bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physically Consistent Modeling of Dike‐Induced Deformation and Seismicity: Application to the 2014 Bárðarbunga Dike, Iceland
Authors: Heimisson Elías R. , Segall Paul 
Published: January 2020

AbstractDike intrusions are often associated with surface deformation and propagating swarms of earthquakes. These are understood to be manifestations of the same underlying physical process, although rarely modeled as such. We construct a physics‐based model of the 2014 Bárðarbunga dike, by far the best observed large dike (
0.5 km
) to date. We constrain the background stress state by the total dike deformation, the time‐dependent dike pressure from continuous GPS and the extent of the seismic swarm, and the spatial dependence of frictional properties via the space‐time evolution of seismicity. We find that the geodetic and earthquake data can be reconciled with a self‐consistent set of parameters. The complex spatial and temporal evolution of the Bárðarbunga seismicity can be explained by dike‐induced elastic stress changes on preexisting faults, constrained by observed focal mechanisms. In particular, the model captures the segmentation of seismicity, where only the newest dike segment is seismically active. Our results indicate that many features of the seismicity result from the interplay between time‐dependent magma pressure within the dike and stress memory effects. The spatial variability in seismicity requires heterogeneity in frictional properties and/or local initial stresses. Modeling suggests that the dike pressure drops during rapid advances and increases during pauses, which primarily causes the segmentation of the seismicity. Joint analysis of multiple data types could potentially lead to improved, physics‐based eruption forecasts.
Phase‐Coherent Amplification of Ocean Swells Over Submarine Canyons
Authors: Tamura Hitoshi , Kawaguchi Koji , Fujiki Takashi 
Published: January 2020

AbstractOcean swells can be a significant coastal hazard, potentially causing coastal disasters with costly damage to infrastructure and tragic loss of lives. We have observed this in the coastal region of Toyama Bay in the Sea of Japan, which has been devastated by severe winter swell events (the so‐called YoriMawari‐nami; YM wave). An extreme swell event was recorded in February 2008 in which the wave height at a site in the bay reached 9+ m, which corresponds to 16 times the local climatological average. Substantial efforts by the Japanese coastal engineering community have been expended to reproduce YM wave events with phase‐averaged wave models but, to our knowledge, with no success. During an archetype YM event, we found that the Noto peninsula filtered the incoming wavefield such that in the bay incident waves were quasi‐monochromatic. The swell then refracted over a submarine canyon resulting in a bimodal directional distribution of wave energy. This initiated conditions favorable for coherent interference, violating the assumptions of the phase‐averaged approach. Coherent interference is the key mechanism for understanding the formation of the large amplitudes and for matching observed high space‐time variability. Our results demonstrate the significance of the coherent interference for wave statistics over coastal bathymetry; only by accounting for phase‐resolving phenomena were we able to adequately reproduce the observations.
Contrasting Patterns of Labile and Semilabile Dissolved Organic Carbon From Continental Waters to the Open Ocean
Authors: LaBrie Richard , Lapierre Jean‐François  , Maranger Roxane 
Published: January 2020

AbstractMarine and freshwater prokaryotes feed primarily on bioavailable labile dissolved organic carbon (BDOCL), as well as the bioavailable fraction of the semilabile DOC (BDOCSL) pool. These fractions are operationally defined here as the DOC consumed within a month and greater than a month to a year and a half, respectively. Organic matter from these different pools comes from various autochthonous and allochthonous sources, but their relative bioavailability is unknown across aquatic ecosystems. To fill this gap, we compiled literature information that included 653 batch culture DOC biodegradation experiments across eight aquatic ecosystem types over the past 20 years. We show that the proportion of BDOCL across all aquatic ecosystems was surprisingly consistent (6.1%) despite a 2 order of magnitude variation in initial DOC concentrations, suggesting an overall tight balance between carbon supply and consumption. A higher proportion of BDOCL, 16.3% on average, was observed in high productivity ecosystems. BDOCSL, on the other hand, gradually decreased from 16.0% in lakes to 7.2% in estuaries to undetectable in the open ocean, suggesting that terrestrial connectivity regulates BDOCSL across the continuum. Our results support that recent primary production fuels short‐term prokaryotic DOC needs with an increasing reliance on the abundant BDOCSL pool as ecosystems approach the land‐water interface. Batch culture experiments show that BDOCSL is metabolizable in freshwater and coastal environments but not in the open ocean. We estimate that BDOCSL can sustain 62% of total prokaryotic biomass in inland waters and coasts and an estimated total of 16.7% across aquatic biomes.
Success and efficiency of phase 2/3 adjunctive trials for MDD funded by industry: a systematic review
Authors: Salloum Naji C. , Fava Maurizio , Ball Sophia , Papakostas George I. 
Published: January 2020

