bluuebunny/crossref_metadata_2025 huggingface dataset:
The PI3K inhibitor copanlisib synergizes with sorafenib to induce cell death in hepatocellular carcinoma
Authors: Ye Liangtao , Mayerle Julia , Ziesch Andreas , Reiter Florian P. , Gerbes Alexander L. , De Toni Enrico N.
Published: April 2019

Sorafenib, a multikinase inhibitor targeting the Ras/Raf/MAPK (mitogen-activated protein kinase) and vascular endothelial growth factor signaling pathways is an established treatment option for patients with advanced-stage hepatocellular carcinoma (HCC); however, despite its clinical benefit, chemoresistance and disease progression eventually occur almost invariably during treatment. Activation of the PI3K/AKT (phosphatidylinositol-3-kinase/serine/threonine kinase) pathway plays a role in the pathogenesis of HCC and may contribute to determine resistance to sorafenib. We thus evaluated in vitro the effects of the combination of sorafenib and copanlisib, a PI3K inhibitor recently approved for clinical use. The effects of copanlisib alone and in combination with sorafenib were assessed in several HCC cell lines by proliferation and colony formation assays, fluorescence-activated cell sorting analyses, and western blot. In addition, sorafenib-resistant cell clones were used. Copanlisib strongly reduced cell viability and colony formation in different native and sorafenib-resistant HCC cell lines by affecting cyclin D1/CDK4/6 signaling and causing cell cycle arrest. Elevation of phosphorylated (p)-AKT was observed upon incubation with sorafenib and was consistently found in six different unstimulated sorafenib-resistant cell clones. Copanlisib counteracted sorafenib-induced phosphorylation of p-AKT and synergistically potentiated its antineoplastic effect. In summary, copanlisib shows potent anticancer activity as a single agent and acts synergistically in combination with sorafenib in human HCC. Combination of sorafenib with copanlisib represents a rational potential therapeutic option for advanced HCC.
Bridge ties bind collective memories
Authors: Momennejad Ida , Duker Ajua , Coman Alin
Published: April 2019

From families to nations, what binds individuals in social groups is, to a large degree, their shared beliefs, norms, and memories. These emergent outcomes are thought to occur because communication among individuals results in community-wide synchronization. Here, we use experimental manipulations in lab-created networks to investigate how the temporal dynamics of conversations shape the formation of collective memories. We show that when individuals that bridge between clusters (i.e., bridge ties) communicate early on in a series of networked interactions, the network reaches higher mnemonic convergence compared to when individuals first interact within clusters (i.e., cluster ties). This effect, we show, is due to the tradeoffs between initial information diversity and accumulated overlap over time. Our approach provides a framework to analyze and design interventions in social networks that optimize information sharing and diminish the likelihood of information bubbles and polarization.
Strong neuron-to-body coupling implies weak neuron-to-neuron coupling in motor cortex
Authors: Kells Patrick A. , Gautam Shree Hari , Fakhraei Leila , Li Jingwen , Shew Woodrow L.
Published: April 2019

Cortical neurons can be strongly or weakly coupled to the network in which they are embedded, firing in sync with the majority or firing independently. Both these scenarios have potential computational advantages in motor cortex. Commands to the body might be more robustly conveyed by a strongly coupled population, whereas a motor code with greater information capacity could be implemented by neurons that fire more independently. Which of these scenarios prevails? Here we measure neuron-to-body coupling and neuron-to-population coupling for neurons in motor cortex of freely moving rats. We find that neurons with high and low population coupling coexist, and that population coupling was tunable by manipulating inhibitory signaling. Importantly, neurons with different population coupling tend to serve different functional roles. Those with strong population coupling are not involved with body movement. In contrast, neurons with high neuron-to-body coupling are weakly coupled to other neurons in the cortical population.
On the computational complexity of curing non-stoquastic Hamiltonians
Authors: Marvian Milad , Lidar Daniel A. , Hen Itay
Published: April 2019

Quantum many-body systems whose Hamiltonians are non-stoquastic, i.e., have positive off-diagonal matrix elements in a given basis, are known to pose severe limitations on the efficiency of Quantum Monte Carlo algorithms designed to simulate them, due to the infamous sign problem. We study the computational complexity associated with ‘curing’ non-stoquastic Hamiltonians, i.e., transforming them into sign-problem-free ones. We prove that if such transformations are limited to single-qubit Clifford group elements or general single-qubit orthogonal matrices, finding the curing transformation is NP-complete. We discuss the implications of this result.
A revised biosynthetic pathway for the cofactor F420 in prokaryotes
Authors: Bashiri Ghader , Antoney James , Jirgis Ehab N. M. , Shah Mihir V. , Ney Blair , Copp Janine , Stuteley Stephanie M. , Sreebhavan Sreevalsan , Palmer Brian , Middleditch Martin , Tokuriki Nobuhiko , Greening Chris , Scott Colin , Baker Edward N. , Jackson Colin J.
Published: April 2019

