bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Assessment of Daily Equatorial Plasma Bubble Occurrence Modeling and Forecasting
Authors: Carter B. A. , Currie J. L. , Dao T. , Yizengaw E. , Retterer J. , Terkildsen M. , Groves K. , Caton R.
Published: August 2020

Predicting the daily variability of Equatorial Plasma Bubbles (EPBs) is an ongoing scientific challenge. Various methods for predicting EPBs have been developed, however, the research community is yet to scrutinize the methods for evaluating and comparing these prediction models/techniques. In this study, 12 months of co‐located GPS and UHF scintillation observations spanning South America, Atlantic/Western Africa, Southeast Asia, and Pacific sectors are used to evaluate the Generalized Rayleigh‐Taylor (R‐T) growth rates calculated from the Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM). Various assessment metrics are explored, including the use of significance testing on skill scores for threshold selection. The sensitivity of these skill scores to data set type (i.e., GPS versus UHF) and data set size (30, 50, 60, and 90 days/events) is also investigated. It is shown that between 50 and 90 days is required to achieve a statistically significant skill score. Methods for conducting model‐model comparisons are also explored, including the use of model “sufficiency.” However, it is shown that the results of model‐model comparisons must be carefully interpreted and can be heavily dependent on the data set used. It is also demonstrated that the observation data set must exhibit an appropriate level of daily EPB variability in order to assess the true strength of a given model/technique. Other limitations and considerations on assessment metrics and future challenges for EPB prediction studies are also discussed.
Abiotic Mixing‐Dependent Reaction in a Laboratory Simulated Hyporheic Zone
Authors: Santizo Katherine Y. , Widdowson Mark A. , Hester Erich T.
Published: August 2020

Groundwater (GW) contaminants upwelling toward surface water (SW) can attenuate in the hyporheic zone, with dissolved oxygen (DO) frequently controlling the attenuation. In a laboratory mesocosm, we induced downwelling of SW into the sediments to create a hyporheic flow cell (HFC). We added DO to downwelling SW and sodium sulfite (Na2SO3) to anoxic upwelling GW to induce an abiotic mixing‐dependent reaction along the mixing zone between the HFC and upwelling GW. Using planar optodes and SO4measurements, we observed movement of the DO mixing zone (oxic front position), extent of DO mixing (mixing zone thickness), and location of MD reaction (SO4peak concentration). Oxic front position and mixing zone thickness were stable during nonreactive control experiments, indicating that dispersion of DO across the mixing zone had come into equilibrium with supply of DO to the mixing zone. By contrast, mixing zone thickness shrank over time during the reaction experiments, as MD reaction consumed DO in the mixing zone. The decrease in mixing zone thickness for the reaction experiments indicates steeper DO gradients and greater dispersion (transport) limitation, quantified by Damköhler numbers farther above unity. Maximum SO4concentrations always occurred further from the center of the HFC (i.e., more toward surrounding upwelling GW) than did the oxic front. In most riverbeds, transport and mixing dynamics are thus superimposed upon existing hydraulic dynamics, with implications for monitoring and attenuation of contaminants.
How to Tailor My Process‐Based Hydrological Model? Dynamic Identifiability Analysis of Flexible Model Structures
Authors: Pilz Tobias , Francke Till , Baroni Gabriele , Bronstert Axel
Published: August 2020

In the field of hydrological modeling, many alternative representations of natural processes exist. Choosing specific process formulations when building a hydrological model is therefore associated with a high degree of ambiguity and subjectivity. In addition, the numerical integration of the underlying differential equations and parametrization of model structures influence model performance. Identifiability analysis may provide guidance by constraining the a priori range of alternatives based on observations. In this work, a flexible simulation environment is used to build an ensemble of semidistributed, process‐based hydrological model configurations with alternative process representations, numerical integration schemes, and model parametrizations in an integrated manner. The flexible simulation environment is coupled with an approach for dynamic identifiability analysis. The objective is to investigate the applicability of the framework to identify the most adequate model. While an optimal model configuration could not be clearly distinguished, interesting results were obtained when relating model identifiability with hydro‐meteorological boundary conditions. For instance, we tested the Penman‐Monteith and Shuttleworth & Wallace evapotranspiration models and found that the former performs better under wet and the latter under dry conditions. Parametrization of model structures plays a dominant role as it can compensate for inadequate process representations and poor numerical solvers. Therefore, it was found that numerical solvers of high order of accuracy do often, though not necessarily, lead to better model performance. The proposed coupled framework proved to be a straightforward diagnostic tool for model building and hypotheses testing and shows potential for more in‐depth analysis of process implementations and catchment functioning.
C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins—possible link to metabolic programming?
Authors: Lewandowski Krzysztof C. , Biesiada L. , Grzesiak M. , Sakowicz A.
Published: August 2020

