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Article ; Online: Phylogenetic Analysis That Models Compositional Heterogeneity over the Tree.

Foster, Peter G

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2569, Page(s) 119–135

Abstract: Molecular sequences in a phylogenetic analysis can differ in composition, and that shows that the process of evolution can change over time. However, models of evolution in common use are homogeneous over the tree, and if used in a phylogenetic analysis ... ...

Abstract	Molecular sequences in a phylogenetic analysis can differ in composition, and that shows that the process of evolution can change over time. However, models of evolution in common use are homogeneous over the tree, and if used in a phylogenetic analysis with compositionally tree-heterogeneous datasets these models can recover incorrect trees. The NDCH or Node-Discrete Compositional Heterogeneity model is able to model such data by accommodating differences in composition over the tree. Usage, problems, and limitations of this model are discussed, and a modification, the NDCH2 model, is described that can ameliorate some of these problems and limitations. Using these models can greatly increase the fit of the model to the data and can find better tree topologies. These models and various statistical tests are illustrated using a bacterial SSU rRNA dataset. These models are implemented in the software P4, and files for the analyses described here are made available.
MeSH term(s)	Bayes Theorem ; Evolution, Molecular ; Models, Genetic ; Phylogeny
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2691-7_6
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Article ; Online: A Gaussian copula joint model for longitudinal and time-to-event data with random effects

Zhang, Zili / Charalambous, Christiana / Foster, Peter

Computational Statistics and Data Analysis. 2023 May, v. 181 p.107685-

2023

Abstract: Longitudinal and survival sub-models are two building blocks for joint modelling of longitudinal and time-to-event data. Extensive research indicates separate analysis of these two processes could result in biased outputs due to their associations. ... ...

Abstract	Longitudinal and survival sub-models are two building blocks for joint modelling of longitudinal and time-to-event data. Extensive research indicates separate analysis of these two processes could result in biased outputs due to their associations. Conditional independence between measurements of biomarkers and event time process given latent classes or random effects is a conventional approach for characterising the association between the two sub-models while taking the heterogeneity among the population into account. However, this assumption is difficult to validate because of the unobservable latent variables. Thus a Gaussian copula joint model with random effects is proposed to accommodate the scenarios where the conditional independence assumption is questionable. The conventional joint model assuming conditional independence is a special case of the proposed model when the association parameters in the Gaussian copula shrink to zero. Simulation studies and real data application are carried out to evaluate the performance of the proposed model with different correlation structures. In addition, personalised dynamic predictions of survival probabilities are obtained based on the proposed model and comparisons are made to the predictions obtained under the conventional joint model.
Keywords	biomarkers ; data analysis ; models ; statistics ; Copula ; Conditional independence ; Dynamic prediction ; Joint modelling ; Longitudinal data ; Time-to-event data
Language	English
Dates of publication	2023-05
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	1478763-5
ISSN	0167-9473
ISSN	0167-9473
DOI	10.1016/j.csda.2022.107685
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Article ; Online: Data-specific substitution models improve protein-based phylogenetics.

Brazão, João M / Foster, Peter G / Cox, Cymon J

PeerJ

2023 Volume 11, Page(s) e15716

Abstract: Calculating amino-acid substitution models that are specific for individual protein data sets is often difficult due to the computational burden of estimating large numbers of rate parameters. In this study, we tested the computational efficiency and ... ...

