bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraints, the identifiability problem and the forecasting of mortality
Authors: Currie Iain D. 
Published: March 2020

AbstractModels of mortality often require constraints in order that parameters may be estimated uniquely. It is not difficult to find references in the literature to the “identifiability problem”, and papers often give arguments to justify the choice of particular constraint systems designed to deal with this problem. Many of these models are generalised linear models, and it is known that the fitted values (of mortality) in such models are identifiable, i.e., invariant with respect to the choice of constraint systems. We show that for a wide class of forecasting models, namely ARIMA
$(p,\delta, q)$
models with a fitted mean and
$\delta = 1$
or 2, identifiability extends to the forecast values of mortality; this extended identifiability continues to hold when some model terms are smoothed. The results are illustrated with data on UK males from the Office for National Statistics for the age-period model, the age-period-cohort model, the age-period-cohort-improvements model of the Continuous Mortality Investigation and the Lee–Carter model.
Dynamical Coupling of Energetic Electrons and Upper‐Hybrid Thermal Fluctuations in the Earth's Radiation Belt
Authors: Yoon Peter H. , Hwang Junga 
Published: March 2020

AbstractThe inner magnetosphere including the radiation belt environment is replete with quasi‐electrostatic fluctuations with peak frequency in the upper‐hybrid frequency range. Some examples are demonstrated with the Van Allen Probe spacecraft data. These features have recently been explained in the framework of spontaneously emitted thermal noise theory. Such an environment is also characterized by quasi‐isotropic population of energized electrons, which naturally leads one to ask whether these electrons and the upper‐hybrid fluctuations influence each other. The present paper explores the potential causal relationship between the two features via kinetic theory. It is shown that indeed, isotropic energetic electrons and upper‐hybrid frequency thermal fluctuations can be dynamically coupled and that they could coexist in a quasi‐steady state manner.
Topographic, Hydraulic, and Vegetative Controls on Bar and Island Development in Mixed Bedrock‐Alluvial, Multichanneled, Dryland Rivers
Authors: Milan D. J. , Tooth S. , Heritage G. L. 
Published: March 2020

AbstractWe investigate processes of bedrock‐core bar and island development in a bedrock‐influenced anastomosed reach of the Sabie River, Kruger National Park, eastern South Africa. For sites subject to alluvial stripping during an extreme flood event (~4,470–5,630 m3 s−1) in 2012, preflood and postflood aerial photographs and LiDAR data, 2‐D morphodynamic simulations, and field observations reveal that the thickest surviving alluvial deposits tend to be located over bedrock topographic lows. At a simulated peak discharge (~4,500 m3 s−1), most sediment (sand, fine gravel) is mobile but localized deposition on bedrock topographic highs is possible. At lower simulated discharges (<1,000 m3 s−1), topographic highs are not submerged, and deposition occurs in lower elevation areas, particularly in areas disconnected from the main channels during falling stage. Field observations suggest that in addition to discharge, rainwash between floods may redistribute sediments from bedrock topographic highs to lower elevation areas, and also highlight the critical role of vegetation colonization in bar stability, and in trapping of additional sediment and organics. These findings challenge the assumptions of preferential deposition on topographic highs that underpin previous analyses of Kruger National Park river dynamics, and are synthesized in a new conceptual model that demonstrates how initial bedrock topographic lows become topographic highs (bedrock‐core bars and islands) in the latter stages of sediment accumulation. The model provides particular insight into the development of mixed bedrock‐alluvial anastomosing along the Kruger National Park rivers, but similar processes of bar/island development likely occur along numerous other bedrock‐influenced rivers across dryland southern Africa and farther afield.
The essential role of fructose-1,6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress
Authors: Park Hyun-Jun , Jang Hye Rim , Park Shi-Young , Kim Young-Bum , Lee Hui-Young , Choi Cheol Soo 
Published: March 2020