Cofactor F420 plays critical roles in primary and secondary metabolism in a range of bacteria and archaea as a low-potential hydride transfer agent. It mediates a variety of important redox transformations involved in bacterial persistence, antibiotic biosynthesis, pro-drug activation and methanogenesis. However, the biosynthetic pathway for F420 has not been fully elucidated: neither the enzyme that generates the putative intermediate 2-phospho-l-lactate, nor the function of the FMN-binding C-terminal domain of the γ-glutamyl ligase (FbiB) in bacteria are known. Here we present the structure of the guanylyltransferase FbiD and show that, along with its archaeal homolog CofC, it accepts phosphoenolpyruvate, rather than 2-phospho-l-lactate, as the substrate, leading to the formation of the previously uncharacterized intermediate dehydro-F420-0. The C-terminal domain of FbiB then utilizes FMNH2 to reduce dehydro-F420-0, which produces mature F420 species when combined with the γ-glutamyl ligase activity of the N-terminal domain. These new insights have allowed the heterologous production of F420 from a recombinant F420 biosynthetic pathway in Escherichia coli.
Root traits and belowground herbivores relate to plant–soil feedback variation among congeners
Authors: Wilschut Rutger A. , van der Putten Wim H. , Garbeva Paolina , Harkes Paula , Konings Wouter , Kulkarni Purva , Martens Henk , Geisen Stefan
Published: April 2019

Plant–soil feedbacks contribute to vegetation dynamics by species-specific interactions between plants and soil biota. Variation in plant–soil feedbacks can be predicted by root traits, successional position, and plant nativeness. However, it is unknown whether closely related plant species develop more similar plant–soil feedbacks than more distantly related species. Where previous comparisons included plant species from distant phylogenetic positions, we studied plant–soil feedbacks of congeneric species. Using eight intra-continentally range-expanding and nativeGeraniumspecies, we tested relations between phylogenetic distances, chemical and structural root traits, root microbiomes, and plant–soil feedbacks. We show that root chemistry and specific root length better predict bacterial and fungal community composition than phylogenetic distance. Negative plant–soil feedback strength correlates with root-feeding nematode numbers, whereas microbiome dissimilarity, nativeness, or phylogeny does not predict plant–soil feedbacks. We conclude that root microbiome variation among congeners is best explained by root traits, and that root-feeding nematode abundances predict plant–soil feedbacks.
Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks
Authors: Ha Geun-Hyoung , Ji Jae-Hoon , Chae Sunyoung , Park Jihyun , Kim Suhyeon , Lee Jin-Kwan , Kim Yonghyeon , Min Sunwoo , Park Jeong-Min , Kang Tae-Hong , Lee Ho , Cho Hyeseong , Lee Chang-Woo
Published: April 2019

DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.
NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients
Authors: Jandrey Elisa H. F. , Moura Ricardo P. , Andrade Luciana N. S. , Machado Camila L. , Campesato Luiz Felipe , Leite Katia Ramos M. , Inoue Lilian T. , Asprino Paula F. , da Silva Ana Paula M. , de Barros Alfredo Carlos S. D. , Carvalho Andre , de Lima Vladmir C. , Carraro Dirce M. , Brentani Helena P. , da Cunha Isabela W. , Soares Fernando A. , Parmigiani Raphael B. , Chammas Roger , Camargo Anamaria A. , Costa Érico T.
Published: April 2019

The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20–30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response. Here, we present N-Myc downstream-regulated gene 4 (NDRG4) epigenetic silencing as a mechanistic biomarker of metastasis in ductal invasive breast tumors. While aberrant NDRG4 DNA hypermethylation is significantly associated with the development of metastatic disease, downregulation of NDRG4 transcription and protein expression is functionally associated with enhanced lymph node adhesion and cell mobility. Here, we show that epigenetic silencing of NDRG4 modulates integrin signaling by assembling β1-integrins into large punctate clusters at the leading edge of tumor cells to promote an “adhesive switch,” decreasing cell adhesion to fibronectin and increasing cell adhesion and migration towards vitronectin, an important component of human lymph nodes. Taken together, our functional and clinical observations suggest that NDRG4 is a potential mechanistic biomarker in breast cancer that is functionally associated with metastatic disease.
Heavy ion ranges from first-principles electron dynamics
Authors: Sand Andrea E. , Ullah Rafi , Correa Alfredo A.
Published: April 2019

The effects of incident energetic particles, and the modification of materials under irradiation, are governed by the mechanisms of energy losses of ions in matter. The complex processes affecting projectiles spanning many orders of magnitude in energy depend on both ion and electron interactions. Developing multi-scale modeling methods that correctly capture the relevant processes is crucial for predicting radiation effects in diverse conditions. In this work, we obtain channeling ion ranges for tungsten, a prototypical heavy ion, by explicitly simulating ion trajectories with a method that takes into account both the nuclear and the electronic stopping power. The electronic stopping power of self-ion irradiated tungsten is obtained from first-principles time-dependent density functional theory (TDDFT). Although the TDDFT calculations predict a lower stopping power than SRIM by a factor of three, our result shows very good agreement in a direct comparison with ion range experiments. These results demonstrate the validity of the TDDFT method for determining electronic energy losses of heavy projectiles, and in turn its viability for the study of radiation damage.
Modeling Parkinson’s disease in midbrain-like organoids
Authors: Smits Lisa M. , Reinhardt Lydia , Reinhardt Peter , Glatza Michael , Monzel Anna S. , Stanslowsky Nancy , Rosato-Siri Marcelo D. , Zanon Alessandra , Antony Paul M. , Bellmann Jessica , Nicklas Sarah M. , Hemmer Kathrin , Qing Xiaobing , Berger Emanuel , Kalmbach Norman , Ehrlich Marc , Bolognin Silvia , Hicks Andrew A. , Wegner Florian , Sterneckert Jared L. , Schwamborn Jens C.
Published: April 2019

