivirus) identified during an investigation of Wisconsin River eagle syndrome (WRES). Bald eagle hepacivirus (BeHV) belongs to a divergent clade of avian viruses that share features with members of the genera Hepacivirus and Pegivirus. BeHV infected 31.9% of eagles spanning 4,254 km of the coterminous USA, with negative strand viral RNA demonstrating active replication in liver tissues. Eagles from Wisconsin were approximately 10-fold more likely to be infected than eagles from elsewhere. Eagle mitochondrial DNA sequences were homogeneous and geographically unstructured, likely reflecting a recent population bottleneck, whereas BeHV envelope gene sequences showed strong population genetic substructure and isolation by distance, suggesting localized transmission. Cophylogenetic analyses showed no congruity between eagles and their viruses, supporting horizontal rather than vertical transmission. These results expand our knowledge of the Flaviviridae, reveal a striking pattern of decoupled host/virus coevolution on a continental scale, and highlight knowledge gaps about health and conservation in even the most iconic of wildlife species.
Testing the competition-colonization trade-off and its correlations with functional trait variations among subtropical tree species
Authors: Bin Yue , Lin Guojun , Russo Sabrina E. , Huang Zhongliang , Shen Yong , Cao Honglin , Lian Juyu , Ye Wanhui
Published: October 2019

The competition-colonization trade-off, by which species can partition spatial niches, is a potentially important mechanism allowing the maintenance of species diversity in plant communities. We examined whether there was evidence for this trade-off among tree species in a subtropical forest and how it correlated with eight functional traits. We developed and estimated a metric for colonization ability that incorporates both fecundity and seed dispersal based on seed trap data and the sizes and distributions of adult trees. Competitive ability was estimated as survival probability under high crowding conditions based on neighborhood models. Although we found no significant relationship between colonization and competitive abilities, there was a significant negative correlation between long distance dispersal ability and competitive ability at the 5 cm size class. Colonizers had traits associated with faster growth, such as large leaves and low leaf lamina density, whereas competitors had traits associated with higher survival, such as dense wood. Our results imply that any trade-off between competition and colonization may be more determined by dispersal ability than by fecundity, suggesting that seed dispersal is an important contributor to diversity maintenance. Future work should test how competitive ability covaries with the components of colonization ability, as we did here.
Relationship between Vision-Related Quality of Life and Central 10° of the Binocular Integrated Visual Field in Advanced Glaucoma
Authors: Yamazaki Yoshio , Sugisaki Kenji , Araie Makoto , Murata Hiroshi , Kanamori Akiyasu , Inoue Toshihiro , Ishikawa Shinichiro , Yoshikawa Keiji , Maeda Hidetaka , Yamada Yuko , Negi Akira , Inatani Masaru , Tanihara Hidenobu , Okinami Satoshi , Mizuki Kenji , Mishima Koichi , Uchida Kenichi , Matsumoto Shun
Published: October 2019

To investigate the relationships between sensitivity loss in various subfields of the central 10° of the binocular integrated visual field (IVF) and vision-related quality of life (VRQoL) in 172 patients with advanced glaucoma. Using the Random Forest algorithm, which controls for inter-correlations among various subfields of the IVF, we analysed the relationships among the Rasch analysis-derived person ability index (RADPAI), age, best-corrected visual acuity (BCVA), mean total deviations (mTDs) of eight quadrant subfields in the IVF measured with the Humphrey Field Analyzer (HFA) 10-2 program (10-2 IVF), and mTDs of the upper/lower hemifields in the IVF measured with the HFA 24-2 program (24-2 IVF). Significant contributors to RADPAIs were as follows: the inner and outer lower-right quadrants of the 10-2 IVF contributed to the dining and total tasks; the lower-left quadrant of the 10-2 IVF contributed to the walking, going out and total tasks; the lower hemifield of the 24-2 IVF contributed to the walking, going out, dining, miscellaneous and total tasks; and BCVA contributed more to the letter, sentence, dressing and miscellaneous tasks than to others. The impact of damage in different 10-2 IVF subfields differed significantly across daily tasks in patients with advanced glaucoma.
Ultraviolet and Infrared luminescent Au-rich nanostructure growth in SiO2 by burrowing and inverse Oswald ripening process
Authors: Datta D. P. , Chettah A. , Maiti Arpan , Satpati B. , Sahoo P. K.
Published: October 2019

