cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1266498.v1
title: Restricted Likelihood Ratio Tests for Functional Effects in the Functional Linear Model

description: The goal of our article is to provide a transparent, robust, and computationally feasible statistical approach for testing in the context of scalar-on-function linear regression models. Assuming linearity between response and predictors, we are interested in testing for the necessity of functional effects. Our methods are motivated by and applied to a large longitudinal study involving diffusion tensor imaging of intracranial white matter tracts in a susceptible cohort. In the context of this study, we conduct hypothesis tests that are motivated by anatomical knowledge and support recent findings regarding the relationship between cognitive impairment and white matter demyelination. R code and data are in the examples of refund::rlrt.pfr(). Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.1266499.v2
title: A Distribution-Free Multivariate Phase I Location Control Chart for Subgrouped Data from Elliptical Distributions

description: In quality control, a proper Phase I analysis is essential to the success of Phase II monitoring. A literature review reveals no distribution-free Phase I multivariate techniques in existence. This research develops a Phase I location control chart for multivariate elliptical processes. The resulting in-control reference sample can then be used to estimate the parameters for Phase II monitoring. Using Monte Carlo simulation, the proposed method is compared with the Hotelling's <i>T</i><sup>2</sup> Phase I chart. Although Hotelling's <i>T</i><sup>2</sup> chart is preferred when the data are multivariate normal, the proposed method is shown to perform significantly better under nonnormality. This article has supplementary material online.
DOI: 10.6084/m9.figshare.1266500.v2
title: Fast Parallel Kriging-Based Stepwise Uncertainty Reduction With Application to the Identification of an Excursion Set

description: Stepwise uncertainty reduction (SUR) strategies aim at constructing a sequence of points for evaluating a function <i>f</i> in such a way that the residual uncertainty about a quantity of interest progressively decreases to zero. Using such strategies in the framework of Gaussian process modeling has been shown to be efficient for estimating the volume of excursion of <i>f</i> above a fixed threshold. However, SUR strategies remain cumbersome to use in practice because of their high computational complexity, and the fact that they deliver a single point at each iteration. In this article we introduce several multipoint sampling criteria, allowing the selection of batches of points at which <i>f</i> can be evaluated in parallel. Such criteria are of particular interest when <i>f</i> is costly to evaluate and several CPUs are simultaneously available. We also manage to drastically reduce the computational cost of these strategies through the use of closed form formulas. We illustrate their performances in various numerical experiments, including a nuclear safety test case. Basic notions about kriging, auxiliary problems, complexity calculations, R code, and data are available online as supplementary materials.
DOI: 10.6084/m9.figshare.1266496
title: Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation

description: Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization signals (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been investigated. Here, we focused on the human proteome and found that numerous proteins, previously not identified in this context, are associated with Cdk1-dependent phosphorylation sites adjacent to their NLSs. Interestingly, these proteins are involved in key regulatory events of DNA repair, epigenetics, or RNA editing and splicing. This finding indicates that cell-cycle dependent events of genome editing and gene expression profiling may be controlled by nucleocytoplasmic trafficking. For in-depth investigations, we selected a number of these proteins and analyzed how point mutations, expected to modify the phosphorylation ability of the NLS segments, perturb nucleocytoplasmic localization. In each case, we found that mutations mimicking hyper-phosphorylation abolish nuclear import processes. To understand the mechanism underlying these phenomena, we performed a video microscopy-based kinetic analysis to obtain information on cell-cycle dynamics on a model protein, dUTPase. We show that the NLS-adjacent phosphorylation by Cdk1 of human dUTPase, an enzyme essential for genomic integrity, results in dynamic cell cycle-dependent distribution of the protein. Non-phosphorylatable mutants have drastically altered protein re-import characteristics into the nucleus during the G1 phase. Our results suggest a dynamic Cdk1-driven mechanism of regulation of the nuclear proteome composition during the cell cycle.
DOI: 10.6084/m9.figshare.1266499.v1
title: A Distribution-Free Multivariate Phase I Location Control Chart for Subgrouped Data from Elliptical Distributions