Modeling Parkinson’s disease (PD) using advanced experimental in vitro models is a powerful tool to study disease mechanisms and to elucidate unexplored aspects of this neurodegenerative disorder. Here, we demonstrate that three-dimensional (3D) differentiation of expandable midbrain floor plate neural progenitor cells (mfNPCs) leads to organoids that resemble key features of the human midbrain. These organoids are composed of midbrain dopaminergic neurons (mDANs), which produce and secrete dopamine. Midbrain-specific organoids derived from PD patients carrying the LRRK2-G2019S mutation recapitulate disease-relevant phenotypes. Automated high-content image analysis shows a decrease in the number and complexity of mDANs in LRRK2-G2019S compared to control organoids. The floor plate marker FOXA2, required for mDAN generation, increases in PD patient-derived midbrain organoids, suggesting a neurodevelopmental defect in mDANs expressing LRRK2-G2019S. Thus, we provide a robust method to reproducibly generate 3D human midbrain organoids containing mDANs to investigate PD-relevant patho-mechanisms.
All semiconductor enhanced high-harmonic generation from a single nanostructured cone
Authors: Franz Dominik , Kaassamani Shatha , Gauthier David , Nicolas Rana , Kholodtsova Maria , Douillard Ludovic , Gomes Jean-Thomas , Lavoute Laure , Gaponov Dmitry , Ducros Nicolas , Février Sebastien , Biegert Jens , Shi Liping , Kovacev Milutin , Boutu Willem , Merdji Hamed
Published: April 2019

The enhancement and control of non-linear phenomena at a nanometer scale has a wide range of applications in science and in industry. Among these phenomena, high-harmonic generation in solids is a recent focus of research to realize next generation petahertz optoelectronic devices or compact all solid state EUV sources. Here, we report on the realization of the first nanoscale high harmonic source. The strong field regime is reached by confining the electric field from a few nanojoules femtosecond laser in a single 3D semiconductor waveguide. We reveal a strong competition between enhancement of coherent harmonics and incoherent fluorescence favored by excitonic processes. However, far from the band edge, clear enhancement of the harmonic emission is reported with a robust sustainability offering a compact nanosource for applications. We illustrate the potential of our harmonic nano-device by performing a coherent diffractive imaging experiment. Ultra-compact UV/X-ray nanoprobes are foreseen to have other applications such as petahertz electronics, nano-tomography or nano-medicine.
Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease
Authors: Ranasinghe Kamalini G. , Kothare Hardik , Kort Naomi , Hinkley Leighton B. , Beagle Alexander J. , Mizuiri Danielle , Honma Susanne M. , Lee Richard , Miller Bruce L. , Gorno-Tempini Maria Luisa , Vossel Keith A. , Houde John F. , Nagarajan Srikantan S.
Published: April 2019

Accurate integration of sensory inputs and motor commands is essential to achieve successful behavioral goals. A robust model of sensorimotor integration is the pitch perturbation response, in which speakers respond rapidly to shifts of the pitch in their auditory feedback. In a previous study, we demonstrated abnormal sensorimotor integration in patients with Alzheimer’s disease (AD) with an abnormally enhanced behavioral response to pitch perturbation. Here we examine the neural correlates of the abnormal pitch perturbation response in AD patients, using magnetoencephalographic imaging. The participants phonated the vowel /α/ while a real-time signal processor briefly perturbed the pitch (100 cents, 400 ms) of their auditory feedback. We examined the high-gamma band (65–150 Hz) responses during this task. AD patients showed significantly reduced left prefrontal activity during the early phase of perturbation and increased right middle temporal activity during the later phase of perturbation, compared to controls. Activity in these brain regions significantly correlated with the behavioral response. These results demonstrate that impaired prefrontal modulation of speech-motor-control network and additional recruitment of right temporal regions are significant mediators of aberrant sensorimotor integration in patients with AD. The abnormal neural integration mechanisms signify the contribution of cortical network dysfunction to cognitive and behavioral deficits in AD.
Fault Dynamics of the 1999 Chi-Chi earthquake: clues from nanometric geochemical analysis of fault gouges
Authors: Li Wen-Hsien , Lee Chi-Hung , Ma Ma-Hsuan , Huang Ping Jung , Wu Sheng Yun
Published: April 2019

The 1999 Chi-Chi, Taiwan earthquake (Mw 7.6) produced surface ruptures for about 90 km along the north-south trending Chelungpu fault, with surface displacements of up to 12 m. Based on the combination of nanoscopic investigation and geochemistry analysis of core samples from a 450 m long inclined borehole drilled through the slip zone, we suggest the dynamical processes that likely occurred in the northern portion of the Chelungpu fault during the faulting. Our analysis revealed that the frictional heating could have reached 1200 °C, which would cause most of the siderite in the fault gouge to evaporate, resulting in a large amount of nano-size siderite grains with a mean diameter 20 nm. These nano grains could have acted as a mechanical lubricant to reduce the dynamic frictional resistance during sliding, giving rise to the large but smooth type of slipping seen in the north.
Generating retinal flow maps from structural optical coherence tomography with artificial intelligence
Authors: Lee Cecilia S. , Tyring Ariel J. , Wu Yue , Xiao Sa , Rokem Ariel S. , DeRuyter Nicolaas P. , Zhang Qinqin , Tufail Adnan , Wang Ruikang K. , Lee Aaron Y.
Published: April 2019