Children born small for gestational age (SGA) are at increased risk of future glucose intolerance and type 2 diabetes, possibly after due intrauterine metabolic programming. Soluble leptin receptor (SLR) limits leptin access to signal-transducing membrane receptors. The present study examines whether SGA and appropriate for gestational age (AGA) twins differ with regard to their C-peptide, glucose and leptin systems. The markers C-peptide, glucose, fetal leptin, and SLR in cord blood were assessed in children from dichorionic twin pregnancies at delivery. In 32 cases, weight differed by >15% between twins: one demonstrated Intrauterine Growth Retardation (IUGR) (<10th percentile-SGA), while the other did not (AGAI). The other 67 pairs presented appropriate weight for gestational age (AGAII). Placental leptin and placental leptin receptor content were also assessed. Despite the same concentrations of glucose, the SGA twins maintained a higher level of C-peptide [44.48 pmol/l vs. 20.91 pmol/l, p < 0.05] than the AGAI co-twins, higher HOMA index, calculated as [C-peptide] x [Glucose] (p = 0.045), in cord blood, and a higher level of SLR [SGA vs AGAI—mean: 28.63 ng/ml vs. 19.91 ng/ml, p < 0.01], without any differences in total leptin (p = 0.37). However, SGA placentas demonstrated higher leptin level [130.1 pg/100 g total protein vs 83.8 pg/100 g total protein, p = 0.03], without differences in placental leptin receptor (p = 0.66). SGA/IUGR twins demonstrate relative insulin resistance accompanied by decreased fetal and increased placental leptin signaling. We speculate that relative insulin resistance and changes in the leptin system might be the first evidence of processes promoting deleterious metabolic programming for post-natal life.
Alleviation of salt-induced exacerbation of cardiac, renal, and visceral fat pathology in rats with metabolic syndrome by surgical removal of subcutaneous fat
Authors: Aoyama Kiyoshi , Komatsu Yuki , Yoneda Mamoru , Nakano Shiho , Ashikawa Sao , Kawai Yumeno , Cui Xixi , Ikeda Katsuhide , Nagata Kohzo
Published: August 2020

Objectives

Evidence suggests that visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) should be considered as distinct types of white fat. Although VAT plays a key role in metabolic syndrome (MetS), the role of subcutaneous adipose tissue (SAT) has been unclear. DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of MetS, develop adipocyte hypertrophy and inflammation to similar extents in SAT and VAT. We have now investigated the effects of salt loading and SAT removal on cardiac, renal, and VAT pathology in DS/obese rats.

Methods

DS/obese rats were subjected to surgical removal of inguinal SAT or sham surgery at 8 weeks of age. They were provided with a 0.3% NaCl solution as drinking water or water alone for 4 weeks from 9 weeks of age.

Results

Salt loading exacerbated hypertension, insulin resistance, as well as left ventricular (LV) hypertrophy, inflammation, fibrosis, and diastolic dysfunction in DS/obese rats. It also reduced both SAT and VAT mass but aggravated inflammation only in VAT. Although SAT removal did not affect LV hypertrophy in salt-loaded DS/obese rats, it attenuated hypertension, insulin resistance, and LV injury as well as restored fat mass and alleviated inflammation and the downregulation of adiponectin gene expression in VAT. In addition, whereas salt loading worsened renal injury as well as upregulated the expression of renin–angiotensin-aldosterone system-related genes in the kidney, these effects were suppressed by removal of SAT.

Conclusions

SAT removal attenuated salt-induced exacerbation of MetS and LV and renal pathology in DS/obese rats. These beneficial effects of SAT removal are likely attributable, at least in part, to inhibition of both VAT and systemic inflammation.
Cortisol reactivity in patients with anorexia nervosa after stress induction
Authors: Schmalbach Ileana , Herhaus Benedict , Pässler Sebastian , Runst Sarah , Berth Hendrik , Wolff-Stephan Silvia , Petrowski Katja
Published: August 2020

