bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lack of QBO‐MJO Connection in CMIP6 Models
Authors: Kim Hyemi , Caron Julie M. , Richter Jadwiga H. , Simpson Isla R. 
Published: May 2020

AbstractObservational analysis has indicated a strong connection between the stratospheric quasi‐biennial oscillation (QBO) and tropospheric Madden‐Julian oscillation (MJO), with MJO activity being stronger during the easterly phase than the westerly phase of the QBO. We assess the representation of this QBO‐MJO connection in 30 models participating in the Coupled Model Intercomparison Project 6. While some models reasonably simulate the QBO during boreal winter, none of them capture a difference in MJO activity between easterly and westerly QBO that is larger than that which would be expected from the random sampling of internal variability. The weak signal of the simulated QBO‐MJO connection may be due to the weaker amplitude of the QBO than observed, especially between 100 to 50 hPa. This weaker amplitude in the models is seen both in the QBO‐related zonal wind and temperature, the latter of which is thought to be critical for destabilizing tropical convection.
Survey of ex vivo drug combination effects in chronic lymphocytic leukemia reveals synergistic drug effects and genetic dependencies
Authors: Lukas Marina , Velten Britta , Sellner Leopold , Tomska Katarzyna , Hüellein Jennifer , Walther Tatjana , Wagner Lena , Muley Carolin , Wu Bian , Oleś Małgorzata , Dietrich Sascha , Jethwa Alexander , Bohnenberger Hanibal , Lu Junyan , Huber Wolfgang , Zenz Thorsten 
Published: May 2020

AbstractDrug combinations that target critical pathways are a mainstay of cancer care. To improve current approaches to combination treatment of chronic lymphocytic leukemia (CLL) and gain insights into the underlying biology, we studied the effect of 352 drug combination pairs in multiple concentrations by analysing ex vivo drug response of 52 primary CLL samples, which were characterized by “omics” profiling. Known synergistic interactions were confirmed for B-cell receptor (BCR) inhibitors with Bcl-2 inhibitors and with chemotherapeutic drugs, suggesting that this approach can identify clinically useful combinations. Moreover, we uncovered synergistic interactions between BCR inhibitors and afatinib, which we attribute to BCR activation by afatinib through BLK upstream of BTK and PI3K. Combinations of multiple inhibitors of BCR components (e.g., BTK, PI3K, SYK) had effects similar to the single agents. While PI3K and BTK inhibitors produced overall similar effects in combinations with other drugs, we uncovered a larger response heterogeneity of combinations including PI3K inhibitors, predominantly in CLL with mutated IGHV, which we attribute to the target’s position within the BCR-signaling pathway. Taken together, our study shows that drug combination effects can be effectively queried in primary cancer cells, which could aid discovery, triage and clinical development of drug combinations.
Quantum hydrodynamics of a single particle
Authors: Suárez-Forero Daniel Gustavo , Ardizzone Vincenzo , Covre da Silva Saimon Filipe , Reindl Marcus , Fieramosca Antonio , Polimeno Laura , Giorgi Milena De , Dominici Lorenzo , Pfeiffer Loren N. , Gigli Giuseppe , Ballarini Dario , Laussy Fabrice , Rastelli Armando , Sanvitto Daniele 
Published: May 2020

AbstractSemiconductor devices are strong competitors in the race for the development of quantum computational systems. In this work, we interface two semiconductor building blocks of different dimensionalities with complementary properties: (1) a quantum dot hosting a single exciton and acting as a nearly ideal single-photon emitter and (2) a quantum well in a 2D microcavity sustaining polaritons, which are known for their strong interactions and unique hydrodynamic properties, including ultrafast real-time monitoring of their propagation and phase mapping. In the present experiment, we can thus observe how the injected single particles propagate and evolve inside the microcavity, giving rise to hydrodynamic features typical of macroscopic systems despite their genuine intrinsic quantum nature. In the presence of a structural defect, we observe the celebrated quantum interference of a single particle that produces fringes reminiscent of wave propagation. While this behavior could be theoretically expected, our imaging of such an interference pattern, together with a measurement of antibunching, constitutes the first demonstration of spatial mapping of the self-interference of a single quantum particle impinging on an obstacle.
Prediction of clinical diagnosis of Alzheimer’s disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years
Authors: Stocker H. , Perna L. , Weigl K. , Möllers T. , Schöttker B. , Thomsen H. , Holleczek B. , Rujescu D. , Brenner H. 
Published: May 2020

