bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance
Authors: Stamoulis Georgios , Garieri Marco , Makrythanasis Periklis , Letourneau Audrey , Guipponi Michel , Panousis Nikolaos , Sloan-Béna Frédérique , Falconnet Emilie , Ribaux Pascale , Borel Christelle , Santoni Federico , Antonarakis Stylianos E. 
Published: October 2019

AbstractAneuploidy is a major source of gene dosage imbalance due to copy number alterations (CNA), and viable human trisomies are model disorders of altered gene expression. We study gene and allele-specific expression (ASE) of 9668 single-cell fibroblasts from trisomy 21 (T21) discordant twins and from mosaic T21, T18, T13 and T8. We examine 928 single cells with deep scRNAseq. Expected and observed overexpression of trisomic genes in trisomic vs. diploid bulk RNAseq is not detectable in trisomic vs. diploid single cells. Instead, for trisomic genes with low-to-average expression, their altered gene dosage is mainly due to the higher fraction of trisomic cells simultaneously expressing these genes, in agreement with a stochastic 2-state burst-like model of transcription. These results, confirmed in a further analysis of 8740 single fibroblasts with shallow scRNAseq, suggest that the specific transcriptional profile of each gene contributes to the phenotypic variability of trisomies. We propose an improved model to understand the effects of CNA and, generally, of gene regulation on gene dosage imbalance.
Gain-through-filtering enables tuneable frequency comb generation in passive optical resonators
Authors: Bessin Florent , Perego Auro M. , Staliunas Kestutis , Turitsyn Sergei K. , Kudlinski Alexandre , Conforti Matteo , Mussot Arnaud 
Published: October 2019

AbstractOptical frequency combs (OFCs), consisting of a set of phase-locked, equally spaced laser frequency lines, have enabled a great leap in precision spectroscopy and metrology since seminal works of Hänsch et al. Nowadays, OFCs are cornerstones of a wealth of further applications ranging from chemistry and biology to astrophysics and including molecular fingerprinting and light detection and ranging (LIDAR) systems, among others. Driven passive optical resonators constitute the ideal platform for OFC generation in terms of compactness and low energy footprint. We propose here a technique for the generation of OFCs with a tuneable repetition rate in externally driven optical resonators based on the gain-through-filtering process, a simple and elegant method, due to asymmetric spectral filtering on one side of the pump wave. We demonstrate a proof-of-concept experimental result in a fibre resonator, pioneering a new technique that does not require specific engineering of the resonator dispersion to generate frequency-agile OFCs.
Rh single atoms on TiO2 dynamically respond to reaction conditions by adapting their site
Authors: Tang Yan , Asokan Chithra , Xu Mingjie , Graham George W. , Pan Xiaoqing , Christopher Phillip , Li Jun , Sautet Philippe 
Published: October 2019

AbstractSingle-atom catalysts are widely investigated heterogeneous catalysts; however, the identification of the local environment of single atoms under experimental conditions, as well as operando characterization of their structural changes during catalytic reactions are still challenging. Here, the preferred local coordination of Rh single atoms is investigated on TiO2 during calcination in O2, reduction in H2, CO adsorption, and reverse water gas shift (RWGS) reaction conditions. Theoretical and experimental studies clearly demonstrate that Rh single atoms adapt their local coordination and reactivity in response to various redox conditions. Single-atom catalysts hence do not have static local coordinations, but can switch from inactive to active structure under reaction conditions, hence explaining some conflicting literature accounts. The combination of approaches also elucidates the structure of the catalytic active site during reverse water gas shift. This insight on the real nature of the active site is key for the design of high-performance catalysts.
A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1
Authors: Botello-Smith Wesley M. , Jiang Wenjuan , Zhang Han , Ozkan Alper D. , Lin Yi-Chun , Pham Christine N. , Lacroix Jérôme J. , Luo Yun 
Published: October 2019

AbstractMechanosensitive Piezo1 and Piezo2 channels transduce various forms of mechanical forces into cellular signals that play vital roles in many important biological processes in vertebrate organisms. Besides mechanical forces, Piezo1 is selectively activated by micromolar concentrations of the small molecule Yoda1 through an unknown mechanism. Here, using a combination of all-atom molecular dynamics simulations, calcium imaging and electrophysiology, we identify an allosteric Yoda1 binding pocket located in the putative mechanosensory domain, approximately 40 Å away from the central pore. Our simulations further indicate that the presence of the agonist correlates with increased tension-induced motions of the Yoda1-bound subunit. Our results suggest a model wherein Yoda1 acts as a molecular wedge, facilitating force-induced conformational changes, effectively lowering the channel’s mechanical threshold for activation. The identification of an allosteric agonist binding site in Piezo1 channels will pave the way for the rational design of future Piezo modulators with clinical value.
Enhancing electron diffusion length in narrow-bandgap perovskites for efficient monolithic perovskite tandem solar cells
Authors: Yang Zhibin , Yu Zhenhua , Wei Haotong , Xiao Xun , Ni Zhenyi , Chen Bo , Deng Yehao , Habisreutinger Severin N. , Chen Xihan , Wang Kang , Zhao Jingjing , Rudd Peter N. , Berry Joseph J. , Beard Matthew C. , Huang Jinsong 
Published: October 2019