There is a need of experimental studies on biomarkers in patients with anorexia nervosa (PAN), especially in the context of stress, in order to foster understanding in illness maintenance. To this end, the cortisol response to an acute stressor was investigated inn = 26 PAN(BMI: 19.3 ± 3.4 kg/m2), age, and gender matched ton = 26 healthy controls (HC; BMI: 23.08 ± 3.3 kg/m2). For this purpose, salivary cortisol parameters were assessed in two experimental conditions: (1) rest/no intervention and (2) stress intervention (TSST; Trier Social Stress Test). In addition, psychological indicators of stress were assessed (Primary Appraisal Secondary Appraisal, Visual Analogue Scale, and Trier Inventory for the assessment of Chronic Stress), as well as psychological distress, depression, and eating disorder (ED) symptoms. A 2 × 2 × 8 ANOVA demonstrated elevated cortisol levels in PANin the resting condition. In the stress intervention no significantgroupeffect in terms ofcortisol(F(1, 50) = 0.69;p = 0.410;$$\eta _p^2 = 0.014$$ηp2=0.014). A significantcondition(F(1, 50) = 20.50;p = 0.000;$$\eta _p^2 = 0.291$$ηp2=0.291) andtimeeffect (F(2.71, 135.44) = 11.27;p = 0.000;$$\eta _p^2 = 0.20$$ηp2=0.20) were revealed, as well as two significant interaction effects. First:Condition × group(F(1, 50) = 4.17,p = 0.046;$$\eta _p^2 = 0.077$$ηp2=0.077) and second:Condition × time(F(2.71, 135.44) = 16.07,p = 0.000,$$\eta _p^2 = 0.24.$$ηp2=0.24.). In terms of AUCG, no significant differences between both groups were exhibited. Regardless, significant results were evinced in terms of an increase (AUCi:F(1, 50) = 20.66,p = 0.015,$$\eta _p^2 = 0.113$$ηp2=0.113), baseline to peak (+20 min post-TSST:t5 = 16.51 (9.02),p = 0.029) and reactivity (MPAN = 0.73 vs.MHC = 4.25,p = 0.036). In addition, a significant correlation between AUCGand BMI:r(24) = −0.42,p = 0.027 was demonstrated, but not between AUCiand BMI (r(24) = −0.26,p = 0.20). Psychological indices suggested higher levels of chronic and perceived stress in PANrelative to HC. However, stress perception in the stress condition (VAS) was comparable. Additional analyses demonstrated that ED-symptoms are highly correlated with psychological distress and depression, but not with BMI. In addition, it could be demonstrated that reactivity is rather related to ED-symptoms and psychological burden than to BMI. In conclusion, PANshowed elevated basal cortisol levels at rest and exhibited a blunted cortisol reactivity to the TSST as evinced by salivary cortisol parameters. Further, it was shown that weight recovery influences reversibility of hypercortisolemia, i.e., cortisol levels normalize with weight gain. However, HPAA (hypothalamus–pituitary–adrenal axis) irregularities in terms of reactivity persist even at a BMI ≤ 19.3 (±3.4). Our data suggest that pronounced psychological burden in PAN, have a greater impact on the HPAA functionality (secondary to the ED) than BMI itself.
A machine-learning framework for robust and reliable prediction of short- and long-term treatment response in initially antipsychotic-naïve schizophrenia patients based on multimodal neuropsychiatric data
Authors: Ambrosen Karen S. , Skjerbæk Martin W. , Foldager Jonathan , Axelsen Martin C. , Bak Nikolaj , Arvastson Lars , Christensen Søren R. , Johansen Louise B. , Raghava Jayachandra M. , Oranje Bob , Rostrup Egill , Nielsen Mette Ø. , Osler Merete , Fagerlund Birgitte , Pantelis Christos , Kinon Bruce J. , Glenthøj Birte Y. , Hansen Lars K. , Ebdrup Bjørn H.
Published: August 2020

The reproducibility of machine-learning analyses in computational psychiatry is a growing concern. In a multimodal neuropsychiatric dataset of antipsychotic-naïve, first-episode schizophrenia patients, we discuss a workflow aimed at reducing bias and overfitting by invoking simulated data in the design process and analysis in two independent machine-learning approaches, one based on a single algorithm and the other incorporating an ensemble of algorithms. We aimed to (1) classify patients from controls to establish the framework, (2) predict short- and long-term treatment response, and (3) validate the methodological framework. We included 138 antipsychotic-naïve, first-episode schizophrenia patients with data on psychopathology, cognition, electrophysiology, and structural magnetic resonance imaging (MRI). Perinatal data and long-term outcome measures were obtained from Danish registers. Short-term treatment response was defined as change in Positive And Negative Syndrome Score (PANSS) after the initial antipsychotic treatment period. Baseline diagnostic classification algorithms also included data from 151 matched controls. Both approaches significantly classified patients from healthy controls with a balanced accuracy of 63.8% and 64.2%, respectively. Post-hoc analyses showed that the classification primarily was driven by the cognitive data. Neither approach predicted short- nor long-term treatment response. Validation of the framework showed that choice of algorithm and parameter settings in the real data was successfully guided by results from the simulated data. In conclusion, this novel approach holds promise as an important step to minimize bias and obtain reliable results with modest sample sizes when independent replication samples are not available.
Correction: Depression, mitochondrial bioenergetics, and electroconvulsive therapy: a new approach towards personalized medicine in psychiatric treatment - a short review and current perspective
Authors: Karabatsiakis Alexander , Schönfeldt-Lecuona Carlos
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ
Authors: Miligy Islam M. , Toss Michael S. , Shiino Sho , Oni Georgette , Syed Binafsha M. , Khout Hazem , Tan Qing Ting , Green Andrew R. , Macmillan R. Douglas , Robertson John F. R. , Rakha Emad A.
Published: August 2020

Background

Oestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value. In this study, we investigated the value of ER expression in ductal carcinoma in situ (DCIS) in terms of outcome and the impact on ET decision.

Methods

In total, 643 pure DCIS, diagnosed at Nottingham University Hospitals, were assessed for ER. Clinicopathological data were correlated against ER status, together with assessment of recurrence rate.

Results

ER positivity was observed in 74% (475/643) of cases. ER positivity was associated with clinicopathological variables of good prognosis; however, outcome analysis revealed that ER status was not associated with local recurrence. In the intermediate- and high-grade ER-positive DCIS, 58% (11/19) and 63% (15/24) of the recurrences were invasive, respectively, comprising 7% and 6% of all ER-positive DCIS, respectively. Invasive recurrence in low-grade DCIS was infrequent (2%), and none of these patients died of BC. The ER status of the recurrent invasive tumours matched the primary DCIS ER status (94% in ipsilateral and 90% of contralateral recurrence).