Despite advances in artificial intelligence (AI), its application in medical imaging has been burdened and limited by expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard optical coherence tomography (OCT) images, exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer flow from single structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). Our model allows generating flow maps from large volumes of previously collected OCT data in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed inferences of tissue function from structure imaging.
Bubble cascade in Guinness beer is caused by gravity current instability
Authors: Watamura Tomoaki , Iwatsubo Fumiya , Sugiyama Kazuyasu , Yamamoto Kenichiro , Yotsumoto Yuko , Shiono Takashi
Published: April 2019

The downward movement of the bubble-texture in a glass of Guinness beer is a fascinating fluid flow driven by the buoyant force of a large number of small-diameter bubbles. This texture motion is a frequently observed phenomenon on pub tables. The physical mechanism of the texture-formation has been discussed previously, but inconsistencies exist between these studies. We performed experiments on the bubble distribution in Guinness poured in an inclined container, and observed how the texture forms. We also report the texture-formation in controllable experiments using particle suspensions with precisely specified diameters and volume-concentrations. Our specific measurement methods based on laser-induced-fluorescence provide details of the spatio-temporal profile of the liquid phase velocity. The hydrodynamic condition for the texture-formation is analogous to the critical point of the roll-wave instability in a fluid film, which can be commonly observed in water films sliding downhill on a rainy day. Here, we identify the critical condition for the texture-formation and conclude that the roll-wave instability of the gravity current is responsible for the texture-formation in a glass of Guinness beer.
Measuring Liquid Drop Properties on Nanoscale 1D Patterned Photoresist Structures
Authors: Faria-Briceno Juan J. , Neumann Alexander , Schunk P. Randall , Brueck S. R. J.
Published: April 2019

This communication reports liquid wetting properties of DI-water on one-dimensional nano-patterned photoresist lines atop a silicon substrate as the pattern period is varied from 0.3- to 1.0-µm. Both constant photoresist height and constant width/height ratios are investigated. The line/period ratio was fixed at 0.3 (0.4) for different measurement sequences. The surface of the photoresist was treated with a short CHF3 reactive ion etch to ensure consistent hydrophobic photoresist: water surface energies. Average parallel contact angle (θ||), average perpendicular contact angle (θ⊥), drop width (W), and drop length (L) at constant volume were measured on nano-patterned surfaces fabricated with interferometric lithography. Both θ|| and θ⊥ contact angles increase as the period (0.3- to 1-μm) increases; the θ|| spreading rate is faster than θ⊥ due to pinning on the grooves resulting in an elongated drop shape. The traditional Wenzel and Cassie-Baxter models of drop contact angles were developed for isotropic random 2D roughness and do not account for the anisotropy induced by the 1D line patterns. The observed angular variations with period are not consistent with either model. Understanding liquid wetting properties and hydrophobicity on 1D silicon surfaces has many applications in lab-on-a-chip, micro/nano-fluidic devices, roll-to-roll nano-imprint fabrication, self-cleaning surfaces, and micro-reactors.
Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes
Authors: Rombaut Dries , Chiu Hua-Sheng , Decaesteker Bieke , Everaert Celine , Yigit Nurten , Peltier Agathe , Janoueix-Lerosey Isabelle , Bartenhagen Christoph , Fischer Matthias , Roberts Stephen , D’Haene Nicky , De Preter Katleen , Speleman Frank , Denecker Geertrui , Sumazin Pavel , Vandesompele Jo , Lefever Steve , Mestdagh Pieter
Published: April 2019

Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genesMYCN,ALKandPHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAsMIATandMEG3andMYCNandPHOX2Bactivity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs.
Age-Related Differences in the Late Positive Potential during Emotion Regulation between Adolescents and Adults
Authors: Deng Xinmei , Sang Biao , Ku Yixuan , Sai Liyang
Published: April 2019

The late positive potential (LPP) has been well documented in predicting the effect of emotion regulation in previous developmental literature. However, few studies have examined age-related changes in emotion regulation from adolescence to adulthood using this biomarker. To test this, Reactivity and Regulation-Image Task was used to test 18 young adolescents and 22 adults to examine the modulation of LPP during emotion regulation. Results revealed that (a) on the behavioral level, adults reported higher intensity of emotional experience than adolescents when they were asked to use up-regulation. Down-regulation showed no age effect for self-reported rating; (b) adolescents showed higher amplitudes of LPP than adults when using different regulatory strategies in all windows; (c) In late time window, regulation effect was larger when using up-regulation strategy than down-regulation strategy for adolescents, while the difference between the two strategies was negligible for adults. (d) In early time window, reactivity effect was larger in negative conditions than in positive conditions for adolescents, while the difference between the two conditions was again negligible for adults. Differences in the amplitudes and time courses of LPP during emotion regulation between adolescents and adults suggested that age-related changes in emotion regulation may occur during adolescence.
Poly(N-vinylcaprolactam) Nanogels with Antiviral Behavior against HIV-1 Infection
Authors: Macchione Micaela A. , Guerrero-Beltrán Carlos , Rosso Anabella P. , Euti Esteban M. , Martinelli Marisa , Strumia Miriam C. , Muñoz-Fernández Maria Ángeles
Published: April 2019

