bluuebunny/crossref_metadata_2025 huggingface dataset:
FM14 Session 1: Bridging the Astronomy Research and Outreach Communities - Recent Highlights, Emerging Collaborations, Best Practices and Support Structures
Authors: Cheung Sze-leung , Vauclair Sylvie D. , Cui Chenzhou , Li Shanshan , Hanaoka Yoichiro , Hunt Sharon E. , Kawagoe Shio K. , Kusakabe Nobuhiko , Nakamura Shigeru , Maravelias Grigoris , Vourliotis Emmanouel , Marouda Krinio , Belias Ioannis , Kardasis Emmanouel , Papadeas Pierros , Strikis Iakovos D. , Vakalopoulos Eleftherios , Voutyras Orfefs , Marchetti Lucia , Jarrett Thomas H. , Marchis Franck , Malvache Arnaud , Marfisi Laurent , Borot Antonin , Arbouch Emmanuel , Villicaña-Pedraza I. , Carreto-Parra F. , Prugh S. , Lopez K. , Nuss J. , Cadena D. , Lopez V. , Shah Priya
Published: March 2020

Section 1 of the FM14 focus on bridging the astronomy research and outreach communities - recent highlights, emerging collaborations, best practices and support structures. This paper also contains supplementary materials that point to contributed talks and poster presentations that can be found online.
The IAU Strategic Plan for 2020-2030: OAO
Authors: van Dishoeck Ewine F. , Meloy Elmegreen Debra
Published: March 2020

The IAU Strategic Plan for 2020-2030 presents an overview of all of the activities of the IAU along with priorities, key goals, mandates, and specific actions. Here future plans and goals are outlined for the Office of Astronomy for Development (OAO).
Evaluation of NCEP‐FNL and ERA‐Interim Data Sets in Detecting Tibetan Plateau Vortices in May–August of 2000–2015
Authors: Li Lun , Zhang Renhe , Wu Peili
Published: March 2020

Tibetan Plateau vortices (TPVs) are important rainfall triggers in southwestern and eastern China after they move off the plateau. Characteristics of the moving‐off TPVs derived from two gridded data sets, the final operational global analysis data from the Global Forecasting System of National Centers for Environment Prediction (NCEP‐FNL) and the ERA‐interim data from the European Centre for Medium‐Range Weather Forecasts, are evaluated against the Yearbooks of Tibetan Plateau Vortex and Shear Line (YB). Generally, NCEP‐FNL captures more moving‐off TPVs in YB than ERA‐interim does. Both gridded data sets perform the best in capturing the TPVs in YB in May and the worst in July. Zonal propagation distances of TPVs are apparently better revealed in NCEP‐FNL than in ERA‐interim, and the performances of NCEP‐FNL and ERA‐interim in showing the meridional propagation distances and lifespans are similar. Positional deviations of TPVs in NCEP‐FNL and ERA‐interim reveal that both data sets show good skills in presenting the TPVs locations, and NCEP‐FNL generally performs better than ERA‐interim. In both gridded data sets, positional deviations of TPVs are larger before the TPVs move off the plateau than after moving off, and zonal deviations are always larger than meridional deviations. Before the TPVs move off, NCEP‐FNL shows no specific preference for the directions of positional deviations, whereas ERA‐interim tends to present further west TPVs locations relative to those in YB. After the TPVs move off, TPVs in both gridded data sets are always observed to the west and north of the TPVs in YB, which is more significant in ERA‐interim.
Plutonic‐Squishy Lid: A New Global Tectonic Regime Generated by Intrusive Magmatism on Earth‐Like Planets
Authors: Lourenço Diogo L. , Rozel Antoine B. , Ballmer Maxim D. , Tackley Paul J.
Published: March 2020

The thermal and chemical evolution of rocky planets is controlled by their surface tectonics and magmatic processes. On Earth, magmatism is dominated by plutonism/intrusion versus volcanism/extrusion. However, the role of plutonism on planetary tectonics and long‐term evolution of rocky planets has not been systematically studied. We use numerical simulations to systematically investigate the effect of plutonism combined with eruptive volcanism. At low‐to‐intermediate intrusion efficiencies, results reproduce the three common tectonic/convective regimes as are usually obtained in simulations using a viscoplastic rheology: stagnant‐lid (a one‐plate planet), episodic (where the lithosphere is usually stagnant and sometimes overturns into the mantle), and mobile‐lid (similar to plate tectonics). At high intrusion efficiencies, we observe a new additional regime called “plutonic‐squishy lid.” This regime is characterized by a set of small, strong plates separated by warm and weak regions generated by plutonism. Eclogitic drippings and lithospheric delaminations often occur close to these weak regions, which leads to significant surface velocities toward the focus of delamination, even if subduction is not active. The location of the plate boundaries is strongly time dependent and mainly occurs in regions of magma intrusion, leading to small, ephemeral plates. The plutonic‐squishy‐lid regime is also distinctive from other regimes because it generates a thin lithosphere, which results in high conductive heat fluxes and lower internal mantle temperatures when compared to a stagnant lid. This regime has the potential to be applicable to the Early Archean Earth and present‐day Venus, as it combines elements of both protoplate tectonic and vertical tectonic models.
Finite‐Frequency Sensitivity Kernels for Seismic Noise Interferometry Based on Differential Time Measurements
Authors: Liu Xin
Published: March 2020