AbstractSkeletal muscle is a major organ for glucose disposal and thermogenesis. While hepatic fructose-1,6-bisphosphatase is well known as a key enzyme for gluconeogenesis, the role of muscle fructose-1,6-bisphosphatase 2 (Fbp2) in glucose disposal and thermogenesis is unknown. Here, using Fbp2 knockout (KO) mice, we assessed the physiological role of Fbp2 in energy and glucose metabolism and thermogenesis. In vivo assessments of energy metabolism, glucose metabolism, and thermogenesis were performed by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and cold challenge studies, respectively. Under both feeding and fasting conditions, Fbp2 KO mice showed similar phenotypes regarding energy and glucose metabolism compared to wild-type (WT) mice. However, Fbp2 KO mice were severely intolerant to cold challenge under fasting conditions. Mechanistically, the cold-induced intramuscular conversion of lactate to glycogen (glyconeogenesis) is completely abolished in the KO muscle, which leads to a lack of glycogen source for thermogenesis in Fbp2 KO mice. The cold-intolerant phenotype of KO mice disappeared after feeding, and the KO mice were equally as cold tolerant as the WT mice and survived during the cold challenge for three weeks. Taken together, these data demonstrate that Fbp2 is essential for muscle thermogenesis by replenishing the intramuscular glycogen pool through glyconeogenesis when the exogenous glucose source is limited. These data imply the physiological importance of Fbp2 in thermal homeostasis and suggest a potential novel therapy targeted to increase glycogen replenishment upon cold stress.
On-chip single-mode CdS nanowire laser
Authors: Bao Qingyang , Li Weijia , Xu Peizhen , Zhang Ming , Dai Daoxin , Wang Pan , Guo Xin , Tong Limin 
Published: March 2020

AbstractBy integrating a free-standing cadmium sulfide (CdS) nanowire onto a silicon nitride (SiN) photonic chip, we demonstrate a highly compact on-chip single-mode CdS nanowire laser. The mode selection is realized using a Mach-Zehnder interferometer (MZI) structure. When the pumping intensity exceeds the lasing threshold of 4.9 kW/cm2, on-chip single-mode lasing at ~518.9 nm is achieved with a linewidth of 0.1 nm and a side-mode suppression ratio of up to a factor of 20 (13 dB). The output of the nanowire laser is channelled into an on-chip SiN waveguide with high efficiency (up to 58%) by evanescent coupling, and the directional coupling ratio between the two output ports can be varied from 90 to 10% by predesigning the coupling length of the SiN waveguide. Our results open new opportunities for both nanowire photonic devices and on-chip light sources and may pave the way towards a new category of hybrid nanolasers for chip-integrated applications.
Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism
Authors: Chen Hao , Zhang Haifeng , Zheng Yue , Min Xiaohui , Luo Yujun , Zhou Weijie , Ma Faxin , Li Jinliang , Lu Quan , Zhang Chen , Cai Huihua , Sha Weihong 
Published: March 2020

AbstractTreatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or shPHD2-GFP constructs (PHDMSC), followed by intraperitoneal injection of the PHDMSC-conditioned medium (PHDMSC-CM) or the GFP-MSC-conditioned medium (MSC-CM) into a rat pup model of NEC. Our results showed that systemic infusion of PHDMSC-CM, but not MSC-CM, significantly improved intestinal damage and survival of NEC rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of Treg cells function and pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of PHDMSC is related to a higher release of pivotal factor IGF-1 and TGF-β2. NF-κB activation was induced by PHD2 silencing to induce IGF-1 and TGF-β2 secretion via binding to IGF-1 and TGF-β2 gene promoter. Our work indicated that PHD2 silencing enhanced the paracrine effect of BM-MSCs on NEC via the NF-κB-dependent mechanism which may be a novel strategy for stem cell therapy on NEC.
Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90
Authors: Mader Sophie L. , Lopez Abraham , Lawatscheck Jannis , Luo Qi , Rutz Daniel A. , Gamiz-Hernandez Ana P. , Sattler Michael , Buchner Johannes , Kaila Ville R. I. 
Published: March 2020

AbstractThe heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control the folding and activation of several client proteins in the eukaryotic cell. To elucidate how the local ATPase reaction in the active site couples to the global conformational dynamics of Hsp90, we integrate here large-scale molecular simulations with biophysical experiments. We show that the conformational switching of conserved ion pairs between the N-terminal domain, harbouring the active site, and the middle domain strongly modulates the catalytic barrier of the ATP-hydrolysis reaction by electrostatic forces. Our combined findings provide a mechanistic model for the coupling between catalysis and protein dynamics in Hsp90, and show how long-range coupling effects can modulate enzymatic activity.
Lupus autoantibodies act as positive allosteric modulators at GluN2A-containing NMDA receptors and impair spatial memory
Authors: Chan Kelvin , Nestor Jacquelyn , Huerta Tomás S. , Certain Noele , Moody Gabrielle , Kowal Czeslawa , Huerta Patricio T. , Volpe Bruce T. , Diamond Betty , Wollmuth Lonnie P. 
Published: March 2020

