cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6283058.v1
title: Ciliogenesis is reciprocally regulated by PPARA and NR1H4/FXR through controlling autophagy in vitro and in vivo

description: The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated. Here, we present direct evidence for the involvement of macroautophagic/autophagic regulators in controlling ciliogenesis. We showed that activation of PPARA facilitated ciliogenesis independently of cellular nutritional states. Importantly, PPARA-induced ciliogenesis was mediated by controlling autophagy, since either pharmacological or genetic inactivation of autophagy significantly repressed ciliogenesis. Moreover, we showed that pharmacological activator of autophagy, rapamycin, recovered repressed ciliogenesis in <i>ppara<sup>−</sup><sup>/−</sup> </i> cells. Conversely, activation of NR1H4 repressed cilia formation, while knockdown of NR1H4 enhanced ciliogenesis by inducing autophagy. The reciprocal activities of PPARA and NR1H4 in regulating ciliogenesis were highlighted in a condition where de-repressed ciliogenesis by NR1H4 knockdown was further enhanced by PPARA activation. The in vivo roles of PPARA and NR1H4 in regulating ciliogenesis were examined in greater detail in <i>ppara<sup>−</sup><sup>/</sup><sup>−</sup> </i> mice. In response to starvation, ciliogenesis was facilitated in wild-type mice via enhanced autophagy in kidney, while <i>ppara<sup>−</sup><sup>/</sup><sup>−</sup> </i> mice displayed impaired autophagy and kidney damage resembling ciliopathy. Furthermore, an NR1H4 agonist exacerbated kidney damage associated with starvation in <i>ppara<sup>−</sup><sup>/</sup><sup>−</sup> </i> mice. These findings indicate a previously unknown role for PPARA and NR1H4 in regulating the autophagy-ciliogenesis axis in vivo.
DOI: 10.6084/m9.figshare.6283055
title: Drumlins in the Nordenskiöldbreen forefield, Svalbard

description: The study of glacial landforms is important for understanding past subglacial processes and dynamics. The Nordenskiöldbreen forefield hosts numerous streamlined landforms resulting from a late Holocene glacier advance. Here, we present a geomorphological map constructed from remotely sensed imagery of both the marine and terrestrial environments. Sixteen drumlin bedforms have been identified in the mapped forefield – ten terrestrial and six submarine. A sedimentological investigation of drumlins in the Nordenskiöldbreen forefield shows that they are composed of pre-existing sediments draped by a thin layer of till which formed during the most recent advance of the glacier. Analysis of recent (2008–2012), high-resolution aerial imagery of all the glacier forelands in Svalbard suggests drumlin features are widespread. Here, we have identified 49 previously undocumented terrestrial glacier forefields, where subglacially streamlined landforms occur within the margins of the late Holocene glacier extent. Additionally, the location of 53 previously published submarine sites with streamlined landscape have been mapped. Thirty of these are sites with streamlines of late Holocene origin and 18 with Last Glacial Maximum (LGM) origin. Based on our detailed case study at the Nordenskiöldbreen forefield, and remote sensing survey, we suggest that drumlins in Svalbard form predominantly in forefields of glaciers with low-elevation termini, in areas with abundant fine-grained sediments, and where the glaciers are able to advance into an area of unconstrained topography.
DOI: 10.6084/m9.figshare.6283055.v1
title: Drumlins in the Nordenskiöldbreen forefield, Svalbard

description: The study of glacial landforms is important for understanding past subglacial processes and dynamics. The Nordenskiöldbreen forefield hosts numerous streamlined landforms resulting from a late Holocene glacier advance. Here, we present a geomorphological map constructed from remotely sensed imagery of both the marine and terrestrial environments. Sixteen drumlin bedforms have been identified in the mapped forefield – ten terrestrial and six submarine. A sedimentological investigation of drumlins in the Nordenskiöldbreen forefield shows that they are composed of pre-existing sediments draped by a thin layer of till which formed during the most recent advance of the glacier. Analysis of recent (2008–2012), high-resolution aerial imagery of all the glacier forelands in Svalbard suggests drumlin features are widespread. Here, we have identified 49 previously undocumented terrestrial glacier forefields, where subglacially streamlined landforms occur within the margins of the late Holocene glacier extent. Additionally, the location of 53 previously published submarine sites with streamlined landscape have been mapped. Thirty of these are sites with streamlines of late Holocene origin and 18 with Last Glacial Maximum (LGM) origin. Based on our detailed case study at the Nordenskiöldbreen forefield, and remote sensing survey, we suggest that drumlins in Svalbard form predominantly in forefields of glaciers with low-elevation termini, in areas with abundant fine-grained sediments, and where the glaciers are able to advance into an area of unconstrained topography.
DOI: 10.6084/m9.figshare.6283049
title: Dataset for: Zinc toxicity to <i>Daphnia magna</i> in a two-species microcosm can be predicted from single-species test data: the effects of phosphorus supply and pH