Conclusion

The strong correlation between DCIS and invasive recurrence ER status and the clinical impact of ET justify discussion of the use of ET in ER-positive DCIS treated by breast-conserving surgery. The excellent outcome of low-grade DCIS, which was almost always ER-positive, does not, in the opinion of authors, justify the use of risk-reducing ET. Therefore, the decision on ET for DCIS should be personalised and consider grade, ER status and other characteristics.
An in vivo strategy for knockdown of circular RNAs
Authors: Pamudurti Nagarjuna Reddy , Patop Ines Lucia , Krishnamoorthy Aishwarya , Ashwal-Fluss Reut , Bartok Osnat , Kadener Sebastian
Published: August 2020

Exonic circular RNAs (circRNAs) are highly abundant RNAs generated mostly from exons of protein-coding genes. Assaying the functions of circRNAs is not straightforward as common approaches for circRNA depletion tend to also alter the levels of mRNAs generated from the hosting gene. Here we describe a methodology for specific knockdown of circRNAs in vivo with tissue and cell resolution. We also describe an experimental and computational platform for determining the potential off-target effects as well as for verifying the obtained phenotypes. Briefly, we utilize shRNAs targeted to the circRNA-specific back-splice junction to specifically downregulate the circRNA. We utilized this methodology to downregulate five circRNAs that are highly expressed in Drosophila. There were no effects on the levels of their linear counterparts or any RNA with complementarity to the expressed shRNA. Interestingly, downregulation of circCtrip resulted in developmental lethality that was recapitulated with a second shRNA. Moreover, downregulation of individual circRNAs caused specific changes in the fly head transcriptome, suggesting roles for these circRNAs in the fly nervous system. Together, our results provide a methodological approach that enables the comprehensive study of circRNAs at the organismal and cellular levels and generated for the first time flies in which specific circRNAs are downregulated.
Cataract management in children: a review of the literature and current practice across five large UK centres
Authors: Self J. E. , Taylor R. , Solebo A. L. , Biswas S. , Parulekar M. , Dev Borman A. , Ashworth J. , McClenaghan R. , Abbott J. , O’Flynn E. , Hildebrand D. , Lloyd I. C.
Published: August 2020

Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK ‘state of play’ in the management of paediatric cataracts.
Electronic correlations and flattened band in magnetic Weyl semimetal candidate Co3Sn2S2
Authors: Xu Yueshan , Zhao Jianzhou , Yi Changjiang , Wang Qi , Yin Qiangwei , Wang Yilin , Hu Xiaolei , Wang Luyang , Liu Enke , Xu Gang , Lu Ling , Soluyanov Alexey A. , Lei Hechang , Shi Youguo , Luo Jianlin , Chen Zhi-Guo
Published: August 2020

The interplay between electronic correlations and topological protection may offer a rich avenue for discovering emergent quantum phenomena in condensed matter. However, electronic correlations have so far been little investigated in Weyl semimetals (WSMs) by experiments. Here, we report a combined optical spectroscopy and theoretical calculation study on the strength and effect of electronic correlations in a magnet Co3Sn2S2. The electronic kinetic energy estimated from our optical data is about half of that obtained from single-particle ab initio calculations in the ferromagnetic ground state, which indicates intermediate-strength electronic correlations in this system. Furthermore, comparing the energy and side-slope ratios between the interband-transition peaks at high energies in the experimental and single-particle-calculation-derived optical conductivity spectra with the bandwidth-renormalization factors obtained by many-body calculations enables us to estimate the Coulomb-interaction strength (U ∼ 4 eV) in Co3Sn2S2. Besides, a sharp experimental optical conductivity peak at low energy, which is absent in the single-particle-calculation-derived spectrum but is consistent with the optical conductivity peaks obtained by many-body calculations withU ∼ 4 eV, indicates that an electronic band connecting the two Weyl cones is flattened by electronic correlations and emerges near the Fermi energy in Co3Sn2S2. Our work paves the way for exploring flat-band-generated quantum phenomena in WSMs.
Topological flat bands in frustrated kagome lattice CoSn
Authors: Kang Mingu , Fang Shiang , Ye Linda , Po Hoi Chun , Denlinger Jonathan , Jozwiak Chris , Bostwick Aaron , Rotenberg Eli , Kaxiras Efthimios , Checkelsky Joseph G. , Comin Riccardo
Published: August 2020

Electronic flat bands in momentum space, arising from strong localization of electrons in real space, are an ideal stage to realize strongly-correlated phenomena. Theoretically, the flat bands can naturally arise in certain geometrically frustrated lattices, often with nontrivial topology if combined with spin-orbit coupling. Here, we report the observation of topological flat bands in frustrated kagome metal CoSn, using angle-resolved photoemission spectroscopy and band structure calculations. Throughout the entire Brillouin zone, the bandwidth of the flat band is suppressed by an order of magnitude compared to the Dirac bands originating from the same orbitals. The frustration-driven nature of the flat band is directly confirmed by the chiral d-orbital texture of the corresponding real-space Wannier functions. Spin-orbit coupling opens a large gap of 80 meV at the quadratic touching point between the Dirac and flat bands, endowing a nonzero Z2 invariant to the flat band. These findings demonstrate that kagome-derived flat bands are a promising platform for novel emergent phases of matter at the confluence of strong correlation and topology.
Turbulent hydrodynamics in strongly correlated Kagome metals
Authors: Di Sante Domenico , Erdmenger Johanna , Greiter Martin , Matthaiakakis Ioannis , Meyer René , Fernández David Rodríguez , Thomale Ronny , van Loon Erik , Wehling Tim
Published: August 2020

