cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3463199.v1
title: Benchmarking HIP

description: Dataset for Benchmarking postoperative pain in total hip replacement
DOI: 10.6084/m9.figshare.3463019
title: Nutrition has a pervasive impact on cardiac microRNA expression in isogenic mice

description: The complex interaction between obesity, Western-style diets, and cardiovascular disease is of increasing interest, with a growing number of children being born to obese parents with poor lifestyle choices. These offspring have themselves an increased susceptibility to obesity and subsequent cardiovascular disease in adult life, which may be ‘programmed’ by their intrauterine environment. Cardiac microRNAs (miRNAs) are affected by multiple disease states, and have also been shown to be capable of exerting a hormone-like control on whole body metabolism. Here we sought to determine the effect of prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on miRNA expression in the heart. Unbiased small RNA sequencing was carried out on cardiac tissue from young adult mice born to lean or obese mothers; offspring were weaned onto either a low-fat control diet or a high-fat Western-style diet. We found 8 cardiac miRNAs that were significantly altered in response to maternal obesity, but only when the offspring were challenged postnatally with the Western diet. In contrast, postnatal exposure to the diet alone induced significant changes to the expression of a much larger number of miRNAs (33 in offspring of lean and 46 in offspring of obese). Many of the affected miRNAs have previously been implicated in various cardiac pathologies. The pervasive cardiac miRNA changes induced by a Western diet suggest that an individual's lifestyle choices outweigh the impact of any programming effects by maternal obesity on miRNA-related cardiac health.
DOI: 10.6084/m9.figshare.3463019.v1
title: Nutrition has a pervasive impact on cardiac microRNA expression in isogenic mice

description: The complex interaction between obesity, Western-style diets, and cardiovascular disease is of increasing interest, with a growing number of children being born to obese parents with poor lifestyle choices. These offspring have themselves an increased susceptibility to obesity and subsequent cardiovascular disease in adult life, which may be ‘programmed’ by their intrauterine environment. Cardiac microRNAs (miRNAs) are affected by multiple disease states, and have also been shown to be capable of exerting a hormone-like control on whole body metabolism. Here we sought to determine the effect of prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on miRNA expression in the heart. Unbiased small RNA sequencing was carried out on cardiac tissue from young adult mice born to lean or obese mothers; offspring were weaned onto either a low-fat control diet or a high-fat Western-style diet. We found 8 cardiac miRNAs that were significantly altered in response to maternal obesity, but only when the offspring were challenged postnatally with the Western diet. In contrast, postnatal exposure to the diet alone induced significant changes to the expression of a much larger number of miRNAs (33 in offspring of lean and 46 in offspring of obese). Many of the affected miRNAs have previously been implicated in various cardiac pathologies. The pervasive cardiac miRNA changes induced by a Western diet suggest that an individual's lifestyle choices outweigh the impact of any programming effects by maternal obesity on miRNA-related cardiac health.
DOI: 10.6084/m9.figshare.3462992
title: Generalized Additive Models for Gigadata: Modeling the U.K. Black Smoke Network Daily Data

description: We develop scalable methods for fitting penalized regression spline based generalized additive models with of the order of 10<sup>4</sup> coefficients to up to 10<sup>8</sup> data. Computational feasibility rests on: (i) a new iteration scheme for estimation of model coefficients and smoothing parameters, avoiding poorly scaling matrix operations; (ii) parallelization of the iteration’s pivoted block Cholesky and basic matrix operations; (iii) the marginal discretization of model covariates to reduce memory footprint, with efficient scalable methods for computing required crossproducts directly from the discrete representation. Marginal discretization enables much finer discretization than joint discretization would permit. We were motivated by the need to model four decades worth of daily particulate data from the U.K. Black Smoke and Sulphur Dioxide Monitoring Network. Although reduced in size recently, over 2000 stations have at some time been part of the network, resulting in some 10 million measurements. Modeling at a daily scale is desirable for accurate trend estimation and mapping, and to provide daily exposure estimates for epidemiological cohort studies. Because of the dataset size, previous work has focused on modeling time or space averaged pollution levels, but this is unsatisfactory from a health perspective, since it is often acute exposure locally and on the time scale of days that is of most importance in driving adverse health outcomes. If computed by conventional means our black smoke model would require a half terabyte of storage just for the model matrix, whereas we are able to compute with it on a desktop workstation. The best previously available reduced memory footprint method would have required three orders of magnitude more computing time than our new method. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.3462992.v2
title: Generalized Additive Models for Gigadata: Modeling the U.K. Black Smoke Network Daily Data

