bluuebunny/crossref_metadata_2025_split huggingface dataset:
HARM3D+NUC: GRMHD, nuclear tables and neutrino leakage
Authors: Murguia-Berthier Ariadna , Noble Scott C. , Roberts Luke F. , Ramirez-Ruiz Enrico 
Published: February 2023

AbstractOn August 17, 2017, the LIGO/VIRGO collaboration detected the first gravitational wave signal coming from the merger of two neutron stars. This groundbreaking discovery, referred to as GW170817, revealed to us how heavy elements, such as gold and platinum, are synthesized through a mechanism known as rapid neutron capture (r-process). In order to fully understand these signals, we need to simulate the resulting accretion disk around a black hole, and its outflows. This task requires efficient computing codes that include general relativity magnetohydrodynamics (GRMHD), neutrino physics, and a model for matter at high densities. We present the implementation of a tabulated equation of state that takes care of matter at high densities and a neutrino leakage scheme that considers the impact of neutrinos into HARM3D, a GRMHD parallelized code. We also apply the tools to a magnetized torus.
THE ZHOU ORDINAL OF LABELLED MARKOV PROCESSES OVER SEPARABLE SPACES
Authors: MORONI MARTÍN SANTIAGO , SÁNCHEZ TERRAF PEDRO 
Published: February 2023

AbstractThere exist two notions of equivalence of behavior between states of a Labelled Markov Process (LMP): state bisimilarity and event bisimilarity. The first one can be considered as an appropriate generalization to continuous spaces of Larsen and Skou’s probabilistic bisimilarity, whereas the second one is characterized by a natural logic. C. Zhou expressed state bisimilarity as the greatest fixed point of an operator
$\mathcal {O}$
, and thus introduced an ordinal measure of the discrepancy between it and event bisimilarity. We call this ordinal the Zhou ordinal of
$\mathbb {S}$
,
$\mathfrak {Z}(\mathbb {S})$
. When
$\mathfrak {Z}(\mathbb {S})=0$
,
$\mathbb {S}$
satisfies the Hennessy–Milner property. The second author proved the existence of an LMP
$\mathbb {S}$
with
$\mathfrak {Z}(\mathbb {S}) \geq 1$
and Zhou showed that there are LMPs having an infinite Zhou ordinal. In this paper we show that there are LMPs
$\mathbb {S}$
over separable metrizable spaces having arbitrary large countable
$\mathfrak {Z}(\mathbb {S})$
and that it is consistent with the axioms of
$\mathit {ZFC}$
that there is such a process with an uncountable Zhou ordinal.
AXIOMS FOR TYPE-FREE SUBJECTIVE PROBABILITY
Authors: CIEŚLIŃSKI CEZARY , HORSTEN LEON , LEITGEB HANNES 
Published: February 2023

AbstractWe formulate and explore two basic axiomatic systems of type-free subjective probability. One of them explicates a notion of finitely additive probability. The other explicates a concept of infinitely additive probability. It is argued that the first of these systems is a suitable background theory for formally investigating controversial principles about type-free subjective probability.
Characteristics of Electron Precipitation Directly Driven by Poloidal ULF Waves
Authors: Yin Ze‐Fan , Zhou Xu‐Zhi , Li Wen , Shen Xiao‐Chen , Rankin Robert , Liu Ji , Hu Ze‐Jun , Liu Jian‐Jun , Zong Qiu‐Gang , Li Li , Wang Yong‐Fu 
Published: February 2023

AbstractA mechanism recently proposed for magnetospheric electron loss into the atmosphere is the precipitation directly driven by ultralow‐frequency (ULF) waves. In this study, we quantitatively analyze the properties of ULF wave‐induced precipitation by simulating the electron bounce and drift motion in poloidal‐mode waves excited in a dipole magnetic field. Our results reveal that precipitation occurs only when electrons encounter a westward‐directed wave electric field in the magnetosphere, which leads to cross‐field energy enhancements and reduces their mirror heights. The simulations also demonstrate longer duration electron precipitation at the drift‐resonance energy. We calculate the temporal variations of the energy spectrum for precipitating electrons and the total precipitating energy fluxes. These results improve our understanding of ULF wave‐induced electron precipitation as well as provide a point of comparison for observations from balloons or ground‐based instruments.
A New P‐Wave Tomographic Model (CAP22) for North America: Implications for the Subduction and Cratonic Metasomatic Modification History of Western Canada and Alaska
Authors: Boyce A. , Liddell M. V. , Pugh S. , Brown J. , McMurchie E. , Parsons A. , Estève C. , Burdick S. , Darbyshire F. A. , Cottaar S. , Bastow I. D. , Schaeffer A. J. , Audet P. , Schutt D. L. , Aster R. C. 
Published: February 2023