A current challenge in condensed matter physics is the realization of strongly correlated, viscous electron fluids. These fluids can be described by holography, that is, by mapping them onto a weakly curved gravitational theory via gauge/gravity duality. The canonical system considered for realizations has been graphene. In this work, we show that Kagome systems with electron fillings adjusted to the Dirac nodes provide a much more compelling platform for realizations of viscous electron fluids, including non-linear effects such as turbulence. In particular, we find that in Scandium Herbertsmithite, the fine-structure constant, which measures the effective Coulomb interaction, is enhanced by a factor of about 3.2 as compared to graphene. We employ holography to estimate the ratio of the shear viscosity over the entropy density in Sc-Herbertsmithite, and find it about three times smaller than in graphene. These findings put the turbulent flow regime described by holography within the reach of experiments.
Land use and pollinator dependency drives global patterns of pollen limitation in the Anthropocene
Authors: Bennett Joanne M. , Steets Janette A. , Burns Jean H. , Burkle Laura A. , Vamosi Jana C. , Wolowski Marina , Arceo-Gómez Gerardo , Burd Martin , Durka Walter , Ellis Allan G. , Freitas Leandro , Li Junmin , Rodger James G. , Ştefan Valentin , Xia Jing , Knight Tiffany M. , Ashman Tia-Lynn
Published: August 2020

Land use change, by disrupting the co-evolved interactions between plants and their pollinators, could be causing plant reproduction to be limited by pollen supply. Using a phylogenetically controlled meta-analysis on over 2200 experimental studies and more than 1200 wild plants, we ask if land use intensification is causing plant reproduction to be pollen limited at global scales. Here we report that plants reliant on pollinators in urban settings are more pollen limited than similarly pollinator-reliant plants in other landscapes. Plants functionally specialized on bee pollinators are more pollen limited in natural than managed vegetation, but the reverse is true for plants pollinated exclusively by a non-bee functional group or those pollinated by multiple functional groups. Plants ecologically specialized on a single pollinator taxon were extremely pollen limited across land use types. These results suggest that while urbanization intensifies pollen limitation, ecologically and functionally specialized plants are at risk of pollen limitation across land use categories.
Orbitofrontal-striatal potentiation underlies cocaine-induced hyperactivity
Authors: Bariselli Sebastiano , Miyazaki Nanami L. , Creed Meaghan C. , Kravitz Alexxai V.
Published: August 2020

Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion; however, their effects on striatal pathway function in vivo remain unclear. One model that has been proposed to account for these motor effects suggests that stimulants drive hyperactivity via activation and inhibition of direct and indirect pathway striatal neurons, respectively. Although this hypothesis is consistent with the cellular actions of dopamine receptors and received support from optogenetic and chemogenetic studies, it has been rarely tested with in vivo recordings. Here, we test this model and observe that cocaine increases the activity of both pathways in the striatum of awake mice. These changes are linked to a dopamine-dependent cocaine-induced strengthening of upstream orbitofrontal cortex (OFC) inputs to the dorsomedial striatum (DMS) in vivo. Finally, depressing OFC-DMS pathway with a high frequency stimulation protocol in awake mice over-powers the cocaine-induced potentiation of OFC-DMS pathway and attenuates the expression of locomotor sensitization, directly linking OFC-DMS potentiation to cocaine-induced hyperactivity.
Developmental potential of aneuploid human embryos cultured beyond implantation
Authors: Shahbazi Marta N. , Wang Tianren , Tao Xin , Weatherbee Bailey A. T. , Sun Li , Zhan Yiping , Keller Laura , Smith Gary D. , Pellicer Antonio , Scott Richard T. , Seli Emre , Zernicka-Goetz Magdalena
Published: August 2020

Aneuploidy, the presence of an abnormal number of chromosomes, is a major cause of early pregnancy loss in humans. Yet, the developmental consequences of specific aneuploidies remain unexplored. Here, we determine the extent of post-implantation development of human embryos bearing common aneuploidies using a recently established culture platform. We show that while trisomy 15 and trisomy 21 embryos develop similarly to euploid embryos, monosomy 21 embryos exhibit high rates of developmental arrest, and trisomy 16 embryos display a hypo-proliferation of the trophoblast, the tissue that forms the placenta. Using human trophoblast stem cells, we show that this phenotype can be mechanistically ascribed to increased levels of the cell adhesion protein E-CADHERIN, which lead to premature differentiation and cell cycle arrest. We identify three cases of mosaicism in embryos diagnosed as full aneuploid by pre-implantation genetic testing. Our results present the first detailed analysis of post-implantation development of aneuploid human embryos.
Ultrafast photoinduced band splitting and carrier dynamics in chiral tellurium nanosheets
Authors: Jnawali Giriraj , Xiang Yuan , Linser Samuel M. , Shojaei Iraj Abbasian , Wang Ruoxing , Qiu Gang , Lian Chao , Wong Bryan M. , Wu Wenzhuo , Ye Peide D. , Leng Yongsheng , Jackson Howard E. , Smith Leigh M.
Published: August 2020