AbstractThe strongest genetic risk factor for Alzheimer’s disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) andAPOEstatus to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excludingAPOE) from the most recent genome-wide association meta-analysis data was calculated andAPOEstatus was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS andAPOEwas assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score andAPOE4positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45–1.99;APOE4: 3.34, 2.24–4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability ofAPOEto discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort.
Synodic lunar phases and suicide: based on 2605 suicides over 23 years, a full moon peak is apparent in premenopausal women from northern Finland
Authors: Meyer-Rochow Victor Benno , Hakko Tapani , Hakko Helinä , Riipinen Pirkko , Timonen Markku 
Published: May 2020

AbstractSuicide data for this study were available for the period of March 1988 to June 2011, and involved 2111 male and 494 female victims from the Finnish province of Oulu. Data for lunar phases during that period were categorised into three groups: new moon (<25% visible), full moon (>75% visible) and other times with values in between. Seasonal effects were controlled with definitions for winter (Nov, Dec, Jan), spring (Feb, Mar, Apr), summer (May, June, July), and autumn (Aug, Sep, Oct). Suicide occurrences during different lunar phases were compared with their expected distribution using multinomial tests with all tests being two-tailed. Statistical significance was set atp < 0.05. No correlation between suicides and moon phase in any of the four seasons was apparent for male victims, but in winter for women it was (p = 0.001). Further analysis of the data revealed that the full moon association was statistically significant only for premenopausal women, defined as female victims younger than 45 years of age. To explain this unexpected finding a number of factors were considered, e.g., the darkness of a northern Finnish winter with increases of SAD and depression especially in premenopausal women, the influence of the lunar periodicity on the menstrual cycle, and cosmogeophysical effects on the humoral and autonomous nervous system.
Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
Authors: Kantrowitz Joshua T. , Grinband Jack , Goff Donald C. , Lahti Adrienne C. , Marder Stephen R. , Kegeles Lawrence S. , Girgis Ragy R. , Sobeih Tarek , Wall Melanie M. , Choo Tse-Hwei , Green Michael F. , Yang Yvonne S. , Lee Junghee , Horga Guillermo , Krystal John H. , Potter William Z. , Javitt Daniel C. , Lieberman Jeffrey A. 
Published: May 2020

AbstractGlutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were conducted contemporaneously. 95 healthy volunteers were randomized to POMA and 63 to TS-134. High-dose POMA significantly reduced ketamine-induced BPRS total symptoms within and between-groups (p < 0.01, d = −0.41; p = 0.04, d = −0.44, respectively), but neither POMA dose significantly suppressed ketamine-induced dACC pharmacoBOLD. In contrast, low-dose TS-134 led to moderate to large within and between group reductions in both BPRS positive symptoms (p = 0.02, d = −0.36; p = 0.008, d = −0.82, respectively) and dACC pharmacoBOLD (p = 0.004, d = −0.56; p = 0.079, d = −0.50, respectively) using pooled across-study placebo data. High-dose POMA exerted significant effects on clinical symptoms, but not on target engagement, suggesting a higher dose may yet be needed, while the low dose of TS-134 showed evidence of symptom reduction and target engagement. These results support further investigation of mGluR2/3 and other glutamate-targeted treatments for schizophrenia.
USP38 regulates the stemness and chemoresistance of human colorectal cancer via regulation of HDAC3
Authors: Zhan Wei , Liao Xin , Liu Jing , Tian Tian , Yu Lei , Li Rui 
Published: May 2020

AbstractHistone modification represents a crucial level of gene expression regulation and is actively involved in the carcinogenesis of human colorectal cancer. Histone acetyltransferases and deacetylases modulate the landscape of histone acetylation, which controls key genes of colorectal cancer pathology. However, the fine tune of histone deacetylases, especially the modification of histone deacetylases that facilitate colorectal cancer, remains elusive. Here, we identified that an ubiquitin-specific protease (USP), USP38, was downregulated in clinical colorectal cancer samples and colorectal cancer cell lines. Importantly, our results showed that USP38 was a specific deubiquitinase of histone deacetylase 3 (HDAC3), which cleaved the lysine 63 ubiquitin chain. Ubiquitination of HDAC3 resulted in a decreased level of histone acetylation and finally led to upregulation of cancer stem cell-related genes. In addition, our results demonstrated a tumor suppressor role of USP38 in colorectal cancer via inhibiting cancer stem cell populations. Most importantly, the ubiquitination level of HDAC3 was responsible for USP38 mediated regulation of cancer stem cell-related transcripts. Our data provided functional insights of USP38 and HDAC3 in colorectal cancer and revealed novel mechanisms of ubiquitination mediated epigenetic regulation.
Osteoblasts are inherently programmed to repel sensory innervation
Authors: Leitão Luís , Neto Estrela , Conceição Francisco , Monteiro Ana , Couto Marina , Alves Cecília J. , Sousa Daniela M. , Lamghari Meriem 
Published: May 2020

AbstractTissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons. Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development. Yet, the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited. Here, we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth, evidenced under sensory neurons and osteoblastic-lineage cells crosstalk. The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression. We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A, Wnt4, and Shh expression culminating at late stage of OB differentiation. We noted a correlation between Shh expression profile, OB differentiation stages, and OB-mediated axonal repulsion. Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons. Finally, to strengthen our model, we localized the expression of Shh by osteoblasts in bone tissue. Overall, our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation, and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.
Chemotaxing neutrophils enter alternate branches at capillary bifurcations
Authors: Wang Xiao , Hossain Mokarram , Bogoslowski Ania , Kubes Paul , Irimia Daniel 
Published: May 2020

AbstractUpon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time. The migration through a limited number of paths through tissues and capillary networks seems efficient and ‘traffic jams’ are generally avoided. However, the mechanisms that guide efficient trafficking of large numbers of neutrophils through capillary networks are not well understood. Here we show that pairs of neutrophils arriving closely one after another at capillary bifurcations migrate to alternating branches in vivo and in vitro. Perturbation of chemoattractant gradients and the increased hydraulic resistance induced by the first neutrophil in one branch biases the migration of the following neutrophil towards the other branch. These mechanisms guide neutrophils to efficiently navigate through capillary networks and outline the effect of inter-neutrophil interactions during migration on overall lymphocyte trafficking patterns in confined environments.
Effect of sulfur on sound velocity of liquid iron under Martian core conditions
Authors: Nishida Keisuke , Shibazaki Yuki , Terasaki Hidenori , Higo Yuji , Suzuki Akio , Funamori Nobumasa , Hirose Kei 
Published: May 2020

AbstractSulfur has been considered to be a predominant light element in the Martian core, and thus the sound velocity of Fe-S alloys at relevant high pressure and temperature is of great importance to interpret its seismological data. Here we measured the compressional sound velocity (VP) of liquid Fe, Fe80S20 and Fe57S43 using ultrasonic pulse-echo overlap method combined with a Kawai-type multi-anvil apparatus up to 20 GPa, likely corresponding to the condition at the uppermost core of Mars. The results demonstrate that the VP of liquid iron is least sensitive to its sulfur concentration in the Mars’ whole core pressure range. The comparison of seismic wave speeds of Fe-S liquids with future observations will therefore tell whether the Martian core is molten and contains impurity elements other than sulfur.
Controlling interlayer excitons in MoS2 layers grown by chemical vapor deposition
Authors: Paradisanos Ioannis , Shree Shivangi , George Antony , Leisgang Nadine , Robert Cedric , Watanabe Kenji , Taniguchi Takashi , Warburton Richard J. , Turchanin Andrey , Marie Xavier , Gerber Iann C. , Urbaszek Bernhard 
Published: May 2020

AbstractCombining MoS2 monolayers to form multilayers allows to access new functionalities. Deterministic assembly of large area van der Waals structures requires concrete indicators of successful interlayer coupling in bilayers grown by chemical vapor deposition. In this work, we examine the correlation between the stacking order and the interlayer coupling of valence states in both as-grown MoS2 homobilayer samples and in artificially stacked bilayers from monolayers, all grown by chemical vapor deposition. We show that hole delocalization over the bilayer is only allowed in 2H stacking and results in strong interlayer exciton absorption and also in a larger A-B exciton separation as compared to 3R bilayers. Comparing 2H and 3R reflectivity spectra allows to extract an interlayer coupling energy of about t⊥ = 49 meV. Beyond DFT calculations including excitonic effects confirm signatures of efficient interlayer coupling for 2H stacking in agreement with our experiments.
Characterization of the development of the mouse cochlear epithelium at the single cell level
Authors: Kolla Likhitha , Kelly Michael C. , Mann Zoe F. , Anaya-Rocha Alejandro , Ellis Kathryn , Lemons Abigail , Palermo Adam T. , So Kathy S. , Mays Joseph C. , Orvis Joshua , Burns Joseph C. , Hertzano Ronna , Driver Elizabeth C. , Kelley Matthew W. 
Published: May 2020

