bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspartate/asparagine-β-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern
Authors: Pfeffer Inga , Brewitz Lennart , Krojer Tobias , Jensen Sacha A. , Kochan Grazyna T. , Kershaw Nadia J. , Hewitson Kirsty S. , McNeill Luke A. , Kramer Holger , Münzel Martin , Hopkinson Richard J. , Oppermann Udo , Handford Penny A. , McDonough Michael A. , Schofield Christopher J. 
Published: October 2019

AbstractAspH is an endoplasmic reticulum (ER) membrane-anchored 2-oxoglutarate oxygenase whose C-terminal oxygenase and tetratricopeptide repeat (TPR) domains present in the ER lumen. AspH catalyses hydroxylation of asparaginyl- and aspartyl-residues in epidermal growth factor-like domains (EGFDs). Here we report crystal structures of human AspH, with and without substrate, that reveal substantial conformational changes of the oxygenase and TPR domains during substrate binding. Fe(II)-binding by AspH is unusual, employing only two Fe(II)-binding ligands (His679/His725). Most EGFD structures adopt an established fold with a conserved Cys1–3, 2–4, 5–6 disulfide bonding pattern; an unexpected Cys3–4 disulfide bonding pattern is observed in AspH-EGFD substrate complexes, the catalytic relevance of which is supported by studies involving stable cyclic peptide substrate analogues and by effects of Ca(II) ions on activity. The results have implications for EGFD disulfide pattern processing in the ER and will enable medicinal chemistry efforts targeting human 2OG oxygenases.
Randomized phase-II evaluation of letrozole plus dasatinib in hormone receptor positive metastatic breast cancer patients
Authors: Paul Devchand , Vukelja Svetislava J. , Ann Holmes Frankie , Blum Joanne L. , McIntyre Kristi J. , Lindquist Deborah L. , Osborne Cynthia R. , Sanchez Ines J. , Goldschmidt Jerome H. , Wang Yunfei , Asmar Lina , Strauss Lewis , O’Shaughnessy Joyce 
Published: October 2019

AbstractThe non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.
Inhaled corticosteroids in COPD and onset of type 2 diabetes and osteoporosis: matched cohort study
Authors: Price David B. , Voorham Jaco , Brusselle Guy , Clemens Andreas , Kostikas Konstantinos , Stephens Jeffrey W. , Park Hye Yun , Roche Nicolas , Fogel Robert 
Published: October 2019

AbstractSome studies suggest an association between onset and/or poor control of type 2 diabetes mellitus and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD), and also between increased fracture risk and ICS therapy; however, study results are contradictory and these associations remain tentative and incompletely characterized. This matched cohort study used two large UK databases (1983–2016) to study patients (≥ 40 years old) initiating ICS or long-acting bronchodilator (LABD) for COPD from 1990–2015 in three study cohorts designed to assess the relation between ICS treatment and (1) diabetes onset (N = 17,970), (2) diabetes progression (N = 804), and (3) osteoporosis onset (N = 19,898). Patients had ≥ 1-year baseline and ≥ 2-year outcome data. Matching was via combined direct matching and propensity scores. Conditional proportional hazards regression, adjusting for residual confounding after matching, was used to compare ICS vs. LABD and to model ICS exposures. Median follow-up was 3.7–5.6 years/treatment group. For patients prescribed ICS, compared with LABD, the risk of diabetes onset was significantly increased (adjusted hazard ratio 1.27; 95% CI, 1.07–1.50), with overall no increase in risk of diabetes progression (adjusted hazard ratio 1.04; 0.87–1.25) or osteoporosis onset (adjusted hazard ratio 1.13; 0.93–1.39). However, the risks of diabetes onset, diabetes progression, and osteoporosis onset were all significantly increased, with evident dose–response relationships for all three outcomes, at mean ICS exposures of 500 µg/day or greater (vs. < 250 µg/day, fluticasone propionate–equivalent). Long-term ICS therapy for COPD at mean daily exposure of ≥ 500 µg is associated with an increased risk of diabetes, diabetes progression, and osteoporosis.
A public data set of spatio-temporal match events in soccer competitions
Authors: Pappalardo Luca , Cintia Paolo , Rossi Alessio , Massucco Emanuele , Ferragina Paolo , Pedreschi Dino , Giannotti Fosca 
Published: October 2019