Full waveform adjoint tomography has achieved great success in applications from global Earth structure using earthquakes to exploration seismology using active sources. When combined with ambient seismic noise data, however, the ambient noise cross correlations are subject to strong variability and bias due to nonstationary and unevenly distributed noise sources. As a result, the shape of the structure sensitivity kernel can deviate significantly from the classic banana‐doughnut kernel of a point source, which has been used in previous studies as an inference from empirical Green's function and contains bias. In this study I calculate the sensitivity kernel for ambient noise cross correlation by introducing an additional station to the classic two‐station setting. I compute sensitivity kernels for differential traveltime measurements. These differential sensitivity kernels show promise for canceling the overlapping part of the original source and structure kernels for pairs of stations in interferometry, thus significantly reducing the effect of nonisotropically distributed and nonstationary noise sources. I apply the ambient noise differential sensitivity kernel to synthetic data examples based on 2‐D membrane waves, though the approach will apply for 3‐D as well. Our results for multiple station pairs show promise for velocity tomography based on seismic noise interferometry when perfect information on noise source distribution is not available.
The Lithospheric Thickness Control on the Compositional Variation of Continental Intraplate Basalts: A Demonstration Using the Cenozoic Basalts and Clinopyroxene Megacrysts From Eastern China
Authors: Sun Pu , Niu Yaoling , Guo Pengyuan , Duan Meng , Wang Xiaohong , Gong Hongmei , Xiao Yuanyuan
Published: March 2020

Studies on intraplate ocean island basalts have demonstrated the control of lithosphere thickness on the extent of melting and pressure of melt extraction (i.e., the lid effect). However, whether lithosphere thickness also controls the composition of within‐continent basalts remains unclear. Here, we test this hypothesis by studying the Cenozoic basalts contaitning clinopyroxene megacrysts from 10 localities throughout eastern continental China with a north‐south spatial coverage in excess of 2,500 km. Indeed, the geochemical parameters (e.g., abundances and ratios of major and trace elements) correlate well with the depth of the lithosphere‐asthenosphere boundary (LAB) calculated using the clinopyroxene barometry, showing significant lithospheric thickness control on basalt compositions. These observations offer further evidence for melt pooling (a melt rich layer) close beneath the LAB as a “stable magma reservoir” for crystallizing compositionally uniform clinopyroxene megacrysts to be carried by subsequent pulses of melt transport and eruption.
Biophysical Interactions in Driving the Summer Monsoon Chlorophyll Bloom Off the Somalia Coast
Authors: Lakshmi R. S. , Chatterjee Abhisek , Prakash Satya , Mathew Teesha
Published: March 2020

The biophysical interactions along the Somali coast are discussed during summer monsoon based on a numerical model study. The Somali coast is known to be the fifth largest upwelling region of the world ocean and one of the most productive regions of the globe. Based on scattered observations, mostly dated back to 1960s, it is widely accepted that the strong chlorophyll bloom along the Somali coast during summer is driven by upwelled nutrient flux. We show that the upwelling‐driven productivity is primarily limited to the northern part of the coast when examined along the shelf break off the Somalia coast. In contrast, productivity in the south of 9°N is driven by weaker upwelling in the early half of the summer monsoon but later dominated by the wind‐based mixing induced entrainment and therefore shows much weaker chlorophyll concentration than the north. Further, the strong poleward alongshore currents advect the upwelled nutrients away from the southern and central parts of the coast to the north, thereby controlling the biological community over the Somali region. This abundant locally upwelled and remotely advected nutrients support the enhanced growth of diatoms in the northern part of the transect as earlier observed from in situ measurements. However, limited nutrients allow smaller phytoplankton communities to grow in the southern and central sections. We show that nitrate is the primary limiting nutrient for the phytoplankton growth in the central and southern parts of the Somalia coast.
Process‐Based Simulation of Aerosol‐Cloud Interactions in a One‐Dimensional Cirrus Model
Authors: Kärcher B.
Published: March 2020