AbstractMammalian hearing requires the development of the organ of Corti, a sensory epithelium comprising unique cell types. The limited number of each of these cell types, combined with their close proximity, has prevented characterization of individual cell types and/or their developmental progression. To examine cochlear development more closely, we transcriptionally profile approximately 30,000 isolated mouse cochlear cells collected at four developmental time points. Here we report on the analysis of those cells including the identification of both known and unknown cell types. Trajectory analysis for OHCs indicates four phases of gene expression while fate mapping of progenitor cells suggests that OHCs and their surrounding supporting cells arise from a distinct (lateral) progenitor pool. Tgfβr1 is identified as being expressed in lateral progenitor cells and a Tgfβr1 antagonist inhibits OHC development. These results provide insights regarding cochlear development and demonstrate the potential value and application of this data set.
Constraints on nonlocality in networks from no-signaling and independence
Authors: Gisin Nicolas , Bancal Jean-Daniel , Cai Yu , Remy Patrick , Tavakoli Armin , Zambrini Cruzeiro Emmanuel , Popescu Sandu , Brunner Nicolas 
Published: May 2020

AbstractThe possibility of Bell inequality violations in quantum theory had a profound impact on our understanding of the correlations that can be shared by distant parties. Generalizing the concept of Bell nonlocality to networks leads to novel forms of correlations, the characterization of which is, however, challenging. Here, we investigate constraints on correlations in networks under the natural assumptions of no-signaling and independence of the sources. We consider the triangle network with binary outputs, and derive strong constraints on correlations even though the parties receive no input, i.e., each party performs a fixed measurement. We show that some of these constraints are tight, by constructing explicit local models (i.e. where sources distribute classical variables) that can saturate them. However, we also observe that other constraints can apparently not be saturated by local models, which opens the possibility of having nonlocal (but non-signaling) correlations in the triangle network with binary outputs.
Bedrock geochemistry influences vegetation growth by regulating the regolith water holding capacity
Authors: Jiang Zihan , Liu Hongyan , Wang Hongya , Peng Jian , Meersmans Jeroen , Green Sophie M. , Quine Timothy A. , Wu Xiuchen , Song Zhaoliang 
Published: May 2020

AbstractAlthough low vegetation productivity has been observed in karst regions, whether and how bedrock geochemistry contributes to the low karstic vegetation productivity remain unclear. In this study, we address this knowledge gap by exploring the importance of bedrock geochemistry on vegetation productivity based on a critical zone investigation across a typical karst region in Southwest China. We show silicon and calcium concentrations in bedrock are strongly correlated with the regolith water loss rate (RWLR), while RWLR can predict vegetation productivity more effectively than previous models. Furthermore, the analysis based on 12 selected karst regions worldwide further suggest that lithological regulation has the potential to obscure and distort the influence of climate change. Our study implies that bedrock geochemistry could exert effects on vegetation growth in karst regions and highlights that the critical role of bedrock geochemistry for the karst region should not be ignored in the earth system model.
Global radiation in a rare biosphere soil diatom
Authors: Pinseel Eveline , Janssens Steven B. , Verleyen Elie , Vanormelingen Pieter , Kohler Tyler J. , Biersma Elisabeth M. , Sabbe Koen , Van de Vijver Bart , Vyverman Wim 
Published: May 2020

AbstractSoil micro-organisms drive the global carbon and nutrient cycles that underlie essential ecosystem functions. Yet, we are only beginning to grasp the drivers of terrestrial microbial diversity and biogeography, which presents a substantial barrier to understanding community dynamics and ecosystem functioning. This is especially true for soil protists, which despite their functional significance have received comparatively less interest than their bacterial counterparts. Here, we investigate the diversification of Pinnularia borealis, a rare biosphere soil diatom species complex, using a global sampling of >800 strains. We document unprecedented high levels of species-diversity, reflecting a global radiation since the Eocene/Oligocene global cooling. Our analyses suggest diversification was largely driven by colonization of novel geographic areas and subsequent evolution in isolation. These results illuminate our understanding of how protist diversity, biogeographical patterns, and members of the rare biosphere are generated, and suggest allopatric speciation to be a powerful mechanism for diversification of micro-organisms.
Model-Free Cluster Analysis of Physical Property Data using Information Maximizing Self-Argument Training
Authors: Sawada Ryohto , Iwasaki Yuma , Ishida Masahiko 
Published: May 2020

AbstractWe present semi-supervised information maximizing self-argument training (IMSAT), a neural network-based classification method that works without the preparation of labeled data. Semi-supervised IMSAT can amplify specific differences and avoid undesirable misclassification in accordance with the purpose. We demonstrate that semi-supervised IMSAT has a comparable performance with existing methods for semi-supervised learning of image classification and can also classify real experimental data (X-ray diffraction patterns and thermoelectric hysteresis curves) in the same way even though their shape and dimensions are different. Our algorithm will contribute to the automation of big data processing and artificial intelligence-driven material development.