cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3085588.v2
title: Morphological Clustering of Cell Cultures Based on Size, Shape, and Texture Features

description: High content screening for drug discovery in cancer research relies increasingly on cell-based models, using microscopic imaging as a primary readout. In combination, microscopic imaging and cell culturing provide powerful tools for studying cancer-relevant cell biology in vitro. As a result, an enormous amount of complex biometric image data is generated that can be used for high throughput and high content analyses. We present a method for computationally efficient and flexible quantification of multicellular structures or tumor spheroids, conducted in a semi-unsupervised manner. Our phenotypic clustering approach is based on morphological features, in particular, on size and novel shape and texture features. It consists of multiple automated steps in which the information characterizing the most relevant morphological features is first extracted from the images, the dimension of the features is reduced, and finally, structures are clustered into biologically meaningful groups. Local central moments and local binary operators characterize the texture, whereas shape features are obtained by an alignment to elliptical and smooth reference shapes. Using simulation studies, we show that the cluster identification performs well and demonstrates good repeatability in the presence of random orientation, size, rescaling, and texture. We show how the method can be applied to an actual high-content imaging dataset to find an intuitive and flexible summary of high content screens, not achievable with existing tools. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.3085582.v2
title: Adaptive Designs for Two Candidate Primary Time-to-Event Endpoints

description: In clinical trials, the choice of an adequate primary endpoint is often difficult. Besides its clinical relevance, the endpoint must be measurable within reasonable time and must allow differentiating between the treatments. Often, the most relevant endpoint is ‘’time-to-death,” but if the overall survival prognosis is good, only a few deaths are observed during the study duration. A possible solution is to use surrogate endpoints instead. However, various examples from the literature demonstrate that surrogates do not always perform as intended. Sometimes, the surrogate effect is smaller than for the original endpoint, or the latter shows a higher effect than anticipated so using the surrogate is not reasonable. In this work, different adaptive design strategies for two candidate endpoints are proposed to solve these problems. The idea is to base the efficacy proof on the significance of at least one endpoint. At an interim analysis, both candidates are evaluated. If it is not possible to stop the study early, the sample size is recalculated based on the more promising endpoint. The new methods are illustrated by a clinical study example and compared in terms of power and sample size using Monte Carlo simulations. The software code is provided as supplementary material.
DOI: 10.6084/m9.figshare.3085582.v1
title: Adaptive Designs for two Candidate Primary Time-to-Event Endpoints

description: In clinical trials, the choice of an adequate primary endpoint is often difficult. Besides its clinical relevance, the endpoint must be measurable within reasonable time and must allow differentiating between the treatments. Often, the most relevant endpoint is ’time-to-death’, but if the overall survival prognosis is good, only a few deaths are observed during the study duration. A possible solution is to use surrogate endpoints instead. However, various examples from the literature demonstrate that surrogates do not always perform as intended. Sometimes, the surrogate effect is smaller than for the original endpoint, or the latter shows a higher effect than anticipated so using the surrogate is not reasonable. In this work, different adaptive design strategies for two candidate endpoints are proposed to solve these problems. The idea is to base the efficacy proof on the significance of at least one endpoint. At an interim analysis, both candidates are evaluated. If it is not possible to stop the study early, the sample size is recalculated based on the more promising endpoint. The new methods are illustrated by a clinical study example and compared in terms of power and sample size using Monte-Carlo simulations. The software code is provided as supplementary material.
DOI: 10.6084/m9.figshare.3085588.v1
title: Morphological Clustering of Cell Cultures Based on Size, Shape and Texture Features

description: High content screening for drug discovery in cancer research relies increasingly on cell-based models, using microscopic imaging as a primary readout. In combination, microscopic imaging and cell culturing provide powerful tools for studying cancer-relevant cell biology <i>in vitro</i>. As the result, an enormous amount of complex biometric image data is generated that can be utilized for high throughput and high content analyses. We present a method for computationally efficient and flexible quantification of multicellular structures or tumor spheroids, conducted in a semi-unsupervised manner. Our phenotypic clustering approach is based on morphological features, in particular, on size and novel shape and texture features. It consists of multiple automated steps in which the information characterizing the most relevant morphological features is first extracted from the images, the dimension of the features is reduced, and finally, structures are clustered into biologically meaningful groups. Local central moments and local binary operators characterize the texture, whereas shape features are obtained by an alignment to elliptical and smooth reference shapes. Using simulation studies, we show that the cluster identification performs well and demonstrates good repeatability in the presence of random orientation, size, re-scaling, and texture. We show how the method can be applied to an actual high-content imaging data set to find an intuitive and flexible summary of high content screens, not achievable with existing tools.
DOI: 10.6084/m9.figshare.3085546.v1
title: test.zip

