bluuebunny/crossref_metadata_2025 huggingface dataset:
E-Learning: Grundlagen der Sonografie
Authors: Lüthi Lisa , Jeker Lia , Woermann Ulrich , Hari Roman , Hofer Matthias
Published: June 2020

Zusammenfassung. Die Vermittlung theoretischer und physikalischer Grundlagen der Sonografie stellt für viele Kursleitende von Ultraschallkursen eine Herausforderung dar, weshalb sich der Einsatz von e-Learning anbietet. Ein solches Lernprogramm wurde im Rahmen eines Projekts der SGUM bereits als Modul «Grundlagen der Sonografie» realisiert und nun didaktisch sowie inhaltlich weiterentwickelt, um für Teilnehmende verschiedener Ultraschallkurse als «Pre-Course-Assignment» angeboten zu werden. Basierend auf theoretischen Erkenntnissen sowie der Evaluation des bisherigen e-Learnings wurden die Grundsätze für die Überarbeitung des Lernprogramms erarbeitet und anschliessend umgesetzt. Nach Bearbeitung der vier Kapitel sollen die Nutzer bereit sein, ein Ultraschallgerät zu bedienen und die groben physikalischen Grundsätze zu verstehen. Dieser Artikel beschreibt das didaktische Konzept der Überarbeitung dieses e-Learnings, die Inhalte des Endprodukts und deren Bedeutung für die Praxis.
Design and Research of CAS‐CIG for Earth System Models
Authors: Wang T. , Jiang J. , Zhang M. , Zhang H. , He J. , Hao H. , Chi X.
Published: June 2020

The Chinese Academy of Sciences Coupling Interface Generator (CAS‐CIG) is designed to address the complexities of the development and coupling of different component models in Earth System Models based on the Coupler 7 of the Community Earth System Model (CESM). Its application in the Chinese Academy of Sciences Earth System Model (CAS‐ESM) is described. The CAS‐CIG automatically generates the coupler code through a simple configuration file when a component model is accessed, enabling different component models to be easily ported to CPL7 to create simulation cases. Combined with the automatic generation of compile scripts, the precompilation and run directories are directly formed. The component model integration, model selection, experimental setup, and platform migration can be all accomplished in the CAS‐CIG. Verification of the CAS‐CIG is presented to show that the automatically generated codes can identically reproduce the simulation results of CAS‐ESM. CAS‐CIG presents a software tool for modeling centers to investigate the impact of component model selections on simulations of climate and weather.
Projected Changes in Extreme Precipitation in a 60‐km AGCM Large Ensemble and Their Dependence on Return Periods
Authors: Mizuta Ryo , Endo Hirokazu
Published: June 2020

The dependence of projected changes in extreme precipitation on the return period, as well as on the temporal and spatial scales, is investigated using a large ensemble climate simulation with a 60‐km resolution global atmospheric model. The rate of increase in extreme precipitation is noticeably larger for longer return values in most parts of the world. While thermodynamic contribution to this increase generally follows the Clausius‐Clapeyron relationship for all return periods, dynamic contribution determines the dependence on the return periods. While the dependence on the temporal scales of precipitation has similar characteristics, that on spatial scales is not large. Composites for days with the 100‐year return value show that upward motion is enhanced in the middle and upper troposphere, accompanied by the enhanced horizontal water vapor convergence below. It suggests that an increase in latent heat release due to the water vapor increase plays a significant role in the dynamic contribution.
Global Land Monsoon Precipitation Changes in CMIP6 Projections
Authors: Chen Ziming , Zhou Tianjun , Zhang Lixia , Chen Xiaolong , Zhang Wenxia , Jiang Jie
Published: June 2020

Changes in global land monsoon (GLM) precipitation determine the local water resource, affecting two thirds of global population. The future changes in GLM summer precipitation and the sources of projection uncertainty under four scenarios are investigated using the Coupled Model Intercomparison Project Phase 6 (CMIP6) models. The GLM summer precipitation is projected to increase by 1.76 ± 1.57% (2.54 ± 2.22%), 1.33 ± 1.97% (3.52 ± 3.05%), 0.96 ± 2.04% (3.51 ± 4.97%), and 1.71 ± 2.38% (5.75 ± 5.92%) in the near (long) term under Shared Socioeconomic Pathway (SSP) 1–2.6, SSP2–4.5, SSP3–7.0, and SSP5–8.5, respectively. The enhancement is caused by thermodynamic responses due to increased moisture, which is partly offset by dynamic responses due to weakened circulation. The uncertainty in GLM precipitation projection is the largest in SSP5–8.5 long‐term projection. The uncertainty of submonsoon precipitation projections is larger than that in GLM precipitation. The uncertainty of monsoon precipitation projection arises from the circulation changes, which can be partly explained by model‐dependent response to uniform sea surface temperature warming.
Thermospheric Neutral Winds Above the Oukaimeden Observatory: Effects of Geomagnetic Activity
Authors: Loutfi A. , Bounhir A. , Pitout F. , Benkhaldoun Z. , Makela J. J.
Published: June 2020