Trigonal tellurium (Te) is a chiral semiconductor that lacks both mirror and inversion symmetries, resulting in complex band structures with Weyl crossings and unique spin textures. Detailed time-resolved polarized reflectance spectroscopy is used to investigate its band structure and carrier dynamics. The polarized transient spectra reveal optical transitions between the uppermost spin-split H4 and H5 and the degenerate H6 valence bands (VB) and the lowest degenerate H6 conduction band (CB) as well as a higher energy transition at the L-point. Surprisingly, the degeneracy of the H6 CB (a proposed Weyl node) is lifted and the spin-split VB gap is reduced upon photoexcitation before relaxing to equilibrium as the carriers decay. Using ab initio density functional theory (DFT) calculations, we conclude that the dynamic band structure is caused by a photoinduced shear strain in the Te film that breaks the screw symmetry of the crystal. The band-edge anisotropy is also reflected in the hot carrier decay rate, which is a factor of two slower along the c-axis than perpendicular to it. The majority of photoexcited carriers near the band-edge are seen to recombine within 30 ps while higher lying transitions observed near 1.2 eV appear to have substantially longer lifetimes, potentially due to contributions of intervalley processes in the recombination rate. These new findings shed light on the strong correlation between photoinduced carriers and electronic structure in anisotropic crystals, which opens a potential pathway for designing novel Te-based devices that take advantage of the topological structures as well as strong spin-related properties.
PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity
Authors: Helou Doumet Georges , Shafiei-Jahani Pedram , Lo Richard , Howard Emily , Hurrell Benjamin P. , Galle-Treger Lauriane , Painter Jacob D. , Lewis Gavin , Soroosh Pejman , Sharpe Arlene H. , Akbari Omid
Published: August 2020

Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.
Transparent flexible thin-film p–n junction thermoelectric module
Authors: Wang Xizu , Suwardi Ady , Lim Siew Lay , Wei Fengxia , Xu Jianwei
Published: August 2020

Transparent and flexible thermoelectrics has been highly sought after for future wearable devices. However, the main stumbling block to prevent its widespread adoption is the lack of p-type transparent thermoelectrics and the stringent criteria of electrical and thermal properties matching appropriately between p-legs and n-legs. This work demonstrates the fabrication of p-type PEDOT:PSS films whose optical properties, electrical conductivity, thermal conductivity, and Seebeck coefficient were engineered to perfectly match the n-type indium tin oxide (ITO) counterparts. The dense p-type PEDOT:PSS and n-type ITO thin films show a thermoelectric figure of merit of zT = 0.30 and 0.29 at 450 K, and a thermal conductivity of 0.22 and 0.32 W m−1 K−1, respectively. A flexible thermoelectric generator (TEG) module with a high transmittance of >81% in the visible wavelength range of 400–800 nm is fabricated using 10 pairs of p-type PEDOT:PSS and n-type ITO thin film legs. An ultra-high power density of 22.2 W m−2 at a temperature gradient of 80 K was observed, which is the highest power density reported for organic/hybrid-based flexible TEGs so far. Our transparent flexible thin-film p–n junction thermoelectric module with exceptionally high power generation may take a tremendous step forward towards multi-functional wearable devices.
“Groupitizing”: a strategy for numerosity estimation
Authors: Anobile Giovanni , Castaldi Elisa , Moscoso Paula A. Maldonado , Burr David C. , Arrighi Roberto
Published: August 2020

Previous work has shown that when arrays of objects are grouped within clusters, participants can enumerate their numerosity more rapidly than when objects are randomly scattered, a phenomenon termed “groupitizing”. Importantly, the magnitude of the grouping advantage correlates with math abilities in children. Here we show that sensory precision of numerosity estimation is also improved when grouping cues are available, by up to 20%. The grouping can be induced by color and/or spatial proximity, and occurs in temporal sequences as well as spatial arrays. The improvement is strongest for participants with the highest thresholds in the random, ungrouped conditions. Taken together with previous research, our data suggest that measurements correlations between numerosity estimation and formal math skills may be driven by grouping strategies, which require a minimal level of basic arithmetic.
Long-term and longitudinal nutrient stoichiometry changes in oligotrophic cascade reservoirs with trout cage aquaculture
Authors: Miao Shiyu , Jian Shenglong , Liu Yang , Li Changzhong , Guan Hongtao , Li Kemao , Wang Guojie , Wang Zhenji
Published: August 2020

The potential nutrient stoichiometry changes caused by trout cage aquaculture is concerned especially in oligotrophic waters. Long-term total nitrogen (N), total phosphorus (P) and N:P ratio changes in 6 cascade reservoirs with rainbow trout cage aquaculture in the oligotrophic upstream Yellow River (UYR) were studied from 2013 to 2017 in this paper. The 5-year monitoring results showed that N, P and N:P ratio levels showed no obvious long-term changes in high-altitude oligotrophic waters with rainbow trout cage aquaculture. No obvious longitudinal N, P and N:P ratio level changes were observed in the 6 cascade reservoirs from upstream Longyangxia Reservoir (LYR) to downstream Jishixia Reservoir (JSR). The increased N and P resulting from the cage aquaculture accounted only for 1.74% and 5.2% of the natural N and P levels, respectively, with a fish production of 10,000 tonnes. The upstream Yellow River remained oligotrophic and phosphorus-limited. Results in this study proved that trout cage aquaculture do not necessarily cause nitrogen, phosphorus and N:P ratio changes even in oligotrophic waters. Phosphorus should be considered first when identifying priority nitrogen and phosphorus sources and the corresponding control measures in waters with high N:P ratio.
Regulated expression and function of the GABAB receptor in human pancreatic beta cell line and islets
Authors: Rachdi Latif , Maugein Alicia , Pechberty Severine , Armanet Mathieu , Hamroune Juliette , Ravassard Philippe , Marullo Stefano , Albagli Olivier , Scharfmann Raphael
Published: August 2020