We study the evolution of nanoparticle morphology through successive stages when Au-Si bilayer on SiO2 is irradiated with 500 keV Xe-ions and resulting luminescence in the UV, Visible and infrared range. An array of nanoscale island morphology is developed on the silica surface in the initial stage of evolution which undergoes gradual burrowing in the silica matrix accompanied by elongation of large ones in the direction of incident ions under cumulative ion irradiation. Burrowing is found to occur in order to minimize the surface free energy of the nanoparticles. Numerical simulation based on the unified thermal spike model shows formation of molten latent tracks due to ions energy release which drive the dewetting of the metal layer and further give mobility to nanoparticle atoms leading to burrowing in the later stage of evolution and elongation of large nanoparticles. Satellite nanoparticles are observed to grow around Au nanoparticles embedded in silica through nucleation of Au atoms dissolved in the matrix by incident ions. The varying diameters of the Au satellite nanoparticles seem to result in luminescence in the UV and infrared range. The observed structure may find application in surface enhanced Raman scattering, catalysis, and LEDs.
Positive non-linear capacitance: the origin of the steep subthreshold-slope in ferroelectric FETs
Authors: Alam Md Nur K. , Roussel P. , Heyns M. , Van Houdt J.
Published: October 2019

We show that the non-linear positive capacitance (PC) of ferroelectrics (FE) can explain the steep subthreshold-slope (SS) observed in FE based MOSFETs and often attributed to the existence of a negative capacitance in FE capacitors. Physically attainable and unattainable regions of the S-shape curve used in the negative capacitance theory are investigated by self-consistently solving Landau-Khalatnikov and Maxwell equations and by experimental validation. Finally, the conditions for attaining a steep SS in FE based MOSFETs assuming only positive capacitances are discussed.
Laboratory Study Phenomenon of Coal and Gas Outburst Based on a Mid-scale Simulation System
Authors: Nie Baisheng , Ma Yankun , Hu Shoutao , Meng Junqing
Published: October 2019

Outburst simulation experiments facilitate understanding coal and gas outburst in underground mining. With the help of the mid-scale simulation system, a model based on similitude principle, coal seam sandwiched by roof and floor, was constructed to conduct an outburst experiment. It had a three-dimensional size of 1500 mm × 600 mm × 1000 mm with 0.5 MPa gas pressure. The experimental procedures include specimen preparation, moulding, sealing, gas charging and adsorption, and completion. The outburst process was investigated by analyzing the gas pressure variation, temperature variation, outburst propagation velocity, particle size of outburst coal and energy transformation. During the experiment, each gas charging was accompanied with gas pressure or temperature fluctuation because of coal behavior of gas adsorption-desorption. The outburst propagation velocity was 17.2 m/s, obtained by a mass-weighted calculation of velocities of outburst coal. The small-size coal particles have a higher desorption rate and tend to participate in outburst process. According to energy conservation law, the energy forms of the outburst included elastic strain energy (Ee), gas expansion energy (Ep), internal energy of coal (ΔU), breakage work (W1), throwing out work (W2) and gas-flow loss energy (ΔE), and each was calculated respectively. Gas potential energy, including gas expansion energy and internal energy of coal, registered a larger percent and was far greater than the strain energy. And it can be the main factor influencing the occurrence of low-threshold outburst. The experimental system provides a feasible way to study the initiation and evolution of coal and gas outbursts.
Quantum speedup, non-Markovianity and formation of bound state
Authors: Ahansaz Bahram , Ektesabi Abbas
Published: October 2019