In the context of space weather, we investigate the effect of geomagnetic activity on Earth's thermosphere above the Oukaimeden Observatory in Morocco (geographic coordinates: 31.206°N, 7.866°W; magnetic latitude: 22.77°N) over 3 years from 2014 to 2016. The observatory is equipped with a Fabry‐Perot interferometer (FPI) that provides measurements of thermospheric wind speed. In this study 41 disturbed nights (with SYM‐H ≤ −50 nT, Kp ≥ 5) were identified and analyzed. We have characterized the meridional and zonal winds variability and dependence on the solar cycle, during both quiet and disturbed conditions. We have classified the storm time meridional neutral winds into three types of variation. The first type is characterized by traveling atmospheric disturbance (TAD)‐induced circulation: the first TAD coming from the north and the second TAD being transequatorial, coming from the south. This type of storm with TAD‐induced circulation accounts for 59% of the cases. The second type exhibits only slight discrepancies between the disturbed and quiet night flows. These cases account for 33% of the cases. The third type is characterized by the transequatorial wind in whole the night. This last type accounts for 8% of the cases. Finally, we apply a superposed epoch analysis method on the FPI data, and the effect of each phase of the geomagnetic storm on the wind flow and vertical total electron content VTEC has been quantified.
Continental Crustal Growth Processes Revealed by Detrital Zircon Petrochronology: Insights From Zealandia
Authors: Campbell Matthew J. , Rosenbaum Gideon , Allen Charlotte M. , Spandler Carl
Published: June 2020

Establishing spatial, temporal, and geochemical relationships between magmatism and the broader tectonics of accretionary orogens is important for understanding continental crustal growth processes. Here we reconstruct the Paleozoic and Mesozoic evolution of the active continental margin of Zealandia (eastern Gondwana), using a combination of detrital zircon geochronology, trace element geochemistry and Hf isotope data. We find that zircon grains dated 360–160 Ma from New Zealand are characterized by εHfi (+15 to +2) and trace element compositions typical of predominantly juvenile magmatic sources. In contrast, the εHfi (+15 to −5) and trace element compositions of detrital zircon grains dated 245–140 Ma from New Caledonia reflect a mix of juvenile and evolved crustal sources. Secular trends in trace element and Hf isotope compositions of zircon grains suggest that magmatism and continental crustal growth in Zealandia during the Devonian‐Cretaceous were controlled by switches from trench advance to trench retreat. Orogenesis and crustal growth were controlled by a long‐lived westward dipping subduction system, which during the Permian‐Triassic, was intermittently affected by distinct phases of arc accretion (e.g., of the Brook Street intraoceanic arc) and orogenesis (e.g., driven by trench advance). These phases of orogenesis coincided with the Gondwanide Orogen (265–230 Ma), which might have been controlled by a plate‐scale reorganization event following the final assembly of Pangea supercontinent.
El Niño Diversity Across Boreal Spring Predictability Barrier
Authors: Wang Bin , Luo Xiao , Sun Weiyi , Yang Young‐Min , Liu Jian
Published: June 2020

El Niño exerts widespread hydroclimate impacts during boreal summer. However, the current prediction of El Niño across boreal spring has the most severe forecast errors, partially due to the lack of understanding diversified El Niño onset and decay. Here we show, through nonlinear k‐means cluster analysis of evolutions of 40 El Niño events since 1870, El Niño exhibits complex and diverse flavors in its onset and decay across boreal spring predictability barrier. We detected three types of El Niño onset and three types of decay. Each type exhibits distinct coupled dynamics, precursors, and hydroclimate impacts. The results guide the prediction of different types of El Niño transition amid spring predictability barrier and global land precipitation during early and late boreal summer. The new classification offers a metric to evaluate performances of climate models and to project future change of El Niño properties and its predictability.
The Influence of Magma Mixing on the Composition of Andesite Magmas and Silicic Eruption Style
Authors: Hodge K. F. , Jellinek A. M.
Published: June 2020

Although inhibited on established fluid mechanical grounds, extensive magma mixing can play a critical role in creating andesite magmas at volcanic arcs and triggering effusive or explosive volcanism. We use analog experiments, scaling theory, and thermodynamic modeling of natural volcanic systems to show that mechanical mixing is enhanced if an intruding magma crystallizes to acquire a yield strength. Mafic magmas intruding highly silicic reservoirs will fragment as crystal‐sized blobs/enclaves to produce textural homogeneity at the outcrop scale and heterogeneity at the scale of individual crystals. Rapid degassing from these enclaves can favor the production of permeable magmatic foams that facilitate gas loss from the reservoir and effusive volcanism. Crystallizing magmas intruding similar composition reservoirs of comparable or smaller effective viscosity will fragment at scales approaching the dike width. Sluggish degassing and consequent volatile retention in the reservoir can enhance volatile exsolution in an erupting conduit and tendency for explosive volcanism.
The Impact of Sediment Supply on the Initiation and Magnitude of Runoff‐Generated Debris Flows
Authors: Tang Hui , McGuire Luke A. , Kean Jason W. , Smith Joel B.
Published: June 2020