Abstract	Calculating amino-acid substitution models that are specific for individual protein data sets is often difficult due to the computational burden of estimating large numbers of rate parameters. In this study, we tested the computational efficiency and accuracy of five methods used to estimate substitution models, namely Codeml, FastMG, IQ-TREE, P4 (maximum likelihood), and P4 (Bayesian inference). Data-specific substitution models were estimated from simulated alignments (with different lengths) that were generated from a known simulation model and simulation tree. Each of the resulting data-specific substitution models was used to calculate the maximum likelihood score of the simulation tree and simulated data that was used to calculate the model, and compared with the maximum likelihood scores of the known simulation model and simulation tree on the same simulated data. Additionally, the commonly-used empirical models, cpREV and WAG, were assessed similarly. Data-specific models performed better than the empirical models, which under-fitted the simulated alignments, had the highest difference to the simulation model maximum-likelihood score, clustered further from the simulation model in principal component analysis ordination, and inferred less accurate trees. Data-specific models and the simulation model shared statistically indistinguishable maximum-likelihood scores, indicating that the five methods were reasonably accurate at estimating substitution models by this measure. Nevertheless, tree statistics showed differences between optimal maximum likelihood trees. Unlike other model estimating methods, trees inferred using data-specific models generated with IQ-TREE and P4 (maximum likelihood) were not significantly different from the trees derived from the simulation model in each analysis, indicating that these two methods alone were the most accurate at estimating data-specific models. To show the benefits of using data-specific protein models several published data sets were reanalysed using IQ-TREE-estimated models. These newly estimated models were a better fit to the data than the empirical models that were used by the original authors, often inferred longer trees, and resulted in different tree topologies in more than half of the re-analysed data sets. The results of this study show that software availability and high computation burden are not limitations to generating better-fitting data-specific amino-acid substitution models for phylogenetic analyses.
MeSH term(s)	Amino Acid Substitution ; Bayes Theorem ; Computer Simulation ; Models, Genetic ; Phylogeny ; Proteins/genetics ; Classification/methods
Chemical Substances	Proteins
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.15716
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Article ; Online: Microscopic interactions control a structural transition in active mixtures of microtubules and molecular motors.

Najma, Bibi / Wei, Wei-Shao / Baskaran, Aparna / Foster, Peter J / Duclos, Guillaume

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 2, Page(s) e2300174121

Abstract: Microtubules and molecular motors are essential components of the cellular cytoskeleton, driving fundamental processes in vivo, including chromosome segregation and cargo transport. When reconstituted in vitro, these cytoskeletal proteins serve as energy- ...

Abstract	Microtubules and molecular motors are essential components of the cellular cytoskeleton, driving fundamental processes in vivo, including chromosome segregation and cargo transport. When reconstituted in vitro, these cytoskeletal proteins serve as energy-consuming building blocks to study the self-organization of active matter. Cytoskeletal active gels display rich emergent dynamics, including extensile flows, locally contractile asters, and bulk contraction. However, it is unclear how the protein-protein interaction kinetics set their contractile or extensile nature. Here, we explore the origin of the transition from extensile bundles to contractile asters in a minimal reconstituted system composed of stabilized microtubules, depletant, adenosine 5'-triphosphate (ATP), and clusters of kinesin-1 motors. We show that the microtubule-binding and unbinding kinetics of highly processive motor clusters set their ability to end-accumulate, which can drive polarity sorting of the microtubules and aster formation. We further demonstrate that the microscopic time scale of end-accumulation sets the emergent time scale of aster formation. Finally, we show that biochemical regulation is insufficient to fully explain the transition as generic aligning interactions through depletion, cross-linking, or excluded volume interactions can drive bundle formation despite end-accumulating motors. The extensile-to-contractile transition is well captured by a simple self-assembly model where nematic and polar aligning interactions compete to form either bundles or asters. Starting from a five-dimensional organization phase space, we identify a single control parameter given by the ratio of the different component concentrations that dictates the material-scale organization. Overall, this work shows that the interplay of biochemical and mechanical tuning at the microscopic level controls the robust self-organization of active cytoskeletal materials.
MeSH term(s)	Microtubules/metabolism ; Cytoskeleton/metabolism ; Kinesins/metabolism ; Cell Movement ; Chromosome Segregation
Chemical Substances	Kinesins (EC 3.6.4.4)
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2300174121
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Article: Joint modelling of longitudinal measurements and survival times via a multivariate copula approach.

Zhang, Zili / Charalambous, Christiana / Foster, Peter

Journal of applied statistics

2022 Volume 50, Issue 13, Page(s) 2739–2759

Abstract: Joint modelling of longitudinal and time-to-event data is usually described by a joint model which uses shared or correlated latent effects to capture associations between the two processes. Under this framework, the joint distribution of the two ... ...

Abstract	Joint modelling of longitudinal and time-to-event data is usually described by a joint model which uses shared or correlated latent effects to capture associations between the two processes. Under this framework, the joint distribution of the two processes can be derived straightforwardly by assuming conditional independence given the random effects. Alternative approaches to induce interdependency into sub-models have also been considered in the literature and one such approach is using copulas to introduce non-linear correlation between the marginal distributions of the longitudinal and time-to-event processes. The multivariate Gaussian copula joint model has been proposed in the literature to fit joint data by applying a Monte Carlo expectation-maximisation algorithm. In this paper, we propose an exact likelihood estimation approach to replace the more computationally expensive Monte Carlo expectation-maximisation algorithm and we consider results based on using both the multivariate Gaussian and
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1476802-1
ISSN	1360-0532 ; 0266-4763
ISSN (online)	1360-0532
ISSN	0266-4763
DOI	10.1080/02664763.2022.2081965
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Article ; Online: A Physiologist's War: Captain T. Graham Brown RAMC (1915-1919).

