cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5296351
title: Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3 eukaryotic kingdoms

description: Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate autophagic degradation of peroxisomes in the budding yeast <i>Saccharomyces cerevisiae</i>. Being a pathway-specific rather than a target-driven assay, we identified small molecule modulators that acted at key steps of autophagic flux. Two of the inhibitors, Bay11 and ZPCK, obtained from the screen were further characterized using secondary assays in yeast. Bay11 inhibited autophagy at a step before fusion with the vacuole whereas ZPCK inhibited the cargo degradation inside the vacuole. Furthermore, we demonstrated that these molecules altered the process of autophagy in mammalian cells as well. Strikingly, these molecules also modulated autophagic flux in a novel model plant, <i>Aponogeton madagascariensis</i>. Thus, using small molecule modulators identified by using a newly developed HTS autophagy assay, our results support that macroautophagy is a conserved process across fungal, animal and plant kingdoms.
DOI: 10.6084/m9.figshare.5296357
title: News-Processed-Dataset

description: News after cleaned and processed.
DOI: 10.6084/m9.figshare.5296348
title: Financial News unprocessed

description: Raw News JSON files
DOI: 10.6084/m9.figshare.5296351.v1
title: Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3 eukaryotic kingdoms

description: Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate autophagic degradation of peroxisomes in the budding yeast <i>Saccharomyces cerevisiae</i>. Being a pathway-specific rather than a target-driven assay, we identified small molecule modulators that acted at key steps of autophagic flux. Two of the inhibitors, Bay11 and ZPCK, obtained from the screen were further characterized using secondary assays in yeast. Bay11 inhibited autophagy at a step before fusion with the vacuole whereas ZPCK inhibited the cargo degradation inside the vacuole. Furthermore, we demonstrated that these molecules altered the process of autophagy in mammalian cells as well. Strikingly, these molecules also modulated autophagic flux in a novel model plant, <i>Aponogeton madagascariensis</i>. Thus, using small molecule modulators identified by using a newly developed HTS autophagy assay, our results support that macroautophagy is a conserved process across fungal, animal and plant kingdoms.
DOI: 10.6084/m9.figshare.5296366
title: TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway

description: <b>Rationale</b>: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. <b>Objective</b>: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action. <b>Methods and Results</b>: Freshly isolated CMs were obtained from murine heart and loaded with Fura-2 AM. Simultaneous measurement of intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and contractility was performed in individual CMs paced at 0.3 Hz. Our findings demonstrate that TRPA1 stimulation with AITC results in a dose-dependent increase in peak [Ca<sup>2+</sup>]<sub>i</sub> and a concomitant increase in CM fractional shortening. Further analysis revealed a dose-dependent acceleration in time to peak [Ca<sup>2+</sup>]<sub>i</sub> and velocity of shortening as well as an acceleration in [Ca<sup>2+</sup>]<sub>i</sub> decay and velocity of relengthening. These effects of TRPA1 stimulation were not observed in CMs pre-treated with the TRPA1 antagonist, HC-030031 (10 µmol/L) nor in CMs obtained from TRPA1<sup>−/−</sup> mice. Moreover, we observed no significant increase in cAMP levels or PKA activity in response to TRPA1 stimulation and the PKA inhibitor peptide (PKI 14–22; 100 nmol/L) failed to have any effect on the TRPA1-mediated increase in CM contractile function. However, TRPA1 stimulation resulted in a rapid phosphorylation of Ca<sup>2+</sup>/calmodulin-dependent kinase II (CaMKII) (1–5 min) that correlated with increases in CM [Ca<sup>2+</sup>]<sub>i</sub> and contractile function. Finally, all aspects of TRPA1-dependent increases in CM [Ca<sup>2+</sup>]<sub>i</sub>, contractile function and CaMKII phosphorylation were virtually abolished by the CaMKII inhibitors, KN-93 (10 µmol/L) and autocamtide-2-related peptide (AIP; 20 µmol/L). <b>Conclusions</b>: These novel findings demonstrate that stimulation of TRPA1 ion channels in CMs results in activation of a CaMKII-dependent signaling pathway resulting in modulation of intracellular Ca<sup>2+</sup> availability and handling leading to increases in CM contractile function. Cardiac TRPA1 ion channels may represent a novel therapeutic target for increasing the inotropic and lusitropic state of the heart.
DOI: 10.6084/m9.figshare.5296303
title: US-Stock-Tickers-Main