Rainfall intensity‐duration (ID) thresholds are commonly used to assess the potential for runoff‐generated debris flows, but the sensitivity of these thresholds to sediment supply, which can change rapidly with time, is relatively unexplored. Furthermore, debris flows often self‐organize into distinct surges, but the factors controlling the magnitude and frequency of these surges, including sediment supply and grain size, are poorly constrained. We use a combination of numerical modeling and debris flow monitoring data from Chalk Cliffs, Colorado, USA, to explore how sediment supply influences rainfall ID thresholds for debris flows and surge properties. Results suggest that rainfall ID thresholds only become sensitive to sediment supply below a sediment thickness threshold. Surge magnitude is a nonmonotonic function of sediment supply (i.e., channel bed sediment thickness and grain size) with the largest surges tending to form at intermediate values of sediment availability with intermediate grain sizes.
Shear‐Parallel Tropical Convective Systems: Importance of Cold Pools and Wind Shear
Authors: Grant Leah D. , Moncrieff Mitchell W. , Lane Todd P. , van den Heever Susan C.
Published: June 2020

The impact of cold pools on line‐orientated convective systems is assessed using idealized simulations of tropical oceanic convection under weak, moderate, and strong wind shear regimes. Cold pools are weakened by suppressing evaporation in the shallow subcloud layer. Analysis of objectively identified convective systems reveals that the convection with weaker cold pools is more often oriented parallel, rather than perpendicular, to the wind shear. The cold pool‐induced orientation changes are most pronounced in the strong shear environment. Interactions between convective orientation and the tropical atmosphere are assessed. Simulations with shear‐parallel convection demonstrate more top‐of‐atmosphere upwelling longwave radiation and less reflected shortwave radiation due to changes in convective anvils, faster‐propagating larger‐scale gravity waves, narrower cross‐shear moisture distributions, and differences in convective momentum fluxes. The results highlight critical interactions across convective scales, mesoscales, and climate scales, as well as avenues for parameterizing structural modes of mesoscale‐organized convection in global models.
Morphodynamic Hierarchy and the Fabric of the Sedimentary Record
Authors: Ganti Vamsi , Hajek Elizabeth A. , Leary Kate , Straub Kyle M. , Paola Chris
Published: June 2020

The low temporal completeness of fluvial strata could indicate that recorded events represent unusual and extreme conditions. However, field observations suggest that preserved strata predominantly record relatively common transport conditions—a paradox termed the strange ordinariness of fluvial strata. We theorize that the self‐organization of fluvial systems into a morphodynamic hierarchy that spans bed to basin scales facilitates the preservation of ordinary events in fluvial strata. Using a new probabilistic model and existing field and experimental data sets across these scales, we show that fluvial morphodynamic hierarchy enhances the stratigraphic preservation of medial topography—ordinary events. We show that lower‐order landforms have a higher likelihood of complete preservation when the kinematic rates of evolution of successive levels in the morphodynamic hierarchy are comparable. We highlight how relative changes in kinematic rates of evolution of successive levels in the morphodynamic hierarchy can manifest as major shifts in stratigraphic architecture through Earth history.
Spatial Dependence of Floods Shaped by Spatiotemporal Variations in Meteorological and Land‐Surface Processes
Authors: Brunner Manuela I. , Gilleland Eric , Wood Andy , Swain Daniel L. , Clark Martyn
Published: June 2020

Floods often affect large regions and cause adverse societal impacts. Regional flood hazard and risk assessments therefore require a realistic representation of spatial flood dependencies to avoid the overestimation or underestimation of risk. However, it is not yet well understood how spatial flood dependence, that is, the degree of co‐occurrence of floods at different locations, varies in space and time and which processes influence the strength of this dependence. We identify regions in the United States with seasonally similar flood behavior and analyze processes governing spatial dependence. We find that spatial flood dependence varies regionally and seasonally and is generally strongest in winter and spring and weakest in summer and fall. Moreover, we find that land‐surface processes are crucial in shaping the spatiotemporal characteristics of flood events. We conclude that the regional and seasonal variations in spatial flood dependencies must be considered when conducting current and future flood risk assessments.
Feedback and Ballooning Instabilities in the Magnetosphere‐Ionosphere Coupling
Authors: Watanabe T.‐H.
Published: June 2020