AbstractDeveloping multijunction perovskite solar cells (PSCs) is an attractive route to boost PSC efficiencies to above the single-junction Shockley-Queisser limit. However, commonly used tin-based narrow-bandgap perovskites have shorter carrier diffusion lengths and lower absorption coefficient than lead-based perovskites, limiting the efficiency of perovskite-perovskite tandem solar cells. In this work, we discover that the charge collection efficiency in tin-based PSCs is limited by a short diffusion length of electrons. Adding 0.03 molar percent of cadmium ions into tin-perovskite precursors reduce the background free hole concentration and electron trap density, yielding a long electron diffusion length of 2.72 ± 0.15 µm. It increases the optimized thickness of narrow-bandgap perovskite films to 1000 nm, yielding exceptional stabilized efficiencies of 20.2 and 22.7% for single junction narrow-bandgap PSCs and monolithic perovskite-perovskite tandem cells, respectively. This work provides a promising method to enhance the optoelectronic properties of narrow-bandgap perovskites and unleash the potential of perovskite-perovskite tandem solar cells.
Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis
Authors: Boehm Dylan T. , Wolf M. Allison , Hall Jesse M. , Wong Ting Y. , Sen-Kilic Emel , Basinger Hayden D. , Dziadowicz Sebastian A. , Gutierrez Maria de la Paz , Blackwood Catherine B. , Bradford Shelby D. , Begley Katherine A. , Witt William T. , Varney Melinda E. , Barbier Mariette , Damron F. Heath 
Published: October 2019

AbstractCurrent acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogenBordetella pertussisresulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti-B. pertussisand anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect againstB. pertussischallenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production ofB. pertussis-specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation.
Contactless transient carrier spectroscopy and imaging technique using lock-in free carrier emission and absorption
Authors: Rougieux Fiacre E. , Kwapil Wolfram , Heinz Friedemann , Siriwardhana Manjula , Schubert Martin C. 
Published: October 2019

AbstractIn this paper we present a contactless transient carrier spectroscopy and imaging technique for traps in silicon. At each pixel, we fit the transient decay of the trap emission which allows us to obtain both the trap time constant and trap concentration. Here we show that this technique allows for high-resolution images. Furthermore, this technique also allows to discriminate between the presence of thermal donors or oxygen precipitates in as-grown wafers, without requiring a thermal donor killing step.
Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo
Authors: de la Fuente Revenga Mario , Shin Jong M. , Vohra Hiba Z. , Hideshima Kelsey S. , Schneck Matthew , Poklis Justin L. , González-Maeso Javier 
Published: October 2019

AbstractHead-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT2A receptor (5-HT2AR) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse’s head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of this fully automated HTR detection system was tested with the psychedelic drug DOI in 5-HT2AR-KO mice, and via evaluation of potential sources of false-positive and false-negative HTR events. The increased throughput in data processing achieved via automation afforded the possibility of conducting otherwise time consuming HTR time-course studies. To further assess the versatility of our system, we also explored the pharmacological interactions between 5-HT2AR and the metabotropic glutamate receptor 2 (mGluR2). Our data demonstrate the potentiation effect of the mGluR2/3 antagonist LY341495 on DOI-induced HTR, as well as the HTR-blocking effect of the mGluR2/3 agonist and antipsychotic drug in development LY404039. This fully automated system can contribute to speed up our understanding of 5-HT2AR’s pharmacology and its characteristic behavioral outputs in rodents.
Micro-scale modelling of the urban wind speed for air pollution applications
Authors: Ottosen Thor-Bjørn , Ketzel Matthias , Skov Henrik , Hertel Ole , Brandt Jørgen , Kakosimos Konstantinos E. 
Published: October 2019

