Models for pattern formation in somitogenesis: a marriage of cellular and molecular biology

Somitogenesis, the process by which a bilaterally symmetric pattern of cell aggregations is laid down in a cranio-caudal sequence in early vertebrate development, provides an excellent model study for the coupling of interactions at the molecular and cellular level. Here, we review some of the key experimental results and theoretical models related to this process. We extend a recent chemical pre-pattern model based on the cell cycle Journal of Theoretical Biology 207 (2000) 305-316, by including cell movement and show that the resultant model exhibits the correct spatio-temporal dynamics of cell aggregation. We also postulate a model to account for the recently observed spatio-temporal dynamics at the molecular level

A mathematical formulation for the cell-cycle model in somitogenesis: analysis, parameter constraints and numerical solutions

In this work we present an analysis, supported by numerical simulations, of the formulation of the cell-cycle model for somitogenesis proposed in Collier et al.(J. Theor. Biol. 207 (2000), 305–316). The analysis indicates that by introducing appropriate parameter constraints on model parameters the cell-cycle mechanism can indeed give rise to the periodic pattern of somites observed in normal embryos. The analysis also provides a greater understanding of the signalling process controlling somite formation and allows us to understand which parameters influence somite length

Timing and Reconstruction of the Most Recent Common Ancestor of the Subtype C Clade of Human Immunodeficiency Virus Type 1

Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 55% of HIV-1 infections worldwide. When this subtype first emerged is unknown. We have analyzed all available gag (p17 and p24) and env (C2-V3) subtype C sequences with known sampling dates, which ranged from 1983 to 2000. The majority of these sequences come from the Karonga District in Malawi and include some of the earliest known subtype C sequences. Linear regression analyses of sequence divergence estimates (with four different approaches)were plotted against sample year to estimate the year in which there was zero divergence from the reconstructed ancestral sequence. Here we suggest that the most recent common ancestor of subtype C appeared in the mid- to late 1960s. Sensitivity analyses, by which possible biases due to oversampling from one district were explored, gave very similar estimates

Toward Open Science at the European Scale: Geospatial Semantic Array Programming for Integrated Environmental Modelling

[Excerpt] Interfacing science and policy raises challenging issues when large spatial-scale (regional, continental, global) environmental problems need transdisciplinary integration within a context of modelling complexity and multiple sources of uncertainty. This is characteristic of science-based support for environmental policy at European scale, and key aspects have also long been investigated by European Commission transnational research. Approaches (either of computational science or of policy-making) suitable at a given domain-specific scale may not be appropriate for wide-scale transdisciplinary modelling for environment (WSTMe) and corresponding policy-making. In WSTMe, the characteristic heterogeneity of available spatial information and complexity of the required data-transformation modelling (D-TM) appeal for a paradigm shift in how computational science supports such peculiarly extensive integration processes. In particular, emerging wide-scale integration requirements of typical currently available domain-specific modelling strategies may include increased robustness and scalability along with enhanced transparency and reproducibility. This challenging shift toward open data and reproducible research (open science) is also strongly suggested by the potential - sometimes neglected - huge impact of cascading effects of errors within the impressively growing interconnection among domain-specific computational models and frameworks. Concise array-based mathematical formulation and implementation (with array programming tools) have proved helpful in supporting and mitigating the complexity of WSTMe when complemented with generalized modularization and terse array-oriented semantic constraints. This defines the paradigm of Semantic Array Programming (SemAP) where semantic transparency also implies free software use (although black-boxes - e.g. legacy code - might easily be semantically interfaced). A new approach for WSTMe has emerged by formalizing unorganized best practices and experience-driven informal patterns. The approach introduces a lightweight (non-intrusive) integration of SemAP and geospatial tools - called Geospatial Semantic Array Programming (GeoSemAP). GeoSemAP exploits the joint semantics provided by SemAP and geospatial tools to split a complex D-TM into logical blocks which are easier to check by means of mathematical array-based and geospatial constraints. Those constraints take the form of precondition, invariant and postcondition semantic checks. This way, even complex WSTMe may be described as the composition of simpler GeoSemAP blocks. GeoSemAP allows intermediate data and information layers to be more easily and formally semantically described so as to increase fault-tolerance, transparency and reproducibility of WSTMe. This might also help to better communicate part of the policy-relevant knowledge, often diffcult to transfer from technical WSTMe to the science-policy interface. [...

Free and Open Source Software underpinning the European Forest Data Centre

Worldwide, governments are growingly focusing on free and open source software (FOSS) as a move toward transparency and the freedom to run, copy, study, change and improve the software. The European Commission (EC) is also supporting the development of FOSS [...]. In addition to the financial savings, FOSS contributes to scientific knowledge freedom in computational science (CS) and is increasingly rewarded in the science-policy interface within the emerging paradigm of open science. Since complex computational science applications may be affected by software uncertainty, FOSS may help to mitigate part of the impact of software errors by CS community- driven open review, correction and evolution of scientific code. The continental scale of EC science-based policy support implies wide networks of scientific collaboration. Thematic information systems also may benefit from this approach within reproducible integrated modelling. This is supported by the EC strategy on FOSS: "for the development of new information systems, where deployment is foreseen by parties outside of the EC infrastructure, [F]OSS will be the preferred choice and in any case used whenever possible". The aim of this contribution is to highlight how a continental scale information system may exploit and integrate FOSS technologies within the transdisciplinary research underpinning such a complex system. A European example is discussed where FOSS innervates both the structure of the information system itself and the inherent transdisciplinary research for modelling the data and information which constitute the system content. [...

Simple model for tuberculosis in cattle and badgers

As an aid to the study of bovine tuberculosis (TB), a simple model has been developed of an epidemic involving two species, cattle and badgers. Each species may infect the other. The proportion of animals affected is assumed relatively small so that the usual nonlinear aspects of epidemic theory are avoided. The model is used to study the long-run and transient effect on cattle of culling badgers and the effect of a period without routine testing for TB, such as occurred during the 2001 epidemic of foot-and-mouth disease in Great Britain. Finally, by examining the changes in cattle TB over the last 15 years, and with some other working assumptions, it is estimated that the net reproduction number of the epidemic is 1.1. The implications for controlling the disease are discussed

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

© 2019 H. P. Ellis et al. Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were IDH-wildtype (IDHWT; n = 38) and IDH-mutant (IDHMUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, and IDH1 were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. IDHWT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had BRCA1/2 (18%) variants, including confirmed somatic mutations in haemangioblastoma. IDHWT recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (BRCA2, GNAS, and EGFR) and losses (TERT and SMARCA4). IDHMUT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in KLK1 was possibly pathogenic in IDHMUT. Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in EGFR, PTEN, BRCA1/2, and ATM. This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials

The variation in capacity remunerations requirements in European electricity markets

This paper provides the first EU wide analysis of the variation in Capacity Remuneration Requirements throughout Europe which aim to resolve the “missing money” problems in various member states. The findings of this analysis point to an asymmetric investment case for gas-fired peaking power plants throughout the EU. Under the assumptions of the European Commission Reference Scenario, pan-European power optimisation and investment models are specified for 2030. The results show that future investment in gas generators will depend on the availability of capacity payments. Capacity remuneration mechanisms can provide this “missing money”, but we show that capacity remuneration requirements vary considerably across countries. We consider and model the impacts of country specific climate policy targets, sovereign risk, capital allowances, corporate taxes and future gas network tariffs on investor returns and therefore remuneration requirements. In the context of harmonised energy trading, this raises questions of how generation adequacy should be achieved, particularly in the context of higher penetrations of renewables