AbstractOur understanding of the present‐day state and evolution of the Canadian and Alaskan mantle is hindered by a lack of absolute P‐wavespeed constraints that provide complementary sensitivity to composition in conjunction with existing S‐wavespeed models. Consequently, cratonic modification, orogenic history of western North America and complexities within the Alaskan Proto‐Pacific subduction system remain enigmatic. One challenge concerns the difficulties in extracting absolute arrival‐time measurements from often‐noisy data recorded by temporary seismograph networks required to fill gaps in continental and global databases. Using the Absolute Arrival‐time Recovery Method (AARM), we extract >180,000 new absolute arrival‐time residuals from seismograph stations across Canada and Alaska and combine these data with USArray and global arrival‐time data from the contiguous US and Alaska. We develop a new absolute P‐wavespeed tomographic model, CAP22, spanning North America that significantly improves resolution in Canada and Alaska over previous models. Slow wavespeeds below the Canadian Cordillera sharply abut fast wavespeeds of the continental interior at the Rocky Mountain Trench in southwest Canada. Slow wavespeeds below the Mackenzie Mountains continue farther inland in northwest Canada, indicating Proterozoic‐Archean metasomatism of the Slave craton. Inherited tectonic lineaments colocated with this north‐south wavespeed boundary suggest that both the crust and mantle may control Cordilleran orogenic processes. In Alaska, fast upper mantle wavespeeds below the Wrangell Volcanic Field favor a conventional subduction related mechanism for volcanism. Finally, seismic evidence for the subducted Kula and Yukon slabs indicate tectonic reconstructions of western North America may require revision.
Tracking a Pyroclastic Density Current With Seismic Signals at Mt. Etna (Italy)
Authors: Watson Leighton M. , Cannata Andrea , Andronico Daniele 
Published: February 2023

AbstractPyroclastic density currents (PDCs) are dangerous flows of volcanic rock and gas that are the most deadly proximal volcano hazard. There is significant interest in better understanding PDC dynamics, however, they are challenging to study due to their extreme hazard, unpredictable occurrence, and because complex internal dynamics are obscured by visually opaque clouds of ash. PDCs exert forces on Earth's surface and generate seismic waves. Here, we use seismic data recorded by the permanent monitoring network at Mt. Etna (Italy) to track the 11 February 2014 PDC at second‐scale temporal resolution and calculate a maximum velocity of 76 m/s (274 km/hr). We identify multiple pulses and show that the late‐stage source locations correspond with the mapped coarse‐grained PDC deposits. High temporal and spatial resolution measurements of PDC movement from seismic data can be used to inform numerical modeling of PDC dynamics and aid in hazard assessment by improving our understanding of PDC flow paths. This work illustrates how seismic signals can be used to track surficial mass movements in real‐time.
Machine Learning of Key Variables Impacting Extreme Precipitation in Various Regions of the Contiguous United States
Authors: Lin Xinming , Fan Jiwen , Hou Z. Jason , Wang Jingyu 
Published: February 2023

AbstractAmplification in extreme precipitation intensity and frequency can cause severe flooding and impose significant social and economic consequences. Variations in extreme precipitation intensity, frequencies, and return periods can be attributed to many physical variables across spatial and temporal scales. Here we employ ensemble machine learning (ML) methods, namely random forest (RF), eXtreme Gradient Boosting (XGB), and artificial neural networks (ANN), to explore key contributing variables to monthly extreme precipitation intensity and frequency in six regions over the United States. We further establish emulators for return periods. Results show that the ML models for intensity perform better in regions with obvious seasonality (i.e., Northern Great Plains, Southern Great Plains, and West Coast) than the other three regions (Northeast, Southwest, and Rocky Mountains), while for frequency the models perform well for most regions. The Shapley additive explanation is used to help explain the relationships between extreme precipitation characteristics and identify top variables for RF and XGB. We find that latent heat flux, relative humidity, soil moisture, and large‐scale subsidence are key common variables across the regions for both monthly intensity and frequency, and their compound effects are non‐negligible. The developed ML models capture the probability and return period of extreme precipitation well for all regions and may be used for decision making (e.g., infrastructure planning and design).
Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation
Authors: Guirado Elizabeth , Villani Cassandra , Petho Adrienn , Chen Yinghua , Maienschein-Cline Mark , Lei Zhengdeng , Los Nina , George Anne 
Published: February 2023