G protein-coupled receptors are seven transmembrane signaling molecules that are involved in a wide variety of physiological processes. They constitute a large protein family of receptors with almost 300 members detected in human pancreatic islet preparations. However, the functional role of these receptors in pancreatic islets is unknown in most cases. We generated a new stable human beta cell line from neonatal pancreas. This cell line, named ECN90 expresses both subunits (GABBR1 and GABBR2) of the metabotropic GABAB receptor compared to human islet. In ECN90 cells, baclofen, a specific GABAB receptor agonist, inhibits cAMP signaling causing decreased expression of beta cell-specific genes such as MAFA and PCSK1, and reduced insulin secretion. We next demonstrated that in primary human islets, GABBR2 mRNA expression is strongly induced under cAMP signaling, while GABBR1 mRNA is constitutively expressed. We also found that induction and activation of the GABAB receptor in human islets modulates insulin secretion.
Pavlovian bias in Parkinson’s disease: an objective marker of impulsivity that modulates with deep brain stimulation
Authors: Eisinger Robert S. , Scott Bonnie M. , Le Anh , Ponce Elena M. Torres , Lanese Joseph , Hundley Christopher , Nelson Brawn , Ravy Tasmeah , Lopes Janine , Thompson Sable , Sathish Sneha , O’Connell Rebecca L. , Okun Michael S. , Bowers Dawn , Gunduz Aysegul
Published: August 2020

Impulsivity is a common symptom in Parkinson’s disease (PD). Adaptive behavior is influenced by prepotent action-reward and inaction-avoid loss Pavlovian biases. We aimed to assess the hypothesis that impulsivity in PD is associated with Pavlovian bias, and to assess whether dopaminergic medications and deep brain stimulation (DBS) influence Pavlovian bias. A PD DBS cohort (N = 37) completed a reward-based Go/No-Go task and bias measures were calculated. This DBS cohort completed the task under three conditions: on-med/pre-DBS, off-med/off-DBS, and on-med/on-DBS. Participants also completed self-reported measures of impulsivity. Dopaminergic medication was associated with lower action-reward bias while DBS was associated with higher action-reward bias. Impulsivity was associated with higher action-reward bias but not inaction-avoid loss bias. We furthermore replicated this association in an independent, non-DBS PD cohort (N = 88). Overall we establish an objective behavioral marker of impulsivity and show that DBS affects impulsivity by amplifying automated responding. Our results point to the importance of reward rather than punishment avoidance in driving impulsive behaviors. This work provides insight into the pathophysiological underpinnings of impulsivity and especially medication and DBS-associated impulsivity in PD.
Nonlinear model of cascade failure in weighted complex networks considering overloaded edges
Authors: Chen Chao-Yang , Zhao Yang , Gao Jianxi , Stanley Harry Eugene
Published: August 2020

Considering the elasticity of the real networks, the components in the network have a redundant capacity against the load, such as power grids, traffic networks and so on. Moreover, the interaction strength between nodes is often different. This paper proposes a novel nonlinear model of cascade failure in weighted complex networks considering overloaded edges to describe the redundant capacity for edges and capture the interaction strength of nodes. We fill this gap by studying a nonlinear weighted model of cascade failure with overloaded edges over synthetic and real weighted networks. The cascading failure model is constructed for the first time according to the overload coefficient, capacity parameter, weight coefficient, and distribution coefficient. Then through theoretical analysis, the conditions for stopping failure cascades are obtained, and the analysis shows the superiority of the constructed model. Finally, the cascading invulnerability is simulated in several typical network models and the US power grid. The results show that the model is a feasible and reasonable change of weight parameters, capacity coefficient, distribution coefficient, and overload coefficient can significantly improve the destructiveness of complex networks against cascade failure. Our methodology provides an efficacious reference for the control and prevention of cascading failures in many real networks.
Comparative structural analyses and nucleotide-binding characterization of the four KH domains of FUBP1
Authors: Ni Xiaomin , Knapp Stefan , Chaikuad Apirat
Published: August 2020