A new microphysical cirrus model to simulate ice crystal nucleation, depositional growth, and gravitational settling is described. The model tracks individual simulation ice particles in a vertical column of air and allows moisture and heat profiles to be affected by turbulent diffusion. Ice crystal size‐ and supersaturation‐dependent deposition coefficients are employed in a one‐dimensional model framework. This enables the detailed simulation of microphysical feedbacks influencing the outcome of ice nucleation processes in cirrus. The use of spheroidal water vapor fluxes enables the prediction of primary ice crystal shapes once microscopic models describing the vapor uptake on the surfaces of cirrus ice crystals are better constrained. Two applications addressing contrail evolution and cirrus formation demonstrate the potential of the model for advanced studies of aerosol‐cirrus interactions. It is shown that supersaturation in, and microphysical and optical properties of, cirrus are affected by variable deposition coefficients. Vertical variability in ice supersaturation, ice crystal sedimentation, and high turbulent diffusivity all tend to decrease homogeneously nucleated ice number mixing ratios over time, but low ice growth efficiencies counteract this tendency. Vertical mixing induces a tendency to delay the onset of homogeneous freezing. In situations of sustained large‐scale cooling, natural cirrus clouds may often form in air surrounding persistent contrails.
Paleolakes in the Northwest Hellas Region, Mars: Implications for the Regional Geologic History and Paleoclimate
Authors: Zhao Jiannan , Xiao Long , Glotch Timothy D.
Published: March 2020

Hellas basin is one of the largest and oldest impact basins on the Martian surface. Its surrounding highland regions have undergone complicated geologic processes after the formation of Hellas basin. However, the geologic and climatic histories of the highlands surrounding Hellas are still unclear. Paleolakes provide us clues to answer these questions. In this study, we made a detailed investigation of paleolakes in the northwest Hellas region with high‐resolution imaging, topographic, and spectral data. A total of 64 paleolakes were identified with diameters larger than 4 km, in which 49 are newly reported. We calculated basic hydrologic parameters of the paleolakes and analyzed the sedimentary landforms, resurfacing processes, and aqueous minerals in the lake basins. Comprehensive analyses of the geomorphology, mineralogy, and age of the paleolakes revealed the geologic and climatic histories of the northwest Hellas region: a climate transition from warm and wet to semi‐arid happened in Noachian, and then lakes drained in a cold and dry climate in the early Hesperian, contemporary with or followed by a period of intense volcanic activity peaked around 3.3 Ga, and finally in the Amazonian, an extensive glacial event around 0.9 Ga resurfaced most of the paleolakes in the region south of 25°S. Our study also supports the existence of a “Hellas Ocean” and indicates that the Martian climate could have variations on regional scales and further studies are still needed to clarify the details.
Far‐UV Observations of Lunar Rayed Craters with LRO‐LAMP
Authors: Byron B. D. , Retherford K. D. , Greathouse T. K. , Wyrick D. , Cahill J. T. S. , Hendrix A. R. , Raut U. , Mandt K. E. , Denevi B. W.
Published: March 2020

Using data from the Lunar Reconnaissance Orbiter (LRO) Lyman Alpha Mapping Project (LAMP), we investigate the spectral properties of rayed craters in the far‐ultraviolet (FUV). Because LAMP is sensitive to the uppermost layer of the lunar surface and regolith grains, it is ideal for characterizing regolith maturity and space weathering products such as submicroscopic iron. We find that crater rays from a survey of the largest Copernican‐age craters have high Off‐band (155–190 nm)/On‐band (130–155 nm) albedo (Off/On) LAMP product ratios, consistent with immature regolith and low amounts of submicroscopic iron. The Off/On ratio of the highlands crater rays decreases linearly over time (0.095 per 100 My), and we use this trend to estimate the age of Jackson crater (~152 My). Some large young highlands craters (e.g., Tycho, Jackson, Giordano Bruno, and Necho) display lower ratio halos around the crater cavity, at regions where previous studies have suggested abundant impact melt exists. The lower Off/On ratio is likely due to the increased glass component of the regolith at these highlands regions, which would act to increase absorption at Off‐band wavelengths. We also find that ejecta blankets from large maria craters (e.g., Copernicus and Aristillus) have a similar Off/On ratio to the mature background highlands. This supports previous findings that determined that the rays from these craters are composed of highlands material excavated from beneath the maria and subsequently weathered to maturity.
Up to 70 THz bandwidth from an implanted Ge photoconductive antenna excited by a femtosecond Er:fibre laser
Authors: Singh Abhishek , Pashkin Alexej , Winnerl Stephan , Welsch Malte , Beckh Cornelius , Sulzer Philipp , Leitenstorfer Alfred , Helm Manfred , Schneider Harald
Published: March 2020

Phase-stable electromagnetic pulses in the THz frequency range offer several unique capabilities in time-resolved spectroscopy. However, the diversity of their application is limited by the covered spectral bandwidth. In particular, the upper frequency limit of photoconductive emitters - the most widespread technique in THz spectroscopy – reaches only up to 7 THz in the regular transmission mode due to absorption by infrared-active optical phonons. Here, we present ultrabroadband (extending up to 70 THz) THz emission from an Au-implanted Ge emitter that is compatible with mode-locked fibre lasers operating at wavelengths of 1.1 and 1.55 μm with pulse repetition rates of 10 and 20 MHz, respectively. This result opens up the possibility for the development of compact THz photonic devices operating up to multi-THz frequencies that are compatible with Si CMOS technology.
Tomography of the source zone of the great 2011 Tohoku earthquake
Authors: Hua Yuanyuan , Zhao Dapeng , Toyokuni Genti , Xu Yixian
Published: March 2020

