bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Runoff Volumes of Inland Terminal Lake: A Case Study of Lake Daihai
Authors: Wang Qianxun , Chen Xuekai , Peng Wenqi , Liu Xiaobo , Dong Fei , Huang Aiping , Wang Weihao 
Published: November 2021

AbstractThe reduction of the runoff to lake has become a common phenomenon of the inland lakes in northwest China, and the quantitative calculation of the driving factors affecting the runoff change has always been a challenge in lake research. In this pursuit, the present study was performed on Lake Daihai as an example, based on the relevant data from 1960 to 2018. The quantitative calculations of the runoff driving factors of Lake Daihai from 1982 to 2004 and from 2004 to 2017 were based on the slope change ratio of cumulative quantity (SCRCQ). It was concluded that human activities were the main factors affecting runoff change after 1982. The SCRCQ method was improved, which could carry out the quantitative calculations on the driving factors affecting the runoff change of the Lake Daihai from 1961 to 2017 on a yearly basis. The results show that the dominant factor of runoff changes in Lake Daihai was found to be the climate change before 1975, and it changed into human activities after 1975. Finally, based on the comparative analysis of the results of SCRCQ and improved SCRCQ, the advantages of improved SCRCQ were discussed. In addition, the reasons for the variation of the runoff to lake dominated by different factors in different periods for Lake Daihai were analyzed.
Future Global Convective Environments in CMIP6 Models
Authors: Lepore Chiara , Abernathey Ryan , Henderson Naomi , Allen John T. , Tippett Michael K. 
Published: November 2021

AbstractThe response of severe convective storms to a warming climate is poorly understood outside of a few well studied regions. Here, projections from seven global climate models from the CMIP6 archive, for both historical and future scenarios, are used to explore the global response in variables that describe favorability of conditions for the development of severe storms. The variables include convective available potential energy (CAPE), convection inhibition (CIN), 0–6 km vertical wind shear (S06), storm relative helicity (SRH), and covariate indices (i.e., severe weather proxies) that combine them. To better quantify uncertainty, understand variable sensitivity to increasing temperature, and present results independent from a specific scenario, we consider changes in convective variables as a function of global average temperature increase across each ensemble member. Increases to favorable convective environments show an overall frequency increases on the order of 5%–20% per °C of global temperature increase, but are not regionally uniform, with higher latitudes, particularly in the Northern Hemisphere, showing much larger relative changes. The driving mechanism of these changes is a strong increase in CAPE that is not offset by factors that either resist convection (CIN), or modify the likelihood of storm organization (S06, SRH). Severe weather proxies are not the same as severe weather events. Hence, their projected increases will not necessarily translate to severe weather occurrences, but they allow us to quantify how increases in global temperature will affect the occurrence of conditions favorable to severe weather.
Modeling Subsurface Explosions Recorded on a Distributed Fiber Optic Sensor
Authors: Mellors Robert J. , Abbott Robert , Steedman David , Podrasky David , Pitarka Arben 
Published: November 2021

AbstractFiber optic distributed acoustic sensors (DAS) are becoming a widely used tool for seismic sensing. Here we examine recordings of two subsurface chemical explosions, DAG‐1 and DAG‐3, each of which was about one metric ton (TNT equivalent), that were recorded from a helical fiber installed in two boreholes 80 m away from the source location. Several clear phases including the initial P wave, a weak S wave, and a surface reflected P wave are observed on the helical DAS data. We estimate a velocity model using arrival times measured from the fiber. The DAS waveform data were compared with colocated accelerometers at specific depths in both frequency and time domains. The spectra of the DAS data matched spectra estimated from the accelerometer records. Comparisons of observed waveform shape between the accelerometer records and the fiber measurements (strain‐rate) show reasonable agreement except for the data near the event depth. The DAS data and the accelerometer agreed in relative amplitudes but we had difficulties in matching absolute amplitudes, possibly due to errors in metadata. Synthetic strain‐rate waveforms were calculated using a 2D wavenumber algorithm and matched the waveform shape and relative amplitudes. In general, DAS is effective at recording strong ground motions at high spatial density. Comparison of the synthetic seismograms with observed data indicate that the waveforms are not consistent with a pure isotropic explosion source and that the observed S waves originate from very near the source region.
Dating Continental Subduction Beneath the Samail Ophiolite: Garnet, Zircon, and Rutile Petrochronology of the As Sifah Eclogites, NE Oman
Authors: Garber Joshua M. , Rioux Matthew , Searle Michael P. , Kylander‐Clark Andrew R. C. , Hacker Bradley R. , Vervoort Jeff D. , Warren Clare J. , Smye Andrew J. 
Published: November 2021

