bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cordilleran Ice Sheet Stability During the Last Deglaciation
Authors: Darvill C. M. , Menounos B. , Goehring B. M. , Lesnek A. J. 
Published: May 2022

AbstractWe report 20 10Be exposure ages from glacial erratics and bedrock on the west coast of British Columbia, Canada, which add to existing chronologies of Cordilleran Ice Sheet retreat along ∼600 km of coastal North America. Collectively, these data show the western ice limit reached the present coast by 18–16 ka then retreat slowed for ∼4,000 years until 14–13 ka. We attribute initial retreat to destabilization and grounding line retreat resulting from rising sea level and/or ocean warming in the northern Pacific. Subsequent stability of the ice sheet at the present coastal margin was likely due to the transition from marine to terrestrial margins despite increasing temperatures that may have driven ice sheet thinning. Our findings demonstrate the importance of understanding both climatic and nonclimatic drivers of ice sheet change through time.
Denudation Process of Crystalline Nappes in a Continental Collision Zone Constrained by Inversion of Fission‐Track Data and Thermokinematic Forward Modeling: An Example From Eastern Nepalese Himalaya
Authors: Nakajima Toru , Kawakami Tetsuo , Iwano Hideki , Danhara Tohru , Sakai Harutaka 
Published: May 2022

AbstractThermochronological methods were applied to the Higher Himalayan Crystalline (HHC) nappe and the underlying Lesser Himalayan Sequences (LHS) to elucidate the denudation process for the middle‐ and upper‐crust of eastern Nepal over millions of years. Thermochronological inverse modeling was undertaken for new results of fission‐track (FT) age and FT length data of zircon and apatite in order to reconstruct the time‐temperature (t‐T) paths in the temperature range of 60–350°C. Eight t‐T paths calculated along the across‐strike section show that the cooling process of the HHC nappe in this study area is characterized by the following three aspects: (a) gradual cooling followed by rapid cooling and subsequent gradual cooling, (b) northward‐younging of the timing of the rapid cooling, and (c) gradual cooling followed by <2 Myr rapid cooling in the frontmost part of the HHC nappe. The observed FT ages and t‐T paths were then compared with those predicted by forwarding thermokinematic modeling. The results of the thermokinematic modeling for the “Flat‐Ramp‐Flat MHT model”, in which the HHC and the underlying LHS are denudated in direct proportion to the uplift of rocks transported along the Main Himalayan Thrust (MHT), reproduced the observed t‐T paths and FT ages in eastern Nepal. This indicates that the observed FT ages and t‐T paths reflect a denudation process driven by the movement of the MHT with a flat‐ramp‐flat geometry and that the denudation rate and its spatial distribution have roughly been constant in eastern Nepal since ca. 9 Ma.
Reconstructing Pyroclastic Currents' Source and Flow Parameters From Deposit Characteristics and Numerical Modeling: The Pozzolane Rosse Ignimbrite Case Study (Colli Albani, Italy)
Authors: Calabrò Laura , Esposti Ongaro Tomaso , Giordano Guido , de’ Michieli Vitturi Mattia 
Published: May 2022

AbstractIn this study, we apply a two‐dimensional, transient depth‐averaged model to simulate the inertial flow dynamics of caldera‐forming pyroclastic currents, using the available data about the Pozzolane Rosse ignimbrite (Colli Albani, Italy) eruption (460 ka, 63 km3 DRE). By performing an extensive set of numerical simulations, we test the effects of the initial parameters of the pyroclastic current (Richardson number, mass flow rate, initial flow density) on simulated deposit characteristics which can be compared with selected ignimbrite field observables, including the deposit dispersal along topography, the maximum distance from source, the deposit thickness, the grain size distribution at different distances, and the emplacement temperature. Results permit us to quantify the first‐order dependency of the flow runout on the mass flow rate, and of the deposit thickness decay pattern on the initial mixture density. By using the results of the parametric study we reconstruct the source parameters of the Pozzolane Rosse ignimbrite constrained by the ignimbrite depositional characteristics, including the mass partition into the co‐ignimbrite cloud. Despite uncertainties associated with the complex, non‐linear interplay between the flow variables, the single‐layer, depth‐averaged model demonstrates to be suitable for simulating inertial pyroclastic currents, such as those generating large‐scale caldera‐forming ignimbrites, providing a tool for reconstructing the eruption source parameters from deposits characteristics, and to assess pyroclastic currents' hazard for future eruptions.
Identifying Efficient Ensemble Perturbations for Initializing Subseasonal‐To‐Seasonal Prediction
Authors: Demaeyer Jonathan , Penny Stephen G. , Vannitsem Stéphane 
Published: May 2022