description: test
DOI: 10.6084/m9.figshare.3085489
title: Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers

description: A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30 mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
DOI: 10.6084/m9.figshare.3085489.v2
title: Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers

description: A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30 mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
DOI: 10.6084/m9.figshare.3085489.v1
title: Bismuth Trichloride Mediated Cleavage of Phenolic Methoxymethyl Ethers

description: A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30 mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an eco-friendly bismuth reagent, ease of handling, low cost, operationally simple and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
DOI: 10.6084/m9.figshare.3085546.v2
title: missing_data_raw.zip

description: This archive contains data needed to reconstruct the missing data in Eurostat 1-year population structures and deaths data at NUTS-2 regions level for the period 2003-2013.<br><br>Germany (DE): DED4, DED5, 2003-2010, pop & deaths<br>Denmark (DK): DE01, DE02, DE03, DE 03, DE05, pop & deaths<br>Slovenia (SI): SI01,SI02, 2003-2004, pop
DOI: 10.6084/m9.figshare.3085426
title: Consensus signatures for LINCS L1000 perturbations

description: LINCS L1000 measures the transcriptional response to perturbations. However, a single perturbagen is often assessed at several conditions, such as dosages, timepoints, or cell lines. A consensus signature meta-analyzes several input signatures and condenses them into a single output signature.<br>We've computed consensus signatures for:<br>+ 1,170 DrugBank compounds+ 4,326 gene knockdowns+ 2,413 gene overexpressions+ 38,327 L1000 perturbations<br>Each signature contains dysregulation z-scores for 7,467 genes (978 measured and 6,489 inferred, see `genes.tsv`). The `consensi-{type}.tsv.bz2` files contain the perturbagen × gene matrix of z-scores. The `dysreg-{type}.tsv` files contain significantly dysregulated genes. The `dysreg-{type}-summary.tsv` files provide the counts of significantly up/down-regulated genes per perturbagen.<br>Our methods are available [on Thinklab](https://doi.org/10.15363/thinklab.d43#7). The [project GitHub repository](https://github.com/dhimmel/lincs) contains all of the datasets here besides `consensi-pert_id.tsv.bz2` due to its large file size.<br>If using these datasets, please attribute this figshare deposition and the LINCS L1000 project. Also please abide by the data release policy for the [NIH LINCS Program](http://www.lincsproject.org/data/data-release-policy/).<br>This is not an official LINCS L1000 repository. Users are warned that our modifications may have introduced errors or removed signal that was present the original data. We thank the L1000 team for posting their data and providing support including online office hours.
DOI: 10.6084/m9.figshare.3085405
title: Transcriptome landscape of <i>Lactococcus lactis</i> reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism

description: RNA sequencing has revolutionized genome-wide transcriptome analyses, and the identification of non-coding regulatory RNAs in bacteria has thus increased concurrently. Here we reveal the transcriptome map of the lactic acid bacterial paradigm <i>Lactococcus lactis</i> MG1363 by employing differential RNA sequencing (dRNA-seq) and a combination of manual and automated transcriptome mining. This resulted in a high-resolution genome annotation of <i>L. lactis</i> and the identification of 60 <i>cis</i>-encoded antisense RNAs (asRNAs), 186 <i>trans</i>-encoded putative regulatory RNAs (sRNAs) and 134 novel small ORFs. Based on the putative targets of asRNAs, a novel classification is proposed. Several transcription factor DNA binding motifs were identified in the promoter sequences of (a)sRNAs, providing insight in the interplay between lactococcal regulatory RNAs and transcription factors. The presence and lengths of 14 putative sRNAs were experimentally confirmed by differential Northern hybridization, including the abundant RNA 6S that is differentially expressed depending on the available carbon source. For another sRNA, LLMGnc_147, functional analysis revealed that it is involved in carbon uptake and metabolism. <i>L. lactis</i> contains 13% leaderless mRNAs (lmRNAs) that, from an analysis of overrepresentation in GO classes, seem predominantly involved in nucleotide metabolism and DNA/RNA binding. Moreover, an A-rich sequence motif immediately following the start codon was uncovered, which could provide novel insight in the translation of lmRNAs. Altogether, this first experimental genome-wide assessment of the transcriptome landscape of <i>L. lactis</i> and subsequent sRNA studies provide an extensive basis for the investigation of regulatory RNAs in <i>L. lactis</i> and related lactococcal species.
DOI: 10.6084/m9.figshare.3085405.v1
title: Transcriptome landscape of <i>Lactococcus lactis</i> reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism

description: RNA sequencing has revolutionized genome-wide transcriptome analyses, and the identification of non-coding regulatory RNAs in bacteria has thus increased concurrently. Here we reveal the transcriptome map of the lactic acid bacterial paradigm <i>Lactococcus lactis</i> MG1363 by employing differential RNA sequencing (dRNA-seq) and a combination of manual and automated transcriptome mining. This resulted in a high-resolution genome annotation of <i>L. lactis</i> and the identification of 60 <i>cis</i>-encoded antisense RNAs (asRNAs), 186 <i>trans</i>-encoded putative regulatory RNAs (sRNAs) and 134 novel small ORFs. Based on the putative targets of asRNAs, a novel classification is proposed. Several transcription factor DNA binding motifs were identified in the promoter sequences of (a)sRNAs, providing insight in the interplay between lactococcal regulatory RNAs and transcription factors. The presence and lengths of 14 putative sRNAs were experimentally confirmed by differential Northern hybridization, including the abundant RNA 6S that is differentially expressed depending on the available carbon source. For another sRNA, LLMGnc_147, functional analysis revealed that it is involved in carbon uptake and metabolism. <i>L. lactis</i> contains 13% leaderless mRNAs (lmRNAs) that, from an analysis of overrepresentation in GO classes, seem predominantly involved in nucleotide metabolism and DNA/RNA binding. Moreover, an A-rich sequence motif immediately following the start codon was uncovered, which could provide novel insight in the translation of lmRNAs. Altogether, this first experimental genome-wide assessment of the transcriptome landscape of <i>L. lactis</i> and subsequent sRNA studies provide an extensive basis for the investigation of regulatory RNAs in <i>L. lactis</i> and related lactococcal species.
DOI: 10.6084/m9.figshare.3085396
title: Transmigration characteristics of breast cancer and melanoma cells through the brain endothelium: Role of Rac and PI3K

description: Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer.
DOI: 10.6084/m9.figshare.3085396.v1
title: Transmigration characteristics of breast cancer and melanoma cells through the brain endothelium: Role of Rac and PI3K

description: Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer.
DOI: 10.6084/m9.figshare.3085462.v1
title: Data integration in proteomics

description: Keynote lecture for the Introduction to Integrative Omics course at the EMBL-EBI on 8 March 2016. Two use-cases are presented: (1) Integration of mass spectrometry based proteomics and RNA-Seq transcriptomics - caveats and mapping; (2) Combining exerimental spatial proteomics and third-pary data using transfer learning to improve inference of sub-cellular localisation of proteins.<br><br>
DOI: 10.6084/m9.figshare.3085462.v2
title: Data integration in proteomics

description: Keynote lecture for the Introduction to Integrative Omics course at the EMBL-EBI on 8 March 2016. Two use-cases are presented: (1) Integration of mass spectrometry based proteomics and RNA-Seq transcriptomics - caveats and mapping; (2) Combining exerimental spatial proteomics and third-pary data using transfer learning to improve inference of sub-cellular localisation of proteins.<br><br>
DOI: 10.6084/m9.figshare.3085285
title: data.xls

description: There were 203 young women (under 40-year old) diagnosed with invasive breast cancer in the First Affiliated Hospital of Wenzhou Medical University among 2008 to 2012.
DOI: 10.6084/m9.figshare.3085462.v3
title: Data integration in proteomics

description: Keynote lecture for the Introduction to Integrative Omics course at the EMBL-EBI on 8 March 2016. Two use-cases are presented: (1) Integration of mass spectrometry based proteomics and RNA-Seq transcriptomics - caveats and mapping; (2) Combining exerimental spatial proteomics and third-pary data using transfer learning to improve inference of sub-cellular localisation of proteins.<br><br>
DOI: 10.6084/m9.figshare.3085285.v1
title: data.xls

description: There were 203 young women (under 40-year old) diagnosed with invasive breast cancer in the First Affiliated Hospital of Wenzhou Medical University among 2008 to 2012.
DOI: 10.6084/m9.figshare.3085210.v1
title: missing_data_raw.zip