A unified model for the feedback and ballooning instabilities in the magnetosphere‐ionosphere (M‐I) coupling is developed by means of the reduced magnetohydrodynamic and two‐fluid equations, involving the local current closure and the ionospheric conductivity change in a scale of auroral fine structures, self‐consistently. In a low pressure gradient case, the Alfvén harmonics are destabilized through the feedback mechanism, while the ballooning instability appears if the magnetospheric pressure gradient exceeds a critical value. Transition of the dominant instability between the feedback and ballooning modes is brought by change of the normalized pressure gradient or the convection electric field in the magnetosphere. The obtained results imply a variety of appearance of auroral arcs and beads in the M‐I coupling system.
Short‐term Impacts of Arctic Summer Cyclones on Sea Ice Extent in the Marginal Ice Zone
Authors: Finocchio Peter M. , Doyle James D. , Stern Daniel P. , Fearon Matthew G.
Published: June 2020

The degree to which Arctic cyclones locally affect sea ice cover during the melt season is unclear. To address this, we use the ERA‐5 reanalysis to statistically analyze how surface energy fluxes and wind forcing from Arctic cyclones in the marginal ice zone between May and August (1999–2018) locally affect sea ice extent on 1–10 day time scales. In May and June, cyclones decelerate the local seasonal loss of sea ice extent compared to when no cyclone is present, which we hypothesize is due to cyclones reducing net shortwave radiative fluxes at the surface. By July and August, cyclones no longer decelerate the seasonal loss of sea ice extent, despite still reducing the net surface energy flux. Surface wind forcing across the ice edge only explains up to 13.5% of the variance in local sea ice extent in August, suggesting that processes other than wind‐induced drift and atmospheric energy fluxes drive late‐summer sea ice extent variability.
Inversion of the Energetic Electron “Zebra Stripe” Pattern Present in the Earth's Inner Belt and Slot Region: First Observations and Interpretation
Authors: Lejosne Solène , Mozer F. S.
Published: June 2020

Energetic electron spectra in the Earth's inner belt and slot region usually display extrema at some energies that form uninterrupted lines when color‐coded in two‐dimensional maps in which one axis represents the normalized equatorial distance, L, and the other axis represents kinetic energy. These patterns are called “zebra stripes.” This letter presents the first observations of zebra stripe inversions: Lines of local minima in the electron spectra at low L values (below L = 2) turn into lines of local maxima in the electron spectra at higher L values, and vice versa. The observations are interpreted by specifying the connection between fluctuations in directional differential fluxes and radial disturbances of trapped population drift motion. The analysis highlights the role of flux energy‐ and radial‐gradients when it comes to determining radial motion from particle data. The underlying method applies to a variety of problems, whether at Earth or at the outer planets.
Charon: A Brief History of Tides
Authors: Rhoden Alyssa Rose , Skjetne Helle L. , Henning Wade G. , Hurford Terry A. , Walsh Kevin J. , Stern S. A. , Olkin C. B. , Spencer J. R. , Weaver H. A. , Young L. A. , Ennico K. ,   and the New Horizons Team
Published: June 2020

In 2015, the New Horizons spacecraft flew past Pluto and its moon Charon, providing the first clear look at Charon's surface. New Horizons images revealed an ancient surface, a large, intricate canyon system, and many fractures, among other geologic features. Here, we assess whether tidal stresses played a significant role in the formation of Charon's tensile fractures. Although presently in a circular orbit, most scenarios for Charon's orbital evolution include an eccentric orbit for some period of time and possibly an internal ocean. Past work has shown that these conditions could have generated stresses comparable in magnitude to other tidally fractured moons, such as Europa and Enceladus. However, we find no correlation between observed fracture orientations and those predicted to form due to eccentricity driven tidal stress. It, thus, seems more likely that Charon's orbit circularized before its ocean froze and that either tidal stresses alone were insufficient to fracture the surface or subsequent resurfacing removed these ancient fractures.
The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma
Authors: Crawford Lisa J. , Campbell David C. , Morgan Jonathan J. , Lawson Michelle A. , Down Jennifer M. , Chauhan Dharminder , McAvera Roisin M. , Morris Treen C. , Hamilton Claudia , Krishnan Aswini , Rajalingam Krishnaraj , Chantry Andrew D. , Irvine Alexandra E.
Published: June 2020

Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM.
First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor
Authors: Plummer Ruth , Dua Divyanshu , Cresti Nicola , Drew Yvette , Stephens Peter , Foegh Marie , Knudsen Steen , Sachdev Pallavi , Mistry Bipin M. , Dixit Vaishali , McGonigle Sharon , Hall Nancy , Matijevic Mark , McGrath Shannon , Sarker Debashis
Published: June 2020

Background

This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor.

Methods

E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50–800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines.

Results

Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue,n = 4, 800 mg; anaphylaxis,n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50–800-mg oral dosing.

Conclusion

The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP.

