bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning for Geophysics: Current and Future Trends
Authors: Yu Siwei , Ma Jianwei 
Published: June 2021

AbstractRecently deep learning (DL), as a new data‐driven technique compared to conventional approaches, has attracted increasing attention in geophysical community, resulting in many opportunities and challenges. DL was proven to have the potential to predict complex system states accurately and relieve the “curse of dimensionality” in large temporal and spatial geophysical applications. We address the basic concepts, state‐of‐the‐art literature, and future trends by reviewing DL approaches in various geosciences scenarios. Exploration geophysics, earthquakes, and remote sensing are the main focuses. More applications, including Earth structure, water resources, atmospheric science, and space science, are also reviewed. Additionally, the difficulties of applying DL in the geophysical community are discussed. The trends of DL in geophysics in recent years are analyzed. Several promising directions are provided for future research involving DL in geophysics, such as unsupervised learning, transfer learning, multimodal DL, federated learning, uncertainty estimation, and active learning. A coding tutorial and a summary of tips for rapidly exploring DL are presented for beginners and interested readers of geophysics.
A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival
Authors: Massett Matthew E. , Monaghan Laura , Patterson Shaun , Mannion Niamh , Bunschoten Roderick P. , Hoose Alex , Marmiroli Sandra , Liskamp Robert M. J. , Jørgensen Heather G. , Vetrie David , Michie Alison M. , Huang Xu 
Published: June 2021

AbstractEpigenomic dysregulation is a common pathological feature in human hematological malignancies. H3K9me3 emerges as an important epigenomic marker in acute myeloid leukemia (AML). Its associated methyltransferases, such as SETDB1, suppress AML leukemogenesis, whilst H3K9me3 demethylases KDM4C is required for mixed-lineage leukemia rearranged AML. However, the specific role and molecular mechanism of action of another member of the KDM4 family, KDM4A has not previously been clearly defined. In this study, we delineated and functionally validated the epigenomic network regulated by KDM4A. We show that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing downregulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C. From this regulatory network, we further extracted a KDM4A-9 gene signature enriched with leukemia stem cell activity; the KDM4A-9 score alone or in combination with the known LSC17 score, effectively stratifies high-risk AML patients. Together, these results establish the essential and unique role of KDM4A for AML self-renewal and survival, supporting further investigation of KDM4A and its targets as a potential therapeutic vulnerability in AML.
Sgpl1 deletion elevates S1P levels, contributing to NPR2 inactivity and p21 expression that block germ cell development
Authors: Yuan Feifei , Wang Zhijuan , Sun Yanli , Wei Hongwei , Cui Yanying , Wu Zhanying , Zhang Chunyu , Xie Ke-Ping , Wang Fengchao , Zhang Meijia 
Published: June 2021

AbstractSphingosine phosphate lyase 1 (SGPL1) is a highly conserved enzyme that irreversibly degrades sphingosine-1-phosphate (S1P). Sgpl1-knockout mice fail to develop germ cells, resulting in infertility. However, the molecular mechanism remains unclear. The results of the present study showed that SGPL1 was expressed mainly in granulosa cells, Leydig cells, spermatocytes, and round spermatids. Sgpl1 deletion led to S1P accumulation in the gonads. In the ovary, S1P decreased natriuretic peptide receptor 2 (NPR2) activity in granulosa cells and inhibited early follicle growth. In the testis, S1P increased the levels of cyclin-dependent kinase inhibitor 1A (p21) and apoptosis in Leydig cells, thus resulting in spermatogenesis arrest. These results indicate that Sgpl1 deletion increases intracellular S1P levels, resulting in the arrest of female and male germ cell development via different signaling pathways.
Long-lasting renewable antibacterial porous polymeric coatings enable titanium biomaterials to prevent and treat peri-implant infection
Authors: Wu Shuyi , Xu Jianmeng , Zou Leiyan , Luo Shulu , Yao Run , Zheng Bingna , Liang Guobin , Wu Dingcai , Li Yan 
Published: June 2021

AbstractPeri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Drug repurposing screens identify chemical entities for the development of COVID-19 interventions
Authors: Bakowski Malina A. , Beutler Nathan , Wolff Karen C. , Kirkpatrick Melanie G. , Chen Emily , Nguyen Tu-Trinh H. , Riva Laura , Shaabani Namir , Parren Mara , Ricketts James , Gupta Anil K. , Pan Kastin , Kuo Peiting , Fuller MacKenzie , Garcia Elijah , Teijaro John R. , Yang Linlin , Sahoo Debashis , Chi Victor , Huang Edward , Vargas Natalia , Roberts Amanda J. , Das Soumita , Ghosh Pradipta , Woods Ashley K. , Joseph Sean B. , Hull Mitchell V. , Schultz Peter G. , Burton Dennis R. , Chatterjee Arnab K. , McNamara Case W. , Rogers Thomas F. 
Published: June 2021

AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.
Non-universal current flow near the metal-insulator transition in an oxide interface
Authors: Persky Eylon , Vardi Naor , Monteiro Ana Mafalda R. V. L. , van Thiel Thierry C. , Yoon Hyeok , Xie Yanwu , Fauqué Benoît , Caviglia Andrea D. , Hwang Harold Y. , Behnia Kamran , Ruhman Jonathan , Kalisky Beena 
Published: June 2021

AbstractIn systems near phase transitions, macroscopic properties often follow algebraic scaling laws, determined by the dimensionality and the underlying symmetries of the system. The emergence of such universal scaling implies that microscopic details are irrelevant. Here, we locally investigate the scaling properties of the metal-insulator transition at the LaAlO3/SrTiO3 interface. We show that, by changing the dimensionality and the symmetries of the electronic system, coupling between structural and electronic properties prevents the universal behavior near the transition. By imaging the current flow in the system, we reveal that structural domain boundaries modify the filamentary flow close to the transition point, preventing a fractal with the expected universal dimension from forming.
STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer
Authors: Totten Stephanie P. , Im Young Kyuen , Cepeda Cañedo Eduardo , Najyb Ouafa , Nguyen Alice , Hébert Steven , Ahn Ryuhjin , Lewis Kyle , Lebeau Benjamin , La Selva Rachel , Sabourin Valérie , Martínez Constanza , Savage Paul , Kuasne Hellen , Avizonis Daina , Santos Martínez Nancy , Chabot Catherine , Aguilar-Mahecha Adriana , Goulet Marie-Line , Dankner Matthew , Witcher Michael , Petrecca Kevin , Basik Mark , Pollak Michael , Topisirovic Ivan , Lin Rongtuan , Siegel Peter M. , Kleinman Claudia L. , Park Morag , St-Pierre Julie , Ursini-Siegel Josie 
Published: June 2021

AbstractBioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.
Bulk-surface coupling identifies the mechanistic connection between Min-protein patterns in vivo and in vitro
Authors: Brauns Fridtjof , Pawlik Grzegorz , Halatek Jacob , Kerssemakers Jacob , Frey Erwin , Dekker Cees 
Published: June 2021

AbstractSelf-organisation of Min proteins is responsible for the spatial control of cell division in Escherichia coli, and has been studied both in vivo and in vitro. Intriguingly, the protein patterns observed in these settings differ qualitatively and quantitatively. This puzzling dichotomy has not been resolved to date. Using reconstituted proteins in laterally wide microchambers with a well-controlled height, we experimentally show that the Min protein dynamics on the membrane crucially depend on the micro chamber height due to bulk concentration gradients orthogonal to the membrane. A theoretical analysis shows that in vitro patterns at low microchamber height are driven by the same lateral oscillation mode as pole-to-pole oscillations in vivo. At larger microchamber height, additional vertical oscillation modes set in, marking the transition to a qualitatively different in vitro regime. Our work reveals the qualitatively different mechanisms of mass transport that govern Min protein-patterns for different bulk heights and thus shows that Min patterns in cells are governed by a different mechanism than those in vitro.
Crystal structure of dopamine D1 receptor in complex with G protein and a non-catechol agonist
Authors: Sun Bingfa , Feng Dan , Chu Matthew Ling-Hon , Fish Inbar , Lovera Silvia , Sands Zara A. , Kelm Sebastian , Valade Anne , Wood Martyn , Ceska Tom , Kobilka Tong Sun , Lebon Florence , Kobilka Brian K. 
Published: June 2021

AbstractDopamine D1 receptor (D1R) is an important drug target implicated in many psychiatric and neurological disorders. Selective agonism of D1R are sought to be the therapeutic strategy for these disorders. Most selective D1R agonists share a dopamine-like catechol moiety in their molecular structure, and their therapeutic potential is therefore limited by poor pharmacological properties in vivo. Recently, a class of non-catechol D1R selective agonists with a distinct scaffold and pharmacological properties were reported. Here, we report the crystal structure of D1R in complex with stimulatory G protein (Gs) and a non-catechol agonist Compound 1 at 3.8 Å resolution. The structure reveals the ligand bound to D1R in an extended conformation, spanning from the orthosteric site to extracellular loop 2 (ECL2). Structural analysis reveals that the unique features of D1R ligand binding pocket explains the remarkable selectivity of this scaffold for D1R over other aminergic receptors, and sheds light on the mechanism for D1R activation by the non-catechol agonist.
Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
Authors: Freter Rasmus , Falletta Paola , Omrani Omid , Rasa Mahdi , Herbert Katharine , Annunziata Francesco , Minetti Alberto , Krepelova Anna , Adam Lisa , Käppel Sandra , Rüdiger Tina , Wang Zhao-Qi , Goding Colin R. , Neri Francesco 
Published: June 2021