In this paper, we investigate the relationship between the quantum speedup, non-Markovianity and formation of a system-environment bound state. Previous results show a monotonic relation between these three such that providing bound states with more negative energy can lead to a higher degree of non-Markovianity, and hence to a greater speed of quantum evolution. By studying dynamics of a dissipative two-level system or a V-type three-level system, when similar and additional systems are present, we reveal that the quantum speedup is exclusively related to the formation of the system-environment bound state, while the non-Markovian effect of the system dynamics is neither necessary nor sufficient to speed up the quantum evolution. On the other hand, it is shown that only the formation of the system-environment bound state plays a decisive role in the acceleration of the quantum evolution.
Accuracy of proton magnetic resonance for diagnosing non-alcoholic steatohepatitis: a meta-analysis
Authors: Kim Tae-Hoon , Jeong Chang-Won , Jun Hong Young , Lee ChungSub , Noh SiHyeong , Kim Ji Eon , Kim SeungJin , Yoon Kwon-Ha
Published: October 2019

Liver biopsy is the reference standard test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) in non-alcoholic fatty liver disease (NAFLD), but noninvasive diagnostics are warranted. The diagnostic accuracy in NASH using MR imaging modality have not yet been clearly identified. This study was assessed the accuracy of magnetic resonance imaging (MRI) method for diagnosing NASH. Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area under the receiver operating characteristic(ROC) curve, sensitivity, specificity, likelihood ratios(LR), diagnostic odds ratio(DOR) of MRI method in detecting histopathologically-proven SS(or non-NASH) and NASH. Seven studies were analyzed 485 patients, which included 207 SS and 278 NASH. The pooled sensitivity was 87.4% (95% CI, 76.4–95.3) and specificity was 74.3% (95% CI, 62.4–84.6). Pooled positive LR was 2.59 (95% CI, 1.96–3.42) and negative LR was 0.17 (95% CI, 0.07–0.38). DOR was 21.57 (95% CI, 7.27–63.99). The area under the curve of summary ROC was 0.89. Our meta-analysis shows that the MRI-based diagnostic methods are valuable additions in detecting NASH.
An improved method for the calculation of unsaturated–saturated water flow by coupling the FEM and FDM
Authors: Gao Yulong , Pu Shengyan , Zheng Chunmiao , Yi Shuping
Published: October 2019

Numerical modeling of water movement in both unsaturated soils and saturated groundwater aquifers is important for water resource management simulations. The development of efficient numerical algorithms for coupling unsaturated and saturated flow has been a long-lasting challenge in hydrologic modeling, especially for regional-scale modeling. In this study, a new method coupling the Finite Element Method (FEM) and Finite Difference Method (FDM), FE-FDM, is developed to solve Richards equation for simulating unsaturated–saturated water flow. The FEM is adopted to discretize the governing equation in the horizontal direction, while the FDM is used in the vertical direction. This method combines the advantages of FEM in domain discretization, especially for complex computational domain, and the advantages of FDM in modeling simplicity and efficiency. The validity of the new method is demonstrated with three test cases that show that the FE-FDM solutions are accurate and are applicable for regional scale problems. In the test cases, the FE-FDM solutions are compared with experimental data and numerical results calculated with common software packages including FEFLOW and COMSOL. This study verified that the FE-FDM is applicable for simulating water flow in the unsaturated–saturated zone.
X-ray phase contrast imaging of Vitis spp. buds shows freezing pattern and correlation between volume and cold hardiness
Authors: Kovaleski Alisson P. , Londo Jason P. , Finkelstein Kenneth D.
Published: October 2019