AbstractThe prediction of the weather at subseasonal‐to‐seasonal (S2S) timescales is dependent on both initial and boundary conditions. An open question is how to best initialize a relatively small‐sized ensemble of numerical model integrations to produce reliable forecasts at these timescales. Reliability in this case means that the statistical properties of the ensemble forecast are consistent with the actual uncertainties about the future state of the geophysical system under investigation. In the present work, a method is introduced to construct initial conditions that produce reliable ensemble forecasts by projecting onto the eigenfunctions of the Koopman or the Perron‐Frobenius operators, which describe the time‐evolution of observables and probability distributions of the system dynamics, respectively. These eigenfunctions can be approximated from data by using the Dynamic Mode Decomposition (DMD) algorithm. The effectiveness of this approach is illustrated in the framework of a low‐order ocean‐atmosphere model exhibiting multiple characteristic timescales, and is compared to other ensemble initialization methods based on the Empirical Orthogonal Functions (EOFs) of the model trajectory and on the backward and covariant Lyapunov vectors (CLVs) of the model dynamics. Projecting initial conditions onto a subset of the Koopman or Perron‐Frobenius eigenfunctions that are characterized by time scales with fast‐decaying oscillations is found to produce highly reliable forecasts at all lead times investigated, ranging from one week to two months. Reliable forecasts are also obtained with the adjoint CLVs, which are the eigenfunctions of the Koopman operator in the tangent space. The advantages of these different methods are discussed.
Magnetic Biosignatures of Magnetosomal Greigite From Micromagnetic Calculation
Authors: Bai Fan , Chang Liao , Pei Zhaowen , Harrison Richard J. , Winklhofer Michael 
Published: May 2022

AbstractGreigite magnetosomes produced by magnetotactic bacteria (MTB) are widely distributed in natural environments, but large uncertainties remain regarding their magnetic biosignatures. Here, we have constructed micromagnetic models with realistic biogenic greigite particles to quantify the magnetic properties and magnetotaxis efficiency of greigite‐producing MTB cells. Our calculations suggest coercivity (Bc) of ∼15–21 mT for intact greigite‐producing rod‐shaped MTB and many‐celled magnetotactic prokaryotes, with Bc decreasing to ∼11 mT for greigite magnetofossils with clumped particles. These magnetic signatures make biogenic greigite distinguishable from typical biogenic magnetite and inorganic greigite, providing reliable magnetic criteria to detect biogenic greigite in a wide range of environmental and geological settings. Our numerical calculations suggest that rod‐shaped greigite‐producing MTB have a similar magnetotaxis efficiency to magnetite MTB, likely by biomineralizing more greigite crystals to compensate for the lower saturation magnetization of greigite and less ordered chains in greigite MTB cells, demonstrating biological‐controlled optimization of their magnetic nanostructure.
Comparative metabolomic analysis in plasma and cerebrospinal fluid of humans and in plasma and brain of mice following antidepressant-dose ketamine administration
Authors: Moaddel Ruin , Zanos Panos , Farmer Cristan A. , Kadriu Bashkim , Morris Patrick J. , Lovett Jacqueline , Acevedo-Diaz Elia E. , Cavanaugh Grace W. , Yuan Peixiong , Yavi Mani , Thomas Craig J. , Park Lawrence T. , Ferrucci Luigi , Gould Todd D. , Zarate Carlos A. 
Published: May 2022