AbstractX-linked hypophosphatemia (XLH) represents the most common form of familial hypophosphatemia. Although significant advances have been made in the treatment of bone pathology, patients undergoing therapy continue to experience significantly decreased oral health-related quality of life. The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells. Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved. RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation. RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells, while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation. These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.
Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy
Authors: Moscvin Maria , Liacos Christine Ivy , Chen Tianzeng , Theodorakakou Foteini , Fotiou Despina , Hossain Shahrier , Rowell Sean , Leblebjian Houry , Regan Eileen , Czarnecki Peter , Bagnoli Filippo , Bolli Niccolo’ , Richardson Paul , Rennke Helmut G. , Dimopoulos Meletios A. , Kastritis Efstathios , Bianchi Giada 
Published: February 2023

AbstractThrombotic microangiopathy (TMA) has been reported to occur in multiple myeloma (MM) patients in association with treatment with carfilzomib, an irreversible proteasome inhibitor (PI). The hallmark of TMA is vascular endothelial damage leading to microangiopathic hemolytic anemia, platelet consumption, fibrin deposition and small-vessel thrombosis with resultant tissue ischemia. The molecular mechanisms underlying carfilzomib-associated TMA are not known. Germline mutations in the complement alternative pathway have been recently shown to portend increased risk for the development of atypical hemolytic uremic syndrome (aHUS) and TMA in the setting of allogeneic stem cell transplant in pediatric patients. We hypothesized that germline mutations in the complement alternative pathway may similarly predispose MM patients to carfilzomib-associated TMA. We identified 10 MM patients with a clinical diagnosis of TMA in the context of carfilzomib treatment and assessed for the presence of germline mutations in the complement alternative pathway. Ten, matched MM patients exposed to carfilzomib but without clinical TMA were used as negative controls. We identified a frequency of deletions in the complement Factor H genes 3 and 1 (delCFHR3-CFHR1) and genes 1 and 4 (delCFHR1-CFHR4) in MM patients with carfilzomib-associated TMA that was higher as compared to the general population and matched controls. Our data suggest that complement alternative pathway dysregulation may confer susceptibility to vascular endothelial injury in MM patients and predispose to development of carfilzomib-associated TMA. Larger, retrospective studies are needed to evaluate whether screening for complement mutations may be indicated to properly counsel patients about TMA risk with carfilzomib use.
Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy
Authors: Chemello Francesco , Pozzobon Michela , Tsansizi Lorenza Iolanda , Varanita Tatiana , Quintana-Cabrera Rubèn , Bonesso Daniele , Piccoli Martina , Lanfranchi Gerolamo , Giacomello Marta , Scorrano Luca , Bean Camilla 
Published: February 2023

AbstractThe approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy.
The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2
Authors: García-Caballero Daniel , Hart Jonathan R. , Vogt Peter K. 
Published: February 2023

AbstractMYC controls most of the non-coding genome. Several long noncoding transcripts were originally identified in the human B cell line P496-3 and then shown to be required for MYC-driven proliferation of Burkitt lymphoma-derived RAMOS cells. In this study, we used RAMOS cells exclusively as a representative of the human B cell lineage. One of the MYC-controlled lncRNAs required for RAMOS cell proliferation is ENSG00000254887 which we will term LNROP (long non-coding regulator of POU2F2). In the genome, LNROP is located in close proximity of POU2F2, the gene encoding OCT2. OCT2 is a transcription factor with important roles in sustaining the proliferation of human B cells. Here we show that LNROP is a nuclear RNA and a direct target of MYC. Downregulation of LNROP attenuates the expression of OCT2. This effect of LNROP on the expression of OCT2 is unidirectional as downregulation of OCT2 does not alter the expression of LNROP. Our data suggest that LNROP is a cis-acting regulator of OCT2. To illustrate the downstream reach of LNROP, we chose a prominent target of OCT2, the tyrosine phosphatase SHP-1. Downregulation of OCT2 elevates the expression of SHP-1. Our data suggest the following path of interactions: LNROP enables the proliferation of B cells by positively and unidirectionally regulating the growth-stimulatory transcription factor OCT2. In actively proliferating B cells, OCT2 attenuates the expression and anti-proliferative activity of SHP-1.
The UDPase ENTPD5 regulates ER stress-associated renal injury by mediating protein N-glycosylation
Authors: Xu Lifen , Zhou Yuxia , Wang Guifang , Bo Li , Jin Bangming , Dai Lujun , Lu Qinli , Cai Xueni , Hu Laying , Liu Lu , Wu Yixuan , Chang Xuebing , Huang Yali , Song Lingyu , Zhang Tian , Wang Yuanyuan , Xiao Ying , Zhang Fan , Liu Lingling , Shi Mingjun , Wang Tuanlao , Guo Bing 
Published: February 2023