The mechanism and rupture process of the giant 2011 Tohoku-oki earthquake (Mw 9.0) are still poorly understood due to lack of permanent near-field observations. Using seismic arrival times recorded by dense seismograph networks on land and at ocean floor, we determine a detailed seismic tomography model of the megathrust zone beneath the Tohoku forearc. Our results show that the coseismic slip of the 2011 Tohoku-oki earthquake initiated at a boundary between a down-dip high-velocity anomaly and an up-dip low-velocity anomaly. The slow anomaly at shallow depths near the Japan trench may reflect low-rigidity materials that are close to the free surface, resulting in large slip and weak high-frequency radiation. Our new tomographic model can account for not only large slip near the trench but also weak high-frequency radiation from the shallow rupture areas.
Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans
Authors: Martins D. A. , Mazibuko N. , Zelaya F. , Vasilakopoulou S. , Loveridge J. , Oates A. , Maltezos S. , Mehta M. , Wastling S. , Howard M. , McAlonan G. , Murphy D. , Williams S. C. R. , Fotopoulou A. , Schuschnig U. , Paloyelis Y.
Published: March 2020

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.
Efficient bidirectional piezo-optomechanical transduction between microwave and optical frequency
Authors: Jiang Wentao , Sarabalis Christopher J. , Dahmani Yanni D. , Patel Rishi N. , Mayor Felix M. , McKenna Timothy P. , Van Laer Raphaël , Safavi-Naeini Amir H.
Published: March 2020

Efficient interconversion of both classical and quantum information between microwave and optical frequency is an important engineering challenge. The optomechanical approach with gigahertz-frequency mechanical devices has the potential to be extremely efficient due to the large optomechanical response of common materials, and the ability to localize mechanical energy into a micron-scale volume. However, existing demonstrations suffer from some combination of low optical quality factor, low electrical-to-mechanical transduction efficiency, and low optomechanical interaction rate. Here we demonstrate an on-chip piezo-optomechanical transducer that systematically addresses all these challenges to achieve nearly three orders of magnitude improvement in conversion efficiency over previous work. Our modulator demonstrates acousto-optic modulation with $${V}_{\pi }$$

V

π

= 0.02 V. We show bidirectional conversion efficiency of $$1{0}^{-5}$$
1

0

−
5

with 3.3 μW  red-detuned optical pump, and $$5.5 \%$$
5.5
%
with 323 μW blue-detuned pump. Further study of quantum transduction at millikelvin temperatures is required to understand how the efficiency and added noise are affected by reduced mechanical dissipation, thermal conductivity, and thermal capacity.
Robust weak antilocalization due to spin-orbital entanglement in Dirac material Sr3SnO
Authors: Nakamura H. , Huang D. , Merz J. , Khalaf E. , Ostrovsky P. , Yaresko A. , Samal D. , Takagi H.
Published: March 2020

The presence of both inversion (P) and time-reversal (T) symmetries in solids leads to a double degeneracy of the electronic bands (Kramers degeneracy). By lifting the degeneracy, spin textures manifest themselves in momentum space, as in topological insulators or in strong Rashba materials. The existence of spin textures with Kramers degeneracy, however, is difficult to observe directly. Here, we use quantum interference measurements to provide evidence for the existence of hidden entanglement between spin and momentum in the antiperovskite-type Dirac material Sr3SnO. We find robust weak antilocalization (WAL) independent of the position of EF. The observed WAL is fitted using a single interference channel at low doping, which implies that the different Dirac valleys are mixed by disorder. Notably, this mixing does not suppress WAL, suggesting contrasting interference physics compared to graphene. We identify scattering among axially spin-momentum locked states as a key process that leads to a spin-orbital entanglement.
Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
Authors: Hodge Rebecca D. , Miller Jeremy A. , Novotny Mark , Kalmbach Brian E. , Ting Jonathan T. , Bakken Trygve E. , Aevermann Brian D. , Barkan Eliza R. , Berkowitz-Cerasano Madeline L. , Cobbs Charles , Diez-Fuertes Francisco , Ding Song-Lin , McCorrison Jamison , Schork Nicholas J. , Shehata Soraya I. , Smith Kimberly A. , Sunkin Susan M. , Tran Danny N. , Venepally Pratap , Yanny Anna Marie , Steemers Frank J. , Phillips John W. , Bernard Amy , Koch Christof , Lasken Roger S. , Scheuermann Richard H. , Lein Ed S.
Published: March 2020

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.
The mTOR pathway is necessary for survival of mice with short telomeres
Authors: Ferrara-Romeo Iole , Martinez Paula , Saraswati Sarita , Whittemore Kurt , Graña-Castro Osvaldo , Thelma Poluha Lydia , Serrano Rosa , Hernandez-Encinas Elena , Blanco-Aparicio Carmen , Maria Flores Juana , Blasco Maria A.
Published: March 2020