description: Ecological interactions and abiotic stress factors may significantly affect species sensitivities to toxicants and these are not incorporated in standard single species tests. This study tests the hypothesis if a model, calibrated solely on single species data, can explain abiotic stress factors in a two-species microcosm, a test applied to the effects of nutritional stress (phosphorus (P)-limitation) on zinc (Zn) toxicity to <i>Daphnia magna</i>. A population model was developed based on P- and Zn-dependent algal and daphnid growth. Two separate two-species (phytoplankton <i>Pseudokirchneriella subcapitata</i> and consumer <i>D. magna</i>) microcosm experiments with P×Zn factorial combinations and a different pH (7.3 and 7.8) were set up to validate the model. The 21-day daphnid population size was considerably reduced by increased Zn and by decreased P supply with a significant (p&lt;0.001) interaction among both factors. The observed median effective concentration (EC50) of Zn on <i>D. magna</i> population size varied 12-fold (25 to 310 µg Zn L-1), with the lowest EC50’s found at the highest pH and high P treatments. For both experiments, Zn toxicity to <i>D. magna</i> was correctly predicted within a factor of two for EC50-values and are explained by the model through: (1) a higher phytoplankton Zn sensitivity at higher pH, affecting food supply to <i>D. magna</i> and (2) an increased algal P-content at higher Zn, offering a nutritional benefit to daphnids that counteracts direct Zn toxicity under P-limitation. This study illustrated that indirect effects of Zn via producer-consumer relationships can outweigh the direct toxic effects, and that models calibrated solely on single species test data can help with interpreting these results in two-species systems.
DOI: 10.6084/m9.figshare.6283049.v1
title: Dataset for: Zinc toxicity to <i>Daphnia magna</i> in a two-species microcosm can be predicted from single-species test data: the effects of phosphorus supply and pH

description: Ecological interactions and abiotic stress factors may significantly affect species sensitivities to toxicants and these are not incorporated in standard single species tests. This study tests the hypothesis if a model, calibrated solely on single species data, can explain abiotic stress factors in a two-species microcosm, a test applied to the effects of nutritional stress (phosphorus (P)-limitation) on zinc (Zn) toxicity to <i>Daphnia magna</i>. A population model was developed based on P- and Zn-dependent algal and daphnid growth. Two separate two-species (phytoplankton <i>Pseudokirchneriella subcapitata</i> and consumer <i>D. magna</i>) microcosm experiments with P×Zn factorial combinations and a different pH (7.3 and 7.8) were set up to validate the model. The 21-day daphnid population size was considerably reduced by increased Zn and by decreased P supply with a significant (p&lt;0.001) interaction among both factors. The observed median effective concentration (EC50) of Zn on <i>D. magna</i> population size varied 12-fold (25 to 310 µg Zn L-1), with the lowest EC50’s found at the highest pH and high P treatments. For both experiments, Zn toxicity to <i>D. magna</i> was correctly predicted within a factor of two for EC50-values and are explained by the model through: (1) a higher phytoplankton Zn sensitivity at higher pH, affecting food supply to <i>D. magna</i> and (2) an increased algal P-content at higher Zn, offering a nutritional benefit to daphnids that counteracts direct Zn toxicity under P-limitation. This study illustrated that indirect effects of Zn via producer-consumer relationships can outweigh the direct toxic effects, and that models calibrated solely on single species test data can help with interpreting these results in two-species systems.
DOI: 10.6084/m9.figshare.6283046
title: Enabling appropriate personnel skill-mix for progressive realization of equitable access to assistive technology