AbstractSubanesthetic-dose racemic (R,S)-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical studies found that (2 R,6 R;2 S,6 S)-hydroxynorketamine (HNK), a major circulating metabolite of ketamine, elicits antidepressant effects similar to those of ketamine. To help determine how (2 R,6 R)-HNK contributes to ketamine’s mechanism of action, an exploratory, targeted, metabolomic analysis was carried out on plasma and CSF of nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg). A parallel targeted metabolomic analysis in plasma, hippocampus, and hypothalamus was carried out in mice receiving either 10 mg/kg of ketamine, 10 mg/kg of (2 R,6 R)-HNK, or saline. Ketamine and (2 R,6 R)-HNK both affected multiple pathways associated with inflammatory conditions. In addition, several changes were unique to either the healthy human volunteers and/or the mouse arm of the study, indicating that different pathways may be differentially involved in ketamine’s effects in mice and humans. Mechanisms of action found to consistently underlie the effects of ketamine and/or (2 R,6 R)-HNK across both the human metabolome in plasma and CSF and the mouse arm of the study included LAT1, IDO1, NAD+, the nitric oxide (NO) signaling pathway, and sphingolipid rheostat.
Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML
Authors: Yilmaz Musa , Kantarjian Hagop , Short Nicholas J. , Reville Patrick , Konopleva Marina , Kadia Tapan , DiNardo Courtney , Borthakur Gautam , Pemmaraju Naveen , Maiti Abhishek , Jabbour Elias , Jain Nitin , Issa Ghayas , Takahashi Koichi , Sasaki Koji , Ohanian Maro , Pierce Sherry , Tang Guillin , Loghavi Sanam , Patel Keyur , Wang Sa A. , Garcia-Manero Guillermo , Andreeff Michael , Ravandi Farhad , Daver Naval 
Published: May 2022

AbstractIn older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P < 0.01), and flow-cytometry negativity (83% versus 38%, P < 0.01) than doublets. At the end of the first cycle, the median time to ANC > 0.5 (40 versus 21 days, P = 0.15) and platelet > 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P < 0.01). LIC combined with FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3 mutated AML that should be further validated prospectively.
The dual role of glioma exosomal microRNAs: glioma eliminates tumor suppressor miR-1298-5p via exosomes to promote immunosuppressive effects of MDSCs
Authors: Qi Yanhua , Jin Chuandi , Qiu Wei , Zhao Rongrong , Wang Shaobo , Li Boyan , Zhang Zongpu , Guo Qindong , Zhang Shouji , Gao Zijie , Zhao Shulin , Pan Ziwen , Fan Yang , chen Zihang , Wang Huizhi , Xu Jianye , Deng Lin , Ni Shilei , Wang Jian , Xue Hao , Xue Fuzhong , Li Gang 
Published: May 2022

AbstractClear evidence shows that tumors could secrete microRNAs (miRNAs) via exosomes to modulate the tumor microenvironment (TME). However, the mechanisms sorting specific miRNAs into exosomes are still unclear. In order to study the biological function and characterization of exosomal miRNAs, we performed whole-transcriptome sequencing in 59 patients’ whole-course cerebrospinal fluid (CSF) small extracellular vesicles (sEV) and matched glioma tissue samples. The results demonstrate that miRNAs could be divided into exosome-enriched miRNAs (ExomiRNAs) and intracellular-retained miRNAs (CLmiRNAs), and exosome-enriched miRNAs generally play a dual role. Among them, miR-1298-5p was enriched in CSF exosomes and suppressed glioma progression in vitro and vivo experiments. Interestingly, exosomal miR-1298-5p could promote the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) to facilitate glioma. Therefore, we found miR-1298-5p had different effects on glioma cells and MDSCs. Mechanically, downstream signaling pathway analyses showed that miR-1298-5p plays distinct roles in glioma cells and MDSCs via targeting SETD7 and MSH2, respectively. Moreover, reverse verification was performed on the intracellular-retained miRNA miR-9-5p. Thus, we confirmed that tumor-suppressive miRNAs in glioma cells could be eliminated through exosomes and target tumor-associated immune cells to induce tumor-promoting phenotypes. Glioma could get double benefit from it. These findings uncover the mechanisms that glioma selectively sorts miRNAs into exosomes and modulates tumor immunity.
A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis
Authors: Zhang Yawen , Wang Mengmeng , Meng Fanyi , Yang Man , Chen Yinshuang , Guo Xuqin , Wang Weiwei , Zhu Yifan , Guo Yundi , Feng Chunlai , Tian Shen , Zhang Hongjian , Li Huanqiu , Sun Jing , Wang Weipeng 
Published: May 2022