Telomerase deficiency leads to age-related diseases and shorter lifespans. Inhibition of the mechanistic target of rapamycin (mTOR) delays aging and age-related pathologies. Here, we show that telomerase deficient mice with short telomeres (G2-Terc−/−) have an hyper-activated mTOR pathway with increased levels of phosphorylated ribosomal S6 protein in liver, skeletal muscle and heart, a target of mTORC1. Transcriptional profiling confirms mTOR activation in G2-Terc−/− livers. Treatment of G2-Terc−/− mice with rapamycin, an inhibitor of mTORC1, decreases survival, in contrast to lifespan extension in wild-type controls. Deletion of mTORC1 downstream S6 kinase 1 in G3-Terc−/− mice also decreases longevity, in contrast to lifespan extension in single S6K1−/− female mice. These findings demonstrate that mTOR is important for survival in the context of short telomeres, and that its inhibition is deleterious in this setting. These results are of clinical interest in the case of human syndromes characterized by critically short telomeres.
Molecular and cellular determinants of motor asymmetry in zebrafish
Authors: Horstick Eric J. , Bayleyen Yared , Burgess Harold A.
Published: March 2020

Asymmetries in motor behavior, such as human hand preference, are observed throughout bilateria. However, neural substrates and developmental signaling pathways that impose underlying functional lateralization on a broadly symmetric nervous system are unknown. Here we report that in the absence of over-riding visual information, zebrafish larvae show intrinsic lateralized motor behavior that is mediated by a cluster of 60 posterior tuberculum (PT) neurons in the forebrain. PT neurons impose motor bias via a projection through the habenular commissure. Acquisition of left/right identity is disrupted by heterozygous mutations in mosaic eyes and mindbomb, genes that regulate Notch signaling. These results define the neuronal substrate for motor asymmetry in a vertebrate and support the idea that haploinsufficiency for genes in a core developmental pathway destabilizes left/right identity.
Embracing the dropouts in single-cell RNA-seq analysis
Authors: Qiu Peng
Published: March 2020

One primary reason that makes single-cell RNA-seq analysis challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Almost all computational algorithms developed for single-cell RNA-seq adopted gene selection, dimension reduction or imputation to address the dropouts. Here, an opposite view is explored. Instead of treating dropouts as a problem to be fixed, we embrace it as a useful signal. We represent the dropout pattern by binarizing single-cell RNA-seq count data, and present a co-occurrence clustering algorithm to cluster cells based on the dropout pattern. We demonstrate in multiple published datasets that the binary dropout pattern is as informative as the quantitative expression of highly variable genes for the purpose of identifying cell types. We expect that recognizing the utility of dropouts provides an alternative direction for developing computational algorithms for single-cell RNA-seq analysis.
Comparison of Fever-reducing Effects in Self-reported Data from the Mobile App: Antipyretic Drugs in Pediatric Patients
Authors: Choi Jiyun , Chang Seyun , Ahn Jong Gyun
Published: March 2020

We compared the fever-reducing efficacy of acetaminophen (AA), ibuprofen (IBU), and dexibuprofen (DEX) using data collected from the mobile healthcare application FeverCoach, which provides parents with guidelines for determining their child’s health condition, according to body temperature. Its dataset includes 4.4 million body temperature measurement records and 1.6 million antipyretics treatment records. Changes in body temperature over time were compared after taking one of three different antipyretics (AA, IBU, and DEX), using a one-way ANOVA followed by a post-hoc analysis. A multivariate linear model was used to further analyze the average body temperature differences, calibrating for the influences of age, weight, and sex. Children administered IBU had average body temperatures that were 0.18 °C (0.17–0.19 °C), 0.25 °C (0.24–0.26 °C), and 0.18 °C (0.17–0.20 °C) lower than those of children administered AA, at time intervals of 1–2 hours, 2–3 hours, and 3–4 hours, respectively. Similarly, children administered DEX had average body temperatures that were 0.24 °C (0.24–0.25 °C), 0.28 °C (0.27–0.29 °C), and 0.12 °C (0.10–0.13 °C) lower than those of children administered AA, at time intervals of 1–2, 2–3, and 3–4 hours, respectively. Although the data were collected from the application by non-professional parents, the analysis showed that IBU and DEX were more effective in reducing body temperature than AA was.
Economic Diversification Supported the Growth of Mongolia’s Nomadic Empires
Authors: Wilkin Shevan , Ventresca Miller Alicia , Miller Bryan K. , Spengler Robert N. , Taylor William T. T. , Fernandes Ricardo , Hagan Richard W. , Bleasdale Madeleine , Zech Jana , Ulziibayar S. , Myagmar Erdene , Boivin Nicole , Roberts Patrick
Published: March 2020