description: In quality control, a proper Phase I analysis is essential to the success of Phase II monitoring. A literature review reveals no distribution-free Phase I multivariate techniques in existence. This research develops a Phase I location control chart for multivariate elliptical processes. The resulting in-control reference sample can then be used to estimate the parameters for Phase II monitoring. Using Monte Carlo simulation, the proposed method is compared with the Hotelling's <i>T</i><sup>2</sup> Phase I chart. Although Hotelling's <i>T</i><sup>2</sup> chart is preferred when the data are multivariate normal, the proposed method is shown to perform significantly better under nonnormality. This article has supplementary material online.
DOI: 10.6084/m9.figshare.1279394.v247
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. In mouse and man, this molecule most likely gets its complementary footprints or anti-A reactivity from the early or first, genetically as-yet-undefined, trans-species <i>O</i>-linked GalNAc glycosylations of proteins and subsequent release from the transiently appearing glycopeptides that after depletion of the volatilely expressed “immature” transferase activity provide the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and might explain the anti-Tn cross-reactivities of anti-A specific immunoglobulins and their pronounced occurrence in the plasma of the human histo (blood) group O. In the C57BL/10 mouse, all of the tissues expressed the species-specific Forssman<i> </i>reactivity, and further A-like structures were identified in the male and female reproductive and endodermal organs by reaction with innate human anti-A antibody, while the murine anti-A was exclusively inhibited by syngeneic ovarian glycolipids. Moreover, the early ovarian tissue, which represents a last evolutionary and/or developmental location, showed a developmental polymorphism characterized by reactivity to the lectin from <i>Dolichos biflorus</i> and the agglutinin from <i>Helix pomatia </i>indicating the functional involvement of the <i>O</i>-GalNAc-determined mucin-type A-like, Tn and T (Thomsen-Friedenreich) epitopes that signify malignancy when metabolically accumulating and expressed in non-developmental tissues.
DOI: 10.6084/m9.figshare.1266500.v1
title: Fast Parallel Kriging-Based Stepwise Uncertainty Reduction With Application to the Identification of an Excursion Set

description: Stepwise uncertainty reduction (SUR) strategies aim at constructing a sequence of points for evaluating a function <i>f</i> in such a way that the residual uncertainty about a quantity of interest progressively decreases to zero. Using such strategies in the framework of Gaussian process modeling has been shown to be efficient for estimating the volume of excursion of <i>f</i> above a fixed threshold. However, SUR strategies remain cumbersome to use in practice because of their high computational complexity, and the fact that they deliver a single point at each iteration. In this article we introduce several multipoint sampling criteria, allowing the selection of batches of points at which <i>f</i> can be evaluated in parallel. Such criteria are of particular interest when <i>f</i> is costly to evaluate and several CPUs are simultaneously available. We also manage to drastically reduce the computational cost of these strategies through the use of closed form formulas. We illustrate their performances in various numerical experiments, including a nuclear safety test case. Basic notions about kriging, auxiliary problems, complexity calculations, R code, and data are available online as supplementary materials.
DOI: 10.6084/m9.figshare.1279394.v248
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. In mouse and man, this molecule most likely gets its complementary footprints or anti-A reactivity from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins, and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and its release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivities of anti-A specific immunoglobulins and their pronounced occurrence in the plasma of the human histo (blood) group O. In the C57BL/10 mouse, all of the tissues expressed the species-specific Forssman<i> </i>reactivity, and further A-like structures were identified in the male and female reproductive and endodermal organs by reaction with innate human anti-A antibody, while the murine anti-A was exclusively inhibited by syngeneic ovarian glycolipids. Moreover, the early ovarian tissue, which represents a last evolutionary and/or developmental location, showed a developmental polymorphism characterized by reactivity to the lectin from <i>Dolichos biflorus</i> and the agglutinin from <i>Helix pomatia </i>indicating the functional involvement of the <i>O</i>-GalNAc-determined mucin-type A-like, Tn and T (Thomsen-Friedenreich) epitopes that signify malignancy when metabolically accumulated and expressed in non-developmental tissues.
DOI: 10.6084/m9.figshare.1266496.v1
title: Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation

description: Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization signals (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been investigated. Here, we focused on the human proteome and found that numerous proteins, previously not identified in this context, are associated with Cdk1-dependent phosphorylation sites adjacent to their NLSs. Interestingly, these proteins are involved in key regulatory events of DNA repair, epigenetics, or RNA editing and splicing. This finding indicates that cell-cycle dependent events of genome editing and gene expression profiling may be controlled by nucleocytoplasmic trafficking. For in-depth investigations, we selected a number of these proteins and analyzed how point mutations, expected to modify the phosphorylation ability of the NLS segments, perturb nucleocytoplasmic localization. In each case, we found that mutations mimicking hyper-phosphorylation abolish nuclear import processes. To understand the mechanism underlying these phenomena, we performed a video microscopy-based kinetic analysis to obtain information on cell-cycle dynamics on a model protein, dUTPase. We show that the NLS-adjacent phosphorylation by Cdk1 of human dUTPase, an enzyme essential for genomic integrity, results in dynamic cell cycle-dependent distribution of the protein. Non-phosphorylatable mutants have drastically altered protein re-import characteristics into the nucleus during the G1 phase. Our results suggest a dynamic Cdk1-driven mechanism of regulation of the nuclear proteome composition during the cell cycle.
DOI: 10.6084/m9.figshare.1266496.v3
title: Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation

description: Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization signals (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been investigated. Here, we focused on the human proteome and found that numerous proteins, previously not identified in this context, are associated with Cdk1-dependent phosphorylation sites adjacent to their NLSs. Interestingly, these proteins are involved in key regulatory events of DNA repair, epigenetics, or RNA editing and splicing. This finding indicates that cell-cycle dependent events of genome editing and gene expression profiling may be controlled by nucleocytoplasmic trafficking. For in-depth investigations, we selected a number of these proteins and analyzed how point mutations, expected to modify the phosphorylation ability of the NLS segments, perturb nucleocytoplasmic localization. In each case, we found that mutations mimicking hyper-phosphorylation abolish nuclear import processes. To understand the mechanism underlying these phenomena, we performed a video microscopy-based kinetic analysis to obtain information on cell-cycle dynamics on a model protein, dUTPase. We show that the NLS-adjacent phosphorylation by Cdk1 of human dUTPase, an enzyme essential for genomic integrity, results in dynamic cell cycle-dependent distribution of the protein. Non-phosphorylatable mutants have drastically altered protein re-import characteristics into the nucleus during the G1 phase. Our results suggest a dynamic Cdk1-driven mechanism of regulation of the nuclear proteome composition during the cell cycle.
DOI: 10.6084/m9.figshare.1279394.v249
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. In mouse and man, this molecule most likely gets its complementary footprints or anti-A reactivity from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins, and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and its release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivities of anti-A specific immunoglobulins and their pronounced occurrence in the plasma of the human histo (blood) group O, in which phenotype-specific GalNAc glycosylation of plasma proteins does not occur. In the C57BL/10 mouse, all of the tissues expressed the species-specific Forssman<i> </i>reactivity, and further A-like structures were identified in the male and female reproductive and endodermal organs by reaction with innate human anti-A antibody, while the murine anti-A was exclusively inhibited by syngeneic ovarian glycolipids. Moreover, the early ovarian tissue, which represents a last evolutionary and/or developmental location, showed a developmental polymorphism characterized by reactivity to the lectin from <i>Dolichos biflorus</i> and the agglutinin from <i>Helix pomatia </i>indicating the functional involvement of the <i>O</i>-GalNAc-determined mucin-type A-like, Tn and T (Thomsen-Friedenreich) epitopes that signify malignancy when metabolically accumulated and expressed in non-developmental tissues.
DOI: 10.6084/m9.figshare.1266496.v2
title: Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation

description: Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization signals (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been investigated. Here, we focused on the human proteome and found that numerous proteins, previously not identified in this context, are associated with Cdk1-dependent phosphorylation sites adjacent to their NLSs. Interestingly, these proteins are involved in key regulatory events of DNA repair, epigenetics, or RNA editing and splicing. This finding indicates that cell-cycle dependent events of genome editing and gene expression profiling may be controlled by nucleocytoplasmic trafficking. For in-depth investigations, we selected a number of these proteins and analyzed how point mutations, expected to modify the phosphorylation ability of the NLS segments, perturb nucleocytoplasmic localization. In each case, we found that mutations mimicking hyper-phosphorylation abolish nuclear import processes. To understand the mechanism underlying these phenomena, we performed a video microscopy-based kinetic analysis to obtain information on cell-cycle dynamics on a model protein, dUTPase. We show that the NLS-adjacent phosphorylation by Cdk1 of human dUTPase, an enzyme essential for genomic integrity, results in dynamic cell cycle-dependent distribution of the protein. Non-phosphorylatable mutants have drastically altered protein re-import characteristics into the nucleus during the G1 phase. Our results suggest a dynamic Cdk1-driven mechanism of regulation of the nuclear proteome composition during the cell cycle.
DOI: 10.6084/m9.figshare.1279394.v250
title: Early ovariectomy reveals the germline encoding of the “natural” mammalian anti-A-reactive IgM reflecting developmental malignancy.

description: The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the spleen and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. In mouse and man, this anti-A-reactive molecule most likely gets its complementary footprint from the first, genetically as-yet-undefined trans-species <i>O</i>-linked glycosylation of proteins, and after depletion of the volatilely expressed “immature” <i>O</i>-GalNAc transferase activities and release from the transiently appearing glycopeptides, provides the A-reactive glycosidic sites. Consequently, these volatilely expressed non-somatic <i>O</i>-GalNAc-glycosylations of proteins, involving serine/threonine residues, are either identical or metabolically related with those of the mucin-type “aberrant” monosaccharide GalNAcα1-<i>O</i>-Ser/Thr-R or Tn antigen and explain the anti-Tn cross-reactivity of anti-A specific immunoglobulins and its pronounced occurrence in the plasma of the human histo (blood) group O, in which the species and A-allelic GalNAc glycosylation of plasma proteins does not occur and reduce the anti-Tn levels.