AbstractPatients with Systemic lupus erythematosus (SLE) experience various peripheral and central nervous system manifestations including spatial memory impairment. A subset of autoantibodies (DNRAbs) cross-react with the GluN2A and GluN2B subunits of the NMDA receptor (NMDAR). We find that these DNRAbs act as positive allosteric modulators on NMDARs with GluN2A-containing NMDARs, even those containing a single GluN2A subunit, exhibiting a much greater sensitivity to DNRAbs than those with exclusively GluN2B. Accordingly, GluN2A-specific antagonists provide greater protection from DNRAb-mediated neuronal cell death than GluN2B antagonists. Using transgenic mice to perturb expression of either GluN2A or GluN2B in vivo, we find that DNRAb-mediated disruption of spatial memory characterized by early neuronal cell death and subsequent microglia-dependent pathologies requires GluN2A-containing NMDARs. Our results indicate that GluN2A-specific antagonists or negative allosteric modulators are strong candidates to treat SLE patients with nervous system dysfunction.
Gut microbiome diversity detected by high-coverage 16S and shotgun sequencing of paired stool and colon sample
Authors: Mas-Lloret Joan , Obón-Santacana Mireia , Ibáñez-Sanz Gemma , Guinó Elisabet , Pato Miguel L. , Rodriguez-Moranta Francisco , Mata Alfredo , García-Rodríguez Ana , Moreno Victor , Pimenoff Ville Nikolai 
Published: March 2020

AbstractThe gut microbiome has a fundamental role in human health and disease. However, studying the complex structure and function of the gut microbiome using next generation sequencing is challenging and prone to reproducibility problems. Here, we obtained cross-sectional colon biopsies and faecal samples from nine participants in our COLSCREEN study and sequenced them in high coverage using Illumina pair-end shotgun (for faecal samples) and IonTorrent 16S (for paired feces and colon biopsies) technologies. The metagenomes consisted of between 47 and 92 million reads per sample and the targeted sequencing covered more than 300 k reads per sample across seven hypervariable regions of the 16S gene. Our data is freely available and coupled with code for the presented metagenomic analysis using up-to-date bioinformatics algorithms. These results will add up to the informed insights into designing comprehensive microbiome analysis and also provide data for further testing for unambiguous gut microbiome analysis.
Surface Modification and Charge Injection in a Nanocomposite Of Metal Nanoparticles and Semiconductor Oxide Nanostructures
Authors: Xiao Bo , Rutherford Gugu N. , Sharma Amrit P. , Pradhan Sangram K. , Bonner Carl E. , Bahoura Messaoud J. 
Published: March 2020