AbstractStudies of the high‐pressure (HP) As Sifah eclogites in the NE Saih Hatat Window, Oman, have used different combinations of radiometric dating results (Ar/Ar, Sm‐Nd vs. U‐Pb, Rb‐Sr) to interpret disparate tectonic models for the timing, geometry, and cause of continental subduction—including its relationship to the Samail Ophiolite. To determine the timing of continental subduction, we coupled petrochronological analyses of major (garnet) and accessory phases (zircon and rutile) from the highest grade metamorphic rocks (As Sifah eclogites) in the Saih Hatat. Early Permian (283.8 ± 0.7 Ma) tuffaceous zircon cores are consistent with earlier interpretations that the As Sifah rocks were sourced from a distal portion of the Arabian continental margin. Data from a range of bulk compositions and metamorphic assemblages consistently suggest a single metamorphic event with garnet growth from ∼81 to 77 Ma—though with slight, consistent offsets in the timing of metamorphic (re)crystallization between different lithologies. These new data confirm previous interpretations for continental HP metamorphism in a single NE‐dipping subduction zone beneath the obducted Samail Ophiolite; there is no robust evidence for an ∼110 Ma event or for SW‐dipping subduction beneath the Arabian plate. Combined with other constraints, our data suggest that the As Sifah unit was subducted at rates similar to other small continental HP bodies, followed by two stages of cooling and exhumation—likely associated with the dragging to mantle depths by a mafic root, an initial phase of rapid exhumation from mantle depths, and a lengthy residence (≤40 My) in the lower to middle crust.
Ocean and Sea Ice Retrievals From an End‐To‐End Simulation of the Copernicus Imaging Microwave Radiometer (CIMR) 1.4–36.5 GHz Measurements
Authors: Jiménez Carlos , Tenerelli Joseph , Prigent Catherine , Kilic Lise , Lavergne Thomas , Skarpalezos Sotirios , Høyer Jacob L. , Reul Nicolas , Donlon Craig 
Published: November 2021

AbstractThe Copernicus Imaging Microwave Radiometer (CIMR) is currently being implemented by the European Space Agency (ESA) as a Copernicus Expansion Mission primarily designed to observe the Polar Regions in support of the Integrated European Policy for the Arctic. It is a conically scanning microwave radiometer with polarized channels centered at 1.414, 6.925, 10.65, 18.7, and 36.5 GHz and channel NEΔT between 0.2 and 0.7 K. A large rotating deployable mesh reflector will provide real‐aperture resolutions ranging from 60 (1.4 GHz) to 5 km (36.5 GHz). To evaluate CIMR retrieval performance, a simplified end‐to‐end simulation of the mission has been carried out. The simulation includes important processes and input parameters, such as test geophysical datasets, forward models, an instrument simulator, and retrieval algorithms to derive the key mission geophysical products. The forward modeling is tested by producing Brightness Temperatures (TBs) from 4 global scenes. A comparison with current observations of the open ocean and sea ice at similar frequencies confirmed the realism of the simulations. The produced top‐of‐atmosphere TBs are converted to Antenna brightness Temperatures (TAs), taking into account the instrument design, and are then inverted to retrieve Sea Ice Concentration (SIC), Sea Surface Temperature (SST), and Sea Surface Salinity (SSS). Evaluating the retrieval performance showed that the simulated CIMR instrument can provide SST, SSS, and SIC measurements with precisions and spatial resolutions conforming with the mission requirements. The evaluation also highlighted the challenges of observing the Arctic environment and put in perspective CIMR capabilities compared with current instruments.
Propagating acoustic waves on a culture substrate regulate the directional collective cell migration
Authors: Imashiro Chikahiro , Kang Byungjun , Lee Yunam , Hwang Youn-Hoo , Im Seonghun , Kim Dae-Eun , Takemura Kenjiro , Lee Hyungsuk 
Published: November 2021