Clinical trial registration

www.ClinicalTrials.gov code: NCT01618136.
Properties of structural variants and short tandem repeats associated with gene expression and complex traits
Authors: Jakubosky David , D’Antonio Matteo , Bonder Marc Jan , Smail Craig , Donovan Margaret K. R. , Young Greenwald William W. , Matsui Hiroko ,   i2QTL Consortium, Bonder Marc J. , Cai Na , Carcamo-Orive Ivan , D’Antonio Matteo , Frazer Kelly A. , Young Greenwald William W. , Jakubosky David , Knowles Joshua W. , Matsui Hiroko , McCarthy Davis J. , Mirauta Bogdan A. , Montgomery Stephen B. , Quertermous Thomas , Seaton Daniel D. , Smail Craig , Smith Erin N. , Stegle Oliver , D’Antonio-Chronowska Agnieszka , Stegle Oliver , Smith Erin N. , Montgomery Stephen B. , DeBoever Christopher , Frazer Kelly A.
Published: June 2020

Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.
Multisecond ligand dissociation dynamics from atomistic simulations
Authors: Wolf Steffen , Lickert Benjamin , Bray Simon , Stock Gerhard
Published: June 2020

Coarse-graining of fully atomistic molecular dynamics simulations is a long-standing goal in order to allow the description of processes occurring on biologically relevant timescales. For example, the prediction of pathways, rates and rate-limiting steps in protein-ligand unbinding is crucial for modern drug discovery. To achieve the enhanced sampling, we perform dissipation-corrected targeted molecular dynamics simulations, which yield free energy and friction profiles of molecular processes under consideration. Subsequently, we use these fields to perform temperature-boosted Langevin simulations which account for the desired kinetics occurring on multisecond timescales and beyond. Adopting the dissociation of solvated sodium chloride, trypsin-benzamidine and Hsp90-inhibitor protein-ligand complexes as test problems, we reproduce rates from molecular dynamics simulation and experiments within a factor of 2–20, and dissociation constants within a factor of 1–4. Analysis of friction profiles reveals that binding and unbinding dynamics are mediated by changes of the surrounding hydration shells in all investigated systems.
Hardening in Au-Ag nanoboxes from stacking fault-dislocation interactions
Authors: Patil Radhika P. , Doan David , Aitken Zachary H. , Chen Shuai , Kiani Mehrdad T. , Barr Christopher M. , Hattar Khalid , Zhang Yong-Wei , Gu X. Wendy
Published: June 2020

Porous, nano-architected metals with dimensions down to ~10 nm are predicted to have extraordinarily high strength and stiffness per weight, but have been challenging to fabricate and test experimentally. Here, we use colloidal synthesis to make ~140 nm length and ~15 nm wall thickness hollow Au-Ag nanoboxes with smooth and rough surfaces. In situ scanning electron microscope and transmission electron microscope testing of the smooth and rough nanoboxes show them to yield at 130 ± 45 MPa and 96 ± 31 MPa respectively, with significant strain hardening. A higher strain hardening rate is seen in rough nanoboxes than smooth nanoboxes. Finite element modeling is used to show that the structure of the nanoboxes is not responsible for the hardening behavior suggesting that material mechanisms are the source of observed hardening. Molecular dynamics simulations indicate that hardening is a result of interactions between dislocations and the associated increase in dislocation density.
Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine
Authors: Huang Kerui , Miao Ting , Chang Kai , Kim Jinoh , Kang Ping , Jiang Qiuhan , Simmonds Andrew J. , Di Cara Francesca , Bai Hua
Published: June 2020

Aging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. We show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. We term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity. Thus, our studies identify an important role of hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.
Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
Authors: Verma Kanika , Saxena Kanika , Donaka Rajashekar , Chaphalkar Aseem , Rai Manish Kumar , Shukla Anurag , Zaidi Zainab , Dandage Rohan , Shanmugam Dhanasekaran , Chakraborty Kausik
Published: June 2020

Metabolic changes alter the cellular milieu; can this also change intracellular protein folding? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change protein folding, arguably, it should also alter mutational buffering. Here we find that altered cellular metabolic states inE. colibuffer distinct mutations on model proteins. Buffered-mutants have folding problems in vivo and are differently chaperoned in different metabolic states. Notably, this assistance is dependent upon the metabolites and not on the increase in canonical chaperone machineries. Being able to reconstitute the folding assistance afforded by metabolites in vitro, we propose that changes in metabolite concentrations have the potential to alter protein folding capacity. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in cellular proteostasis.
Impact of alkaloids in food consumption, metabolism and survival in a blood-sucking insect
Authors: Muñoz Ignacio J. , Schilman Pablo E. , Barrozo Romina B.
Published: June 2020