AbstractImpaired protein N-glycosylation leads to the endoplasmic reticulum (ER) stress, which triggers adaptive survival or maladaptive apoptosis in renal tubules in diabetic kidney disease (DKD). Therapeutic strategies targeting ER stress are promising for the treatment of DKD. Here, we report a previously unappreciated role played by ENTPD5 in alleviating renal injury by mediating ER stress. We found that ENTPD5 was highly expressed in normal renal tubules; however, ENTPD5 was dynamically expressed in the kidney and closely related to pathological DKD progression in both human patients and mouse models. Overexpression of ENTPD5 relieved ER stress in renal tubular cells, leading to compensatory cell proliferation that resulted in hypertrophy, while ENTPD5 knockdown aggravated ER stress to induce cell apoptosis, leading to renal tubular atrophy and interstitial fibrosis. Mechanistically, ENTPD5-regulated N-glycosylation of proteins in the ER to promote cell proliferation in the early stage of DKD, and continuous hyperglycemia activated the hexosamine biosynthesis pathway (HBP) to increase the level of UDP-GlcNAc, which driving a feedback mechanism that inhibited transcription factor SP1 activity to downregulate ENTPD5 expression in the late stage of DKD. This study was the first to demonstrate that ENTPD5 regulated renal tubule cell numbers through adaptive proliferation or apoptosis in the kidney by modulating the protein N-glycosylation rate in the ER, suggesting that ENTPD5 drives cell fate in response to metabolic stress and is a potential therapeutic target for renal diseases.
Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors
Authors: Isoyama Sho , Tamaki Naomi , Noguchi Yutaka , Okamura Mutsumi , Yoshimatsu Yuki , Kondo Tadashi , Suzuki Takeshi , Yaguchi Shin-ichi , Dan Shingo 
Published: February 2023

AbstractTranslocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have yet to be established. We previously reported that a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, ZSTK474, was effective for the treatment of sarcomas in a phase I clinical trial. We also demonstrated the efficacy of ZSTK474 in a preclinical model, particularly in cell lines from synovial sarcoma (SS), Ewing’s sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS), all of which harbor chromosomal translocations. ZSTK474 selectively induced apoptosis in all these sarcoma cell lines, although the precise mechanism underlying the induction of apoptosis remained unclear. In the present study, we aimed to determine the antitumor effect of PI3K inhibitors, particularly with regards to the induction of apoptosis, against various TRS subtypes using cell lines and patient-derived cells (PDCs). All of the cell lines derived from SS (six), ES (two) and ARMS (one) underwent apoptosis accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP) and the loss of mitochondrial membrane potential. We also observed apoptotic progression in PDCs from SS, ES and clear cell sarcoma (CCS). Transcriptional analyses revealed that PI3K inhibitors triggered the induction of PUMA and BIM and the knockdown of these genes by RNA interference efficiently suppressed apoptosis, suggesting their functional involvement in the progression of apoptosis. In contrast, TRS-derived cell lines/PDCs from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. Thus, we conclude that PI3K inhibitors induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and the subsequent loss of mitochondrial membrane potential. This represents proof of concept for PI3K-targeted therapy, particularly such TRS patients.
The double-edged functions of necroptosis
Authors: Ye Keng , Chen Zhimin , Xu Yanfang 
Published: February 2023

AbstractNecroptosis refers to a regulated form of cell death induced by a variety of stimuli. Although it has been implicated in the pathogenesis of many diseases, there is evidence to support that necroptosis is not purely a detrimental process. We propose that necroptosis is a “double-edged sword” in terms of physiology and pathology. On the one hand, necroptosis can trigger an uncontrolled inflammatory cascade response, resulting in severe tissue injury, disease chronicity, and even tumor progression. On the other hand, necroptosis functions as a host defense mechanism, exerting antipathogenic and antitumor effects through its powerful pro-inflammatory properties. Moreover, necroptosis plays an important role during both development and regeneration. Misestimation of the multifaceted features of necroptosis may influence the development of therapeutic approaches targeting necroptosis. In this review, we summarize current knowledge of the pathways involved in necroptosis as well as five important steps that determine its occurrence. The dual role of necroptosis in a variety of physiological and pathological conditions is also highlighted. Future studies and the development of therapeutic strategies targeting necroptosis should fully consider the complicated properties of this type of regulated cell death.
Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming
Authors: Aso Kuniyuki , Kono Michihito , Kanda Masatoshi , Kudo Yuki , Sakiyama Kodai , Hisada Ryo , Karino Kohei , Ueda Yusho , Nakazawa Daigo , Fujieda Yuichiro , Kato Masaru , Amengual Olga , Atsumi Tatsuya 
Published: February 2023

AbstractDysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased RORγt binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.