Grapevine (Vitisspp.) buds must survive winter temperatures in order to resume growth when suitable conditions return in spring. They do so by developing cold hardiness through deep supercooling, but the mechanistic process of supercooling in buds remains largely unknown. Here we use synchrotron X-ray phase contrast imaging to study cold hardiness-related characteristics ofV. amurensis,V. riparia, andV. viniferabuds: time-resolved 2D imaging was used to visualize freezing; and microtomography was used to evaluate morphological changes during deacclimation. Bud cold hardiness was determined (low temperature exotherms; LTEs) using needle thermocouples during 2D imaging as buds were cooled with a N2gas cryostream. Resolution in 2D imaging did not allow for ice crystal identification, but freezing was assessed by movement of tissues coinciding with LTE values. Freezing was observed to propagate from the center of the bud toward the outer bud scales. The freezing events observed lasted several minutes. Additionally, loss of supercooling ability appears to be correlated with increases in bud tissue volume during the process of deacclimation, but major increases in volume occur after most of the supercooling ability is lost, suggesting growth resumption processes are limited by deacclimation state.
Storage media and not extraction method has the biggest impact on recovery of bacteria from the oral microbiome
Authors: Zhou Xiaoyan , Nanayakkara Shanika , Gao Jin-Long , Nguyen Ky-Anh , Adler Christina J.
Published: October 2019

Next Generation sequencing has greatly progressed the exploration of the oral microbiome’s role in dental diseases, however, there has been little focus on the effect of sample storage conditions and their interaction with DNA extraction method. Dental plaque samples collected from 20 healthy participants were pooled and stored in either 75% ethanol or Bead solution for up to 6-months at −80 °C, prior to DNA extraction with either QIAamp (non-bead beating) or PowerSoil (bead-beating) kit, followed by Illumina sequencing of 16S rRNA gene. We found that storage media and not extraction method had the biggest influence on the diversity and abundance of the oral microbiota recovered. Samples stored in Bead solution, independent of the extraction kit, retrieved higher diversity (PowerSoil p = 1.64E-07, QIAamp p = 0.0085) and had dissimilar overall ecologies as indicated by lower level of shared diversity (PowerSoil p = 0.0000237, QIAamp p = 0.0088). Comparatively, samples stored in Bead solution and extracted with PowerSoil recovered a higher abundance of Streptococcus species. These data indicate that Bead solution can preserve the oral microbiome in dental plaque reliably, for periods of up to 6-months at −80 °C, and is compatible, with either a bead-beating or non-bead beating DNA extraction method.
Free-space data-carrying bendable light communications
Authors: Zhu Long , Wang Andong , Wang Jian
Published: October 2019

Bendable light beams have recently seen tremendous applications in optical manipulation, optical imaging, optical routing, micromachining, plasma generation and nonlinear optics. By exploiting curved light beams instead of traditional Gaussian beam for line-of-sight light communications, here we propose and demonstrate the viability of free-space data-carrying bendable light communications along arbitrary trajectories with multiple functionalities. By employing 39.06-Gbit/s 32-ary quadrature amplitude modulation (32-QAM) discrete multi-tone (DMT) signal, we demonstrate free-space bendable light intensity modulated direct detection (IM-DD) communication system under 3 different curved light paths. Moreover, we characterize multiple functionalities of free-space bendable light communications, including bypass obstructions transmission, self-healing transmission, self-broken trajectory transmission, and multi-receiver transmission. The observed results indicate that bendable light beams can make free-space optical communications more flexible, more robust and more multifunctional. The demonstrations may open a door to explore more special light beams enabling advanced free-space light communications with enhanced flexibility, robustness and functionality.
Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates
Authors: Eriksson Olof , Velikyan Irina , Haack Torsten , Bossart Martin , Evers Andreas , Laitinen Iina , Larsen Philip J. , Plettenburg Oliver , Takano Akihiro , Halldin Christer , Antoni Gunnar , Johansson Lars , Pierrou Stefan , Wagner Michael
Published: October 2019