AbstractModelling wind speeds in urban areas have many applications e.g. in relation to assessment of wind energy, modelling air pollution, and building design and engineering. Models for extrapolating the urban wind speed exist, but little attention has been paid to the influence of the upwind terrain and the foundations for the extrapolation schemes. To analyse the influence of the upwind terrain and the foundations for the extrapolation of the urban wind speed, measurements from six urban and non-urban stations were explored, and a model for the urban wind speed with and without upwind influence was developed and validated. The agreement between the wind directions at the stations is found to be good, and the influence of atmospheric stability, horizontal temperature gradients, land-sea breeze, temperature, global radiation and Monin-Obukhov Length is found to be small, although future work should explore if this is valid for other urban areas. Moreover, the model is found to perform reasonably well, but the upwind influence is overestimated. Areas of model improvement are thus identified. The upwind terrain thus influences the modelling of the urban wind speed to a large extent, and the fundamental assumptions for the extrapolation scheme are fulfilled for this specific case.
Cm(III) retention by calcium silicate hydrate (C-S-H) gel and secondary alteration phases in carbonate solutions with high ionic strength: A site-selective TRLFS study
Authors: Wolter Jan-Martin , Schmeide Katja , Huittinen Nina , Stumpf Thorsten 
Published: October 2019

AbstractWe studied the Cm(III) retention by calcium silicate hydrate (C-S-H), portlandite (Ca(OH)2) and their alteration products calcite, vaterite, and aragonite in high ionic strength carbonate-containing solutions representing specific formation waters. For this, we synthesized C-S-H gels with calcium to silicon (C/S) ratios of 1.0 and 2.0 in the absence and presence of Cm(III), resulting in Cm(III)-free and Cm(III) doped C-S-H gel, respectively. For phase identification purposes we applied X-ray diffraction (XRD) while for the identification of the Cm(III)/C-S-H binding mode we applied site-selective time-resolved laser-induced luminescence spectroscopy (TRLFS). The stability of Cm(III) doped phases under repository-relevant conditions was evaluated by studying the time-dependent release of Cm(III) from the Cm(III) doped C-S-H gel into leaching solutions containing 0.02 M NaHCO3 or 2.5 M NaCl/0.02 M NaHCO3 over 60 d. Speciation changes of Cm(III) due to leaching were followed with TRLFS while C-S-H structure alterations and secondary phase formation were monitored with XRD. From the results it could be concluded that Cm(III) is not mobilized by aqueous carbonate but either remains incorporated in the C-S-H structure and portlandite or becomes partially re-immobilized into secondary CaCO3 phases. The presence of NaCl led to an accelerated conversion of metastable secondary CaCO3 phases into calcite.
Radon concentration in self-bottled mineral spring waters as a possible public health issue
Authors: Di Carlo C. , Lepore L. , Venoso G. , Ampollini M. , Carpentieri C. , Tannino A. , Ragno E. , Magliano A. , D’Amario C. , Remetti R. , Bochicchio F. 
Published: October 2019

AbstractSince 2013, the Council Directive 2013/51/Euratom has been regulating the content of radioactive substances in water intended for human consumption. However, mineral waters are exempted from this regulation, including self-bottled springs waters, where higher radon concentration are expected. Therefore, a systematic survey has been conducted on all the 33 mineral spring waters of Lazio (a region of Central Italy) in order to assess if such waters, when self-bottled, may be of concern for public health. Waters have been sampled in two different ways to evaluate the impact of bottling on radon concentration. Water sampling was possible for 20 different spring waters, with 6 samples for each one. The results show that 2 (10%) of measured mineral spring waters returned radon concentrations higher than 100 Bq L−1, i.e., the parametric value established by the Council Directive. These results, if confirmed by other surveys involving a higher number of mineral spring waters, would suggest regulating also these waters, especially in countries like Italy for which: (i) mineral water consumption is significant; (ii) mineral concession owners generally allow the consumers to fill bottles and containers, intended for transport and subsequent consumption, directly from public fountains or from fountains within the plant; (iii) the consumers’ habit of drinking self-bottled mineral water is widespread.
Bayesian spatial analysis of cholangiocarcinoma in Northeast Thailand
Authors: Suwannatrai Apiporn T. , Thinkhamrop Kavin , Clements Archie C. A. , Kelly Matthew , Suwannatrai Kulwadee , Thinkhamrop Bandit , Khuntikeo Narong , Gray Darren J. , Wangdi Kinley 
Published: October 2019

AbstractCholangiocarcinoma (CCA) is a malignant neoplasm of the biliary tract. Thailand reports the highest incidence of CCA in the world. The aim of this study was to map the distribution of CCA and identify spatial disease clusters in Northeast Thailand. Individual-level data of patients with histopathologically confirmed CCA, aggregated at the sub-district level, were obtained from the Cholangiocarcinoma Screening and Care Program (CASCAP) between February 2013 and December 2017. For analysis a multivariate Zero-inflated, Poisson (ZIP) regression model was developed. This model incorporated a conditional autoregressive (CAR) prior structure, with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling. Covariates included in the models were age, sex, normalized vegetation index (NDVI), and distance to water body. There was a total of 1,299 cases out of 358,981 participants. CCA incidence increased 2.94 fold (95% credible interval [CrI] 2.62–3.31) in patients >60 years as compared to ≤60 years. Males were 2.53 fold (95% CrI: 2.24–2.85) more likely to have CCA when compared to females. CCA decreased with a 1 unit increase of NDVI (Relative Risk =0.06; 95% CrI: 0.01–0.63). When posterior means were mapped spatial clustering was evident after accounting for the model covariates. Age, sex and environmental variables were associated with an increase in the incidence of CCA. When these covariates were included in models the maps of the posterior means of the spatially structured random effects demonstrated evidence of spatial clustering.
Development of superluminal pulse propagation in a serial array of high-Q ring resonators
Authors: Morita Yuma , Tomita Makoto 
Published: October 2019