AbstractDormancy, a reversible quiescent cellular state characterized by greatly reduced metabolic activity, protects from genetic damage, prolongs survival and is crucial for tissue homeostasis and cellular response to injury or transplantation. Dormant cells have been characterized in many tissues, but their identification, isolation and characterization irrespective of tissue of origin remains elusive. Here, we develop a live cell ratiometric fluorescent Optical Stem Cell Activity Reporter (OSCAR) based on the observation that phosphorylation of RNA Polymerase II (RNApII), a hallmark of active mRNA transcription elongation, is largely absent in dormant stem cells from multiple lineages. Using the small intestinal crypt as a model, OSCAR reveals in real time the dynamics of dormancy induction and cellular differentiation in vitro, and allows the identification and isolation of several populations of transcriptionally diverse OSCARhigh and OSCARlow intestinal epithelial cell states in vivo. In particular, this reporter is able to identify a dormant OSCARhigh cell population in the small intestine. OSCAR therefore provides a tool for a better understanding of dormant stem cell biology.
Changes in antibiotic prescription following an education strategy for acute respiratory infections
Authors: Delsors Eloisa , Monsó Francisco , López-Román Francisco Javier , Menárguez-Puche Juan Francisco , Gonzalez-Barberá María , Hukelova Hana , Martínez-Ros Maria Teresa , López-Santiago Asensio 
Published: June 2021

AbstractThe objective of this study was to assess the impact of an education intervention for primary health care physicians, based on the knowledge of clinical practice guidelines and availability of rapid antigen detection test for group A streptococci (GAS), on the improvement of antibiotic prescription for patients with acute respiratory tract infections. Before and after the intervention, physicians collected data from ten consecutive patients who attended during a 3-week period. This process was performed twice a year for 6 consecutive years (2012–2017). A total of 18,001 patients were visited by 391 primary care physicians during the study period, 55.6% before intervention and 44.4% after intervention. After intervention, the antibiotic prescription decreased significantly, from 33.0 to 23.4% (p < 0.01). However, there was a statistically significant increase (p < 0.01) in the use of penicillins. This study, carried out in daily practice conditions, confirms that the educational strategy was associated with an overall reduction in the use of antibiotics and an improvement in the antibiotic prescription profile in acute respiratory tract infections.
Integrating multiple chemical tracers to elucidate the diet and habitat of Cookiecutter Sharks
Authors: Carlisle Aaron B. , Allan Elizabeth Andruszkiewicz , Kim Sora L. , Meyer Lauren , Port Jesse , Scherrer Stephen , O’Sullivan John 
Published: June 2021

AbstractThe Cookiecutter shark (Isistius brasiliensis) is an ectoparasitic, mesopelagic shark that is known for removing plugs of tissue from larger prey, including teleosts, chondrichthyans, cephalopods, and marine mammals. Although this species is widely distributed throughout the world’s tropical and subtropical oceanic waters, like many deep-water species, it remains very poorly understood due to its mesopelagic distribution. We used a suite of biochemical tracers, including stable isotope analysis (SIA), fatty acid analysis (FAA), and environmental DNA (eDNA), to investigate the trophic ecology of this species in the Central Pacific around Hawaii. We found that large epipelagic prey constituted a relatively minor part of the overall diet. Surprisingly, small micronektonic and forage species (meso- and epipelagic) are the most important prey group for Cookiecutter sharks across the studied size range (17–43 cm total length), with larger mesopelagic species or species that exhibit diel vertical migration also being important prey. These results were consistent across all the tracer techniques employed. Our results indicate that Cookiecutter sharks play a unique role in pelagic food webs, feeding on prey ranging from the largest apex predators to small, low trophic level species, in particular those that overlap with the depth distribution of the sharks throughout the diel cycle. We also found evidence of a potential shift in diet and/or habitat with size and season. Environmental DNA metabarcoding revealed new prey items for Cookiecutter sharks while also demonstrating that eDNA can be used to identify recent prey in stomachs frozen for extended periods. Integrating across chemical tracers is a powerful tool for investigating the ecology of elusive and difficult to study species, such as meso- and bathypelagic chondrichthyans, and can increase the amount of information gained from small sample sizes. Better resolving the foraging ecology of these mesopelagic predators is critical for effective conservation and management of these taxa and ecosystems, which are intrinsically vulnerable to overfishing and exploitation.
Phase separation during blood spreading
Authors: Benabdelhalim Houssine , Brutin David 
Published: June 2021