Stimuli-responsive nanogels offer promising perspectives for the development of next generation formulations for biomedical applications. In this work, poly(N-vinylcaprolactam) nanogels were synthesized varying the concentration of monomer and crosslinking agent. Thus, the inhibitory effect of poly(N-vinylcaprolactam) nanogels against HIV-1 infection is presented for the first time. In particular, we have demonstrated that one of the synthesized poly(N-vinylcaprolactam) nanogels with initial concentration of 80 mg of vinylcaprolactam and 4% of crosslinking agent shows antiviral behavior against HIV-1 infection since this nanogel inhibits the viral replication in TZM.bl target cells.
Microwear and isotopic analyses on cave bear remains from Toll Cave reveal both short-term and long-term dietary habits
Authors: Ramírez-Pedraza Iván , Tornero Carlos , Pappa Spyridoula , Talamo Sahra , Salazar-García Domingo C. , Blasco Ruth , Rosell Jordi , Rivals Florent
Published: April 2019

Dietary habits of the extinct Ursus spelaeus have always been a controversial topic in paleontological studies. In this work, we investigate carbon and nitrogen values in the bone collagen and dental microwear of U. spelaeus specimens recovered in Level 4 from Toll Cave (Moià, Catalonia, NE Iberian Peninsula). These remains have been dated to > 49,000 14C BP. The ability of both proxies to provide data on the diet of U. spelaeus at different times in the life-history (isotopes: average diet of life; microwear: last days/weeks before death), allows us to generate high-resolution and complementary data. Our results show lower values (δ13C & δ15N) in cave bears than in strict herbivores (i.e. Cervus elaphus) recovered from the same level of Toll Cave. On the other hand, 12 lower molars (m1) were analysed through low-magnification microwear technique. The cave bears from Toll Cave show a microwear pattern like that of extant bears with omnivorous and carnivorous diets. These data are discussed in the framework of all available data in Europe and add new information about the plasticity of the dietary habits of this species at the southern latitudes of Europe during Late Pleistocene periods.
Mechanism of subsidence of the Northeast Japan forearc during the late period of a gigantic earthquake cycle
Authors: Sasajima Ryohei , Shibazaki Bunichiro , Iwamori Hikaru , Nishimura Takuya , Nakai Yoshihiko
Published: April 2019

The forearc in Northeast Japan subsided (3–4 mm/year) in the interseismic ~100 years before the 2011 Tohoku earthquake (MW9.1) just like it did during this event. This study attempts to understand the mechanism of the vertical displacement of the forearc during gigantic earthquake cycles via numerical modeling. The results suggest that the interseismic subsidence rate in the forearc increases with the duration of the locking of the asperity of the gigantic earthquake over several hundred years, due to the increasing slip deficit rate on the deeper parts of the plate interface. The increasing slip deficit rate is caused by both the decreasing the shear stress in the shear zone owing to the continuous locking of the asperity and the increasing the mobility of the continental lithosphere owing to the viscoelastic relaxation in the mantle wedge. The deep slip deficit rate extending to ~100 km depth of the plate interface is necessary to explain the observed interseismic forearc subsidence rate. The results also suggest hundreds of years of continuous locking of the asperities of a gigantic earthquake in the western Kuril subduction zone, where fast forearc subsidence has been observed as well.
Effect of prey size and structural complexity on the functional response in a nematode- nematode system
Authors: Kreuzinger-Janik Bianca , Brüchner- Hüttemann Henrike , Traunspurger Walter
Published: April 2019

The functional response of a predatory nematode and the influence of different prey sizes and habitat structure on the concerning parameters were analyzed. We hypothesized that the handling of small prey would be less time-consuming, whereas feeding on larger prey would be more efficient. Therefore, type II functional response curves were expected for large prey and a trend towards type III curves for small prey. We expected the introduction of prey refuges to shift the functional response curves from hyperbolic to sigmoidal and that the effect would be even more pronounced with smaller prey.P. muscorumconsumed large amounts of small and largeC. elegans, with dailyper capitaingestion of prey reaching a maximum of 19.8 µg fresh weight, which corresponds to 4.8 times the predator’s biomass. Regardless of prey size and habitat structure,P. muscorumexhibit a type III functional response. Overall, the allometric effect of prey size had a greater effect on the predator’s functional response than did the addition of substrate, presumably due to the similar body shape and mobility of the two nematode species. Our results demonstrate that individual factors such as feeding behavior are important determinants of functional responses and therefore of ecosystem stability.
Optimal blood pressure after reperfusion therapy in patients with acute ischemic stroke
Authors: Choi Kang-Ho , Kim Jae-Myung , Kim Ja-Hae , Kim Joon-Tae , Park Man-Seok , Choi Seong-Min , Lee Seung-Han , Kim Byeong C. , Kim Myeong-Kyu , Cho Ki-Hyun
Published: April 2019