AbstractWe experimentally examined the development of superluminal pulse propagation through a serial array of high-Q ring resonators that provides a dynamic recurrent loop. As the propagation distance, i.e., the number of ring resonators that the pulses passed through increased, the pulse advancement increased linearly, largely maintaining its Gaussian shape. The sharp edge encoded at the front of the pulse was, however, neither advanced nor delayed, in good accordance with the idea that information propagates at the speed of light. We also carried out a numerical simulation on the superluminal to subluminal transition of the pulse velocity, which appeared after the pulse had propagated a long distance. The time delays, which we calculated using the saddle point method and based on the net delay, were in good agreement with our results, even when predictions based on the traditional group delay failed completely. This demonstrates the superluminal to subluminal transition of the propagation velocity.
Polyamine supplementation reduces DNA damage in adipose stem cells cultured in 3-D
Authors: Minguzzi Manuela , Guidotti Serena , Platano Daniela , D’Adamo Stefania , Cetrullo Silvia , Assirelli Elisa , Santi Spartaco , Mariani Erminia , Trisolino Giovanni , Filardo Giuseppe , Flamigni Flavio , Borzì Rosa Maria 
Published: October 2019

AbstractAccording to previous research, natural polyamines exert a role in regulating cell committment and differentiation from stemness during skeletal development. In order to assess whether distinct polyamine patterns are associated with different skeletal cell types, primary cultures of stem cells, chondrocytes or osteoblasts were dedicated for HPLC analysis of intracellular polyamines. Spermine (SPM) and Spermidine (SPD) levels were higher in adipose derived stem cells (ASC) compared to mature skeletal cells, i.e. chondrocytes and osteoblasts, confirming the connection of polyamine content with stemness. To establish whether polyamines can protect ASC against oxidative DNA damage in a 3-D differentiation model, the level of γH2AX was measured by western blot, and found to correlate with age and BMI of patients. Addition of either polyamine to ASC was able to hinder DNA damage in the low micromolecular range, with marked reduction of γH2AX level at 10 µM SPM and 5 µM SPD. Molecular analysis of the mechanisms that might underlie the protective effect of polyamine supplementation evidences a possible involvement of autophagy. Altogether, these results support the idea that polyamines are able to manage both stem cell differentiation and cell oxidative damage, and therefore represent appealing tools for regenerative and cell based applications.
ADP-dependent glucokinase regulates energy metabolism via ER-localized glucose sensing
Authors: Imle Roland , Wang Bei-Tzu , Stützenberger Nicolas , Birkenhagen Jana , Tandon Amol , Carl Matthias , Himmelreich Nastassja , Thiel Christian , Gröne Hermann-Josef , Poschet Gernot , Völkers Mirko , Gülow Karsten , Schröder Anne , Carillo Sara , Mittermayr Stefan , Bones Jonathan , Kamiński Marcin Mikołaj , Kölker Stefan , Sauer Sven Wolfgang 
Published: October 2019

AbstractModulation of energy metabolism to a highly glycolytic phenotype, i.e. Warburg effect, is a common phenotype of cancer and activated immune cells allowing increased biomass-production for proliferation and cell division. Endoplasmic reticulum (ER)-localized ADP-dependent glucokinase (ADPGK) has been shown to play a critical role in T cell receptor activation-induced remodeling of energy metabolism, however the underlying mechanisms remain unclear. Therefore, we established and characterized in vitro and in vivo models for ADPGK-deficiency using Jurkat T cells and zebrafish. Upon activation, ADPGK knockout Jurkat T cells displayed increased cell death and ER stress. The increase in cell death resulted from a metabolic catastrophe and knockout cells displayed severely disturbed energy metabolism hindering induction of Warburg phenotype. ADPGK knockdown in zebrafish embryos led to short, dorsalized body axis induced by elevated apoptosis. ADPGK hypomorphic zebrafish further displayed dysfunctional glucose metabolism. In both model systems loss of ADPGK function led to defective N- and O-glycosylation. Overall, our data illustrate that ADPGK is part of a glucose sensing system in the ER modulating metabolism via regulation of N- and O-glycosylation.