bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Decade of Annual Arctic DOC Export With Polar Surface Water in the East Greenland Current
Authors: Gonçalves‐Araujo Rafael , Stedmon Colin A. , de Steur Laura , Osburn Christopher L. , Granskog Mats A. 
Published: October 2020

AbstractThe export of dissolved organic carbon (DOC) from the Arctic Ocean is expected to change due to warming and increased river runoff. Here we present a method to quantify DOC transport with the East Greenland Current combining synoptic and year‐round data (2009–2018). An algorithm based on quantitative and qualitative aspects of colored dissolved organic matter (CDOM) was developed to provide DOC estimates. Combined with mooring‐derived monthly Polar Surface Water (PSW) volume transports, we estimate DOC exports for the period from 2003–2017. For much of the period DOC exports have been reasonably constant at 46.8 (±6.2) Tg yr−1, while the reduction in PSW export in recent years has resulted in lower annual DOC exports (below 39 Tg C yr−1). We now have a technique to resolve seasonal and annual fluctuations in Arctic carbon export, offering a significant improvement over earlier bulk estimates and represents a baseline to detect future change.
Increased Aerosol Extinction Efficiency Hinders Visibility Improvement in Eastern China
Authors: Liu Jingyi , Ren Chuanhua , Huang Xin , Nie Wei , Wang Jiaping , Sun Peng , Chi Xuguang , Ding Aijun 
Published: October 2020

AbstractThough China has witnessed substantial particular matter pollution mitigation owing to the strict emission control in recent years, the frequency of haze events with low visibility is not improved as much as expected, especially in cold seasons. Here, 6‐year wintertime observations, satellite retrievals, a thermodynamic model, and theoretical calculation were integrated to better understand the complex influence of aerosol chemical composition and hygroscopic behaviors on visibility impairment. We found that the proportion of nitrate in aerosol mass concentration increased by approximately 10% from 2013 to 2018. Such a transition in aerosol chemical compositions together with increasing ambient humidity in past years jointly enhanced aerosol extinction efficiency, and the elevated proportion of nitrate played an increasingly critical role after 2017. The increased aerosol extinction efficiency is responsible for the less improved visibility despite large decrease in aerosol mass concentrations in eastern China.
A Universal Form of Power Law Relationships for River and Stream Channels
Authors: Xu Fan , Coco Giovanni , Zhou Zeng , Townend Ian , Guo Leicheng , He Qing 
Published: October 2020

AbstractThe description of the geomorphic characteristics in power law forms has been the subject of research, over the past 70 years, and has become the cornerstone of regime theory. However, just why power functions should represent such geomorphic relationships remains poorly understood. Hence, differences in the values of the regime exponents observed for different river systems remain largely unexplained. To address this issue, we derived generic forms of the power law relationships without postulating any power functions of the discharge. The theoretical approach accurately captures the systematic variations of the regime exponents shown by a number of large data sets from previous research. We also explain how frictional resistance is responsible for the systematic variability of regime exponents. Overall, our study provides a robust mechanism to describe the variations of the exponents, along with a deductive explanation of the power laws at the core of fluvial hydraulic geometry.
Widespread Mesoscale Dipoles in the Global Ocean
Authors: Ni Qinbiao , Zhai Xiaoming , Wang Guihua , Hughes Chris W. 
Published: October 2020

AbstractMesoscale eddies are ubiquitous and energetic features in the ocean. Although eddies are known to form dipoles from time to time, it is unclear how often they do so. Using satellite altimetry data, here we show that mesoscale dipoles are surprisingly widespread in the global ocean. About 30–40% of the mesoscale eddies identified in altimeter data are paired up as dipoles, and the percentage is even higher in energetic regions such as the Gulf Stream and the Southern Ocean. Composite analysis involving Argo float data further reveals that these mesoscale dipoles have a relatively uniform three‐dimensional structure. We find that the presence of mesoscale dipoles can strongly enhance wind Ekman pumping velocity and lead to deep‐reaching vertical motions inside the dipoles via eddy deformation and frontogenesis. Such strong vertical exchanges promoted by mesoscale dipoles may play an important role in regulating the Earth's biogeochemical processes.
SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN
Authors: Shen Xuefang , Chen Xiangyuan , Wang Jing , Liu Jing , Wang Zhiyao , Hua Qing , Wu Qichao , Su Yanguang , He Huanzhong , Hu Yuqin , Meng Zhipeng , Xiong Wanxia , Zhu Minmin 
Published: October 2020

AbstractHyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.
The role of integrins in inflammation and angiogenesis
Authors: Mezu-Ndubuisi Olachi J. , Maheshwari Akhil 
Published: October 2020

AbstractIntegrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis. This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants. We have included evidence from our own laboratory studies and from an extensive literature search in databases PubMed, EMBASE, Scopus, and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed’s Medical Subject Heading (MeSH) thesaurus.ImpactIntegrins are a family of ubiquitous αβ heterodimeric receptors that interact with numerous ligands in physiology and disease. Integrins play a key role in cell proliferation, tissue repair, inflammation, infection, and angiogenesis.This review summarizes current evidence from human and animal studies on integrin structure and molecular signaling and promising role in diseases of inflammation, infection, and angiogenesis in infants.This review shows that integrin receptors and ligands are novel therapeutic targets of clinical interest and hold promise as novel therapeutic targets in the management of several neonatal diseases.
Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer
Authors: Hussain Arif , Tripathi Abhishek , Pieczonka Christopher , Cope Diane , McNatty Andrea , Logothetis Christopher , Guise Theresa 
Published: October 2020

AbstractBackgroundOsteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment.MethodsWe searched peer-reviewed literature on the PubMed database using key words “androgen-deprivation therapy,” “androgen receptor inhibitors,” “bone,” “bone complications,” and “nonmetastatic prostate cancer” from 2000 to present.ResultsWe discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health.ConclusionsIn patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.
Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms
Authors: Bernard Charles , Li Yanyan , Lopez Philippe , Bapteste Eric 
Published: October 2020

Abstract
The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the “arbitrium” quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined “Rapφ-Phrφ”, is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered “Rapφ-Phrφ” QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.
Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatom Seminavis robusta
Authors: Bilcke Gust , Van den Berge Koen , De Decker Sam , Bonneure Eli , Poulsen Nicole , Bulankova Petra , Osuna-Cruz Cristina Maria , Dickenson Jack , Sabbe Koen , Pohnert Georg , Vandepoele Klaas , Mangelinckx Sven , Clement Lieven , De Veylder Lieven , Vyverman Wim 
Published: October 2020

Abstract
Sexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in natural circumstances and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatom Seminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S phase progression, chloroplast division, mitosis, and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin. Our data further suggest an important role for reactive oxygen species, energy metabolism, and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological specialization, such as the production of the attraction pheromone diproline in mating type − (MT−) and mate-searching behavior in mating type + (MT+). Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations.
The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence
Authors: Rabbie Roy , Ferguson Peter , Wong Kim , Couturier Dominique-Laurent , Moran Una , Turner Clinton , Emanuel Patrick , Haas Kerstin , Saunus Jodi M. , Davidson Morgan R. , Lakhani Sunil R. , Shivalingam Brindha , Long Georgina V. , Parkinson Christine , Osman Iman , Scolyer Richard A. , Corrie Pippa , Adams David J. 
Published: October 2020

AbstractBrain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.
Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma
Authors: Lee Chung-Han , Motzer Robert J. , Glen Hilary , Michaelson M. D. , Larkin James , Minoshima Yukinori , Kanekiyo Michio , Ikezawa Hiroki , Sachdev Pallavi , Dutcus Corina E. , Funahashi Yasuhiro , Voss Martin H. 
Published: October 2020

Abstract
Background
No biomarkers have been established to predict treatment efficacy in renal cell carcinoma (RCC). In an exploratory retrospective analysis of a Phase 2 study, we constructed composite biomarker scores (CBSs) to predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic RCC randomised to receive lenvatinib-plus-everolimus.

Methods
Of 40 biomarkers tested, the 5 most strongly associated with PFS (HGF, MIG, IL-18BP, IL-18, ANG-2) or OS (TIMP-1, M-CSF, IL-18BP, ANG-2, VEGF) were used to make a 5-factor PFS-CBS or OS-CBS, respectively. A 2-factor CBS was generated with biomarkers common to PFS-CBS and OS-CBS. Patients were divided into groups accordingly (5-factor-CBS high: 3−5, CBS-low: 0–2; 2-factor-CBS high: 1–2, CBS-low: 0).

Results
PFS/OS with lenvatinib-plus-everolimus were significantly longer in the 5-factor CBS-high group versus the CBS-low group (P = 0.0022/P < 0.0001, respectively). In the CBS-high group, PFS/OS were significantly longer with lenvatinib-plus-everolimus versus everolimus (P < 0.001/P = 0.0079, respectively); PFS was also significantly longer with lenvatinib-plus-everolimus versus lenvatinib (P = 0.0046). The 5-factor-CBS had a predictive role in PFS and OS after multivariate analysis. Similar trends were observed with the 2-factor-CBS for PFS (i.e., lenvatinib-plus-everolimus versus everolimus).

Conclusions
The 5-factor CBS may identify patients with metastatic RCC who would benefit from lenvatinib-plus-everolimus versus everolimus; additional validation is required.

Clinical trial registration
The clinical trial registration number is NCT01136733.
Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5
Authors: Young Eric D. , Manley Sharon J. , Beadnell Thomas C. , Shearin Alexander E. , Sasaki Ken , Zimmerman Rosalyn , Kauffman Evan , Vivian Carolyn J. , Parasuram Aishwarya , Iwakuma Tomoo , Grandgenett Paul M. , Hollingsworth Michael A. , O’Neil Maura , Welch Danny R. 
Published: October 2020

Abstract
Background
Previously, we identified ITIH5 as a suppressor of pancreatic ductal adenocarcinoma (PDAC) metastasis in experimental models. Expression of ITIH5 correlated with decreased cell motility, invasion and metastasis without significant inhibition of primary tumour growth. Here, we tested whether secretion of ITIH5 is required to suppress liver metastasis and sought to understand the role of ITIH5 in human PDAC.