We investigated the relationship between the mean blood pressure (BP) at 24–72 h and the clinical outcomes after acute ischemic stroke (AIS) in patients treated with reperfusion therapy. The primary outcome was measured using the modified Rankin Scale (mRS) at 3 months after AIS, and was based on the mean systolic BP at 24–72 h post-AIS. Favorable outcome was defined as mRS scores of 0–2. A total of 1,540 patients treated with reperfusion therapy were enrolled in the study. Favorable outcomes occurred more frequently in patients with BP ≤ 130/80 mmHg, and the risks of symptomatic intracranial hemorrhage and early neurological deterioration were lower in this optimal BP group. Multivariable analysis showed a significant association between mean BP ≤ 130/80 mmHg at 24–72 h and favorable outcomes at 3 months after AIS (odds ratio 2.95, 95% confidence interval 2.32–3.77, p < 0.001). Prespecified subgroup analyses showed that BP ≤ 130/80 mmHg had a more significant impact on clinical outcome in patients with recanalization than in those without recanalization. These data indicate that a mean BP of ≤ 130/80 mmHg at 24–72 h post-AIS is independently associated with favorable outcomes in patients treated with reperfusion therapy, particularly in those with recanalization.
Analysis of fibrosis in control or pressure overloaded rat hearts after mechanical unloading by heterotopic heart transplantation
Authors: Schaefer Andreas , Schneeberger Yvonne , Schulz Steven , Krasemann Susanne , Werner Tessa , Piasecki Angelika , Höppner Grit , Müller Christian , Morhenn Karoline , Lorenz Kristina , Wieczorek David , Schwoerer Alexander P. , Eschenhagen Thomas , Ehmke Heimo , Reichenspurner Hermann , Stenzig Justus , Cuello Friederike
Published: April 2019

Mechanical unloading (MU) by implantation of left ventricular assist devices (LVAD) has become clinical routine. This procedure has been shown to reverse cardiac pathological remodeling, with the underlying molecular mechanisms incompletely understood. Most studies thus far were performed in non-standardized human specimens or MU of healthy animal hearts. Our study investigates cardiac remodeling processes in sham-operated healthy rat hearts and in hearts subjected to standardized pathological pressure overload by transverse aortic constriction (TAC) prior to MU by heterotopic heart transplantation (hHTx/MU). Rats underwent sham or TAC surgery. Disease progression was monitored by echocardiography prior to MU by hHTx/MU. Hearts after TAC or TAC combined with hHTx/MU were removed and analyzed by histology, western immunoblot and gene expression analysis. TAC surgery resulted in cardiac hypertrophy and impaired cardiac function. TAC hearts revealed significantly increased cardiac myocyte diameter and mild fibrosis. Expression of hypertrophy associated genes after TAC was higher compared to hearts after hHTx/MU. While cardiac myocyte cell diameter regressed to the level of sham-operated controls in all hearts subjected to hHTx/MU, fibrotic remodeling was significantly exacerbated. Transcription of pro-fibrotic and apoptosis-related genes was markedly augmented in all hearts after hHTx/MU. Sarcomeric proteins involved in excitation-contraction coupling displayed significantly lower phosphorylation levels after TAC and significantly reduced total protein levels after hHTx/MU. Development of myocardial fibrosis, cardiac myocyte atrophy and loss of sarcomeric proteins was observed in all hearts that underwent hHTX/MU regardless of the disease state. These results may help to explain the clinical experience with low rates of LVAD removal due to lack of myocardial recovery.
An application of (4YSZ)0.93(Fe2O3)0.07 in limiting current oxygen sensor
Authors: Wang Xiangnan , Liu Tao , Yu Jingkun
Published: April 2019

(4YSZ)0.93(Fe2O3)0.07 and 9 mol% Y2O3 stabilized ZrO2 (9YSZ) were synthesized by co-precipitation method and their crystalline structure, microstructure, electronic conductivity, total conductivity were characterized. A limiting current oxygen sensor was assembled with (4YSZ)0.93(Fe2O3)0.07 dense diffusion barrier and 9YSZ solid electrolyte by Pt sintered-paste method. Influences of temperature (T), oxygen concentration (x(O2)) and water vapor pressure (p(H2O)) on sensing characteristics of the limiting current oxygen sensor were investigated. The crystalline structure of (4YSZ)0.93(Fe2O3)0.07 and 9YSZ belong to cubic structure with $${\bf{Fm}}\overline{{\bf{3}}}{\bf{m}}$$
Fm

3

¯

m
. The total conductivity of (4YSZ)0.93(Fe2O3)0.07 is higher than that of 9YSZ and the electronic and total conductivities of the samples meet the linear relationship with 1000/T. The limiting current oxygen sensor exhibits excellent sensing characteristics under test conditions. The effects of T, x(O2) and p(H2O) are as follows: Log(IL·T) depends linearly on 1000/T, IL depends linearly on x(O2) and IL is not significantly dependent on p(H2O).
Anticancer Gold Compounds
Authors: Hu Di , Lok Chun-Nam , Che Chi-Ming
Published: April 2019