AbstractSoccer analytics is attracting increasing interest in academia and industry, thanks to the availability of sensing technologies that provide high-fidelity data streams for every match. Unfortunately, these detailed data are owned by specialized companies and hence are rarely publicly available for scientific research. To fill this gap, this paper describes the largest open collection of soccer-logs ever released, containing all the spatio-temporal events (passes, shots, fouls, etc.) that occured during each match for an entire season of seven prominent soccer competitions. Each match event contains information about its position, time, outcome, player and characteristics. The nature of team sports like soccer, halfway between the abstraction of a game and the reality of complex social systems, combined with the unique size and composition of this dataset, provide an ideal ground for tackling a wide range of data science problems, including the measurement and evaluation of performance, both at individual and at collective level, and the determinants of success and failure.
Population centroids of the world administrative units from nighttime lights 1992-2013
Authors: Hall Ola , Bustos Maria Francisca Archila , Olén Niklas Boke , Niedomysl Thomas 
Published: October 2019

AbstractKnowledge about the past, current and future distribution of the human population is fundamental for tackling many global challenges. Censuses are used to collect information about population within a specified spatial unit. The spatial units are usually arbitrarily defined and their numbers, size and shape tend to change over time. These issues make comparisons between areas and countries difficult. We have in related work proposed that the shape of the lit area derived from nighttime lights, weighted by its intensity can be used to analyse characteristics of the population distribution, such as the mean centre of population. We have processed global nighttime lights data for the period 1992–2013 and derived centroids for administrative levels 0–2 of the Database of Global Administrative Areas, corresponding to nations and two levels of sub-divisions, that can be used to analyse patterns of global or local population changes. The consistency of the produced dataset was investigated and distance between true population centres and derived centres are compared using Swedish census data as a benchmark.
Decoupling a tandem-repeat protein: Impact of multiple loop insertions on a modular scaffold
Authors: Perez-Riba Albert , Komives Elizabeth , Main Ewan R. G. , Itzhaki Laura S. 
Published: October 2019

AbstractThe simple topology and modular architecture of tandem-repeat proteins such as tetratricopeptide repeats (TPRs) and ankyrin repeats makes them straightforward to dissect and redesign. Repeat-protein stability can be manipulated in a predictable way using site-specific mutations. Here we explore a different type of modification - loop insertion - that will enable a simple route to functionalisation of this versatile scaffold. We previously showed that a single loop insertion has a dramatically different effect on stability depending on its location in the repeat array. Here we dissect this effect by a combination of multiple and alternated loop insertions to understand the origins of the context-dependent loss in stability. We find that the scaffold is remarkably robust in that its overall structure is maintained. However, adjacent repeats are now only weakly coupled, and consequently the increase in solvent protection, and thus stability, with increasing repeat number that defines the tandem-repeat protein class is lost. Our results also provide us with a rulebook with which we can apply these principles to the design of artificial repeat proteins with precisely tuned folding landscapes and functional capabilities, thereby paving the way for their exploitation as a versatile and truly modular platform in synthetic biology.
Substrate composition directs slime molds behavior
Authors: Patino-Ramirez Fernando , Boussard Aurèle , Arson Chloé , Dussutour Audrey 
Published: October 2019

