bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells
Authors: Kleih Markus , Böpple Kathrin , Dong Meng , Gaißler Andrea , Heine Simon , Olayioye Monilola A. , Aulitzky Walter E. , Essmann Frank 
Published: November 2019

AbstractPatients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell death induction is scarcely investigated. We find that cisplatin sensitive HGSC cell lines contain higher mitochondrial content and higher levels of mitochondrial ROS (mtROS) than cells resistant to cisplatin induced cell death. In clonal sub-lines from OVCAR-3 mitochondrial content and basal oxygen consumption rate correlate with sensitivity to cisplatin induced apoptosis. Mitochondria are in two ways pivotal for cisplatin sensitivity because not only knock-down of BAX and BAK but also the ROS scavenger glutathione diminish cisplatin induced apoptosis. Mitochondrial ROS correlates with mitochondrial content and reduction of mitochondrial biogenesis by knock-down of transcription factors PGC1α or TFAM attenuates both mtROS induction and cisplatin induced apoptosis. Increasing mitochondrial ROS by inhibition or knock-down of the ROS-protective uncoupling protein UCP2 enhances cisplatin induced apoptosis. Similarly, enhancing ROS by high-dose ascorbic acid or H2O2 augments cisplatin induced apoptosis. In summary, mitochondrial content and the resulting mitochondrial capacity to produce ROS critically determine HGSC cell sensitivity to cisplatin induced apoptosis. In line with this observation, data from the human protein atlas (www.proteinatlas.org) indicates that high expression of mitochondrial marker proteins (TFAM and TIMM23) is a favorable prognostic factor in ovarian cancer patients. Thus, we propose mitochondrial content as a biomarker for the response to platinum-based therapies. Functionally, this might be exploited by increasing mitochondrial content or mitochondrial ROS production to enhance sensitivity to cisplatin based anti-cancer therapies.
A suite of global accessibility indicators
Authors: Nelson Andy , Weiss Daniel J. , van Etten Jacob , Cattaneo Andrea , McMenomy Theresa S. , Koo Jawoo 
Published: November 2019

AbstractGood access to resources and opportunities is essential for sustainable development. Improving access, especially in rural areas, requires useful measures of current access to the locations where these resources and opportunities are found. Recent work has developed a global map of travel times to cities with more than 50,000 people in the year 2015. However, the provision of resources and opportunities will differ across the broad spectrum of settlements that range from small towns to megacities, and access to this spectrum of settlement sizes should also be measured. Here we present a suite of nine global travel-time accessibility indicators for the year 2015, at approximately one-kilometre spatial resolution, for a range of settlement size classes. We validated the travel-time estimates against journey times from a Google driving directions application across 1,511 2° × 2° tiles representing 47,812 journeys. We observed very good agreement, though our estimates were more frequently shorter than those from the Google application with a median difference of −13.7 minutes and a median percentage difference of −16.9%.
Fabrication of atomic junctions with experimental parameters optimized using ground-state searches of Ising spin computing
Authors: Sakai Shotaro , Hirata Yosuke , Ito Mitsuki , Shirakashi Jun-ichi 
Published: November 2019

AbstractFeedback-controlled electromigration (FCE) is employed to control metal nanowires with quantized conductance and create nanogaps and atomic junctions. In the FCE method, the experimental parameters are commonly selected based on experience. However, optimization of the parameters by way of tuning is intractable because of the impossibility of attempting all different combinations systematically. Therefore, we propose the use of the Ising spin model to optimize the FCE parameters, because this approach can search for a global optimum in a multidimensional solution space within a short calculation time. The FCE parameters were determined by using the energy convergence properties of the Ising spin model. We tested these parameters in actual FCE experiments, and we demonstrated that the Ising spin model could improve the controllability of the quantized conductance in atomic junctions. This result implies that the proposed method is an effective tool for the optimization of the FCE process in which an intelligent machine can conduct the research instead of humans.
Turbulence mediates marine aggregate formation and destruction in the upper ocean
Authors: Takeuchi Marika , Doubell Mark J. , Jackson George A. , Yukawa Misuzu , Sagara Yosuke , Yamazaki Hidekatsu 
Published: November 2019