Foster, Peter

Journal of the history of the neurosciences

2015 Volume 24, Issue 4, Page(s) 361–370

Abstract: During the five years before the outbreak of the First World War, Thomas Graham Brown (1882-1965) conducted research into the control of locomotion that gained him a deserved and long-lasting reputation as a neuroscientist and, in 1927, was recognized by ...

Abstract	During the five years before the outbreak of the First World War, Thomas Graham Brown (1882-1965) conducted research into the control of locomotion that gained him a deserved and long-lasting reputation as a neuroscientist and, in 1927, was recognized by election to the Fellowship of the Royal Society. In 1915, with the First World War raging, he agonized about continuing his research or joining the Royal Army Medical Corps (RAMC). Told by his father to seek a commission, he served two and half years in Macedonia with the British Salonika Force. Whilst in Greece, he kept a daily diary. The entries from June 1916 to May 1917 are extant. They are unpublished and provide the background to the narrative to follow. Casualties with traumatic injury to the brain and spinal cord afforded him the opportunity to carry out careful observations, particularly concerning sensory localization, which resulted in novel findings and his observations on shell shock led to him being called as an expert witness to the national inquiry into the nature and treatment of the condition. In 1920, Graham Brown was appointed to the Chair of Physiology in Cardiff, which he held until 1947.
MeSH term(s)	Biomedical Research ; Brain Injuries/history ; Combat Disorders/history ; History, 20th Century ; Humans ; Military Medicine/history ; Military Personnel/history ; Physiology/history ; United Kingdom ; World War I
Language	English
Publishing date	2015
Publishing country	England
Document type	Biography ; Historical Article ; Journal Article
ZDB-ID	1233549-6
ISSN	1744-5213 ; 0964-704X
ISSN (online)	1744-5213
ISSN	0964-704X
DOI	10.1080/0964704X.2015.1016289
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Book ; Online: Digital identity architectures

Mole, Callum / Chalstrey, Ed / Foster, Peter / Hobson, Tim

comparing goals and vulnerabilities

2023

Abstract: Digital identity systems have the promise of efficiently facilitating access to services for a nation's citizens while increasing security and convenience. There are many possible system architectures, each with strengths and weaknesses that should be ... ...

Abstract	Digital identity systems have the promise of efficiently facilitating access to services for a nation's citizens while increasing security and convenience. There are many possible system architectures, each with strengths and weaknesses that should be carefully considered. This report first establishes a set of goals and vulnerabilities faced by any identity system, then evaluates the trade-offs of common digital identity architectures, principally comparing centralised and decentralised systems.
Keywords	Computer Science - Cryptography and Security
Publishing date	2023-02-20
Publishing country	us
Document type	Book ; Online
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Article: The manufacture of blood plasma products in Scotland: a brief history.

Foster, Peter R

Scottish medical journal

2016 Volume 61, Issue 1, Page(s) 34–41

Abstract: A number of essential clinical products are derived from human blood plasma, including immunoglobulin products for the treatment of infections and disorders of immunity; albumin for protein and fluid replacement and coagulation factors for the treatment ... ...

Abstract	A number of essential clinical products are derived from human blood plasma, including immunoglobulin products for the treatment of infections and disorders of immunity; albumin for protein and fluid replacement and coagulation factors for the treatment of haemophilia and other disorders of haemostasis. For many years, these protein pharmaceuticals were manufactured by the Scottish National Blood Transfusion Service (SNBTS) at its Scottish Protein Fractionation Centre (PFC) in Edinburgh, a contribution which ended with the closure of the PFC in 2008. The origins and development of plasma fractionation in Scotland are summarised in this article, as well as issues which contributed to the closure of the PFC.
MeSH term(s)	Cell Fractionation/history ; Cell Fractionation/methods ; Commerce/history ; Commerce/methods ; Factor VIII/history ; History, 20th Century ; History, 21st Century ; Humans ; Immunoglobulins/history ; Plasma ; Scotland
Chemical Substances	Immunoglobulins ; Factor VIII (9001-27-8)
Language	English
Publishing date	2016-02
Publishing country	Scotland
Document type	Historical Article ; Journal Article
ZDB-ID	414085-0
ISSN	2045-6441 ; 0036-9330
ISSN (online)	2045-6441
ISSN	0036-9330
DOI	10.1177/0036933015619311
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Article ; Online: Correction to "Nonadiabatic Eigenfunctions Can Have Amplitude, Signed Conical Nodes, or Signed Higher Order Nodes at a Conical Intersection with Circular Symmetry".