Methods
We expressed mutant ITIH5 with deletion of the N-terminal secretion sequence (ITIH5Δs) in highly metastatic human PDAC cell lines. We used a human tissue microarray (TMA) to compare ITIH5 levels in uninvolved pancreas, primary and metastatic PDAC.

Results
Secretion-deficient ITIH5Δs was sufficient to suppress liver metastasis. Similar to secreted ITIH5, expression of ITIH5Δs was associated with rounded cell morphology, reduced cell motility and reduction of liver metastasis. Expression of ITIH5 is low in both human primary PDAC and matched metastases.

Conclusions
Metastasis suppression by ITIH5 may be mediated by an intracellular mechanism. In human PDAC, loss of ITIH5 may be an early event and ITIH5-low PDAC cells in primary tumours may be selected for liver metastasis. Further defining the ITIH5-mediated pathway in PDAC could establish future therapeutic exploitation of this biology and reduce morbidity and mortality associated with PDAC metastasis.
Versatile direct-writing of dopants in a solid state host through recoil implantation
Authors: Fröch Johannes E. , Bahm Alan , Kianinia Mehran , Mu Zhao , Bhatia Vijay , Kim Sejeong , Cairney Julie M. , Gao Weibo , Bradac Carlo , Aharonovich Igor , Toth Milos 
Published: October 2020

AbstractModifying material properties at the nanoscale is crucially important for devices in nano-electronics, nanophotonics and quantum information. Optically active defects in wide band gap materials, for instance, are critical constituents for the realisation of quantum technologies. Here, we demonstrate the use of recoil implantation, a method exploiting momentum transfer from accelerated ions, for versatile and mask-free material doping. As a proof of concept, we direct-write arrays of optically active defects into diamond via momentum transfer from a Xe+ focused ion beam (FIB) to thin films of the group IV dopants pre-deposited onto a diamond surface. We further demonstrate the flexibility of the technique, by implanting rare earth ions into the core of a single mode fibre. We conclusively show that the presented technique yields ultra-shallow dopant profiles localised to the top few nanometres of the target surface, and use it to achieve sub-50 nm positional accuracy. The method is applicable to non-planar substrates with complex geometries, and it is suitable for applications such as electronic and magnetic doping of atomically-thin materials and engineering of near-surface states of semiconductor devices.
One-pot biocatalytic route from cycloalkanes to α,ω‐dicarboxylic acids by designed Escherichia coli consortia
Authors: Wang Fei , Zhao Jing , Li Qian , Yang Jun , Li Renjie , Min Jian , Yu Xiaojuan , Zheng Gao-Wei , Yu Hui-Lei , Zhai Chao , Acevedo-Rocha Carlos G. , Ma Lixin , Li Aitao 
Published: October 2020

AbstractAliphatic α,ω‐dicarboxylic acids (DCAs) are a class of useful chemicals that are currently produced by energy-intensive, multistage chemical oxidations that are hazardous to the environment. Therefore, the development of environmentally friendly, safe, neutral routes to DCAs is important. We report an in vivo artificially designed biocatalytic cascade process for biotransformation of cycloalkanes to DCAs. To reduce protein expression burden and redox constraints caused by multi-enzyme expression in a single microbe, the biocatalytic pathway is divided into three basic Escherichia coli cell modules. The modules possess either redox-neutral or redox-regeneration systems and are combined to form E. coli consortia for use in biotransformations. The designed consortia of E. coli containing the modules efficiently convert cycloalkanes or cycloalkanols to DCAs without addition of exogenous coenzymes. Thus, this developed biocatalytic process provides a promising alternative to the current industrial process for manufacturing DCAs.
Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines
Authors: Li Zhan , Wang Ke-Feng , Zhao Xin , Ti Huihui , Liu Xu-Ge , Wang Honggen 
Published: October 2020

AbstractAlkyl carboxylic acids as well as primary amines are ubiquitous in all facets of biological science, pharmaceutical science, chemical science and materials science. By chemical conversion to redox-active esters (RAE) and Katritzky’s N-alkylpyridinium salts, respectively, alkyl carboxylic acids and primary amines serve as ideal starting materials to forge new connections. In this work, a Mn-mediated reductive decarboxylative/deaminative functionalization of activated aliphatic acids and primary amines is disclosed. A series of C-X (X = S, Se, Te, H, P) and C-C bonds are efficiently constructed under simple and mild reaction conditions. The protocol is applicable to the late-stage modification of some structurally complex natural products or drugs. Preliminary mechanistic studies suggest the involvement of radicals in the reaction pathway.