AbstractCombining two materials in a nanoscale level can create a composite with new functionalities and improvements in their physical and chemical properties. Here we present a high-throughput approach to produce a nanocomposite consisting of metal nanoparticles and semiconductor oxide nanostructures. Volmer-Weber growth, though unfavorable for thin films, promotes nucleation of dense and isolated metal nanoparticles on crystalline oxide nanostructures, resulting in new material properties. We demonstrate such a growth of Au nanoparticles on SnO2 nanostructures and a remarkable sensitivity of the nanocomposite for detecting traces of analytes in surface enhanced Raman spectroscopy. Au nanoparticles with tunable size enable us to modify surface wettability and convert hydrophilic oxide surfaces into super-hydrophobic with contact angles over 150°. We also find that charge injection through electron beam exposure shows the same effect as photo-induced charge separation, providing an extra Raman enhancement up to an order of magnitude.
Enhanced, coordinated conservation efforts required to avoid extinction of critically endangered Eastern Pacific leatherback turtles
Authors:   The Laúd OPO Network, Ábrego Marino Eugenio , Acuña-Perales Nicolás , Alfaro-Shigueto Joanna , Azócar Jorge , Barragán Rocha Ana Rebeca , Baquero Andrés , Cotto Alejandro , Darquea Jodie , de Paz Nelly , Donoso Miguel , Dutton Peter H. , Fonseca Luis , Gadea Velkiss , García Débora , Genovart Meritxell , Jimenez Astrid , del Rosario Juárez María , López Sánchez Karla Cecilia , Mangel Jeffrey C. , Martínez Suzano Mayra Leticia , Miranda Cristina , Ocampo Enrique , Ordaz Becerra Ana , Ortiz-Alvarez Clara , Paladino Frank V. , Pasara-Polack Andrea , Pingo Sergio , Piedra Chacón Rotney , Quiñones Javier , Rguez-Baron Juan M. , Salas Jiménez Jorge Carlos , Salazar Heydi , Santidrián Tomillo Pilar , Sarti Martínez Adriana Laura , Spotila James R. , Tavera Alejandro , Urteaga Jose , Vallejo Felipe , Velez Elizabeth , Wallace Bryan P. , Williard Amanda S. , Zárate Patricia M. 
Published: March 2020

AbstractFailure to improve the conservation status of endangered species is often related to inadequate allocation of conservation resources to highest priority issues. Eastern Pacific (EP) leatherbacks are perhaps the most endangered sea turtle population in the world, and continue on a path to regional extinction. To provide coherent, regional conservation targets, we developed a population viability analysis and examined hypothetical scenarios describing effects of conservation activities that either reduced mortality or increased production of hatchlings (or both). Under status quo conditions, EP leatherbacks will be extirpated in <60 yr. To ensure a positive, long-term population trajectory, conservation efforts must increase adult survivorship (i.e., reduce adult mortality) by ≥20%, largely through reduction of fisheries bycatch mortality. Positive trajectories can be accelerated by increased production of hatchlings through enhanced nest protection and treatment. We estimate that these efforts must save approximately 200–260 adult and subadult leatherbacks and produce approximately 7,000–8,000 more hatchlings annually. Critically, reductions in late-stage mortality must begin within 5 years and reach 20% overall within the next 10–15 years to ensure population stabilization and eventual increase. These outcomes require expanded, sustained, coordinated, high-priority efforts among several entities working at multiple scales. Fortunately, such efforts are underway.
New imaging modes for analyzing suspended ultra-thin membranes by double-tip scanning probe microscopy
Authors: Elibol Kenan , Hummel Stefan , Bayer Bernhard C. , Meyer Jannik C. 
Published: March 2020

AbstractScanning probe microscopy (SPM) techniques are amongst the most important and versatile experimental methods in surface- and nanoscience. Although their measurement principles on rigid surfaces are well understood and steady progress on the instrumentation has been made, SPM imaging on suspended, flexible membranes remains difficult to interpret. Due to the interaction between the SPM tip and the flexible membrane, morphological changes caused by the tip can lead to deformations of the membrane during scanning and hence significantly influence measurement results. On the other hand, gaining control over such modifications can allow to explore unknown physical properties and functionalities of such membranes. Here, we demonstrate new types of measurements that become possible with two SPM instruments (atomic force microscopy, AFM, and scanning tunneling microscopy, STM) that are situated on opposite sides of a suspended two-dimensional (2D) material membrane and thus allow to bring both SPM tips arbitrarily close to each other. One of the probes is held stationary on one point of the membrane, within the scan area of the other probe, while the other probe is scanned. This way new imaging modes can be obtained by recording a signal on the stationary probe as a function of the position of the other tip. The first example, which we term electrical cross-talk imaging (ECT), shows the possibility of performing electrical measurements across the membrane, potentially in combination with control over the forces applied to the membrane. Using ECT, we measure the deformation of the 2D membrane around the indentation from the AFM tip. In the second example, which we term mechanical cross-talk imaging (MCT), we disentangle the mechanical influence of a scanning probe tip (e.g. AFM) on a freestanding membrane by means of independently recording the response of the opposing tip. In this way we are able to separate the tip-induced membrane deformation topography from the (material-dependent) force between the tip and the membrane. Overall, the results indicate that probing simultaneously both surfaces of ultra-thin membranes, such as suspended 2D materials, could provide novel insights into the electronic properties of the materials.
Microbial inoculation in rice regulates antioxidative reactions and defense related genes to mitigate drought stress
Authors: Singh Dhananjaya P. , Singh Vivek , Gupta Vijai K. , Shukla Renu , Prabha Ratna , Sarma Birinchi K. , Patel Jai Singh 
Published: March 2020