description: tickers from NASDAQ, NYSE, AMEX
DOI: 10.6084/m9.figshare.5296366.v2
title: TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway

description: <b>Rationale</b>: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. <b>Objective</b>: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action. <b>Methods and Results</b>: Freshly isolated CMs were obtained from murine heart and loaded with Fura-2 AM. Simultaneous measurement of intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and contractility was performed in individual CMs paced at 0.3 Hz. Our findings demonstrate that TRPA1 stimulation with AITC results in a dose-dependent increase in peak [Ca<sup>2+</sup>]<sub>i</sub> and a concomitant increase in CM fractional shortening. Further analysis revealed a dose-dependent acceleration in time to peak [Ca<sup>2+</sup>]<sub>i</sub> and velocity of shortening as well as an acceleration in [Ca<sup>2+</sup>]<sub>i</sub> decay and velocity of relengthening. These effects of TRPA1 stimulation were not observed in CMs pre-treated with the TRPA1 antagonist, HC-030031 (10 µmol/L) nor in CMs obtained from TRPA1<sup>−/−</sup> mice. Moreover, we observed no significant increase in cAMP levels or PKA activity in response to TRPA1 stimulation and the PKA inhibitor peptide (PKI 14–22; 100 nmol/L) failed to have any effect on the TRPA1-mediated increase in CM contractile function. However, TRPA1 stimulation resulted in a rapid phosphorylation of Ca<sup>2+</sup>/calmodulin-dependent kinase II (CaMKII) (1–5 min) that correlated with increases in CM [Ca<sup>2+</sup>]<sub>i</sub> and contractile function. Finally, all aspects of TRPA1-dependent increases in CM [Ca<sup>2+</sup>]<sub>i</sub>, contractile function and CaMKII phosphorylation were virtually abolished by the CaMKII inhibitors, KN-93 (10 µmol/L) and autocamtide-2-related peptide (AIP; 20 µmol/L). <b>Conclusions</b>: These novel findings demonstrate that stimulation of TRPA1 ion channels in CMs results in activation of a CaMKII-dependent signaling pathway resulting in modulation of intracellular Ca<sup>2+</sup> availability and handling leading to increases in CM contractile function. Cardiac TRPA1 ion channels may represent a novel therapeutic target for increasing the inotropic and lusitropic state of the heart.
DOI: 10.6084/m9.figshare.5296366.v1
title: TRPA1 Ion Channel Stimulation Enhances Cardiomyocyte Contractile Function via a CaMKII-dependent Pathway

description: <b>Rationale:</b> Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disc, costamere and intercalated disc. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. <b>Objective:</b> To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action. <b>Methods and Results:</b> Freshly isolated CMs were obtained from murine heart and loaded with Fura-2 AM. Simultaneous measurement of intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and contractility was performed in individual CMs paced at 0.3 Hz. Our findings demonstrate that TRPA1 stimulation with AITC results in a dose-dependent increase in peak [Ca<sup>2+</sup>]<sub>i</sub> and a concomitant increase in CM fractional shortening. Further analysis revealed a dose-dependent acceleration in time to peak [Ca<sup>2+</sup>]<sub>i</sub> and velocity of shortening as well as an acceleration in [Ca<sup>2+</sup>]<sub>i</sub> decay and velocity of relengthening. These effects of TRPA1 stimulation were not observed in CMs pre-treated with the TRPA1 antagonist, HC-030031 (10 µmol/L) nor in CMs obtained from TRPA1<sup>−/−</sup> mice. Moreover, we observed no significant increase in cAMP levels or PKA activity in response to TRPA1 stimulation and the PKA inhibitor peptide (PKI 14–22; 100 nmol/L) failed to have any effect on the TRPA1-mediated increase in CM contractile function. However, TRPA1 stimulation resulted in a rapid phosphorylation of Ca<sup>2+</sup>/calmodulin-dependent kinase II (CaMKII) (1-5 min) that correlated with increases in CM [Ca<sup>2+</sup>]<sub>i</sub> and contractile function. Finally, all aspects of TRPA1-dependent increases in CM [Ca<sup>2+</sup>]<sub>i</sub>, contractile function and CaMKII phosphorylation were virtually abolished by the CaMKII inhibitors, KN-93 (10 µmol/L) and autocamtide-2-related peptide (AIP; 20 µmol/L). <b>Conclusions:</b> These novel findings demonstrate that stimulation of TRPA1 ion channels in CMs results in activation of a CaMKII-dependent signaling pathway resulting in modulation of intracellular Ca<sup>2+</sup> availability and handling leading to increases in CM contractile function. Cardiac TRPA1 ion channels may represent a novel therapeutic target for increasing the inotropic and lusitropic state of the heart.
DOI: 10.6084/m9.figshare.5296348.v1
title: Reuters_Raw_Full_Detailed_News