The sense of taste provides information about the “good” or “bad” quality of a food source, which may be potentially nutritious or toxic. Most alkaloids taste bitter to humans, and because bitter taste is synonymous of noxious food, they are generally rejected. This response may be due to an innate low palatability or due to a malaise that occurs after food ingestion, which could even lead to death. We investigated in the kissing bug Rhodnius prolixus, whether alkaloids such as quinine, caffeine and theophylline, are merely distasteful, or if anti-appetitive responses are caused by a post-ingestion physiological effect, or both of these options. Although anti-appetitive responses were observed for the three alkaloids, only caffeine and theophylline affect metabolic and respiratory parameters that reflected an underlying physiological stress following their ingestion. Furthermore, caffeine caused the highest mortality. In contrast, quinine appears to be a merely unpalatable compound. The sense of taste helps insects to avoid making wrong feeding decisions, such as the intake of bitter/toxic foods, and thus avoid potentially harmful effects on health, a mechanism preserved in obligate hematophagous insects.
Genome-enabled phylogenetic and functional reconstruction of an araphid pennate diatom Plagiostriata sp. CCMP470, previously assigned as a radial centric diatom, and its bacterial commensal
Authors: Sato Shinya , Nanjappa Deepak , Dorrell Richard G. , Vieira Fabio Rocha Jimenez , Kazamia Elena , Tirichine Leila , Veluchamy Alaguraj , Heilig Roland , Aury Jean-Marc , Jaillon Olivier , Wincker Patrick , Fussy Zoltan , Obornik Miroslav , Muñoz-Gómez Sergio A. , Mann David G. , Bowler Chris , Zingone Adriana
Published: June 2020

Diatoms are an ecologically fundamental and highly diverse group of algae, dominating marine primary production in both open-water and coastal communities. The diatoms include both centric species, which may have radial or polar symmetry, and the pennates, which include raphid and araphid species and arose within the centric lineage. Here, we use combined microscopic and molecular information to reclassify a diatom strain CCMP470, previously annotated as a radial centric species related to Leptocylindrus danicus, as an araphid pennate species in the staurosiroid lineage, within the genus Plagiostriata. CCMP470 shares key ultrastructural features with Plagiostriata taxa, such as the presence of a sternum with parallel striae, and the presence of a highly reduced labiate process on its valve; and this evolutionary position is robustly supported by multigene phylogenetic analysis. We additionally present a draft genome of CCMP470, which is the first genome available for a staurosiroid lineage. 270 Pfams (19%) found in the CCMP470 genome are not known in other diatom genomes, which otherwise does not hold big novelties compared to genomes of non-staurosiroid diatoms. Notably, our DNA library contains the genome of a bacterium within the Rhodobacterales, an alpha-proteobacterial lineage known frequently to associate with algae. We demonstrate the presence of commensal alpha-proteobacterial sequences in other published algal genome and transcriptome datasets, which may indicate widespread and persistent co-occurrence.
Self-healing capacity of fiber-reinforced calcium phosphate cements
Authors: Boehm Anne V. , Meininger Susanne , Gbureck Uwe , Müller Frank A.
Published: June 2020

A major problem concerning the mechanical properties of calcium phosphate cements (CPC) is related to their inherent brittleness, which limits their applicability to non-load bearing bone defects. In this work the preparation of a damage tolerant CPC is presented, where the incorporation of functionalized carbon fibers facilitates steady state flat crack propagation with crack openings below 10 µm. A subsequent self-healing process in simulated body fluid, that mimics the in vivo mineralization of bioactive surfaces, closes the cracks and completely restores the mechanical properties. Hereby, two pathways of self-healing are presented: i) intrinsic healing that bases on the inherent bioactive properties of the cement matrix and chemically treated fibers, and ii) capsule based extrinsic healing, where H2PO4- is released as an initiator for the apatite formation. Such damage tolerant CPCs with self-healing capacity are of particular interest to increase the lifetime of implants as well as in the field of load-bearing bioceramics.
Asymmetric electrode incorporated 2D GeSe for self-biased and efficient photodetection
Authors: Hussain Muhammad , Aftab Sikandar , Jaffery Syed Hassan Abbas , Ali Asif , Hussain Sajjad , Cong Dinh Nguyen , Akhtar Raheel , Seo Yongho , Eom Jonghwa , Gautam Praveen , Noh Hwayong , Jung Jongwan
Published: June 2020

2D layered germanium selenide (GeSe) with p-type conductivity is incorporated with asymmetric contact electrode of chromium/Gold (Cr/Au) and Palladium/Gold (Pd/Au) to design a self-biased, high speed and an efficient photodetector. The photoresponse under photovoltaic effect is investigated for the wavelengths of light (i.e. ~220, ~530 and ~850 nm). The device exhibited promising figures of merit required for efficient photodetection, specifically the Schottky barrier diode is highly sensitive to NIR light irradiation at zero voltage with good reproducibility, which is promising for the emergency application of fire detection and night vision. The high responsivity, detectivity, normalized photocurrent to dark current ratio (NPDR), noise equivalent power (NEP) and response time for illumination of light (~850 nm) are calculated to be 280 mA/W, 4.1 × 109 Jones, 3 × 107 W−1, 9.1 × 10−12 WHz−1/2 and 69 ms respectively. The obtained results suggested that p-GeSe is a novel candidate for SBD optoelectronics-based technologies.
Idiopathic Pulmonary Fibrosis Serum proteomic analysis before and after nintedanib therapy
Authors: Landi Claudia , Bergantini Laura , Cameli Paolo , d’Alessandro Miriana , Carleo Alfonso , Shaba Enxhi , Rottoli Paola , Bini Luca , Bargagli Elena
Published: June 2020

