School of Mathematics and Statistics - Research Publications
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ItemNo Preview AvailableHBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells(American Society for Microbiology, 2020-02-01)HBO1 (MYST2/KAT7) is essential for histone 3 lysine 14 acetylation (H3K14ac) but is dispensable for H4 acetylation and DNA replication in mouse tissues. In contrast, previous studies using small interfering RNA (siRNA) knockdown in human cell lines have suggested that HBO1 is essential for DNA replication. To determine if HBO1 has distinctly different roles in immortalized human cell lines and normal mouse cells, we performed siRNA knockdown of HBO1. In addition, we used CRISPR/Cas9 to generate 293T, MCF7, and HeLa cell lines lacking HBO1. Using both techniques, we show that HBO1 is essential for all H3K14ac in human cells and is unlikely to have a direct effect on H4 acetylation and only has minor effects on cell proliferation. Surprisingly, the loss of HBO1 and H3K14ac in HeLa cells led to the secondary loss of almost all H4 acetylation after 4 weeks. Thus, HBO1 is dispensable for DNA replication and cell proliferation in immortalized human cells. However, while cell proliferation proceeded without HBO1 and H3K14ac, HBO1 gene deletion led to profound changes in cell adhesion, particularly in 293T cells. Consistent with this phenotype, the loss of HBO1 in both 293T and HeLa principally affected genes mediating cell adhesion, with comparatively minor effects on other cellular processes.
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ItemEvaluation of blood parameters by linear discriminant models for the detection of testosterone administration(WILEY, 2021-07)The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Multiple recent studies have suggested that monitoring of blood parameters may provide enhanced detectability of exogenous testosterone administration. Transdermal and intramuscular testosterone administration studies were carried out in 15 subjects, and the effect on blood steroidal levels, hematological parameters, and gonadotropins was evaluated. Serum testosterone and dihydrotestosterone levels increased while gonadotropin levels were suppressed after administration. A modest increase in reticulocytes was also observed. The blood parameters that were responsive to the administrations were combined into several linear discriminant models targeting both administration (on) and washout (off) phases. The models were effective in detecting the large dose intramuscular administration but were less successful in the detection of the lower dose transdermal application. The blood profiling models may provide complementary value but do not appear to be substantially more advantageous than longitudinal urinary profiling.
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ItemAsymptotics for the critical level and a strong invariance principle for high intensity shot noise fields( 2021-11-17)We study _ne properties of the convergence of a high intensity shot noise _eld towards the Gaussian _eld with the same covariance structure. In particular we (i) establish a strong invariance principle, i.e. a quantitative coupling between a high intensity shot noise _eld and the Gaussian limit such that they are uniformly close on large domains with high probability, and (ii) use this to derive an asymptotic expansion for the critical level above which the excursion sets of the shot noise _eld percolate.
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ItemInformation content of stepped wedge designs with unequal cluster-period sizes in linear mixed models: Informing incomplete designs.(Wiley, 2021-03-30)In practice, stepped wedge trials frequently include clusters of differing sizes. However, investigations into the theoretical aspects of stepped wedge designs have, until recently, typically assumed equal numbers of subjects in each cluster and in each period. The information content of the cluster-period cells, clusters, and periods of stepped wedge designs has previously been investigated assuming equal cluster-period sizes, and has shown that incomplete stepped wedge designs may be efficient alternatives to the full stepped wedge. How this changes when cluster-period sizes are not equal is unknown, and we investigate this here. Working within the linear mixed model framework, we show that the information contributed by design components (clusters, sequences, and periods) does depend on the sizes of each cluster-period. Using a particular trial that assessed the impact of an individual education intervention on log-length of stay in rehabilitation units, we demonstrate how strongly the efficiency of incomplete designs depends on which cells are excluded: smaller incomplete designs may be more powerful than alternative incomplete designs that include a greater total number of participants. This also serves to demonstrate how the pattern of information content can be used to inform a set of incomplete designs to be considered as alternatives to the complete stepped wedge design. Our theoretical results for the information content can be extended to a broad class of longitudinal (ie, multiple period) cluster randomized trial designs.
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ItemNo Preview AvailableInterdependence of Software and Progress of Mathematics in OR: Some Illustrative Cases and Challenges(Scientific Research Publishing, Inc., 2021)
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ItemNo Preview AvailableOff-lattice and parallel implementations of the pivot algorithm(IOP Publishing, 2021-12-09)Abstract The pivot algorithm is the most efficient known method for sampling polymer configurations for self-avoiding walks and related models. Here we introduce two recent improvements to an efficient binary tree implementation of the pivot algorithm: an extension to an off-lattice model, and a parallel implementation.
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ItemNo Preview AvailableDifferential operators mod p: analytic continuation and consequences(MATHEMATICAL SCIENCE PUBL, 2021)
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ItemNo Preview AvailableThe effect of object-scene associations upon representational similarity dissociates structured from image-based representations(Association for Research in Vision and Ophthalmology (ARVO), 2021-09-27)
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ItemNo Preview AvailableA field guide to cultivating computational biology(PUBLIC LIBRARY SCIENCE, 2021-10)Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.
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ItemNo Preview AvailableAN IRRATIONAL-SLOPE THOMPSON'S GROUP(UNIV AUTONOMA BARCELONA, 2021)