AbstractBlood pools can spread on several types of substrates depending on the surrounding environment and conditions. Understanding the influence of these parameters on the spreading of blood pools can provide crime scene investigators with useful information. The focus of the present study is on phase separation, that is, when the serum spreads outside the main blood pool. For this purpose, blood pools with constant initial masses on wooden floors that were either varnished or not were created at ambient temperatures of $$21~^{\circ }\hbox {C}$$

21

∘

C

, $$29~^{\circ }\hbox {C}$$

29

∘

C

, and $$37~^{\circ }\hbox {C}$$

37

∘

C

with a relative humidity varying from 20 to 90%. The range $$21~^{\circ }\hbox {C}$$

21

∘

C

to $$37~^{\circ }\hbox {C}$$

37

∘

C

covers almost all worldwide indoor cases. The same whole blood from the same donor was used for all experiments. As a result, an increase in relative humidity was found to result in an increase in the final pool area. In addition, at the three different experimental temperatures, the serum spread outside the main pool at relative humidity levels above 50%. This phase separation is more significant on varnished substrates, and does not lead to any changes in the drying morphology. This phenomenon is explained by the competition between coagulation and evaporation.
Transformation of SOX9+ cells by Pten deletion synergizes with steatotic liver injury to drive development of hepatocellular and cholangiocarcinoma
Authors: Chen Jingyu , Debebe Anketse , Zeng Ni , Kopp Janel , He Lina , Sander Maike , Stiles Bangyan L. 
Published: June 2021

AbstractSOX9 (Sex-determining region Y Box 9) is a well-characterized transcription factor that is a marker for progenitor cells in various tissues. In the liver, cells delineated by SOX9 are responsible for regenerating liver parenchyma when cell proliferation is impaired following chronic injury. However, whether these SOX9+ cells play a role in liver carcinogenesis has not been fully understood, although high SOX9 expression has been linked to poor survival outcome in liver cancer patients. To address this question, we developed a liver cancer mouse model (PtenloxP/loxP; Sox9-CreERT+; R26RYFP) where tumor suppressor Pten (phosphatase and tensin homolog deleted on chromosome ten) is deleted in SOX9+ cells following tamoxifen injection. In this paper, we employ lineage-tracing to demonstrate the tumorigenicity potential of the Pten-, SOX9+ cells. We show that these cells are capable of giving rise to mixed-lineage tumors that manifest features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA). Our results suggest that PTEN loss induces the transformation of SOX9+ cells. We further show that to activate these transformed SOX9+ cells, the presence of liver injury is crucial. Liver injury, induced by hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or high-fat diet (HFD), substantially increases tumor incidence and accelerates liver carcinogenesis from SOX9+ cells in Pten null mice but not in control mice. We further examine the mechanisms underlying tumor formation in this model to show that concurrent with the induction of niche signal (i.e., Wnt signaling), liver injury significantly stimulates the expansion of tumor-initiating cells (TICs). Together, these data show that (1) SOX9+ cells have the potential to become TICs following the primary transformation (i.e. Pten deletion) and that (2) liver injury is necessary for promoting the activation and proliferation of transformed SOX9+ cells, resulting in the genesis of mixed-lineage liver tumors.
Roughness of retinal layers in Alzheimer’s disease
Authors: Jáñez-García Lucía , Bachtoula Omar , Salobrar-García Elena , de Hoz Rosa , Ramirez Ana I. , Gil Pedro , Ramirez José M. , Jáñez-Escalada Luis 
Published: June 2021

AbstractThere is growing evidence that thinned retinal regions are interspersed with thickened regions in all retinal layers of patients with Alzheimer’s disease (AD), causing roughness to appear on layer thickness maps. The hypothesis is that roughness of retinal layers, assessed by the fractal dimension (FD) of their thickness maps, is an early biomarker of AD. Ten retinal layers have been studied in macular volumes of optical coherence tomography from 24 healthy volunteers and 19 patients with mild AD (Mini-Mental State Examination 23.42 ± 3.11). Results show that FD of retinal layers is greater in the AD group, the differences being statistically significant (p < 0.05). Correlation of layer FD with cognitive score, visual acuity and age reach statistical significance at 7 layers. Nearly all (44 out of 45) FD correlations among layers are positive and half of them reached statistical significance (p < 0.05). Factor analysis unveiled two independent factors identified as the dysregulation of the choroidal vascular network and the retinal inflammatory process. Conclusions: surface roughness is a holistic feature of retinal layers that can be assessed by the FD of their thickness maps and it is an early biomarker of AD.