AbstractMarine aggregates formed through particle coagulation, large ones (>0.05 cm) also called marine snow, make a significant contribution to the global carbon flux by sinking from the euphotic zone, impacting the Earth’s climate. Since aggregate sinking velocity and carbon content are size-dependent, understanding the physical mechanisms controlling aggregate size distribution is fundamental to determining the biological carbon pump efficiency. Theoretical, laboratory and in-situ studies of flocculation have suggested that turbulence in the benthic boundary layer is important for aggregate formation and destruction, but the small number of field observations has limited our understanding of the role of turbulence on aggregation processes in the ocean surface layer away from energetic boundaries. Using simultaneous field observations of turbulence and aggregates, we show how aggregate formation, destruction, morphology and size distribution in the ocean surface layer (10–100 m) are mediated by interactions between turbulence and aggregate concentration. Our findings suggest that turbulence enhances aggregate formation up to a critical turbulent kinetic energy dissipation rate of 10−6 (W kg−1), above which the smallest turbulent eddies limit aggregate size.
Assessment of hardening due to non-coherent precipitates in tungsten-rhenium alloys at the atomic scale
Authors: Bonny G. , Bakaev A. , Terentyev D. 
Published: November 2019

AbstractIn metallurgical applications, precipitation strengthening is of great technological importance to engineer materials with the required strength. While precipitation hardening is essential for many applications involving operation at elevated temperatures, its subsequent embrittlement can be a showstopper for the overall performance of a component. In the nuclear industry, irradiation-induced/enhanced precipitation and the resulting embrittlement often limit the lifetime of components. In fusion applications, tungsten (W) based alloys are known to harden and embrittle as a result of irradiation-assisted transmutation to rhenium (Re) and its subsequent precipitation into non-coherent precipitates. Hence, a fundamental understanding of the interaction of dislocations with non-coherent precipitates is of great interest. In the present work, the interaction of dislocations with non-coherent Re-rich σ, χ and hcp phase precipitates embedded in a bcc W matrix is assessed. Large-scale atomistic simulations are performed to clarify the interaction mechanisms and derive the obstacle strength of the precipitates in the quasi-static limit. Thereby the impact of precipitate shape, size, interspacing and composition is assessed. Based on those results, an analytical model to predict precipitation hardening of σ, χ and hcp phase particles in bcc W is proposed and compared to available experimental data from mechanical tests on irradiated materials.
Two-dimensional Peripheral Refraction and Retinal Image Quality in Emmetropic Children
Authors: Lan Weizhong , Lin Zhenghua , Yang Zhikuang , Artal Pablo 
Published: November 2019

AbstractThe relationship between the optical properties of the eye in the periphery and myopia development is still under debate. To further clarify this issue, we provide here baseline data of two-dimensional peripheral optics results in a group of emmetropic Chinese children. Peripheral aberrations were measured under cycloplegia by using an open-view Hartmann-Shack wavefront sensor (VPR, Voptica SL, Spain). This instrument allows to measure fast in the horizontal visual field from temporal 30° to nasal 30° every 1°. Two-dimensional (2D) maps were retrieved from a series of horizonal scans taken every 4° from 20° superior to 16° inferior covering a visual field of 60 × 36°. A relatively homogeneous pattern of the 2D relative peripheral refraction was found across all these emmetropic subjects. Using cluster analysis followed by manual visual refinement, the 2D maps were identified to fit into four categories. More than 70% of the subjects showed a nearly flat horizontal refraction with a slightly myopic shift in the superior retina. Peripheral astigmatism was quite constant across subjects and similar to that expected theoretically. Peripheral aberrations were also similar to those in the fovea for a large retinal area. These baseline data would offer an important reference to compare with the future evolution with time, as well as with other refractive or age groups of subjects, to better understand the role of peripheral optical properties in myopia development.
Intracellular K+ and water content in human blood lymphocytes during transition from quiescence to proliferation
Authors: Marakhova Irina , Yurinskaya Valentina , Aksenov Nikolay , Zenin Valeriy , Shatrova Alla , Vereninov Alexey 
Published: November 2019