AbstractMicrobial inoculation in drought challenged rice triggered multipronged steps at enzymatic, non-enzymatic and gene expression level. These multifarious modulations in plants were related to stress tolerance mechanisms. Drought suppressed growth of rice plants but inoculation withTrichoderma,Pseudomonasand their combination minimized the impact of watering regime. InducedPALgene expression and enzyme activity due to microbial inoculation led to increased accumulation of polyphenolics in plants. Enhanced antioxidant concentration of polyphenolics from microbe inoculated and drought challenged plants showed substantially high values of DPPH, ABTS, Fe-ion reducing power and Fe-ion chelation activity, which established the role of polyphenolic extract as free radical scavengers. Activation of superoxide dismutase that catalyzes superoxide (O2−) and leads to the accumulation of H2O2was linked with the hypersensitive cell death response in leaves. Microbial inoculation in plants enhanced activity of peroxidase, ascorbate peroxidase, glutathione peroxidase and glutathione reductase enzymes. This has further contributed in reducing ROS burden in plants. Genes of key metabolic pathways including phenylpropanoid (PAL), superoxide dismutation (SODs), H2O2peroxidation (APX,PO) and oxidative defense response (CAT) were over-expressed due to microbial inoculation. Enhanced expression ofOSPiPlinked to less-water permeability, drought-adaptation geneDHNand dehydration related stress inducibleDREBgene in rice inoculated with microbial inoculants after drought challenge was also reported. The impact ofPseudomonason gene expression was consistently remained the most prominent. These findings suggested that microbial inoculation directly caused over-expression of genes linked with defense processes in plants challenged with drought stress. Enhanced enzymatic and non-enzymatic antioxidant reactions that helped in minimizing antioxidative load, were the repercussions of enhanced gene expression in microbe inoculated plants. These mechanisms contributed strongly towards stress mitigation. The study demonstrated that microbial inoculants were successful in improving intrinsic biochemical and molecular capabilities of rice plants under stress. Results encouraged us to advocate that the practice of growing plants with microbial inoculants may find strategic place in raising crops under abiotic stressed environments.
Structural and evolutionary analyses of the Plasmodium falciparum chloroquine resistance transporter
Authors: Coppée Romain , Sabbagh Audrey , Clain Jérôme 
Published: March 2020

AbstractMutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to several antimalarial drugs such as chloroquine (CQ) or piperaquine (PPQ), a partner molecule in current artemisinin-based combination therapies. As a member of the Drug/Metabolite Transporter (DMT) superfamily, the vacuolar transporter PfCRT may translocate substrate molecule(s) across the membrane of the digestive vacuole (DV), a lysosome-like organelle. However, the physiological substrate(s), the transport mechanism and the functional regions of PfCRT remain to be fully characterized. Here, we hypothesized that identification of evolutionary conserved sites in a tertiary structural context could help locate putative functional regions of PfCRT. Hence, site-specific substitution rates were estimated over Plasmodium evolution at each amino acid sites, and the PfCRT tertiary structure was predicted in both inward-facing (open-to-vacuole) and occluded states through homology modeling using DMT template structures sharing <15% sequence identity with PfCRT. We found that the vacuolar-half and membrane-spanning domain (and especially the transmembrane helix 9) of PfCRT were more conserved, supporting that its physiological substrate is expelled out of the parasite DV. In the PfCRT occluded state, some evolutionary conserved sites, including positions related to drug resistance mutations, participate in a putative binding pocket located at the core of the PfCRT membrane-spanning domain. Through structural comparison with experimentally-characterized DMT transporters, we identified several conserved PfCRT amino acid sites located in this pocket as robust candidates for mediating substrate transport. Finally, in silico mutagenesis revealed that drug resistance mutations caused drastic changes in the electrostatic potential of the transporter vacuolar entry and pocket, facilitating the escape of protonated CQ and PPQ from the parasite DV.