description: We develop scalable methods for fitting penalized regression spline based generalized additive models with of the order of 10<sup>4</sup> coefficients to up to 10<sup>8</sup> data. Computational feasibility rests on: (i) a new iteration scheme for estimation of model coefficients and smoothing parameters, avoiding poorly scaling matrix operations; (ii) parallelization of the iteration’s pivoted block Cholesky and basic matrix operations; (iii) the marginal discretization of model covariates to reduce memory footprint, with efficient scalable methods for computing required crossproducts directly from the discrete representation. Marginal discretization enables much finer discretization than joint discretization would permit. We were motivated by the need to model four decades worth of daily particulate data from the U.K. Black Smoke and Sulphur Dioxide Monitoring Network. Although reduced in size recently, over 2000 stations have at some time been part of the network, resulting in some 10 million measurements. Modeling at a daily scale is desirable for accurate trend estimation and mapping, and to provide daily exposure estimates for epidemiological cohort studies. Because of the dataset size, previous work has focused on modeling time or space averaged pollution levels, but this is unsatisfactory from a health perspective, since it is often acute exposure locally and on the time scale of days that is of most importance in driving adverse health outcomes. If computed by conventional means our black smoke model would require a half terabyte of storage just for the model matrix, whereas we are able to compute with it on a desktop workstation. The best previously available reduced memory footprint method would have required three orders of magnitude more computing time than our new method. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.3462992.v1
title: Generalized additive models for gigadata: modelling the UK black smoke network daily data

description: We develop scalable methods for fitting penalized regression spline based generalized additive models with of the order of 10<sup>4</sup> coefficients to up to 10<sup>8</sup> data. Computational feasibility rests on: (i) a new iteration scheme for estimation of model coefficients and smoothing parameters, avoiding poorly scaling matrix operations; (ii) parallelization of the iteration’s pivoted block Cholesky and basic matrix operations; (iii) the marginal discretization of model covariates to reduce memory footprint, with efficient scalable methods for computing required crossproducts directly from the discrete representation. Marginal discretization enables much finer discretization than joint discretization would permit. We were motivated by the need to model four decades worth of daily particulate data from the UK Black Smoke and Sulphur Dioxide monitoring network. Although reduced in size recently, over 2000 stations have at some time been part of the network, resulting in some 10 million measurements. Modelling at a daily scale is desirable for accurate trend estimation and mapping, and to provide daily exposure estimates for epidemiological cohort studies. Because of the data set size, previous work has focussed on modelling time or space averages pollution levels, but this is unsatisfactory from a health perspective, since it is often acute exposure locally and on the time scale of days that is of most importance in driving adverse health outcomes. If computed by conventional means our black smoke model would require a half terabyte of storage just for the model matrix, whereas we are able to compute with it on a desktop workstation. The best previously available reduced memory footprint method would have required three orders of magnitude more computing time than our new method.
DOI: 10.6084/m9.figshare.3462935
title: HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress

description: Multiple myeloma (MM) is still an incurable hematological malignancy. Despite recent progress due to new anti-myeloma agents, the pathology is characterized by a high frequency of <i>de novo</i> or acquired resistance. Delineating the mechanisms of MM resistance is essential for therapeutic advances. We previously showed that long-term genotoxic stress induces the establishment of a senescence-associated secretory phenotype, a pro-inflammatory response that favors the emergence of cells with cancer stem-like properties. Here, we studied the short-term response of MM cells following treatment with various DNA damaging agents such as the energetic C-ion irradiation. MM cells are highly resistant to all treatments and do not enter apoptosis after they arrest cycling at the G2 phase. Although the DNA damage response pathway was activated, DNA breaks remained chronically in damaged MM cells. We found, using a transcriptomic approach that <i>RAD50</i>, a major DNA repair gene was downregulated early after genotoxic stress. In two gerosuppression situations: induction of hypoxia and inhibition of the mammalian target of rapamycin (mTOR) pathway, we observed, after the treatment with a DNA damaging agent, a normalization of RAD50 expression concomitant with the absence of cell cycle arrest. We propose that combining inhibitors of mTOR with genotoxic agents could avoid MM cells to senesce and secrete pro-inflammatory factors responsible for cancer stem-like cell emergence and, in turn, relapse of MM patients.
DOI: 10.6084/m9.figshare.3462935.v1
title: HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress

description: Multiple myeloma (MM) is still an incurable hematological malignancy. Despite recent progress due to new anti-myeloma agents, the pathology is characterized by a high frequency of <i>de novo</i> or acquired resistance. Delineating the mechanisms of MM resistance is essential for therapeutic advances. We previously showed that long-term genotoxic stress induces the establishment of a senescence-associated secretory phenotype, a pro-inflammatory response that favors the emergence of cells with cancer stem-like properties. Here, we studied the short-term response of MM cells following treatment with various DNA damaging agents such as the energetic C-ion irradiation. MM cells are highly resistant to all treatments and do not enter apoptosis after they arrest cycling at the G2 phase. Although the DNA damage response pathway was activated, DNA breaks remained chronically in damaged MM cells. We found, using a transcriptomic approach that <i>RAD50</i>, a major DNA repair gene was downregulated early after genotoxic stress. In two gerosuppression situations: induction of hypoxia and inhibition of the mammalian target of rapamycin (mTOR) pathway, we observed, after the treatment with a DNA damaging agent, a normalization of RAD50 expression concomitant with the absence of cell cycle arrest. We propose that combining inhibitors of mTOR with genotoxic agents could avoid MM cells to senesce and secrete pro-inflammatory factors responsible for cancer stem-like cell emergence and, in turn, relapse of MM patients.
DOI: 10.6084/m9.figshare.3462935.v3
title: HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress

description: Multiple myeloma (MM) is still an incurable hematological malignancy. Despite recent progress due to new anti-myeloma agents, the pathology is characterized by a high frequency of <i>de novo</i> or acquired resistance. Delineating the mechanisms of MM resistance is essential for therapeutic advances. We previously showed that long-term genotoxic stress induces the establishment of a senescence-associated secretory phenotype, a pro-inflammatory response that favors the emergence of cells with cancer stem-like properties. Here, we studied the short-term response of MM cells following treatment with various DNA damaging agents such as the energetic C-ion irradiation. MM cells are highly resistant to all treatments and do not enter apoptosis after they arrest cycling at the G2 phase. Although the DNA damage response pathway was activated, DNA breaks remained chronically in damaged MM cells. We found, using a transcriptomic approach that <i>RAD50</i>, a major DNA repair gene was downregulated early after genotoxic stress. In two gerosuppression situations: induction of hypoxia and inhibition of the mammalian target of rapamycin (mTOR) pathway, we observed, after the treatment with a DNA damaging agent, a normalization of RAD50 expression concomitant with the absence of cell cycle arrest. We propose that combining inhibitors of mTOR with genotoxic agents could avoid MM cells to senesce and secrete pro-inflammatory factors responsible for cancer stem-like cell emergence and, in turn, relapse of MM patients.
DOI: 10.6084/m9.figshare.3462935.v2
title: HIF-1<b>α</b> and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress

description: Multiple myeloma (MM) is still an incurable hematological malignancy. Despite recent progress due to new anti-myeloma agents, the pathology is characterized by a high frequency of <i>de novo</i> or acquired resistance. Delineating the mechanisms of MM resistance is essential for therapeutic advances. We previously showed that long-term genotoxic stress induces the establishment of a senescence-associated secretory phenotype, a pro-inflammatory response that favors the emergence of cells with cancer stem-like properties. Here, we studied the short-term response of MM cells following treatment with various DNA damaging agents such as the energetic C-ion irradiation. MM cells are highly resistant to all treatments and do not enter apoptosis after they arrest cycling at the G2 phase. Although the DNA damage response pathway was activated, DNA breaks remained chronically in damaged MM cells. We found, using a transcriptomic approach that <i>RAD50</i>, a major DNA repair gene was downregulated early after genotoxic stress. In two gerosuppression situations: induction of hypoxia and inhibition of the mammalian target of rapamycin (mTOR) pathway, we observed, after the treatment with a DNA damaging agent, a normalization of RAD50 expression concomitant with the absence of cell cycle arrest. We propose that combining inhibitors of mTOR with genotoxic agents could avoid MM cells to senesce and secrete pro-inflammatory factors responsible for cancer stem-like cell emergence and, in turn, relapse of MM patients.
DOI: 10.6084/m9.figshare.3462932
title: EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

description: EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.
DOI: 10.6084/m9.figshare.3462932.v1
title: EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

description: EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.
DOI: 10.6084/m9.figshare.3462908
title: Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma

description: While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.
DOI: 10.6084/m9.figshare.3462908.v1
title: Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma

description: While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.
DOI: 10.6084/m9.figshare.3462803
title: MDS of random walks in 1 to 10K dimensions

description: 2D multidimensional scaling of random walks in 1 (light gray) to 10K (black) dimensions
DOI: 10.6084/m9.figshare.3462803.v2
title: MDS of random walks in 1 to 10K dimensions

description: 2D multidimensional scaling of random walks in 1 (light gray) to 10K (black) dimensions
DOI: 10.6084/m9.figshare.3462785
title: jakubec_plosone_2016.tar.gz

description: Data set of interaction energies of amino acid--DNA base and amino acid--deoxynucleotide dimers in various dielectric environments.<br>
DOI: 10.6084/m9.figshare.3462785.v1
title: jakubec_plosone_2016.tar.gz

description: Data set of interaction energies of amino acid--DNA base and amino acid--deoxynucleotide dimers in various dielectric environments.<br>
DOI: 10.6084/m9.figshare.3462782
title: Excel ITJP-D-15-00215R1.xls

description: Case-control dataset from a cohort of children who participated in two large school-based health surveys in Cyprus. In a case-control design, we invited all those children who on the second survey (ISAAC questionnaire) reported wheezing in the past 12 months to participate in the study along with a triplicate number of healthy controls.
DOI: 10.6084/m9.figshare.3462773
title: The Triassic–Jurassic boundary event from an equatorial carbonate platform (Ghalilah Formation, United Arab Emirates)

description: δ13C<sub>carb</sub> data from bulk rock
DOI: 10.6084/m9.figshare.3462782.v1
title: Excel ITJP-D-15-00215R1.xls

description: Case-control dataset from a cohort of children who participated in two large school-based health surveys in Cyprus. In a case-control design, we invited all those children who on the second survey (ISAAC questionnaire) reported wheezing in the past 12 months to participate in the study along with a triplicate number of healthy controls.
DOI: 10.6084/m9.figshare.3462773.v1
title: The Triassic–Jurassic boundary event from an equatorial carbonate platform (Ghalilah Formation, United Arab Emirates)

description: δ13C<sub>carb</sub> data from bulk rock