AbstractMany evidence shows that K+ ions are required for cell proliferation, however, changes in intracellular K+ concentration during transition of cells from quiescence to cycling are insufficiently studied. Here, we show using flame emission assay that a long-term increase in cell K+ content per g cell protein is a mandatory factor for transition of quiescent human peripheral blood lymphocytes (PBL) to proliferation induced by phytohemagglutinin, phorbol ester with ionomycin, and anti-CD3 antibodies with interleukin-2 (IL-2). The long-term increase in K+ content is associated with IL-2-dependent stage of PBL activation and accompanies the growth of small lymphocytes and their transformation into blasts. Inhibition of PBL proliferation with drugs specific for different steps of G0/G1/S transit prevented both blast-transformation and an increase in K+ content per cell protein. Determination of the water content in cells by measuring the density of cells in the Percoll gradient showed that, unlike the K+ content, the concentration of K+ in cell water remains unchanged, since water and K+ change in parallel. Correlation of proliferation with high cell K+ and water content has been confirmed by the data obtained in comparative study of PBL and permanently cycling Jurkat cells. Our data suggest that K+ is important for successful proliferation as the main intracellular ion that participates in regulation of cell water content during cell transition from quiescence to proliferation. We concluded that high K+ content in cells and the associated high water content is a characteristic feature of proliferating cells.
Treatment response and predictors in patients with newly diagnosed epilepsy in Ethiopia: a retrospective cohort study
Authors: Gidey Kidu , Chelkeba Legese , Gemechu Tadesse Dukessa , Daba Fekede Bekele 
Published: November 2019

AbstractEpilepsy is a chronic neurological disease with a variable therapeutic response. To design effective treatment strategies for epilepsy, it is important to understand treatment responses and predictive factors. However, limited data are available in Africa, including Ethiopia. The aim of this study was therefore to assess treatment response and identify prognostic predictors among patients with epilepsy at Jimma university medical center, Ethiopia. We conducted a retrospective cohort study of 404 newly diagnosed adult epilepsy patients receiving antiepileptic treatment between May 2010 and May 2015. Demographic, clinical, and outcome data were collected for all patients with a minimum follow-up of two years. Cox proportional hazards model was used to identify predictors of poor seizure remission. Overall, 261 (64.6%) of the patients achieved seizure remission for at least one year. High number of pre-treatment seizures (adjusted hazard ratios (AHR) = 0.64, 95% CI: 0.49–0.83) and poor adherence (AHR = 0.57, 95% CI: 0.44–0.75) were significant predictors of poor seizure remission. In conclusion, our study showed that only about two-thirds of patients had achieved seizure remission. The high number of pre-treatment seizures and non-adherence to antiepileptic medications were predictors of poor seizure remission. Patients with these characteristics should be given special attention.
Analysis and classification of droplet characteristics from atomizers using multifractal analysis
Authors: Godavarthi V. , Dhivyaraja K. , Sujith R. I. , Panchagnula M. V. 
Published: November 2019