AbstractCollective cell migration plays a critical role in physiological and pathological processes such as development, wound healing, and metastasis. Numerous studies have demonstrated how various types of chemical, mechanical, and electrical cues dictate the collective migratory behaviors of cells. Although an acoustic cue can be advantageous because of its noninvasiveness and biocompatibility, cell migration in response to acoustic stimulation remains poorly understood. In this study, we developed a device that is able to apply surface acoustic waves to a cell culture substrate and investigated the effect of propagating acoustic waves on collective cell migration. The migration distance estimated at various wave intensities revealed that unidirectional cell migration was enhanced at a critical wave intensity and that it was suppressed as the intensity was further increased. The increased migration might be attributable to cell orientation alignment along the direction of the propagating wave, as characterized by nucleus shape. Thicker actin bundles indicative of a high traction force were observed in cells subjected to propagating acoustic waves at the critical intensity. Our device and technique can be useful for regulating cellular functions associated with cell migration.
AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility
Authors: Ma Qian , Cao Congcong , Zhuang Changshui , Luo Xiaomin , Li Xiaofeng , Wan Huijuan , Ye Jing , Chen Fangfang , Cui Lina , Zhang Yan , Wen Yujiao , Yuan Shuiqiao , Gui Yaoting 
Published: November 2021

AbstractSpermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly,Axdnd1knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia.Axdnd1mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.
A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity
Authors: Colon-Moran Winston , Baer Alan , Lamture Gauri , Stapleton Jack T. , Fischer Joseph W. , Bhattarai Nirjal 
Published: November 2021

AbstractViral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy. We hypothesized that modulation of TCA by incorporating a novel viral immunomodulatory factor into a viral vector may reduce unwanted TCA and immune responses during gene therapy. To test this hypothesis, we identified an immunomodulatory domain of the hepatitis C virus (HCV) NS protein 5A (NS5A) protein and studied the effect of viral vectors expressing NS5A peptide on TCA. Lentiviral vector-mediated expression of a short 20-mer peptide derived from the NS5A protein in human T cells was sufficient to inhibit TCA. Synthetic 20-mer NS5A peptide also inhibited TCA in primary human T cells. Mechanistically, the NS5A protein interacted with Lck and inhibited proximal TCR signaling. Importantly, NS5A peptide expression did not cause global T cell signaling dysfunction as distal T cell signaling was not inhibited. Finally, recombinant adeno-associated virus (AAV) vector expressing the 20-mer NS5A peptide reduced both the recall antigen and the TCR-mediated activation of human T cells and did not cause global T cell signaling dysfunction. Together, these data suggest that expression of a 20-mer NS5A peptide by an AAV vector may reduce unwanted TCA and may contribute to lower vector immunogenicity during gene therapy.
A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo
Authors: Hernandez J. O. R. , Wang X. , Vazquez-Segoviano M. , Lopez-Marfil M. , Sobral-Reyes M. F. , Moran-Horowich A. , Sundberg M. , Lopez-Cantu D. O. , Probst C. K. , Ruiz-Esparza G. U. , Giannikou K. , Abdi R. , Henske E. P. , Kwiatkowski D. J. , Sahin M. , Lemos D. R. 
Published: November 2021