AbstractCells, including unicellulars, are highly sensitive to external constraints from their environment. Amoeboid cells change their cell shape during locomotion and in response to external stimuli. Physarum polycephalum is a large multinucleated amoeboid cell that extends and develops pseudopods. In this paper, changes in cell behavior and shape were measured during the exploration of homogenous and non-homogenous environments that presented neutral, and nutritive and/or adverse substances. In the first place, we developed a fully automated image analysis method to measure quantitatively changes in both migration and shape. Then we measured various metrics that describe the area covered, the exploration dynamics, the migration rate and the slime mold shape. Our results show that: (1) Not only the nature, but also the spatial distribution of chemical substances affect the exploration behavior of slime molds; (2) Nutritive and adverse substances both slow down the exploration and prevent the formation of pseudopods; and (3) Slime mold placed in an adverse environment preferentially occupies previously explored areas rather than unexplored areas using mucus secretion as a buffer. Our results also show that slime molds migrate at a rate governed by the substrate up until they get within a critical distance to chemical substances.
Morphology control of organic halide perovskites by adding BiFeO3 nanostructures for efficient solar cell
Authors: Xu Haowen , Zhang Heyi , Ma Yuhui , Jiang Mao , Zhang Yewei , Wu Yinan , Zhang Haoran , Xia Ruidong , Niu Qiaoli , Li Xing’ao , Huang Wei 
Published: October 2019

AbstractThe morphology of perovskite light-absorption layer plays an important role in the performance of perovskite solar cells (PSCs). In this work, BiFeO3 (BFO) nanostructures were used as additive for CH3NH3PbI3 (MAPbI3) via anti-solvent method. The addition of BFO nanostructures greatly enhanced the crystallinity, grain size and film uniformity of MAPbI3. As a result, the charge carrier mobility and electron diffusion length increased, leading to the increase of the short circuit current (JSC) of PSCs. This work provides a very simple but effective approach to improve the morphology of perovskite layer for efficient PSCs.
Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases
Authors: Herraiz Tomás , Guillén Hugo , González-Peña Diana , Arán Vicente J. 
Published: October 2019

AbstractMalaria caused by Plasmodium affects millions people worldwide. Plasmodium consumes hemoglobin during its intraerythrocytic stage leaving toxic heme. Parasite detoxifies free heme through formation of hemozoin (β-hematin) pigment. Proteolysis of hemoglobin and formation of hemozoin are two main targets for antimalarial drugs. Quinoline antimarial drugs and analogs (β-carbolines or nitroindazoles) were studied as inhibitors of β-hematin formation. The most potent inhibitors were quinacrine, chloroquine, and amodiaquine followed by quinidine, mefloquine and quinine whereas 8-hydroxyquinoline and β-carbolines had no effect. Compounds that inhibited β-hematin increased free hemin that promoted peroxidative reactions as determined with TMB and ABTS substrates. Hemin-catalyzed peroxidative reactions were potentiated in presence of proteins (i.e. globin or BSA) while antioxidants and peroxidase inhibitors decreased peroxidation. Free hemin increased by chloroquine action promoted oxidative reactions resulting in inhibition of proteolysis by three cysteine proteases: papain, ficin and cathepsin B. Glutathione reversed inhibition of proteolysis. These results show that active quinolines inhibit hemozoin and increase free hemin which in presence of H2O2 that abounds in parasite digestive vacuole catalyzes peroxidative reactions and inhibition of cysteine proteases. This work suggests a link between the action of quinoline drugs with biochemical processes of peroxidation and inhibition of proteolysis.
Time and rate dependent synaptic learning in neuro-mimicking resistive memories
Authors: Ahmed Taimur , Walia Sumeet , Mayes Edwin L. H. , Ramanathan Rajesh , Bansal Vipul , Bhaskaran Madhu , Sriram Sharath , Kavehei Omid 
Published: October 2019