Foster, Peter W / Jonas, David M

The journal of physical chemistry. A

2019 Volume 123, Issue 6, Page(s) 1273

Language	English
Publishing date	2019-02-04
Publishing country	United States
Document type	Journal Article ; Published Erratum
ISSN	1520-5215
ISSN (online)	1520-5215
DOI	10.1021/acs.jpca.9b00380
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Article: Rheology of starch dispersions at high temperatures

Ahuja, Amit / Lee, Reginald / Latshaw, Alina / Foster, Peter

Journal of texture studies. 2020 Aug., v. 51, no. 4

2020

Abstract: In the food industry, many food products experience extreme processing conditions of high temperature and high shear stresses. The measurements of sample behavior for water‐based formulations above 100°C is extremely challenging due to changes in ... ...

Abstract	In the food industry, many food products experience extreme processing conditions of high temperature and high shear stresses. The measurements of sample behavior for water‐based formulations above 100°C is extremely challenging due to changes in material composition from the boiling of volatile ingredients. We have developed a high‐sensitivity, pressurized starch pasting cell (up to 5 bar) which utilizes a design free of mechanical bearings and seals, resulting in an order‐of‐magnitude improvement in torque sensitivity (1 μN.m in oscillatory and 10 μN.m in shear flows) compared to traditional pressure cells. A pressurized atmosphere in the cell suppresses boiling of the volatile components, allowing the characterization of the structure–property relationships of the sample over a range of testing conditions (−5 to 150°C) which simulate industrial processing and storage conditions. This cell is employed to investigate the pasting properties of a commercial starch dispersed in water. In situ gelatinization of starch dispersions of varying starch particle weight fractions (ϕ) subjected to a high temperature (120°C) at elevated pressure and at a fixed shear rate is studied. A phase transition, from an initial flowable starch slurry to a paste, takes place during which the viscosity evolves by several orders of magnitude. Typical parameters associated with the viscosity evolution during gelatinization such as onset temperature, peak temperature, and peak viscosity are analyzed to probe the impact of high temperature on the gelation process and the rheological properties of the final starch paste. Furthermore, yield stresses of the final paste, measured at 120°C, are examined for varying ϕ through traditional rheological methods such as flow ramps, oscillatory shear, and stress growth, demonstrating the capabilities of this cell for studies of steady shear and nonlinear viscoelastic behavior of the starch pastes. The yield stress values are found to be in good agreement when comparing various testing methods. Yield stresses range from 0.25 to 6.5 Pa for ϕ between 0.05 and 0.15, with 0.05 being the minimum starch weight fraction for which there is any measurable yield stress. The yield stress and the paste viscosity both scale with starch particle weight fraction as (ϕ − ϕc) ᵐ, where ϕc = 0.04 as no yield stress is observed for ϕ ≤ 0.04. The exponent, m, for yield stress is found to be in the range of 1.15–1.4 depending on the analytical method used and the definition of yield stress while for peak and breakdown viscosities it is noted to be 1.6 and 1.1, respectively. The Herschel‐Bulkley model is found to fit the flow curves well. The starch pastes are found to exhibit shear‐thinning and significant thixotropic behavior.
Keywords	analytical methods ; food industry ; gelatinization ; gelation ; models ; rheology ; slurries ; starch ; temperature ; texture ; torque ; viscoelasticity ; viscosity
Language	English
Dates of publication	2020-08
Size	p. 575-584.
Publishing place	John Wiley & Sons, Inc.
Document type	Article
Note	NAL-AP-2-clean ; JOURNAL ARTICLE
ZDB-ID	242507-5
ISSN	1745-4603 ; 0022-4901
ISSN (online)	1745-4603
ISSN	0022-4901
DOI	10.1111/jtxs.12517
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