The FUBP1-FUSE complex is an essential component of a transcription molecular machinery that is necessary for tight regulation of expression of many key genes including c-Myc and p21. FUBP1 utilizes its four articulated KH modules, which function cooperatively, for FUSE nucleotide binding. To understand molecular mechanisms fundamental to the intermolecular interaction, we present a set of crystal structures, as well ssDNA-binding characterization of FUBP1 KH domains. All KH1-4 motifs were highly topologically conserved, and were able to interact with FUSE individually and independently. Nevertheless, differences in nucleotide binding properties among the four KH domains were evident, including higher nucleotide-binding potency for KH3 as well as diverse nucleotide sequence preferences. Variations in amino acid compositions at one side of the binding cleft responsible for nucleobase resulted in diverse shapes and electrostatic charge interaction, which might feasibly be a contributing factor for different nucleotide-binding propensities among KH1-4. Nonetheless, conservation of structure and nucleotide-binding property in all four KH motifs is essential for the cooperativity of multi KH modules present in FUBP1 towards nanomolar affinity for FUSE interaction. Comprehensive structural comparison and ssDNA binding characteristics of all four KH domains presented here provide molecular insights at a fundamental level that might be beneficial for elucidating the mechanisms of the FUBP1-FUSE interaction.
Whole genome and in-silico analyses of G1P[8] rotavirus strains from pre- and post-vaccination periods in Rwanda
Authors: Rasebotsa Sebotsana , Mwangi Peter N. , Mogotsi Milton T. , Sabiu Saheed , Magagula Nonkululeko B. , Rakau Kebareng , Uwimana Jeannine , Mutesa Leon , Muganga Narcisse , Murenzi Didier , Tuyisenge Lisine , Jaimes Jose , Esona Mathew D. , Bowen Michael D. , Mphahlele M. Jeffrey , Seheri Mapaseka L. , Mwenda Jason M. , Nyaga Martin M.
Published: August 2020

Rwanda was the first low-income African country to introduce RotaTeq vaccine into its Expanded Programme on Immunization in May 2012. To gain insights into the overall genetic make-up and evolution of Rwandan G1P[8] strains pre- and post-vaccine introduction, rotavirus positive fecal samples collected between 2011 and 2016 from children under the age of 5 years as part of ongoing surveillance were genotyped with conventional RT-PCR based methods and whole genome sequenced using the Illumina MiSeq platform. From a pool of samples sequenced (n = 158), 36 were identified as G1P[8] strains (10 pre-vaccine and 26 post-vaccine), of which 35 exhibited a typical Wa-like genome constellation. However, one post vaccine strain, RVA/Human-wt/RWA/UFS-NGS:MRC-DPRU442/2012/G1P[8], exhibited a RotaTeq vaccine strain constellation of G1-P[8]-I2-R2-C2-M2-A3-N2-T6-E2-H3, with most of the gene segments having a close relationship with a vaccine derived reassortant strain, previously reported in USA in 2010 and Australia in 2012. The study strains segregated into two lineages, each containing a paraphyletic pre- and post-vaccine introduction sub-lineages. In addition, the study strains demonstrated close relationship amongst each other when compared with globally selected group A rotavirus (RVA) G1P[8] reference strains. For VP7 neutralization epitopes, amino acid substitutions observed at positions T91A/V, S195D and M217T in relation to the RotaTeq vaccine were radical in nature and resulted in a change in polarity from a polar to non-polar molecule, while for the VP4, amino acid differences at position D195G was radical in nature and resulted in a change in polarity from a polar to non-polar molecule. The polarity change at position T91A/V of the neutralizing antigens might play a role in generating vaccine-escape mutants, while substitutions at positions S195D and M217T may be due to natural fluctuation of the RVA. Surveillance of RVA at whole genome level will enhance further assessment of vaccine impact on circulating strains, the frequency of reassortment events under natural conditions and epidemiological fitness generated by such events.
Reactive saccade adaptation boosts orienting of visuospatial attention
Authors: Nicolas Judith , Bidet-Caulet Aurélie , Pélisson Denis
Published: August 2020

Attention and saccadic eye movements are critical components of visual perception. Recent studies proposed the hypothesis of a tight coupling between saccadic adaptation (SA) and attention: SA increases the processing speed of unpredictable stimuli, while increased attentional load boosts SA. Moreover, their cortical substrates partially overlap. Here, we investigated for the first time whether this coupling in the reactive/exogenous modality is specific to the orienting system of attention. We studied the effect of adaptation of reactive saccades (RS), elicited by the double-step paradigm, on exogenous orienting, measured using a Posner-like detection paradigm. In 18 healthy subjects, the attentional benefit—the difference in reaction time to targets preceded by informative versus uninformative cues—in a control exposure condition was subtracted from that of each adaptation exposure condition (backward and forward); then, this cue benefit difference was compared between the pre- and post-exposure phases. We found that, the attentional benefit significantly increased for cued-targets presented in the left hemifield after backward adaptation and for cued-targets presented in the right hemifield after forward adaptation. These findings provide strong evidence in humans for a coupling between RS adaptation and attention, possibly through the activation of a common neuronal pool.
Excitation of surface plasma waves and fast electron generation in relativistic laser–plasma interaction
Authors: Raynaud M. , Héron A. , Adam J.-C.
Published: August 2020

The excitation of surface plasma waves (SPW) by an intense short laser pulse is a useful tool to enhance the laser absorption and the electron heating in the target. In this work, the influence of the transverse laser profile and the pulse duration used to excited SPW is investigated from Fluid and 2D Particle-in-Cell simulations. We show the existence of a lobe of surface plasma wave modes. Our results highlight surface plasma waves excitation mechanism and define the laser parameters to optimise the SPW excitation and the kinetic energy of the associated electron trapped in the wave. It opens the door to monitor the spectral mode distribution and temporal shape of the excited surface waves in the high relativistic regime. The most important result of the study is that—at least in 2D—the charge and the energy of the electron bunches depend essentially on the laser energy rather than on temporal or spatial shape of the laser pulse.