description: <b>Background and Methods:</b> This paper reviews the current capacity of personnel in enabling access to assistive technology (AT) as well as the systems and processes within which they work, and was reviewed, discussed, and refined during and following the Global Research, Innovation, and Education in Assistive Technology (GREAT) Summit. <b>Findings:</b> Key concepts addressed include a person-centred team approach; sustainability indicators to monitor, measure, and respond to needs for service design and delivery; education, research, and training for competent practice, using the six rehab-workforce challenges framework; and credentialing frameworks. We propose development of a competence framework and associated education and training programs, and development and implementation of a certification framework for AT personnel. <b>Conclusions:</b> There is a resolve to address the challenges faced by People globally to access assistive technology. Context specific needs assessment is required to understand the AT Personnel landscape, to shape and strengthen credentialing frameworks through competencies and certification, acknowledging both general and specific skill mix requirements.Implications for RehabilitationPersonnel in assistive technology (AT) provision should be trained using a person-centred team approach, which emphasizes appropriate skill-mix to address multiple needs within the community.Sustainability indicators should be used which allow personnel to monitor, measure and respond to needs for service design and delivery.A competence framework with associated education and training program, coupled with the development and implementation of a certification framework for AT personnel needs, will promote quality in AT personnel training globally. Personnel in assistive technology (AT) provision should be trained using a person-centred team approach, which emphasizes appropriate skill-mix to address multiple needs within the community. Sustainability indicators should be used which allow personnel to monitor, measure and respond to needs for service design and delivery. A competence framework with associated education and training program, coupled with the development and implementation of a certification framework for AT personnel needs, will promote quality in AT personnel training globally.
DOI: 10.6084/m9.figshare.6283046.v1
title: Enabling appropriate personnel skill-mix for progressive realization of equitable access to assistive technology

description: <b>Background and Methods:</b> This paper reviews the current capacity of personnel in enabling access to assistive technology (AT) as well as the systems and processes within which they work, and was reviewed, discussed, and refined during and following the Global Research, Innovation, and Education in Assistive Technology (GREAT) Summit. <b>Findings:</b> Key concepts addressed include a person-centred team approach; sustainability indicators to monitor, measure, and respond to needs for service design and delivery; education, research, and training for competent practice, using the six rehab-workforce challenges framework; and credentialing frameworks. We propose development of a competence framework and associated education and training programs, and development and implementation of a certification framework for AT personnel. <b>Conclusions:</b> There is a resolve to address the challenges faced by People globally to access assistive technology. Context specific needs assessment is required to understand the AT Personnel landscape, to shape and strengthen credentialing frameworks through competencies and certification, acknowledging both general and specific skill mix requirements.Implications for RehabilitationPersonnel in assistive technology (AT) provision should be trained using a person-centred team approach, which emphasizes appropriate skill-mix to address multiple needs within the community.Sustainability indicators should be used which allow personnel to monitor, measure and respond to needs for service design and delivery.A competence framework with associated education and training program, coupled with the development and implementation of a certification framework for AT personnel needs, will promote quality in AT personnel training globally. Personnel in assistive technology (AT) provision should be trained using a person-centred team approach, which emphasizes appropriate skill-mix to address multiple needs within the community. Sustainability indicators should be used which allow personnel to monitor, measure and respond to needs for service design and delivery. A competence framework with associated education and training program, coupled with the development and implementation of a certification framework for AT personnel needs, will promote quality in AT personnel training globally.
DOI: 10.6084/m9.figshare.6283037
title: General Framework for Equivalence Testing over a Range of Linear Outcomes with CMC Applications

description: As per regulatory guidance, it is mandatory to demonstrate comparability before and after a change is made to an analytical method for commercial lot release or manufacturing process in the area of Chemistry, Manufacturing, and Controls. The change may include transfer assay or manufacturing process to a different location. Use of statistical methods to assess comparability before and after the change across the range of interest is a regulatory requirement. Regardless of the types of the changes, comparability is often demonstrated using analytical data collected pre- and post-change. For instance, assay transfer requires the demonstration of comparable assay performance over a range of expected responses. Although there are various methods used in practice or proposed in the published literature, there is no consensus on the best practice. For measurements that exhibit linearity in the outcome variable, a general statistical framework of equivalence testing is proposed. The equivalence test can be carried out either through Bayesian or frequentist analyses. The method is illustrated via several real-world examples.
DOI: 10.6084/m9.figshare.6283037.v1
title: General Framework for Equivalence Testing over a Range of Linear Outcomes with CMC Applications

description: As per regulatory guidance, it is mandatory to demonstrate comparability before and after a change is made to an analytical method for commercial lot release or manufacturing process in the area of Chemistry, Manufacturing, and Controls. The change may include transfer assay or manufacturing process to a different location. Use of statistical methods to assess comparability before and after the change across the range of interest is a regulatory requirement. Regardless of the types of the changes, comparability is often demonstrated using analytical data collected pre- and post-change. For instance, assay transfer requires the demonstration of comparable assay performance over a range of expected responses. Although there are various methods used in practice or proposed in the published literature, there is no consensus on the best practice. For measurements that exhibit linearity in the outcome variable, a general statistical framework of equivalence testing is proposed. The equivalence test can be carried out either through Bayesian or frequentist analyses. The method is illustrated via several real-world examples.
DOI: 10.6084/m9.figshare.6283025
title: Regression Analysis of Fold-Increase Endpoints Using a Distributional Approach for Paired Interval-Censored Antibody Data