description: This archive contains data needed to reconstruct the missing data in Eurostat 1-year population structures and deaths data at NUTS-2 regions level for the period 2003-2013.<br><br>Germany (DE): DED4, DED5, 2003-2010, pop & deaths<br>Denmark (DK): DE01, DE02, DE03, DE 03, DE05, pop & deaths<br>Slovenia (SI): SI01,SI02, 2003-2004, pop<br><br>
DOI: 10.6084/m9.figshare.3085162.v2
title: The ASA's statement on p-values: context, process, and purpose

description: The ASA's statement on p-values: context, process, and purpose
DOI: 10.5281/zenodo.3931227
title: Photoisomeric MTV data for Poiseuille flow with CCVJ

description: The data refers to experiments with the molecular rotor 9-(2-Carboxy-2-cyanovinyl) (CCVJ) in ethylene glycole and analysis its suitability for the use in photoisomeric Molecular Tagging Velocimetry (MTV). The data is structure in zip packages for the different experiments. The packages are structured in accordance with the published article, where detailed information on the experimental setup can be found. Each zip package contains a separate README with detailed information on the data structure. The six packages contain: Diffusion coefficient: Measurement for the determination of the diffusion coefficient High Time Difference: Measurements of a Poiseuillle flow with the maximal duration up to 720s Methyl-beta-CD: Flow Measurements with different concentration of Methyl-beta-cyclodextrin Poiseuille Flow: Measurements of a Poiseuille flow up to 200s Recovery Time Constant: Measurements for the determination of the recovery time constant τ<sub>rec</sub> Tagging Time Constant: Measurements for the determination of the tagging time constant τ<sub>tag</sub>
DOI: 10.6084/m9.figshare.3085210.v2
title: missing_data_raw.zip

description: This archive contains data needed to reconstruct the missing data in Eurostat 1-year population structures and deaths data at NUTS-2 regions level for the period 2003-2013.<br><br>Germany (DE): DED4, DED5, 2003-2010, pop & deaths<br>Denmark (DK): DE01, DE02, DE03, DE 03, DE05, pop & deaths<br>Slovenia (SI): SI01,SI02, 2003-2004, pop<br><br>
DOI: 10.6084/m9.figshare.3085162.v3
title: The ASA's statement on p-values: context, process, and purpose

description: The ASA's statement on p-values: context, process, and purpose
DOI: 10.6084/m9.figshare.3085210.v3
title: missing_data_raw.tar

description: This archive contains data needed to reconstruct the missing data in Eurostat 1-year population structures and deaths data at NUTS-2 regions level for the period 2003-2013.<br><br>Germany (DE): DED4, DED5, 2003-2010, pop & deaths<br>Denmark (DK): DE01, DE02, DE03, DE 03, DE05, pop & deaths<br>Slovenia (SI): SI01,SI02, 2003-2004, pop<br><br>
DOI: 10.6084/m9.figshare.3085210.v4
title: missing_data_raw.tar

description: This archive contains data needed to reconstruct the missing data in Eurostat 1-year population structures and deaths data at NUTS-2 regions level for the period 2003-2013.<br><br>Germany (DE): DED4, DED5, 2003-2010, pop & deaths<br>Denmark (DK): DE01, DE02, DE03, DE 03, DE05, pop & deaths<br>Slovenia (SI): SI01,SI02, 2003-2004, pop<br><br>
DOI: 10.6084/m9.figshare.3084970
title: Asymmetric frequency shift in advertisement calls of sympatric frogs

description: Character displacement is commonly observed when species occur in secondary contact zones and traits related to resource competition or reproduction diverge in sympatry. However, few studies have considered the factors determining and delimiting the direction of character evolution in this context. We studied displacement in advertisement calls in two species of hylid frogs from allopatric and sympatric populations, both of which call with similar frequencies but differ substantially in temporal parameters. We found asymmetrical character displacement in sympatry, as only <i>Scinax madeira </i>(but not <i>S. fuscomarginatus</i>) repeatedly showed displacement. Instead of diverging in already existing differences in temporal characters, <i>S. madeirae </i>showed character displacement for frequency-related characters. We explored possible reasons for this specific pattern concerning the displaced characters and tested if socio-functional constraints in specific call parameters are responsible for the shift of only spectral parameters in that species. Finally, we argue that the simultaneous action of ecological and reproductive character displacement, or alternatively, a short-term behavioral response for the same reason (avoidance of hybridization) could explain the pattern. The present study identifies a set of new hypotheses that will stimulate future research on mechanisms of mate recognition and behavioral responses.
DOI: 10.6084/m9.figshare.3085162.v4
title: The ASA's Statement on <i>p</i>-Values: Context, Process, and Purpose

description: The ASA's Statement on <i>p</i>-Values: Context, Process, and Purpose