AbstractAtomizers find applications in diverse fields such as agriculture, pharmaceutics and combustion. Among the most commonly found atomizer classes of designs are pressure swirl, airblast and ultrasonic atomizers. However, it has thus far not been possible to identify the class of an atomizer from spray characteristics. We perform multifractal detrended fluctuation analysis on the droplet inter-arrival times, diameters and axial velocities of pressure swirl, airblast and ultrasonic nebulizer sprays to quantify the differences in complexity in the respective signals. We show that the width of the multifractal spectrum of the signals of droplet diameters and the inter-arrival times, measured at the edge of the spray are robust atomizer identifiers. Further, we show the presence of correlations among the droplet diameters which are otherwise considered as random or derived from a log-normal distribution. This study can be further generalized to classify fluid mechanical systems or biological sprays using an appropriately chosen single point measurement in the flow field.
Random lasing and amplified spontaneous emission from silk inverse opals: Optical gain enhancement via protein scatterers
Authors: Umar Muhammad , Min Kyungtaek , Kim Sookyoung , Kim Sunghwan 
Published: November 2019

AbstractGain amplification and coherent lasing lines through random lasing (RL) can be produced by a random distribution of scatterers in a gain medium. If these amplified light sources can be seamlessly integrated into biological systems, they can have useful bio-optical applications, such as highly accurate sensing and high-resolution imaging. In this paper, a fully biocompatible light source showing RL and amplified spontaneous emission (ASE) with a reduced threshold is reported. Random cavities were induced in a biocompatible silk protein film by incorporating an inverse opal with an inherent disorder and a biocompatible dye for optical gain into the film. By choosing the appropriate air-sphere diameters, clear RL spikes in the emission spectra that were clearly distinguished from those of the ASE were observed in the silk inverse opal (SIO) with optical gain. Additionally, the RL output exhibited spatial coherence; however, the ASE did not. The high surface-to-volume ratio and amplification of the SIO led to highly efficient chemosensing in the detection of hydrogen chloride vapor. Moreover, SIO could be miniaturized to be made suitable for injection into biological tissues and obtain RL signals. Our results, which open the way for the development of a new generation of miniaturized bio-lasers, may be considered as the first example of engineered RL with biocompatible materials.
The relationship between red cell distribution width and all-cause and cause-specific mortality in a general population
Authors: Pan Jingxue , Borné Yan , Engström Gunnar 
Published: November 2019

AbstractRed Cell Distribution Width (RDW) could be a risk factor for developing various chronic diseases, and seems to be a prognostic marker in patients with cardiovascular disease (CVD) or cancer. Our aim was to explore the association between RDW and all-cause and cause-specific mortality in a general population. RDW was measured in 27,063 participants (aged 45–73 years) from the population-based Malmö Diet and Cancer cohort. After a follow-up of 19.8 ± 5.5 years, Cox proportional hazards regression analysis was used to study the relationship between RDW and all-cause and cause-specific mortality, with adjustment for confounding factors. A total of 9388 individuals (4715 men and 4673 women) died during the follow up. High RDW was significantly associated with all-cause mortality (HR, 4th vs. 1st quartile: 1.34, 95%CI: 1.24–1.45), cancer mortality (HR: 1.27, 95%CI: 1.12–1.44), CVD mortality (HR: 1.39, 95%CI: 1.21–1.59), and respiratory disease mortality (HR: 1.47, 95%CI: 1.06–2.03). The C-statistic increased significantly from 0.732 to 0.737 when adding RDW to a model adjusted for age and sex. There was a significant interaction between RDW and BMI with respect to all-cause mortality. We concluded that RDW is associated with mortality and propose that high RDW is a significant, but non-specific marker of mortality risk in the general population.
Acetylation of conserved DVL-1 lysines regulates its nuclear translocation and binding to gene promoters in triple-negative breast cancer
Authors: Sharma Monica , Molehin Deborah , Castro-Piedras Isabel , Martinez Edgar G. , Pruitt Kevin 
Published: November 2019