AbstractAs the modulation of serine/arginine-rich splicing factor 3 (SRSF3) may be therapeutically beneficial to colorectal cancer (CRC) treatment, the identification of novel SRSF3 inhibitors is highly anticipated. However, pharmaceutical agents targeting SRSF3 have not yet been discovered. Here, we propose a functional SRSF3 inhibitor for CRC therapy and elucidate its antitumor mechanisms. We found high expression of SRSF3 in 70.6% CRC tissues. Silencing SRSF3 markedly inhibits the proliferation and migration of CRC cells through suppression of its target gene 24-dehydrocholesterol reductase (DHCR24). This is evidenced by the links between SRSF3 and DHCR24 in CRC tissues. The novel SRSF3 inhibitor SFI003 exhibits potent antitumor efficacy in vitro and in vivo, which drives apoptosis of CRC cells via the SRSF3/DHCR24/reactive oxygen species (ROS) axis. Moreover, SFI003 is druggable with suitable pharmacokinetic properties, bioavailability, and tumor distribution. Thus, SRSF3 is a novel potential therapeutic target for CRC. Its inhibitor SFI003 may be developed as an anticancer therapeutic.
The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data
Authors: Reiff Sarah B. , Schroeder Andrew J. , Kırlı Koray , Cosolo Andrea , Bakker Clara , Mercado Luisa , Lee Soohyun , Veit Alexander D. , Balashov Alexander K. , Vitzthum Carl , Ronchetti William , Pitman Kent M. , Johnson Jeremy , Ehmsen Shannon R. , Kerpedjiev Peter , Abdennur Nezar , Imakaev Maxim , Öztürk Serkan Utku , Çamoğlu Uğur , Mirny Leonid A. , Gehlenborg Nils , Alver Burak H. , Park Peter J. 
Published: May 2022

AbstractThe 4D Nucleome (4DN) Network aims to elucidate the complex structure and organization of chromosomes in the nucleus and the impact of their disruption in disease biology. We present the 4DN Data Portal (https://data.4dnucleome.org/), a repository for datasets generated in the 4DN network and relevant external datasets. Datasets were generated with a wide range of experiments, including chromosome conformation capture assays such as Hi-C and other innovative sequencing and microscopy-based assays probing chromosome architecture. All together, the 4DN data portal hosts more than 1800 experiment sets and 36000 files. Results of sequencing-based assays from different laboratories are uniformly processed and quality-controlled. The portal interface allows easy browsing, filtering, and bulk downloads, and the integrated HiGlass genome browser allows interactive visualization and comparison of multiple datasets. The 4DN data portal represents a primary resource for chromosome contact and other nuclear architecture data for the scientific community.
Physical realization of topological Roman surface by spin-induced ferroelectric polarization in cubic lattice
Authors: Liu Guangxiu , Pi Maocai , Zhou Long , Liu Zhehong , Shen Xudong , Ye Xubin , Qin Shijun , Mi Xinrun , Chen Xue , Zhao Lin , Zhou Bowen , Guo Jia , Yu Xiaohui , Chai Yisheng , Weng Hongming , Long Youwen 
Published: May 2022