AbstractThe lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2−/− hiPSCs but not from isogenic TSC2+/− or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2−/− renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.
Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
Authors: Zhao Xue-Ke , Xing Pengwei , Song Xin , Zhao Miao , Zhao Linxuan , Dang Yonglong , Lei Ling-Ling , Xu Rui-Hua , Han Wen-Li , Wang Pan-Pan , Yang Miao-Miao , Hu Jing-Feng , Zhong Kan , Zhou Fu-You , Han Xue-Na , Meng Chao-Long , Ji Jia-Jia , Chen Xingqi , Wang Li-Dong 
Published: November 2021

AbstractThe role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy
Authors: Verhoef Ellen , Grove Jakob , Shapland Chin Yang , Demontis Ditte , Burgess Stephen , Rai Dheeraj , Børglum Anders D. , St Pourcain Beate 
Published: November 2021

AbstractAutism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610–766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.
Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses
Authors: Contreras-Trujillo Humberto , Eerdeng Jiya , Akre Samir , Jiang Du , Contreras Jorge , Gala Basia , Vergel-Rodriguez Mary C. , Lee Yeachan , Jorapur Aparna , Andreasian Areen , Harton Lisa , Bramlett Charles S. , Nogalska Anna , Xiao Gang , Lee Jae-Woong , Chan Lai N. , Müschen Markus , Merchant Akil A. , Lu Rong 
Published: November 2021

AbstractCellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing
Authors: Sinha Sanju , Barbosa Karina , Cheng Kuoyuan , Leiserson Mark D. M. , Jain Prashant , Deshpande Anagha , Wilson David M. , Ryan Bríd M. , Luo Ji , Ronai Ze’ev A. , Lee Joo Sang , Deshpande Aniruddha J. , Ruppin Eytan 
Published: November 2021

AbstractRecent studies have reported that genome editing by CRISPR–Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framework, we systematically investigated the possibility of selection of additional cancer driver mutations during CRISPR-Cas9 gene editing. We first confirm the previous findings of the selection for pre-existing p53 mutations by CRISPR-Cas9. We next demonstrate that similar to p53, wildtype KRAS may also hamper the growth of Cas9-edited cells, potentially conferring a selective advantage to pre-existing KRAS-mutant cells. These selective effects are widespread, extending across cell-types and methods of CRISPR-Cas9 delivery and the strength of selection depends on the sgRNA sequence and the gene being edited. The selection for pre-existing p53 or KRAS mutations may confound CRISPR-Cas9 screens in cancer cells and more importantly, calls for monitoring patients undergoing CRISPR-Cas9-based editing for clinical therapeutics for pre-existing p53 and KRAS mutations.
Dissection of the amyloid formation pathway in AL amyloidosis
Authors: Kazman Pamina , Absmeier Ramona M. , Engelhardt Harald , Buchner Johannes 
Published: November 2021

AbstractIn antibody light chain (AL) amyloidosis, overproduced light chain (LC) fragments accumulate as fibrils in organs and tissues of patients. In vitro, AL fibril formation is a slow process, characterized by a pronounced lag phase. The events occurring during this lag phase are largely unknown. We have dissected the lag phase of a patient-derived LC truncation and identified structural transitions that precede fibril formation. The process starts with partial unfolding of the VL domain and the formation of small amounts of dimers. This is a prerequisite for the formation of an ensemble of oligomers, which are the precursors of fibrils. During oligomerization, the hydrophobic core of the LC domain rearranges which leads to changes in solvent accessibility and rigidity. Structural transitions from an anti-parallel to a parallel β-sheet secondary structure occur in the oligomers prior to amyloid formation. Together, our results reveal a rate-limiting multi-step mechanism of structural transitions prior to fibril formation in AL amyloidosis, which offers, in the long run, opportunities for therapeutic intervention.