The glucagon receptor (GCGR) is an emerging target in anti-diabetic therapy. Reliable biomarkers for in vivo activity on the GCGR, in the setting of dual glucagon-like peptide 1/glucagon (GLP-1/GCG) receptor agonism, are currently unavailable. Here, we investigated [68Ga]Ga-DO3A-S01-GCG as a biomarker for GCGR occupancy in liver, the tissue with highest GCGR expression, in non-human primates (NHP) by PET. [68Ga]Ga-DO3A-S01-GCG was evaluated by dynamic PET in NHPs by a dose escalation study design, where up to 67 µg/kg DO3A-S01-GCG peptide mass was co-injected. The test-retest reproducibility of [68Ga]Ga-DO3A-S01-GCG binding in liver was evaluated. Furthermore, we investigated the effect of pre-treatment with acylated glucagon agonist 1-GCG on [68Ga]Ga-DO3A-S01-GCG binding in liver. [68Ga]Ga-DO3A-S01-GCG bound to liver in vivo in a dose-dependent manner. Negligible peptide mass effect was observed for DO3A-S01-GCG doses <0.2 µg/kg. In vivo Kd for [68Ga]Ga-DO3A-S01-GCG corresponded to 0.7 µg/kg, which indicates high potency. The test-retest reproducibility for [68Ga]Ga-DO3A-S01-GCG binding in liver was 5.7 ± 7.9%. Pre-treatment with 1-GCG, an acylated glucagon agonist, resulted in a GCGR occupancy of 61.5 ± 9.1% in liver. Predicted human radiation dosimetry would allow for repeated annual [68Ga]Ga-DO3A-S01-GCG PET examinations. In summary, PET radioligand [68Ga]Ga-DO3A-S01-GCG is a quantitative biomarker of in vivo GCGR occupancy.
Simultaneous electrophysiological and morphological assessment of functional damage to neural networks in vitro after 30–300 g impacts
Authors: Rogers Edmond A. , Gross Guenter W.
Published: October 2019

An enigma of mild traumatic brain injury are observations of substantial behavior and performance deficits in the absence of bleeding or other observable structural damage. Altered behavior and performance reflect changes in action potential (AP) patterns within neuronal networks, which could result from subtle subcellular responses that affect synaptic efficacy and AP production. The aim of this study was to investigate and quantify network activity changes after simulated concussions in vitro and therewith develop a platform for simultaneous and direct observations of morphological and electrophysiological changes in neural networks. We used spontaneously active networks grown on microelectrode arrays (MEAs) to allow long-term multisite monitoring with simultaneous optical observations before and after impacts delivered by a ballistic pendulum (30 to 300 g accelerations). The monitoring of AP waveshape templates for long periods before and after impact provided an internal control for cell death or loss of cell-electrode coupling in the observed set of neurons. Network activity patterns were linked in real-time to high power phase contrast microscopy. There was no overt loss of glial or neuronal adhesion, even at high-g impacts. All recording experiments showed repeatable spike production responses: a loss of activity with recovery to near reference in 1 hr, followed by a slow activity decay to a stable, level plateau approximately 30–40% below reference. The initial recovery occurred in two steps: a rapid return of activity to an average 24% below reference, forming a level plateau lasting from 5 to 20 min, followed by a climb to within 10% of reference where a second plateau was established for 1 to 2 hrs. Cross correlation profiles revealed changes in firing hierarchy as well as in Phase 1 in spontaneous network oscillations that were reduced by as much as 20% 6–8 min post impact with only a partial recovery at 30 min. We also observed that normally stable nuclei developed irregular rotational motion after impact in 27 out of 30 networks. The evolution of network activity deficits and recovery can be linked with microscopically observable changes in the very cells that are generating the activity. The repeatable electrophysiological impact response profiles and oscillation changes can provide a quantitative basis for systematic evaluations of pharmacological intervention strategies. Future expansion to include fluorescent microscopy should allow detailed investigations of damage mechanisms on the subcellular level.
Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study
Authors: Vane Matheus F. , Carmona Maria J. C. , Pereira Sergio M. , Kern Karl B. , Timerman Sérgio , Perez Guilherme , Vane Luiz Antonio , Otsuki Denise Aya , Auler Jr José O. C.
Published: October 2019

Data on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80–0.93]), with a sensitivity and specificity of 78.4% [69.6–86.3%] and 89.3% [80.4–96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792–0.956]), with a sensitivity of 79.3% [65.5–93.1%] and specificity of 86.1 [74.4–95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.
Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish
Authors: Brun Nadja R. , van Hage Patrick , Hunting Ellard R. , Haramis Anna-Pavlina G. , Vink Suzanne C. , Vijver Martina G. , Schaaf Marcel J. M. , Tudorache Christian
Published: October 2019

Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.
Structural characterization of HypX responsible for CO biosynthesis in the maturation of NiFe-hydrogenase
Authors: Muraki Norifumi , Ishii Kentaro , Uchiyama Susumu , Itoh Satoru G. , Okumura Hisashi , Aono Shigetoshi
Published: October 2019

Several accessory proteins are required for the assembly of the metal centers in hydrogenases. In NiFe-hydrogenases, CO and CN− are coordinated to the Fe in the NiFe dinuclear cluster of the active center. Though these diatomic ligands are biosynthesized enzymatically, detail mechanisms of their biosynthesis remain unclear. Here, we report the structural characterization of HypX responsible for CO biosynthesis to assemble the active site of NiFe hydrogenase. CoA is constitutionally bound in HypX. Structural characterization of HypX suggests that the formyl-group transfer will take place from N10-formyl-THF to CoA to form formyl-CoA in the N-terminal domain of HypX, followed by decarbonylation of formyl-CoA to produce CO in the C-terminal domain though the direct experimental results are not available yet. The conformation of CoA accommodated in the continuous cavity connecting the N- and C-terminal domains will interconvert between the extended and the folded conformations for HypX catalysis.
Carbon Based Thermoelectric Materials
Authors: Malik Iram , Kar Kamal K.
Published: October 2019

In this chapter, thermoelectric (TE) properties of carbon-based nanomaterials especially graphene, carbon nanotubes (CNT) and their composites have been investigated. The high electrical conductivity of CNT/graphene and low thermal conductivity of other TE materials like Bi2Te3, Cu2Se, Mg2Si, SnSe, etc. and polymer materials help in achieving improved TE properties. But at the same time, the low Seebeck coefficient of carbon nanomaterials has degrading effects on the overall TE properties of material. A comparative study has been done for different carbon-based nanomaterials used as TE materials or in a TE composite. The idea of using carbon-based nanomaterials in TE materials is attractive due to their non-toxic nature, abundance and the particularly extraordinary properties of these nanomaterials, like very high electrical conductivity, modulus, strength, etc. However, high thermal conductivity and low Seebeck coefficient are not desirable and to improve these properties different strategies are used like defect engineering, introducing strain, creating additional interfaces, boundaries, other phonon scattering points, etc. In addition to these strategies, these carbon-based materials can be used with other low thermal conductivity and high Seebeck coefficient materials as composites to utilize their high electrical conductivity and to improve the figure of merit of TE materials.
Retraction: Ni2[LnCl6] (Ln = EuII, CeII, GdII): the first LnII compounds stabilized in a pure inorganic lattice
Authors: Baldo Bianca , Rubio Francisco , Flores Erwin , Vega Andres , Audebrand Nathalie , Venegas-Yazigi Diego , Paredes-García Verónica
Published: October 2019

Retraction of ‘Ni2[LnCl6] (Ln = EuII, CeII, GdII): the first LnII compounds stabilized in a pure inorganic lattice’ by Bianca Baldo et al., Chem. Commun., 2018, 54, 7531–7534.
Photo/electrocatalysis and photosensitization using metal nanoclusters for green energy and medical applications
Authors: Kawawaki Tokuhisa , Negishi Yuichi , Kawasaki Hideya
Published: October 2019

This review summarizes recent developments in the photo/electro catalytic and photosensitizing characteristics of metal and alloy NCs for green energy and medical applications.
Synthesis of sub-micrometer biphasic Au–AuGa2/liquid metal frameworks
Authors: David Romain , Miki Norihisa
Published: October 2019

Biphasic Au nanoparticle–liquid metal shell–core sub-micrometer droplets are synthesized with fine control of the nanoparticle morphology, composition and crystal structure.
Asymmetric amination of α,α-dialkyl substituted aldehydes catalyzed by a simple chiral primary amino acid and its application to the preparation of a S1P1 agonist
Authors: Xiao Qiong , Tang Yifan , Xie Ping , Yin Dali
Published: October 2019