description: Reuters News
DOI: 10.6084/m9.figshare.5296291
title: Intraday-Data-Original-And-Mockup-Missing-Minutes

description: US Stock Intra-day Dataset<br>
DOI: 10.6084/m9.figshare.5296294
title: Novel Object Memory Tests (NOMTs)

description: The NOMTs are 3 reliable tests to measure object recognition ability with novel objects (this includes all images required to run the test, including instructions and practice trials, in the order they appear).
DOI: 10.6084/m9.figshare.5296276
title: Towards A Usability Model for Software Development Process and Practice - Appendix A.pdf

description: This Appendix provides detailed data tables for our research, including expert evaluation results<br>
DOI: 10.6084/m9.figshare.5296264
title: Test item

description: this is just a test file
DOI: 10.6084/m9.figshare.5296267
title: Data-set: The Number of Credit Hours Required for Bachelor's Degrees at Christian Colleges & Universities

description: Supplemental Data for The Number of Credit Hours Required for Bachelor's Degrees at Christian Colleges & Universities
DOI: 10.6084/m9.figshare.5296276.v1
title: Towards A Usability Model for Software Development Process and Practice - Appendix A.pdf

description: This Appendix provides detailed data tables for our research, including expert evaluation results<br>
DOI: 10.6084/m9.figshare.5296267.v1
title: Data-set: The Number of Credit Hours Required for Bachelor's Degrees at Christian Colleges & Universities

description: Supplemental Data for The Number of Credit Hours Required for Bachelor's Degrees at Christian Colleges & Universities
DOI: 10.6084/m9.figshare.5296291.v1
title: Intraday-Data

description: US Stock Intra-day Dataset
DOI: 10.6084/m9.figshare.5294647
title: Chickenpox and shingles ABM

description: This file contains code for the chickenpox and shingles agent-based model, which accompanies the scientific paper entitled "Evaluation of the effect of chickenpox vaccination on shingles epidemiology using agent-based modeling". There are two format: one - is in pdf which provides all code used to create the model, and the other - is in AnyLogic, which would actually allow to run the model. For the model to run in AnyLogic, the third file (_output_template.xlsx) should be placed in the same folder. AnyLogic software is available from https://www.anylogic.com (Professional or University Researcher editions at the cost and Personal Learning Edition is free). Our model was created using Professional edition. Personal Learning edition may not have all features of Professional edition.
DOI: 10.6084/m9.figshare.5293918
title: The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation

description: Development and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO<sub>2</sub> NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE<sup>−/−</sup>, western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO<sub>2</sub> NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m<sup>3</sup> for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO<sub>2</sub> NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE<sup>−/−</sup> mice CeO<sub>2</sub> did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO<sub>2</sub> NPs. These findings show that subacute inhalation of CeO<sub>2</sub> NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO<sub>2</sub> NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials.
DOI: 10.6084/m9.figshare.5293918.v1
title: The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation

description: Development and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO<sub>2</sub> NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE<sup>−/−</sup>, western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO<sub>2</sub> NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m<sup>3</sup> for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO<sub>2</sub> NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE<sup>−/−</sup> mice CeO<sub>2</sub> did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO<sub>2</sub> NPs. These findings show that subacute inhalation of CeO<sub>2</sub> NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO<sub>2</sub> NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials.
DOI: 10.6084/m9.figshare.5294647.v1
title: Chickenpox and shingles ABM

description: This file contains code for the chickenpox and shingles agent-based model, which accompanies the scientific paper entitled "Evaluation of the effect of chickenpox vaccination on shingles epidemiology using agent-based modeling". There are two format: one - is in pdf which provides all code used to create the model, and the other - is in AnyLogic, which would actually allow to run the model. For the model to run in AnyLogic, the third file (_output_template.xlsx) should be placed in the same folder. AnyLogic software is available from https://www.anylogic.com (Professional or University Researcher editions at the cost and Personal Learning Edition is free). Our model was created using Professional edition. Personal Learning edition may not have all features of Professional edition.
DOI: 10.6084/m9.figshare.5293756
title: Supporting Information from the manuscript "Thermal physiology of Amazonian lizards (Reptilia: Squamata)".

description: Preferred, voluntary and critical temperatures from all Amazinian lizards tested in ecophysiological experiments.<br>
DOI: 10.6084/m9.figshare.5293759
title: Is Use of Homeopathy a Proxy Indicator for Poor Prescribing in English Primary Care

description: Data (.csv) and analysis, using Python and Stata, to determine associations between homeopathy prescribing and prescribing measures on OpenPrescribing.net
DOI: 10.6084/m9.figshare.5293783
title: Volunteered Geographic Videos in Physical Geography: Data Mining from YouTube

description: Volunteered geographic information and citizen science have advanced academic and public understanding of geographical and ecological processes. Videos hosted online represent a large data source that could potentially provide meaningful results for studies in physical geography—a concept we term <i>volunteered geographic videos</i> (VGV). Technological advances in image-capturing devices, computing, and image processing have resulted in increasingly sophisticated methods that treat imagery as raw data, such as resolving high-resolution topography with structure from motion or the calculation of surface flow velocity in rivers with particle image velocimetry. The ubiquitous nature of recording devices and citizens who share imagery online have resulted in a vast archive of potentially useful online videos. This article analyzes the potential for using YouTube videos for research in physical geography. We discuss the combination of suitability and availability that has made this possible and emphasize the distinction between moderately suitable imagery that can directly answer research questions and lower suitability imagery that can indirectly support a study. We present example case studies that address (1) initial considerations of using VGV, (2) topographic data extraction from a video taken after a landslide, and (3) data extraction from a video of a flash flood that could support a study of extreme floods and wood transport. Finally, we discuss both the benefits and complicating factors associated with VGV. The results indicate that VGV could be used to support certain studies in physical geography and that this large repository of raw data has been underutilized.
DOI: 10.6084/m9.figshare.5293783.v1
title: Volunteered Geographic Videos in Physical Geography: Data Mining from YouTube

description: Volunteered geographic information and citizen science have advanced academic and public understanding of geographical and ecological processes. Videos hosted online represent a large data source that could potentially provide meaningful results for studies in physical geography—a concept we term <i>volunteered geographic videos</i> (VGV). Technological advances in image-capturing devices, computing, and image processing have resulted in increasingly sophisticated methods that treat imagery as raw data, such as resolving high-resolution topography with structure from motion or the calculation of surface flow velocity in rivers with particle image velocimetry. The ubiquitous nature of recording devices and citizens who share imagery online have resulted in a vast archive of potentially useful online videos. This article analyzes the potential for using YouTube videos for research in physical geography. We discuss the combination of suitability and availability that has made this possible and emphasize the distinction between moderately suitable imagery that can directly answer research questions and lower suitability imagery that can indirectly support a study. We present example case studies that address (1) initial considerations of using VGV, (2) topographic data extraction from a video taken after a landslide, and (3) data extraction from a video of a flash flood that could support a study of extreme floods and wood transport. Finally, we discuss both the benefits and complicating factors associated with VGV. The results indicate that VGV could be used to support certain studies in physical geography and that this large repository of raw data has been underutilized.