AbstractTopology, an important branch of mathematics, is an ideal theoretical tool to describe topological states and phase transitions. Many topological concepts have found their physical entities in real or reciprocal spaces identified by topological invariants, which are usually defined on orientable surfaces, such as torus and sphere. It is natural to investigate the possible physical realization of more intriguing non-orientable surfaces. Herein, we show that the set of spin-induced ferroelectric polarizations in cubic perovskite oxides AMn3Cr4O12 (A = La and Tb) reside on the topological Roman surface—a non-orientable two-dimensional manifold formed by sewing a Möbius strip edge to that of a disc. The induced polarization may travel in a loop along the non-orientable Möbius strip or orientable disc, depending on the spin evolution as controlled by an external magnetic field. Experimentally, the periodicity of polarization can be the same or twice that of the rotating magnetic field, which is consistent with the orientability of the disc and the Möbius strip, respectively. This path-dependent topological magnetoelectric effect presents a way to detect the global geometry of a surface and deepens our understanding of topology in both mathematics and physics.
The barley leaf rust resistance gene Rph3 encodes a predicted membrane protein and is induced upon infection by avirulent pathotypes of Puccinia hordei
Authors: Dinh Hoan X. , Singh Davinder , Gomez de la Cruz Diana , Hensel Goetz , Kumlehn Jochen , Mascher Martin , Stein Nils , Perovic Dragan , Ayliffe Michael , Moscou Matthew J. , Park Robert F. , Pourkheirandish Mohammad 
Published: May 2022

AbstractLeaf rust, caused by Puccinia hordei, is an economically significant disease of barley, but only a few major resistance genes to P. hordei (Rph) have been cloned. In this study, gene Rph3 was isolated by positional cloning and confirmed by mutational analysis and transgenic complementation. The Rph3 gene, which originated from wild barley and was first introgressed into cultivated Egyptian germplasm, encodes a unique predicted transmembrane resistance protein that differs from all known plant disease resistance proteins at the amino acid sequence level. Genetic profiles of diverse accessions indicated limited genetic diversity in Rph3 in domesticated germplasm, and higher diversity in wild barley from the Eastern Mediterranean region. The Rph3 gene was expressed only in interactions with Rph3-avirulent P. hordei isolates, a phenomenon also observed for transcription activator-like effector-dependent genes known as executors conferring resistance to Xanthomonas spp. Like known transmembrane executors such as Bs3 and Xa7, heterologous expression of Rph3 in N. benthamiana induced a cell death response. The isolation of Rph3 highlights convergent evolutionary processes in diverse plant-pathogen interaction systems, where similar defence mechanisms evolved independently in monocots and dicots.
A spin promotion effect in catalytic ammonia synthesis
Authors: Cao Ang , Bukas Vanessa J. , Shadravan Vahid , Wang Zhenbin , Li Hao , Kibsgaard Jakob , Chorkendorff Ib , Nørskov Jens K. 
Published: May 2022

AbstractThe need for efficient ammonia synthesis is as urgent as ever. Over the past two decades, many attempts to find new catalysts for ammonia synthesis at mild conditions have been reported and, in particular, many new promoters of the catalytic rate have been introduced beyond the traditional K and Cs oxides. Herein, we provide an overview of recent experimental results for non-traditional promoters and develop a comprehensive model to explain how they work. The model has two components. First, we establish what is the most likely structure of the active sites in the presence of the different promoters. We then show that there are two effects dictating the catalytic activity. One is an electrostatic interaction between the adsorbed promoter and the N-N dissociation transition state. In addition, we identify a new promoter effect for magnetic catalysts giving rise to an anomalously large lowering of the activation energy opening the possibility of finding new ammonia synthesis catalysts.
Comparative effectiveness over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine
Authors: Islam Nazmul , Sheils Natalie E. , Jarvis Megan S. , Cohen Kenneth 
Published: May 2022

AbstractReal-world analysis of the incidence of SARS-CoV-2 infection post vaccination is important in determining the comparative effectiveness of the available vaccines. In this retrospective cohort study using deidentified administrative claims for Medicare Advantage and commercially insured individuals in a research database we examine over 3.5 million fully vaccinated individuals, including 8,848 individuals with SARS-CoV-2 infection, with a follow-up period between 14 and 151 days after their second dose. Our primary outcome was the rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub-analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals above and below age 65 and those without a prior diagnosis of Covid-19. We show that immunization with mRNA-1273, compared to BNT162b2, provides slightly more protection against SARS-CoV-2 infection that reaches statistical significance at 90 days with a number needed to vaccinate of >290. There are no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer (aOR 1.23, 95% CI (0.67, 2.25)).