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive disease with a median survival of 2–5 years. Nintedanib is a small tyrosine kinase inhibitor that reduces IPF progression, significantly slowing the annual decline in Forced Vital Capacity (FVC). Very little data is available on the molecular mechanisms of this treatment in IPF, despite a growing interest in the definition of IPF pathogenesis and target therapy. A functional proteomic approach was applied to the analysis of serum samples from IPF patients in order to highlight differential proteins potentially indicative of drug-induced molecular pathways modifications and response to therapy. Twelve serum samples were collected from six IPF patients in care at Siena Regional Referral Center for Interstitial Lung Diseases (ILDs) and treated with nintedanib for one year. Serum samples were analyzed at baseline (T0 before starting therapy) and after one year of treatment (T1) and underwent differential proteomic and bioinformatic analysis. Proteomic analysis revealed 13 protein species that were significantly increased after one year of treatment. When the targets of nintedanib (VEGFR, FGFR and PDGFR) were added, enrichment analysis extracted molecular pathways and process networks involved in cell differentiation (haptoglobin and albumin), coagulation (antithrombin III), epithelial mesenchymal transition, cell proliferation and transmigration. PI3K and MAPK induced up-regulation of apolipoprotein C3. Proteomic study found 13 protein species up-regulated in IPF patients after one year of nintedanib treatment. Haptoglobin, a central hub of our analysis was validated by 2D-WB and ELISA as theranostic marker in a more numerous populations of patients.
Characteristics of Adolescents and Young adults with HIV in the Republic of Korea from 2010 through 2015
Authors: Yoo Myeongsu , Seong Jaehyun , Yoon Jae-Gyu , Cha Jeong-ok , Chung Yoon-Seok , Kim Kisoon , Kee Mee-Kyung
Published: June 2020

Although the number of newly diagnosed cases of HIV is decreasing worldwide, those in Korea have been steadily on the rise, especially among adolescents (ages 10–19 years) and young adults (ages 20–29 years). To identify the characteristics in the new diagnosis among these age groups, we analyzed HIV testing sizes and HIV prevalence under the national HIV surveillance system in Korea in the last six years. We collected data of HIV tests conducted at Blood Banks (BB), Public Health Centers (PHCs), and Military Manpower Administration (MMA) nationwide every year from 2010 to 2015, except for anonymous tests. HIV prevalence, calculated as the number of new HIV-diagnosed cases per 10,000 test-takers per year, was analyzed according to sex, age, institution, and reason for HIV testing. Data were analyzed using logistic regression. In the three testing institutes, there were new cases of HIV with 50% and 75% of cases diagnosed in young adults and adolescents, respectively. The total size of HIV tests at the three sites was approximately 3.5 million tests per year; 80% of these were conducted in BBs, 10% in PHCs, and 10% in MMA. HIV prevalence, according to age, increased across all age groups for the six years, especially prevalent in young adults doubled during that period (1.01 per 10,000 test-takers in 2010, 2.45 in 2015). HIV prevalence among the “suspected” young male adults who visited PHCs for tests, was highest during the six years, increasing 6.5 times in the last two years (315.79 per 10,000 test-takers in 2014, 335.55 in 2015) compared to before 2014. We identified the characteristics of growing HIV infection in Korea as the increase of HIV prevalence among the suspected of young male adults at PHCs. Further, we propose that HIV prevalence in MMA can be used as an essential index for national HIV surveillance of adolescent boys in Korea.
Protection of layers and breeders against homologous or heterologous HPAIv by vaccines from Korean national antigen bank
Authors: Kang Yong-Myung , Cho Hyun-Kyu , Kim Hyun-Mi , Lee Chi-Ho , Kim Do-Young , Choi Sang-Hyun , Lee Myoung-Heon , Kang Hyun-Mi
Published: June 2020