The use of gold in medicine has a long history that dates back to ancient times. In modern medicine, gold compounds have been applied as anti-inflammatory agents for the treatment of rheumatoid arthritis. Recently, gold complexes have gained increasing attention in the design of metal-based anticancer chemotherapeutics. Gold(i) and gold(iii) ions are often unstable or reactive via redox reactions under physiological conditions. By judicious selection of coordination ligands, gold(i) and gold(iii) complexes that are stable under physiological conditions can be prepared and harnessed for anticancer applications. In this chapter, our current understanding on the anticancer properties of gold compounds and the approaches to identify their molecular targets and improve anticancer efficiency are reviewed.
Folated pH-degradable nanogels for the simultaneous delivery of docetaxel and an IDO1-inhibitor in enhancing cancer chemo-immunotherapy
Authors: Qiao Haishi , Chen Xingmei , Chen Enping , Zhang Junmei , Huang Dechun , Yang Danqi , Ding Youchao , Qian Hongliang , Feijen Jan , Chen Wei
Published: April 2019

Floated pH-degradable PVA nanogels (FA-NGs) are developed for simultaneous delivery of DTX and IDO1-inhibitor N9 to enhance cancer chemo-immunotherapy.
Effectiveness of phase- and morphology-controlled MnO2 nanomaterials derived from flower-like δ-MnO2 as alternative cathode catalyst in microbial fuel cells
Authors: Valipour Alireza , Hamnabard Nazanin , Meshkati Seyed Mohammad Hadi , Pakan Mahyar , Ahn Young-Ho
Published: April 2019

Crystal phase and morphology variations obtained by simple high-temperature annealing offer promising strategies for employing nanostructured manganese oxide as a cathode catalyst for microbial fuel cells (MFCs).
Recent trends in transition metal dichalcogenide based supercapacitor electrodes
Authors: Cherusseri Jayesh , Choudhary Nitin , Sambath Kumar Kowsik , Jung Yeonwoong , Thomas Jayan
Published: April 2019

The synthesis routes and the electrochemical performance evaluation of transition metal dichalcogenide (TMD) based supercapacitor electrodes are discussed.
Binding thiourea derivatives with dimethyl methylphosphonate for sensing nerve agents
Authors: Chung You Kyoung , Ha Seonggyun , Woo Tae Gyun , Kim Young Dok , Song Changsik , Kim Seong Kyu
Published: April 2019

Binding energies and geometries of 1 : 1 complexes formed between nerve agent simulant DMMP and 13 thiourea derivatives (TUn) were calculated and compared with the sensing efficiencies of TUn from QCM analysis.
Soft ionic liquid multi-point touch sensor
Authors: Fastier-Wooller Jarred , Dinh Toan , Dau Van Thanh , Dao Dzung Viet
Published: April 2019

Here we report on an ionic liquid based soft pressure sensor. Our use of smart structures and ease of fabrication processes enable the development of a soft and low-cost sensor with multiple-point sensing capabilities on a single chip.
Comparative effects of mercury chloride and methylmercury exposure on early neurodevelopment in zebrafish larvae
Authors: Zhu Jun , Wang Chundan , Gao Xingsu , Zhu Jiansheng , Wang Li , Cao Shuyuan , Wu Qian , Qiao Shanlei , Zhang Zhan , Li Lei
Published: April 2019

The metabolomics and neurodevelopmental endpoints were integrated to reveal that abnormal metabolic pathway and expression of Shha, Ngn1 and Nrd may contribute to neurotoxicity induced by MeHg, which was more toxic than HgCl2 in zebrafish larvae.
Quantum-dot light-emitting diode with ultrathin Au electrode embedded in solution-processed phosphomolybdic acid
Authors: Chrzanowski Maciej , Banski Mateusz , Sitarek Piotr , Misiewicz Jan , Podhorodecki Artur
Published: April 2019

We proposed to exploit phosphomolybdic acid (PMA) as a cost-efficient MoOx source for combined spin-coating/sputtering/spin-coating deposition of a MoOx/Au/MoOx (MAM) composite electrode.
Optimal number of linkers per monomer in linker-mediated aggregation
Authors: Antunes G. C. , Dias C. S. , Telo da Gama M. M. , Araújo N. A. M.
Published: April 2019

We study the dynamics of diffusion-limited irreversible aggregation of monomers, where bonds are mediated by linkers.
Realization of ultra-long columnar single crystals in TiO2 nanotube arrays as fast electron transport channels for high efficiency dye-sensitized solar cells
Authors: Fu Nianqing , Duan Yandong , Lu Wei , Zhu Mingshan , Zhang Guoge , Xie Dongmei , Lin Yuan , Wei Mingdeng , Huang Haitao
Published: April 2019

An electrically heterogeneous hierarchical-architecture based on an ultra-long columnar single-crystal based TiO2 nanotube array is built for efficient dye-sensitized solar cells with an efficiency up to 10.1%.
A novel aqueous ammonium dual-ion battery based on organic polymers
Authors: Zhang Yadi , An Yufeng , Yin Bo , Jiang Jiangmin , Dong Shengyang , Dou Hui , Zhang Xiaogang
Published: April 2019

A novel and green aqueous ADIB with high cell voltage based on organic polymers.
An ultrahigh electron-donating quaternary-N-doped reduced graphene oxide@carbon nanotube framework: a covalently coupled catalyst support for enzymatic bioelectrodes
Authors: Li Gangyong , Li Zihan , Xiao Xiang , An Yuanlin , Wang Wei (Alex) , Hu Zongqian
Published: April 2019