Populations in Mongolia from the late second millennium B.C.E. through the Mongol Empire are traditionally assumed, by archaeologists and historians, to have maintained a highly specialized horse-facilitated form of mobile pastoralism. Until recently, a dearth of direct evidence for prehistoric human diet and subsistence economies in Mongolia has rendered systematic testing of this view impossible. Here, we present stable carbon and nitrogen isotope measurements of human bone collagen, and stable carbon isotope analysis of human enamel bioapatite, from 137 well-dated ancient Mongolian individuals spanning the period c. 4400 B.C.E. to 1300 C.E. Our results demonstrate an increase in consumption of C4plants beginning at c. 800 B.C.E., almost certainly indicative of millet consumption, an interpretation supported by archaeological evidence. The escalating scale of millet consumption on the eastern Eurasian steppe over time, and an expansion of isotopic niche widths, indicate that historic Mongolian empires were supported by a diversification of economic strategies rather than uniform, specialized pastoralism.
Generation of a conditional Flpo/FRT mouse model expressing constitutively active TGFβ in fibroblasts
Authors: Cardot-Ruffino Victoire , Chauvet Véronique , Caligaris Cassandre , Bertrand-Chapel Adrien , Chuvin Nicolas , Pommier Roxane M. , Valcourt Ulrich , Vincent David F. , Martel Sylvie , Aires Sophie , Kaniewski Bastien , Dubus Pierre , Cassier Philippe , Sentis Stéphanie , Bartholin Laurent
Published: March 2020

Transforming growth factor (TGFβ) is a secreted factor, which accumulates in tissues during many physio- and pathological processes such as embryonic development, wound healing, fibrosis and cancer. In order to analyze the effects of increased microenvironmental TGFβ concentration in vivo, we developed a conditional transgenic mouse model (Flpo/Frt system) expressing bioactive TGFβ in fibroblasts, a cell population present in the microenvironment of almost all tissues. To achieve this, we created the genetically-engineered [Fsp1-Flpo; FSFTGFβCA] mouse model. The Fsp1-Flpo allele consists in the Flpo recombinase under the control of the Fsp1 (fibroblast-specific promoter 1) promoter. The FSFTGFβCA allele consists in a transgene encoding a constitutively active mutant form of TGFβ (TGFβCA) under the control of a Frt-STOP-Frt (FSF) cassette. The FSFTGFβCA allele was created to generate this model, and functionally validated by in vitro, ex vivo and in vivo techniques. [Fsp1-Flpo; FSFTGFβCA] animals do not present any obvious phenotype despite the correct expression of TGFβCA transgene in fibroblasts. This [Fsp1-Flpo; FSFTGFβCA] model is highly pertinent for future studies on the effect of increased microenvironmental bioactive TGFβ concentrations in mice bearing Cre-dependent genetic alterations in other compartments (epithelial or immune compartments for instance). These dual recombinase system (DRS) approaches will enable scientists to study uncoupled spatiotemporal regulation of different genetic alterations within the same mouse, thus better replicating the complexity of human diseases.
Development of genetic quality tests for good manufacturing practice-compliant induced pluripotent stem cells and their derivatives
Authors: Jo Hye-Yeong , Han Hyo-Won , Jung Inuk , Ju Ji Hyeon , Park Soon-Jung , Moon Sunghwan , Geum Dongho , Kim Hyemin , Park Han-Jin , Kim Sun , Stacey Glyn N. , Koo Soo Kyung , Park Mi-Hyun , Kim Jung-Hyun
Published: March 2020

Although human induced pluripotent stem cell (hiPSC) lines are karyotypically normal, they retain the potential for mutation in the genome. Accordingly, intensive and relevant quality controls for clinical-grade hiPSCs remain imperative. As a conceptual approach, we performed RNA-seq-based broad-range genetic quality tests on GMP-compliant human leucocyte antigen (HLA)-homozygous hiPSCs and their derivatives under postdistribution conditions to investigate whether sequencing data could provide a basis for future quality control. We found differences in the degree of single-nucleotide polymorphism (SNP) occurring in cells cultured at three collaborating institutes. However, the cells cultured at each centre showed similar trends, in which more SNPs occurred in late-passage hiPSCs than in early-passage hiPSCs after differentiation. In eSNP karyotyping analysis, none of the predicted copy number variations (CNVs) were identified, which confirmed the results of SNP chip-based CNV analysis. HLA genotyping analysis revealed that each cell line was homozygous for HLA-A, HLA-B, and DRB1 and heterozygous for HLA-DPB type. Gene expression profiling showed a similar differentiation ability of early- and late-passage hiPSCs into cardiomyocyte-like, hepatic-like, and neuronal cell types. However, time-course analysis identified five clusters showing different patterns of gene expression, which were mainly related to the immune response. In conclusion, RNA-seq analysis appears to offer an informative genetic quality testing approach for such cell types and allows the early screening of candidate hiPSC seed stocks for clinical use by facilitating safety and potential risk evaluation.
Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination
Authors: Bailey Jason A. , Berry Andrea A. , Travassos Mark A. , Ouattara Amed , Boudova Sarah , Dotsey Emmanuel Y. , Pike Andrew , Jacob Christopher G. , Adams Matthew , Tan John C. , Bannen Ryan M. , Patel Jigar J. , Pablo Jozelyn , Nakajima Rie , Jasinskas Algis , Dutta Sheetij , Takala-Harrison Shannon , Lyke Kirsten E. , Laurens Matthew B. , Niangaly Amadou , Coulibaly Drissa , Kouriba Bourema , Doumbo Ogobara K. , Thera Mahamadou A. , Felgner Philip L. , Plowe Christopher V.
Published: March 2020