The chiral catalytic amination of an α,α-dialkyl substituted aldehyde usually proceeds with low enantioselectivity.
In situ K2S activated electrospun carbon nanofibers with hierarchical meso/microporous structures for supercapacitors
Authors: Liu Hua , Song Weiguo , Xing Aihua
Published: October 2019

K2S was found to be an excellent in situ activation agent for the fabrication of electrospun carbon nanofibers with large surface area (835.0 m2 g−1) and hierarchical meso/microporous structures.
Multigram-scale flow synthesis of the chiral key intermediate of (−)-paroxetine enabled by solvent-free heterogeneous organocatalysis
Authors: Ötvös Sándor B. , Pericàs Miquel A. , Kappe C. Oliver
Published: October 2019

The continuous flow synthesis of the chiral key intermediate of (−)-paroxetine is demonstrated via a solvent-free organocatalytic conjugate addition followed by a telescoped reductive amination–lactamization–amide/ester reduction sequence.
Non-monotonic dependence of stiffness on actin crosslinking in cytoskeleton composites
Authors: Francis Madison L. , Ricketts Shea N. , Farhadi Leila , Rust Michael J. , Das Moumita , Ross Jennifer L. , Robertson-Anderson Rae M.
Published: October 2019

We use optical tweezers microrheology and fluorescence confocal microscopy to reveal that the stiffness of actin-microtubule composites displays a surprising non-monotonic dependence on actin crosslinking which is driven by microtubule mobility.
Cavitation, crazing and bond scission in chemically cross-linked polymer nanocomposites
Authors: Zhang Huan , Li Haoxiang , Hu Fengyan , Wang Wencai , Zhao Xiuying , Gao Yangyang , Zhang Liqun
Published: October 2019

It is very important to understand the molecular mechanism of the fracture behavior of chemically cross-linked polymer nanocomposites (PNCs).
Molecular motifs encoding self-assembly of peptide fibers into molecular gels
Authors: Lan Yaqi , Lv Muwen , Guo Shenglan , Nasr Pedram , Ladizhansky Vladimir , Vaz Raoul , Corradini Maria G. , Hou Tao , Ghazani Saeed M. , Marnangoni Alejandro , Rogers Michael A.
Published: October 2019

Peptides are a promising class of gelators, due to their structural simplicity, biocompatibility and versatility.
Assembling polymeric silver nanowires for transparent conductive cellulose nanopaper
Authors: Su Yongxiang , Yuan Shuai , Cao Shaomei , Miao Miao , Shi Liyi , Feng Xin
Published: October 2019

Transparent conductive nanopaper was assembled by using PEDOT:PSS enhanced AgNW networks adsorbed on polydopamine functionalized nanocellulose.
A new promising way for tackling the ‘Pharma Dilemma’: artificial intelligence for clinical trials
Authors: Harrer Stefan , Antony Bhavna , Bayat Akram , Hu Jianying
Published: October 2019

Artificial intelligence (AI) is certainly not a panacea for solving the ‘Pharma Dilemma’, in which the cost of producing new drugs continues to spiral. However, AI can be used to fundamentally change the way we perform essential steps in clinical trial design and execution, from cohort selection to patient monitoring. Merging AI and clinical expertise across engineering and medical disciplines to explore the impact of these changes on trial performance and success rates is one of the most promising leads we have for restoring efficiency and sustainability to the drug development cycle.
Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix
Authors: Cui Lingjuan , Jiang Xiaoyan , Zhang Chengjun , Li Danxia , Yu Shengqiang , Wan Fengchun , Ma Yue , Guo Wei , Shan Zhengfei
Published: October 2019

Many clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.
A novel missense variant c.G644A (p.G215E) of the RPGR gene in a Chinese family causes X-linked retinitis pigmentosa
Authors: Fu Jiewen , Cheng Jingliang , Zhou Qi , Wei Chunli , Chen Hanchun , Lv Hongbin , Fu Junjiang
Published: October 2019

The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.