An ultrahigh electron-donating quaternary-N-doped reduced graphene oxide@carbon nanotube framework boosts the performance of glucose/O2 enzymatic biofuel cells.
Critical work of adhesion for economical patterning of silver nanowire-based transparent electrodes
Authors: Ko Dongwook , Gu Bongjun , Kang Seok Ju , Jo Sungjin , Hyun Dong Choon , Kim Chang Su , Kim Jongbok
Published: April 2019

A simple, economical, and eco-friendly non-photolithographic patterning process for AgNW-embedded and AgNW-exposed flexible transparent electrodes is developed by controlling the work of adhesion.
Low-temperature synthesis of all-inorganic perovskite nanocrystals for UV-photodetectors
Authors: Zhang Hao , Zhang Zihan , Ma Chao , Liu Yuquan , Xie Haipeng , Luo Shiqiang , Yuan Yongbo , Gao Yongli , Zhang Yong , Ming Wenquan , Liu Yi , Pan Anlian , Yang Bin
Published: April 2019

CsPb1−XSnXBr3 perovskite nanocrystals, synthesized by a low-temperature hot-injection method, have been demonstrated as the key for sensitive trap-assisted photomultiplication UV-photodetectors.
Alternative current electroluminescence and flexible light emitting devices
Authors: Jayathilaka Wanasinghe Arachchige Dumith Madushanka , Chinnappan Amutha , Tey Ju Nie , Wei Jun , Ramakrishna Seeram
Published: April 2019

Flexible electroluminescence has become a trending technological breakthrough from large-scale displays to wearable light emitting devices. Among different techniques, alternative current electroluminescence (ACEL) has out-shined due to its intrinsic advantages.
Glutaminolysis and lipoproteins are key factors in late immune recovery in successfully treated HIV-infected patients
Authors: Rosado-Sánchez Isaac , Rodríguez-Gallego Esther , Peraire Joaquim , Viladés Consuelo , Herrero Pol , Fanjul Fran , Gutiérrez Félix , Bernal Enrique , Pelazas Ricardo , Leal Manuel , Veloso Sergi , López-Dupla Miguel , Blanco Julià , Vidal Francesc , Pacheco Yolanda María , Rull Anna
Published: April 2019

The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive combined antiretroviral therapy (cART). Integrated data from nuclear magnetic resonance (NMR)-based lipoprotein profiles, mass spectrometry (MS)-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune recovery status after 96 weeks of suppressive cART. The metabolomic signature of ART-naïve HIV subjects with a subsequent late immune recovery is the expression of pro-inflammatory molecules and glutaminolysis, which is likely related to elevate T-cell turnover in these patients. The knowledge about how these metabolic pathways are interconnected and regulated provides new targets for future therapeutic interventions not only in HIV infection but also in other metabolic disorders such as human cancers where glutaminolysis is the alternative pathway for energy production in tumor cells to meet their requirement of rapid proliferation.
NIR‐red algorithms‐based model for chlorophyll‐a retrieval in highly turbid Inland Densu River Basin in South‐East Ghana, West Africa
Authors: Rani Meenu , Rehman Sufia , Sajjad Haroon , Sidiki Alare Rahinatu , Chaudhary B.S. , Patairiya Shashikanta , Rawat J.S. , Chetri Tilok , Patel Swagatika , Kumar Pavan
Published: April 2019

Chlorophyll‐a concentration is a significant conditioning factor for analysing variation of water quality. It is also an important indicator for examining phytoplankton and biomass both in inland and oceanic waters. The study aims at developing an approach to quantify chlorophyll‐a concentration using Landsat‐8 Optical land imager sensor data in Densu River, West Africa. Twelve water samples across Densu River were collected to measure chlorophyll‐a concentration. Satellite data base chlorophyll‐a concentration was determined using NIR‐red algorithm. The chlorophyll‐a concentration obtained through this algorithm was validated with laboratory‐measured chlorophyll‐a concentration. Regression analysis between laboratory‐measured and modelled chlorophyll‐a concentration revealed strong relationship. Thus, NIR‐red algorithm has proved an effective tool in measuring and mapping chlorophyll‐a concentration. The algorithm can also be utilised for assessing quality of different water bodies at spatial scales.
New BiOXs/TiO2 heterojunction photocatalyst towards efficient degradation of organic pollutants under visible‐light irradiation
Authors: Lun Li , Jinling Song , Baoying Wang , Chenglin Duan , Ruifen Wang , Bangwen Zhang
Published: April 2019

A new heterojunction BiOXs/TiO2 photocatalyst was firstly prepared by a mixed solvothermal method. Several tools were used to characterise the structure and morphologies of as‐obtained samples. The results of photocatalytic experiments indicated that flower‐like BiOXs/TiO2 fabricated by the thinner nanosheets exhibited excellent degradation properties towards methyl orange, bisphenol A and tetracycline under visible‐light irradiation. The reasons could be the good absorption of organic pollutants and light, and the high separation efficiency of photogenic electrons and holes attributed to the construction of BiOXs/TiO2 heterojunction with large special surface areas. The photocatalytic mechanism was proposed. This Letter could provide new ideas to design the visible‐light catalysts.