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes. Vaccination resulted in dramatically increased seroreactivity to all 263 AMA1 whole-protein variants. High-density peptide analysis revealed that vaccinated children had increases in seroreactivity to four distinct epitopes that exceeded responses to natural infection. A single amino acid change was critical to seroreactivity to peptides in a region of AMA1 associated with strain-specific vaccine efficacy. Antibody measurements using whole antigens may be biased towards conserved, immunodominant epitopes. Peptide microarrays may help to identify immunogenic epitopes, define correlates of vaccine protection, and measure strain-specific vaccine-induced antibodies.
Deep learning applied to hyperspectral endoscopy for online spectral classification
Authors: Grigoroiu Alexandru , Yoon Jonghee , Bohndiek Sarah E.
Published: March 2020

Hyperspectral imaging (HSI) is being explored in endoscopy as a tool to extract biochemical information that may improve contrast for early cancer detection in the gastrointestinal tract. Motion artefacts during medical endoscopy have traditionally limited HSI application, however, recent developments in the field have led to real-time HSI deployments. Unfortunately, traditional HSI analysis methods remain unable to rapidly process the volume of hyperspectral data in order to provide real-time feedback to the operator. Here, a convolutional neural network (CNN) is proposed to enable online classification of data obtained during HSI endoscopy. A five-layered CNN was trained and fine-tuned on a dataset of 300 hyperspectral endoscopy images acquired from a planar Macbeth ColorChecker chart and was able to distinguish between its 18 constituent colors with an average accuracy of 94.3% achieved at 8.8 fps. Performance was then tested on a set of images simulating an endoscopy environment, consisting of color charts warped inside a rigid tube mimicking a lumen. The algorithm proved robust to such variations, with classification accuracies over 90% being obtained despite the variations, with an average drop in accuracy of 2.4% being registered at the points of longest working distance and most inclination. For further validation of the color-based classification system, ex vivo videos of a methylene blue dyed pig esophagus and images of different disease stages in the human esophagus were analyzed, showing spatially distinct color classifications. These results suggest that the CNN has potential to provide color-based classification during real-time HSI in endoscopy.
Evolutionary Traits that Enable Scleractinian Corals to Survive Mass Extinction Events
Authors: Dishon Gal , Grossowicz Michal , Krom Michael , Guy Gilad , Gruber David F. , Tchernov Dan
Published: March 2020

Scleractinian “stony” corals are major habitat engineers, whose skeletons form the framework for the highly diverse, yet increasingly threatened, coral reef ecosystem. Fossil coral skeletons also present a rich record that enables paleontological analysis of coral origins, tracing them back to the Triassic (~241 Myr). While numerous invertebrate lineages were eradicated at the last major mass extinction boundary, the Cretaceous-Tertiary/K-T (66 Myr), a number of Scleractinian corals survived. We review this history and assess traits correlated with K-T mass extinction survival. Disaster-related “survival” traits that emerged from our analysis are: (1) deep water residing (>100 m); (2) cosmopolitan distributions, (3) non-symbiotic, (4) solitary or small colonies and (5) bleaching-resistant. We then compared these traits to the traits of modern Scleractinian corals, using to IUCN Red List data, and report that corals with these same survival traits have relatively stable populations, while those lacking them are presently decreasing in abundance and diversity. This shows corals exhibiting a similar dynamic survival response as seen at the last major extinction, the K-T. While these results could be seen as promising, that some corals may survive the Anthropocene extinction, they also highlight how our relatively-fragile Primate order does not possess analogous “survival” characteristics, nor have a record of mass extinction survival as some corals are capable.
TASH: Toolbox for the Automated Segmentation of Heschl’s gyrus
Authors: Dalboni da Rocha Josué Luiz , Schneider Peter , Benner Jan , Santoro Roberta , Atanasova Tanja , Van De Ville Dimitri , Golestani Narly
Published: March 2020