AbstractMemristors have demonstrated immense potential as building blocks in future adaptive neuromorphic architectures. Recently, there has been focus on emulating specific synaptic functions of the mammalian nervous system by either tailoring the functional oxides or engineering the external programming hardware. However, high device-to-device variability in memristors induced by the electroforming process and complicated programming hardware are among the key challenges that hinder achieving biomimetic neuromorphic networks. Here, a simple hybrid complementary metal oxide semiconductor (CMOS)-memristor approach is reported to implement different synaptic learning rules by utilizing a CMOS-compatible memristor based on oxygen-deficient SrTiO3-x (STOx). The potential of such hybrid CMOS-memristor approach is demonstrated by successfully imitating time-dependent (pair and triplet spike-time-dependent-plasticity) and rate-dependent (Bienenstosk-Cooper-Munro) synaptic learning rules. Experimental results are benchmarked against in-vitro measurements from hippocampal and visual cortices with good agreement. The scalability of synaptic devices and their programming through a CMOS drive circuitry elaborates the potential of such an approach in realizing adaptive neuromorphic computation and networks.
Large nearshore storm waves off the Irish coast
Authors: Fedele Francesco , Herterich James , Tayfun Aziz , Dias Frederic 
Published: October 2019

AbstractWe present a statistical analysis of nearshore waves observed during two major North–East Atlantic storms in 2015 and 2017. Surface elevations were measured with a 5-beam acoustic Doppler current profiler (ADCP) at relatively shallow waters off the west coast of Ireland. To compensate for the significant variability of both sea states in time, we consider a novel approach for analyzing the non-stationary surface-elevation series and compare the distributions of crest and wave heights observed with theoretical predictions based on the Forristall, Tayfun and Boccotti models. In particular, the latter two models have been largely applied to and validated for deep-water waves. We show here that they also describe well the characteristics of waves observed in relatively shallow waters. The largest nearshore waves observed during the two storms do not exceed the rogue thresholds as the Draupner, Andrea, Killard or El Faro rogue waves do in intermediate or deep-water depths. Nevertheless, our analysis reveals that modulational instabilities are ineffective, third-order resonances negligible and the largest waves observed here have characteristics quite similar to those displayed by rogue waves for which second order bound nonlinearities are the principal factor that enhances the linear dispersive focusing of extreme waves.
Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress
Authors: Pecoraro Annalisa , Carotenuto Pietro , Russo Giulia , Russo Annapina 
Published: October 2019

AbstractSeveral experimental strategies in the treatment of cancer include drug alteration of cell cycle regulatory pathways as a useful strategy. Extra-ribosomal functions of human ribosomal protein L3 (uL3) may affect DNA repair, cell cycle arrest and apoptosis. In the present study, we demonstrated that uL3 is required for the activation of G1/S transition genes. Luciferase assays established that uL3 negatively regulates the activity of E2F1 promoter. Induced ribosome-free uL3 reduces Cyclin D1 mRNA and protein levels. Using protein/protein immunoprecipitation methods, we demonstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity. Our findings led to the identification of a new pathway mediated by uL3 involving E2F1 and Cyclin D1 in the regulation of cell cycle progression.
Intralesional EBV-DNA load as marker of prognosis for nasopharyngeal cancer
Authors: Nilsson Johan S. , Forslund Ola , Andersson Fredrik C. , Lindstedt Malin , Greiff Lennart 
Published: October 2019

AbstractNasopharyngeal cancer (NPC) is associated with the Epstein-Barr virus (EBV). The clinical presentation and prognosis of NPC is well described, but not in relation to intralesional EBV-DNA load. In a retrospective design, 48 patients with NPC were examined. Patient history was re-evaluated, and diagnostic biopsies were re-examined. Furthermore, intralesional EBV-DNA was quantitated and HPV status determined. Cancer stage, disease-free survival (DFS), and overall survival (OS) were assessed. Of the 48 patients, 36 (75%) patients featured lesions that were positive for EBER (Epstein–Barr virus-encoded small RNA) and 40 (83%) were positive for EBV-DNA. Seven patients (15%) were HPV positive. The levels of EBV-DNA ranged from 0.0005 to 94617 copies/cell. An EBV-DNA load of more than 70 copies/cell was associated with a prolonged DFS for EBV-DNA positive patients treated with curative intent (p = 0.046). In conclusion, the EBV-DNA load in NPC lesions appears to vary greatly. For patients with EBV-DNA positive NPC treated with curative intent, an EBV-DNA load of more than 70 copies/cell is associated with a better outcome in terms of 7-year DFS.
Proteome and Secretome Dynamics of Human Retinal Pigment Epithelium in Response to Reactive Oxygen Species
Authors: Meyer Jesse G. , Garcia Thelma Y. , Schilling Birgit , Gibson Bradford W. , Lamba Deepak A. 
Published: October 2019