AbstractDishevelled (DVL) proteins are central mediators of the Wnt signalling pathway and are versatile regulators of several cellular processes, yet little is known about their post-translational regulation. Acetylation is a reversible post-translational modification (PTM) which regulates the function of several non-histone proteins involved in tumorigenesis. Since we previously demonstrated that lysine deacetylase, SIRT-1, regulates DVL protein levels and its function, we reasoned that DVL could potentially be a substrate for SIRT-1 mediated deacetylation. To further examine the potential role of multiple families of lysine deacetylases in the post-translational regulation of DVL, we screened for novel acetylation sites using liquid chromatography mass-spectrometry (LC-MS/MS) analysis. Herein, we report 12 DVL-1 lysine residues that show differential acetylation in response to changes in oxygen tension and deacetylase inhibition in triple-negative breast cancer (TNBC). PTMs are well documented to influence protein activity, and cellular localization. We also identify that acetylation of two key lysine residues, K69 and K285, present on the DIX and PDZ domains respectively, promote nuclear over cytoplasmic localization of DVL-1, and influences its promoter binding and regulation of genes implicated in cancer. Collectively, these findings for the first time, uncover acetylation as a novel layer of regulation of DVL-1 proteins.
Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis
Authors: Loberman-Nachum Nurit , Sosnovski Katya , Di Segni Ayelet , Efroni Gilat , Braun Tzipi , BenShoshan Marina , Anafi Lait , Avivi Camila , Barshack Iris , Shouval Dror S. , Denson Lee A. , Amir Amnon , Unger Ron , Weiss Batia , Haberman Yael 
Published: November 2019

AbstractCeliac disease is provoked by gluten exposure, but the complete pathogenic process in the duodenum and the loss of tolerance to gluten is not well understood. We aimed to define the core celiac transcriptomic signature and pathologic pathways in pre-treatment formalin-fixed paraffin-embedded (FFPE) duodenum biopsies used for clinical diagnosis. We use mRNAseq to define pre-treatment diagnostic duodenum gene expression in 54 pediatric celiac patients and non-celiac controls, and we validate our key findings in two independent cohorts of 67 adults and pediatric participants that used fresh frozen biopsies. We further define similar and divergent genes and pathways in 177 small bowel Crohn disease patients and controls. We observe a marked suppression of mature epithelial metabolic functions in celiac patients, overlapping substantially with the Crohn disease signature. A marked adaptive immune response was noted for the up-regulated signature including interferon response, alpha-beta, and gamma-delta T-cells that overlapped to some extent with the Crohn disease signature. However, we also identified a celiac disease specific signature linked to increased cell proliferation, nuclear division, and cell cycle activity that was localized primarily to the epithelia as noted by CCNB1 and Ki67 staining. Lastly, we demonstrate the utility of the transcriptomic date to correctly classify disease or healthy states in the discovery and validation cohorts. Our data supplement recently published datasets providing insights into celiac pathogenesis using clinical pathology FFPE samples, and can stimulate new approaches to address this highly prevalent condition.
LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells
Authors: Qi Wenchuan , Li Zhenhua , Xia Longjiang , Dai Jiangshan , Zhang Qiao , Wu Chuanfang , Xu Si 
Published: November 2019

AbstractFerroptosis is a non-apoptotic, iron-dependent oxidative form of cell death that is specifically induced by erastin in RAS mutant cancer cells. Ferroptotic cell death is the result of membrane lipid peroxide damage caused by the accumulation of hydroxyl radicals derived from H2O2 by the Fenton reaction. Peroxidases are key cellular antioxidant enzymes that block such damaging processes. Few studies have examined the roles of long non-coding RNAs (lncRNAs) in the regulation of cellular oxidative stress, especially in ferroptosis. Here, we demonstrated that erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. Such effects critically inhibited the cellular antioxidant capacity and cell viability. Additionally, high expression levels of GABPB1 were correlated with poor prognosis of hepatocellular carcinoma (HCC) Patients, while high GABPB1-AS1 levels in HCC patients correlated with improved overall survival. Collectively, these data demonstrate a mechanistic link between GABPB1 and its antisense lncRNA GABPB1-AS1 in erastin-induced ferroptosis and establish GABPB1 and GABPB1-AS1 as attractive therapeutic targets for HCC.