AbstractTo review the success rate and efficiency of industry-sponsored phase 2/3 clinical trials for adjunctive therapies for antidepressant partial- and non-responders with major depressive disorder (MDD), a systematic search of Pubmed/Medline was conducted, in addition to abstracts of major psychiatric meeting held since 2010, of randomized, placebo-controlled adjunct oral pharmacotherapy trials in this patient population. Forty-six (n = 33,900; 70 drug compactor arms) trials were pooled, yielding only three approved drugs. Twenty-two (31.4%) drug-placebo comparisons were successful. Numerically, success rates for treatment arms from studies with one versus more than one drug-placebo comparison were higher (39.3% versus 26.2%). The antidepressant lead-in employing single-blind placebo and the sequential-parallel comparison design (SPCD) were successful in 50% and 40% of cases, respectively. The direct randomization (no lead-in) design yielded positive results in one third of cases. The success rate of open-label antidepressant lead-ins without placebo or using double-blind placebo was very poor (<15%). There was also a pronounced discrepancy in terms of efficiency across study designs. Accounting for sample size requirements, a phase 3 program using SPCD would have a higher cumulative chance of yielding two positive trials (50%) than a phase 3 program using a single-blind placebo lead-in (40%). Future programs should carefully weigh the need for a lead-in, which is time-consuming, expensive and, in some cases (i.e., open-label antidepressant without placebo or with double-blind placebo) nearly futile. Instead, more effort should involve the use of studies where patients are directly randomized, such as the SPCD, with more investment shifted towards the accurate and independent vetting of subject eligibility.
A psychiatric disease-related circular RNA controls synaptic gene expression and cognition
Authors: Zimmerman Amber J. , Hafez Alexander K. , Amoah Stephen K. , Rodriguez Brian A. , Dell’Orco Michela , Lozano Evelyn , Hartley Brigham J. , Alural Begüm , Lalonde Jasmin , Chander Praveen , Webster Maree J. , Perlis Roy H. , Brennand Kristen J. , Haggarty Stephen J. , Weick Jason , Perrone-Bizzozero Nora , Brigman Jonathan L. , Mellios Nikolaos 
Published: January 2020

AbstractAlthough circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from genes involved in synaptic plasticity and psychiatric disease. Intriguingly, in vivo circHomer1a knockdown in mouse OFC resulted in specific deficits in OFC-mediated cognitive flexibility. Lastly, we demonstrate that the neuronal RNA-binding protein HuD binds to circHomer1a and can influence its synaptic expression in the frontal cortex. Collectively, our data uncover a novel psychiatric disease-associated circRNA that regulates synaptic gene expression and cognitive flexibility.
Anaerobic methane oxidation coupled to manganese reduction by members of the Methanoperedenaceae
Authors: Leu Andy O , Cai Chen , McIlroy Simon J , Southam Gordon , Orphan Victoria J , Yuan Zhiguo , Hu Shihu , Tyson Gene W 
Published: January 2020