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic reactive oxygen species (ROS) in the retinal pigmented epithelium (RPE). The molecular mechanisms leading to RPE dysfunction in response to ROS are unclear. Here, human stem cell-derived RPE samples were stressed with ROS for 1 or 3 weeks, and both intracellular and secreted proteomes were quantified by mass spectrometry. ROS increased glycolytic proteins but decreased mitochondrial complex I subunits, as well as membrane proteins required for endocytosis. RPE secreted over 1,000 proteins, many of which changed significantly due to ROS. Notably, secreted APOE is decreased 4-fold, and urotensin-II, the strongest known vasoconstrictor, doubled. Furthermore, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, our results paint a detailed molecular picture of the retinal stress response in space and time.
Arctic seabirds and shrinking sea ice: egg analyses reveal the importance of ice-derived resources
Authors: Cusset Fanny , Fort Jérôme , Mallory Mark , Braune Birgit , Massicotte Philippe , Massé Guillaume 
Published: October 2019

AbstractIn the Arctic, sea-ice plays a central role in the functioning of marine food webs and its rapid shrinking has large effects on the biota. It is thus crucial to assess the importance of sea-ice and ice-derived resources to Arctic marine species. Here, we used a multi-biomarker approach combining Highly Branched Isoprenoids (HBIs) with δ13C and δ15N to evaluate how much Arctic seabirds rely on sea-ice derived resources during the pre-laying period, and if changes in sea-ice extent and duration affect their investment in reproduction. Eggs of thick-billed murres (Uria lomvia) and northern fulmars (Fulmarus glacialis) were collected in the Canadian Arctic during four years of highly contrasting ice conditions, and analysed for HBIs, isotopic (carbon and nitrogen) and energetic composition. Murres heavily relied on ice-associated prey, and sea-ice was beneficial for this species which produced larger and more energy-dense eggs during icier years. In contrast, fulmars did not exhibit any clear association with sympagic communities and were not impacted by changes in sea ice. Murres, like other species more constrained in their response to sea-ice variations, therefore appear more sensitive to changes and may become the losers of future climate shifts in the Arctic, unlike more resilient species such as fulmars.
The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function
Authors: García-Llorca Andrea , Aspelund Snaefridur Gudmundsdottir , Ogmundsdottir Margret Helga , Steingrimsson Eiríkur , Eysteinsson Thor 
Published: October 2019

AbstractMutations in the microphthalmia-associated transcription factor (Mitf) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different Mitf mutations (Mitfmi-vga9/+, Mitfmi-enu22(398)/Mitfmi-enu22(398), MitfMi-Wh/+ and MitfMi-Wh/Mitfmi) which all have normal eye size with apparently normal eye pigmentation. Here we show that their vision and retinal structures are differentially affected. Hypopigmentation was evident in all the mutants while bright-field fundus images showed yellow spots with non-pigmented areas in the Mitfmi-vga9/+ mice. MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except Mitfmi-vga9/+ mice showed hyperfluorescent areas, whereas FA from both Mitf-Mi-Wh/+ and MitfMi-Wh/Mitfmi mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice are severely impaired functionally whereas the scotopic and photopic ERG responses of Mitfmi-vga9/+ and Mitfmi-enu22(398)/Mitfmi-enu22(398) mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the MitfMi-Wh/+ and MitfMi-Wh/Mitfmi blind mutants. Our results show that Mitf mutations affect eye function, even in the heterozygous condition and that the alleles studied can be arranged in an allelic series in this respect.