description: Biopharmaceutical research often uses a binary “fold-increase” response variable defined by the ratio of a pair of interval-censored measurements taken at baseline and end-of-study. Conventional practice ignores the interval-censoring nature of the data. Moreover, conventional practice dictates that the possible choices for cut-off to define the response must follow a geometric sequence. A novel method based on the “distributional approach” was proposed for the analysis of such paired measurements in a randomized trial context. The degree of fold-increase above which a response is defined can be chosen according to scientific rationale instead of being limited to a geometric sequence. The risk ratio is then estimated for comparison between trial arms. We extend the method to allow for adjustment for baseline covariates in both randomized trial and cohort study settings. The treatment effect is obtained by integrating over the covariate distribution. In the presence of heterogeneity, estimators of the population treatment effect and the average treatment effect are proposed and their performances are evaluated by simulation studies. We apply this method to analyze antibody data measured by the hemagglutination inhibition assay in an influenza study. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.6283025.v1
title: Regression analysis of fold-increase endpoints using a distributional approach for paired interval-censored antibody data

description: Biopharmaceutical research often uses a binary “fold-increase” response variable defined by the ratio of a pair of interval-censored measurements taken at baseline and end-of-study. Conventional practice ignores the interval-censoring nature of the data. Moreover, conventional practice dictates that the possible choices for cut-off to define the response must follow a geometric sequence. A novel method based on the “distributional approach” was proposed for the analysis of such paired measurements in a randomized trial context. The degree of fold-increase above which a response is defined can be chosen according to scientific rationale instead of being limited to a geometric sequence. The risk ratio is then estimated for comparison between trial arms. We extend the method to allow for adjustment for baseline covariates in both randomized trial and cohort study settings. The treatment effect is obtained by integrating over the covariate distribution. In the presence of heterogeneity, estimators of the population treatment effect and the average treatment effect are proposed and their performances are evaluated by simulation studies. We apply this method to analyze antibody data measured by the haemagglutination inhibition assay in an influenza study.
DOI: 10.6084/m9.figshare.6283025.v3
title: Regression Analysis of Fold-Increase Endpoints Using a Distributional Approach for Paired Interval-Censored Antibody Data

description: Biopharmaceutical research often uses a binary “fold-increase” response variable defined by the ratio of a pair of interval-censored measurements taken at baseline and end-of-study. Conventional practice ignores the interval-censoring nature of the data. Moreover, conventional practice dictates that the possible choices for cut-off to define the response must follow a geometric sequence. A novel method based on the “distributional approach” was proposed for the analysis of such paired measurements in a randomized trial context. The degree of fold-increase above which a response is defined can be chosen according to scientific rationale instead of being limited to a geometric sequence. The risk ratio is then estimated for comparison between trial arms. We extend the method to allow for adjustment for baseline covariates in both randomized trial and cohort study settings. The treatment effect is obtained by integrating over the covariate distribution. In the presence of heterogeneity, estimators of the population treatment effect and the average treatment effect are proposed and their performances are evaluated by simulation studies. We apply this method to analyze antibody data measured by the hemagglutination inhibition assay in an influenza study. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.6283025.v2
title: Regression Analysis of Fold-Increase Endpoints Using a Distributional Approach for Paired Interval-Censored Antibody Data

description: Biopharmaceutical research often uses a binary “fold-increase” response variable defined by the ratio of a pair of interval-censored measurements taken at baseline and end-of-study. Conventional practice ignores the interval-censoring nature of the data. Moreover, conventional practice dictates that the possible choices for cut-off to define the response must follow a geometric sequence. A novel method based on the “distributional approach” was proposed for the analysis of such paired measurements in a randomized trial context. The degree of fold-increase above which a response is defined can be chosen according to scientific rationale instead of being limited to a geometric sequence. The risk ratio is then estimated for comparison between trial arms. We extend the method to allow for adjustment for baseline covariates in both randomized trial and cohort study settings. The treatment effect is obtained by integrating over the covariate distribution. In the presence of heterogeneity, estimators of the population treatment effect and the average treatment effect are proposed and their performances are evaluated by simulation studies. We apply this method to analyze antibody data measured by the hemagglutination inhibition assay in an influenza study. Supplementary materials for this article are available online.