Abstract
Anaerobic oxidation of methane (AOM) is a major biological process that reduces global methane emission to the atmosphere. Anaerobic methanotrophic archaea (ANME) mediate this process through the coupling of methane oxidation to different electron acceptors, or in concert with a syntrophic bacterial partner. Recently, ANME belonging to the archaeal family Methanoperedenaceae (formerly known as ANME-2d) were shown to be capable of AOM coupled to nitrate and iron reduction. Here, a freshwater sediment bioreactor fed with methane and Mn(IV) oxides (birnessite) resulted in a microbial community dominated by two novel members of the Methanoperedenaceae, with biochemical profiling of the system demonstrating Mn(IV)-dependent AOM. Genomic and transcriptomic analyses revealed the expression of key genes involved in methane oxidation and several shared multiheme c-type cytochromes (MHCs) that were differentially expressed, indicating the likely use of different extracellular electron transfer pathways. We propose the names “Candidatus Methanoperedens manganicus” and “Candidatus Methanoperedens manganireducens” for the two newly described Methanoperedenaceae species. This study demonstrates the ability of members of the Methanoperedenaceae to couple AOM to the reduction of Mn(IV) oxides, which suggests their potential role in linking methane and manganese cycling in the environment.
Lipids and small metabolites provisioned by ambrosia fungi to symbiotic beetles are phylogeny-dependent, not convergent
Authors: Huang Yin-Tse , Skelton James , Hulcr Jiri 
Published: January 2020

Abstract
Long-term symbiotic associations often lead to reciprocal adaptation between the involved entities. One of the main challenges for studies of such symbioses is differentiating adaptation from neutral processes and phylogenetic background. Ambrosia fungi, cultivated by ambrosia beetles as their sole food source, provide an excellent model to study evolutionary adaptation in a comparative framework because they evolved many times, and each origin bears features seemingly convergently adapted to the symbiosis. We tested whether the symbiotic lifestyle of unrelated ambrosia fungi has led to convergence in the key feature of the symbiotic phenotype—nutrition provisioning to the vector beetles. We compared conidia and mycelium content in three phylogenetic pairs of ambrosia fungi and their closely related nonambrosia relatives using an untargeted metabolomic assay. Multivariate analysis of 311 polar metabolites and 14063 lipid features revealed no convergence of nutrient content across ambrosia lineages. Instead, most variation of the metabolome composition was explained by phylogenetic relationships among the fungi. Thus the overall metabolome evolution of each ambrosia fungus is mostly driven by its inherited metabolism rather than the transition toward symbiosis. We identified eight candidate lipid compounds with expression levels different between the swollen ambrosia spores and other tissues, but they were not consistently elevated across ambrosia fungi. We conclude that ambrosia provisions consist either of nonspecific nutrients in elevated amounts, or of metabolites that are specific to each of the ambrosia symbioses.
The long noncoding RNA TUG1 is required for TGF-β/TWIST1/EMT-mediated metastasis in colorectal cancer cells
Authors: Shen Xuning , Hu Xiu , Mao Jiayan , Wu Ying , Liu Hao , Shen Jian , Yu Jiayin , Chen Wei 
Published: January 2020

AbstractColorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and metastasis is the major cause of CRC-related mortality. Transforming growth factor-beta (TGF-β) has a central role not only in the regulation of the normal colon but also in the development and metastasis of CRC. However, TGF-β is not considered an ideal therapeutic target because it shows both pro-tumorigenic and anti-tumorigenic activity, depending on the tumor stage. Therefore, it is important to find a downstream signaling component of TGF-β that can be targeted to impair CRC metastasis. Here, we show that TGF-β promotes CRC migration and upregulates the expression of long-noncoding RNA Taurine Upregulated Gene 1 (TUG1). TUG1 knockdown inhibited migration, invasion, and epithelial–mesenchymal transition (EMT) of CRC cells in vitro, and reduced CRC lung metastasis in vivo. TGF-β induced metastasis, and TUG1 knockdown inhibited these effects. In addition, TGF-β could not reverse the anti-metastasis effects of TUG1 knockdown. These data demonstrate that TUG1 is a downstream molecular of TGF-β. Moreover, TWIST1 expression was increased with TGF-β treatment, and TUG1 knockdown decreased TWIST1 expression in CRC cells. TWIST1 knockdown inhibited invasion and EMT in CRC cells; these effects were not changed by simultaneous TUG1 knockdown, indicating that TWIST1 is a downstream mediator of TUG1. Moreover, TUG1 was significantly overexpressed in CRC patients. In conclusion, TGF-β promotes metastasis of CRC via a TUG1/TWIST1/EMT signaling pathway. TUG1 may be a promising drug target to inhibit TGF-β pathway activation in the treatment of CRC.
The transcription elongation factor TCEA3 induces apoptosis in rhabdomyosarcoma
Authors: Kazim Noor , Adhikari Abhinav , Oh Teak Jung , Davie Judith 
Published: January 2020

AbstractTCEA3 is one of three genes representing the transcription elongation factor TFIIS family in vertebrates. TCEA3 is upregulated during skeletal muscle differentiation and acts to promote muscle specific gene expression during myogenesis. Rhabdomyosarcoma (RMS) is a pediatric cancer derived from the muscle lineage, but the expression or function of TCEA3 in RMS was uncharacterized. We found that TCEA3 expression was strongly inhibited in RMS cell lines representing both ERMS and ARMS subtypes of RMS. TCEA3 expression correlates with DNA methylation and we show that TBX2 is also involved in the repression of TCEA3 in RMS cell lines. Ectopic expression of TCEA3 inhibited proliferation of RMS cell lines and initiated apoptosis through both the intrinsic and extrinsic pathways. We found that only pan-caspase inhibitors could block apoptosis in the presence of TCEA3. While expression of TCEA3 is highest in skeletal muscle, expression has been detected in other tissues as well, including breast, ovarian and prostate. We found that ectopic expression of TCEA3 also promotes apoptosis in HeLa, MCF7, MDA-231, and PC3 cell lines, representing cervical, breast, and prostate cancer, respectively. Restoration of TCEA3 expression in RMS cell lines enhanced sensitivity to chemotherapeutic drugs, including TRAIL. Thus, TCEA3 presents a novel target for therapeutic strategies to promote apoptosis and enhance sensitivity to current chemotherapeutic drugs.
Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions
Authors: Vokali Efthymia , Yu Shann S. , Hirosue Sachiko , Rinçon-Restrepo Marcela , V. Duraes Fernanda , Scherer Stefanie , Corthésy-Henrioud Patricia , Kilarski Witold W. , Mondino Anna , Zehn Dietmar , Hugues Stéphanie , Swartz Melody A. 
Published: January 2020

AbstractLymphatic endothelial cells (LECs) chemoattract naïve T cells and promote their survival in the lymph nodes, and can cross-present antigens to naïve CD8+ T cells to drive their proliferation despite lacking key costimulatory molecules. However, the functional consequence of LEC priming of CD8+ T cells is unknown. Here, we show that while many proliferating LEC-educated T cells enter early apoptosis, the remainders comprise a long-lived memory subset, with transcriptional, metabolic, and phenotypic features of central memory and stem cell-like memory T cells. In vivo, these memory cells preferentially home to lymph nodes and display rapid proliferation and effector differentiation following memory recall, and can protect mice against a subsequent bacterial infection. These findings introduce a new immunomodulatory role for LECs in directly generating a memory-like subset of quiescent yet antigen-experienced CD8+ T cells that are long-lived and can rapidly differentiate into effector cells upon inflammatory antigenic challenge.
Microscaled proteogenomic methods for precision oncology
Authors: Satpathy Shankha , Jaehnig Eric J. , Krug Karsten , Kim Beom-Jun , Saltzman Alexander B. , Chan Doug W. , Holloway Kimberly R. , Anurag Meenakshi , Huang Chen , Singh Purba , Gao Ari , Namai Noel , Dou Yongchao , Wen Bo , Vasaikar Suhas V. , Mutch David , Watson Mark A. , Ma Cynthia , Ademuyiwa Foluso O. , Rimawi Mothaffar F. , Schiff Rachel , Hoog Jeremy , Jacobs Samuel , Malovannaya Anna , Hyslop Terry , Clauser Karl R. , Mani D. R. , Perou Charles M. , Miles George , Zhang Bing , Gillette Michael A. , Carr Steven A. , Ellis Matthew J. 
Published: January 2020

AbstractCancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48–72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.
Global projections of future urban land expansion under shared socioeconomic pathways
Authors: Chen Guangzhao , Li Xia , Liu Xiaoping , Chen Yimin , Liang Xun , Leng Jiye , Xu Xiaocong , Liao Weilin , Qiu Yue’an , Wu Qianlian , Huang Kangning 
Published: January 2020

AbstractDespite its small land coverage, urban land and its expansion have exhibited profound impacts on global environments. Here, we present the scenario projections of global urban land expansion under the framework of the shared socioeconomic pathways (SSPs). Our projections feature a fine spatial resolution of 1 km to preserve spatial details. The projections reveal that although global urban land continues to expand rapidly before the 2040s, China and many other Asian countries are expected to encounter substantial pressure from urban population decline after the 2050s. Approximately 50–63% of the newly expanded urban land is expected to occur on current croplands. Global crop production will decline by approximately 1–4%, corresponding to the annual food needs for a certain crop of 122–1389 million people. These findings stress the importance of governing urban land development as a key measure to mitigate its negative impacts on food production.
Nuthatches vary their alarm calls based upon the source of the eavesdropped signals
Authors: Carlson Nora V , Greene Erick , Templeton Christopher N 
Published: January 2020

AbstractAnimal alarm calls can contain detailed information about a predator’s threat, and heterospecific eavesdropping on these signals creates vast communication networks. While eavesdropping is common, this indirect public information is often less reliable than direct predator observations. Red-breasted nuthatches (Sitta canadensis) eavesdrop on chickadee mobbing calls and vary their behaviour depending on the threat encoded in those calls. Whether nuthatches propagate this indirect information in their own calls remains unknown. Here we test whether nuthatches propagate direct (high and low threat raptor vocalizations) or indirect (high and low threat chickadee mobbing calls) information about predators differently. When receiving direct information, nuthatches vary their mobbing calls to reflect the predator’s threat. However, when nuthatches obtain indirect information, they produce calls with intermediate acoustic features, suggesting a more generic alarm signal. This suggests nuthatches are sensitive to the source and reliability of information and selectively propagate information in their own mobbing calls.
Uncomputability and complexity of quantum control
Authors: Bondar Denys I. , Pechen Alexander N. 
Published: January 2020

AbstractIn laboratory and numerical experiments, physical quantities are known with a finite precision and described by rational numbers. Based on this, we deduce that quantum control problems both for open and closed systems are in general not algorithmically solvable, i.e., there is no algorithm that can decide whether dynamics of an arbitrary quantum system can be manipulated by accessible external interactions (coherent or dissipative) such that a chosen target reaches a desired value. This conclusion holds even for the relaxed requirement of the target only approximately attaining the desired value. These findings do not preclude an algorithmic solvability for a particular class of quantum control problems. Moreover, any quantum control problem can be made algorithmically solvable if the set of accessible interactions (i.e., controls) is rich enough. To arrive at these results, we develop a technique based on establishing the equivalence between quantum control problems and Diophantine equations, which are polynomial equations with integer coefficients and integer unknowns. In addition to proving uncomputability, this technique allows to construct quantum control problems belonging to different complexity classes. In particular, an example of the control problem involving a two-mode coherent field is shown to be NP-hard, contradicting a widely held believe that two-body problems are easy.