Korean government has selected and stocked five type antigens of two clades as Korean national antigen bank having high possibility of introduction to Korea. We aimed to evaluate the efficacy of the clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines from the Korean avian influenza (AI) national antigen bank for emergency preparedness for their potency and protective efficacy against lethal homologous and heterologous viruses in layer and breeder chickens practically. The PD50 (dose of vaccine that protects 50% of chickens from viral challenge) of all vaccinated groups was >50, which was satisfied with minimum antigen requirement of OIE, and the PD50 levels of the two vaccines differed depending on strain and chicken breed. In homologous challenge, all vaccinated groups exhibited 100% survival with no clinical symptoms and high levels of pre-challenge protective immunity (7.2–8.5 log2), although they did not completely prevent virus shedding. On the other hand, against heterologous virus challenge, vaccinated animals exhibited 62.5–80% survival with lower antibody titers (2.3–3.4 log2) and a longer period of virus shedding (14 days post infection [dpi]). Our results suggest that the clade 2.3.2.1c and 2.3.4.4c H5Nx vaccines are good candidates for emergency vaccination of commercial chickens and support the idea that close genetic matching between vaccine and challenge virus provides the best protection.
Rapeseed-based diet modulates the imputed functions of gut microbiome in growing-finishing pigs
Authors: Umu Özgün Candan Onarman , Mydland Liv Torunn , Øverland Margareth , Press Charles McLean , Sørum Henning
Published: June 2020

Rapeseed meal is a sustainable feed ingredient that can be used as an alternative to imported soybean meal in European pig production. The gut microbiota plays an important role on pig physiology and health but the impact on microbiota of using rapeseed in diets is still not well known. In this study, 84 purebred Norwegian Landrace pigs with average initial weight of 25 kg were divided into two groups and fed for approximately three months with either a control diet containing soybean meal (CON) or a high-fiber experimental diet where 20% rapeseed meal (RSF) was included as an alternative to soybean meal in CON. The composition and function of microbiome in gut digesta samples were analyzed by performing 16S rRNA gene sequencing and culturing of bacteria. The microbiota diversity and composition were similar between the dietary treatments; however, relative abundance of a variety of bacterial groups and imputed functions of microbiome in the ileum and large intestine were altered when the pigs were fed with a rapeseed-based diet. It was notable that the immune-inducing bacterial group Mucispirillum and anti-inflammatory stimulating bacteria Lachnospira were more abundant in the ileum and large intestine of the RSF group, respectively. Moreover, there was a higher abundance of major amino acid fermenters and amylolytic bacteria in the CON group and a high abundance of putative short chain fatty acid producers in RSF group. In comparison with the CON group, the gut microbiome of RSF group possessed an enhanced potential for carbohydrate and energy metabolism and a reduced potential for bacterial pathogenicity-related pathways.
Competitive ability and plasticity of Wedelia trilobata (L.) under wetland hydrological variations
Authors: Javed Qaiser , Sun Jianfan , Azeem Ahmad , Jabran Khawar , Du Daolin
Published: June 2020

Growth behavior of different species under different habitats can be studied by comparing the production of biomass, plasticity index and relative competitive interaction. However, these functional traits of invasive species received rare consideration for determining the invasion success of invasive species at wetlands. Here, we examined the effect of water depth at 5 cm and 15 cm (static and fluctuated) with different nutrient concentrations (full-strength (n1), 1/4-strength (n2) and 1/8-strength (n3) Hoagland solution) on functional traits of invasive Wedelia trilobata and its congener native Wedelia chinensis under mono and mixed culture. Water depth of 5 cm with any of the nutrient treatments (n1, n2 and n3) significantly restrained the photosynthesis, leaf nitrogen and photosynthetic nitrogen use efficiency (PNUE) of both W. trilobata and W. chinensis. While, increase in the water depth to 15 cm with low nutrient treatment (n3) reduced more of biomass of W. chinensis under mixed culture. However, relative competition interaction (RCI) was recorded positive for W. trilobata and seemingly W. trilobata benefited more from RCI under high-fluctuated water depth at 15 cm in mixed culture. Therefore, higher PNUE, more competitive ability and higher plasticity may contribute to the invasiveness of W. trilobata in wetlands.
Structural evolution and mechanism of strain glass transition in Ti48.7Ni51.3 shape memory alloy studied by anomalous small-angle X-ray scattering
Authors: Huang Yung-Chien , Tsao Cheng-Si , Wu Shyi-Kaan
Published: June 2020

The in-situ anomalous small-angle X-ray scattering (ASAXS) technique was used to investigate the strain glass transition (SGT) in as-quenched Ti48.7Ni51.3 shape memory alloy during a thermal cycle of 30 °C to the SGT temperature Tg (−50 °C) and then to 30 °C again. The Ni atoms play a critical role as point defects in the SGT mechanism and are very difficult to characterize using conventional tools. ASAXS identified the distribution of Ni atoms in nanodomains, which have a disk-like core–shell configuration with a Ni-rich shell and a highly Ni-rich core. Moreover, the morphological evolution, growth and shrinkage of the highly Ni-rich core domains during the thermal cycle through Tg are demonstrated. The enhancement and reversible behavior of the local lamellar ordering arrangement of nanodomains during the SGT process at Tg are revealed. The structural evolution and local ordering arrangement of nanodomains can play a role in hindering martensitic transformation. The ASAXS results provide new knowledge about the SGT beyond that from current simulation works. However, this corresponding structure of the nanodomains was destroyed when the specimen was heated to 250 °C.