Auditory cortex volume and shape differences have been observed in the context of phonetic learning, musicianship and dyslexia. Heschl’s gyrus, which includes primary auditory cortex, displays large anatomical variability across individuals and hemispheres. Given this variability, manual labelling is the gold standard for segmenting HG, but is time consuming and error prone. Our novel toolbox, called ‘Toolbox for the Automated Segmentation of HG’ or TASH, automatically segments HG in brain structural MRI data, and extracts measures including its volume, surface area and cortical thickness. TASH builds upon FreeSurfer, which provides an initial segmentation of auditory regions, and implements further steps to perform finer auditory cortex delineation. We validate TASH by showing significant relationships between HG volumes obtained using manual labelling and using TASH, in three independent datasets acquired on different scanners and field strengths, and by showing good qualitative segmentation. We also present two applications of TASH, demonstrating replication and extension of previously published findings of relationships between HG volumes and (a) phonetic learning, and (b) musicianship. In sum, TASH effectively segments HG in a fully automated and reproducible manner, opening up a wide range of applications in the domains of expertise, disease, genetics and brain plasticity.
Intermittent Lactobacilli-containing Vaginal Probiotic or Metronidazole Use to Prevent Bacterial Vaginosis Recurrence: A Pilot Study Incorporating Microscopy and Sequencing
Authors: van de Wijgert Janneke H. H. M. , Verwijs Marijn C. , Agaba Stephen K. , Bronowski Christina , Mwambarangwe Lambert , Uwineza Mireille , Lievens Elke , Nivoliez Adrien , Ravel Jacques , Darby Alistair C.
Published: March 2020

Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7–10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.
CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer
Authors: Friese Christina , Harbst Katja , Borch Troels Holz , Westergaard Marie Christine Wulff , Pedersen Magnus , Kverneland Anders , Jönsson Göran , Donia Marco , Svane Inge Marie , Met Özcan
Published: March 2020

Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) can induce durable complete tumor regression in patients with advanced melanoma. Efforts are currently underway to expand this treatment modality to other cancer types. In the microenvironment of ovarian cancer, the engagement of co-inhibitory immune checkpoint molecules such as CTLA-4 can lead to the inactivation of TILs. Thus, approaches that directly manipulate co-inhibitory pathways within the tumor microenvironment might improve the expansion of tumor-reactive TILs. The initial expansion of TILs for ACT from tumor fragments provides a window of opportunity to manipulate an intact tumor microenvironment and improve CD8+ T-cell output and TIL tumor reactivity. To exploit this, we used a CTLA-4-blocking antibody, added during the initial TIL culture, and found that the blockade of CTLA-4 favored the propagation of CD8+ TILs from ovarian tumor fragments. Interestingly, adding the CTLA-4 blocking antibody in the initial phase of the TIL culture resulted in more potent anti-tumor TILs in comparison to standard TIL cultures. This phenotype was preserved during the rapid expansion phase. Thus, targeting CTLA-4 within the intact tumor microenvironment of tumor fragments enriches tumor-reactive TILs and may improve clinical outcome of TIL-based ACT in ovarian cancer.
Relationships between vocal pitch perception and production: a developmental perspective
Authors: Heller Murray Elizabeth S. , Stepp Cara E.
Published: March 2020

The purpose of this study was to examine the relationships between vocal pitch discrimination abilities and vocal responses to auditory pitch-shifts. Twenty children (6.6–11.7 years) and twenty adults (18–28 years) completed a listening task to determine auditory discrimination abilities to vocal fundamental frequency (fo) as well as two vocalization tasks in which their perceived fo was modulated in real-time. These pitch-shifts were either unexpected, providing information on auditory feedback control, or sustained, providing information on sensorimotor adaptation. Children were subdivided into two groups based on their auditory pitch discrimination abilities; children within two standard deviations of the adult group were classified as having adult-like discrimination abilities (N = 11), whereas children outside of this range were classified as having less sensitive discrimination abilities than adults (N = 9). Children with less sensitive auditory pitch discrimination abilities had significantly larger vocal response magnitudes to unexpected pitch-shifts and significantly smaller vocal response magnitudes to sustained pitch-shifts. Children with less sensitive auditory pitch discrimination abilities may rely more on auditory feedback and thus may be less adept at updating their stored motor programs.
Recombinant collagenase from Grimontia hollisae as a tissue dissociation enzyme for isolating primary cells
Authors: Tanaka Keisuke , Okitsu Teru , Teramura Naoko , Iijima Katsumasa , Hayashida Osamu , Teramae Hiroki , Hattori Shunji
Published: March 2020

Collagenase products are crucial to isolate primary cells in basic research and clinical therapies, where their stability in collagenolytic activity is required. However, currently standard collagenase products fromClostridium histolyticumlack such stability. Previously, we produced a recombinant 74-kDa collagenase fromGrimontia hollisae, which spontaneously became truncated to~60 kDa and possessed no stability. In this study, to generateG. hollisaecollagenase useful as a collagenase product, we designed recombinant 62-kDa collagenase consisting only of the catalytic domain, which exhibits high production efficiency. We demonstrated that this recombinant collagenase is stable and active under physiological conditions. Moreover, it possesses higher specific activity against collagen and cleaves a wider variety of collagens than a standard collagenase product fromC. histolyticum. Furthermore, it dissociated murine pancreata by digesting the collagens within the pancreata in a dose-dependent manner, and this dissociation facilitated isolation of pancreatic islets with masses and numbers comparable to those isolated using the standard collagenase fromC. histolyticum. Implantation of these isolated islets into five diabetic mice led to normalisation of the blood glucose concentrations of all the recipients. These findings suggest that recombinant 62-kDa collagenase fromG. hollisaecan be used as a collagenase product to isolate primary cells.