Identifying the impact of G-quadruplexes on Affymetrix 3' arrays using cloud computing.

A tetramer quadruplex structure is formed by four parallel strands of DNA/ RNA containing runs of guanine. These quadruplexes are able to form because guanine can Hoogsteen hydrogen bond to other guanines, and a tetrad of guanines can form a stable arrangement. Recently we have discovered that probes on Affymetrix GeneChips that contain runs of guanine do not measure gene expression reliably. We associate this finding with the likelihood that quadruplexes are forming on the surface of GeneChips. In order to cope with the rapidly expanding size of GeneChip array datasets in the public domain, we are exploring the use of cloud computing to replicate our experiments on 3' arrays to look at the effect of the location of G-spots (runs of guanines). Cloud computing is a recently introduced high-performance solution that takes advantage of the computational infrastructure of large organisations such as Amazon and Google. We expect that cloud computing will become widely adopted because it enables bioinformaticians to avoid capital expenditure on expensive computing resources and to only pay a cloud computing provider for what is used. Moreover, as well as financial efficiency, cloud computing is an ecologically-friendly technology, it enables efficient data-sharing and we expect it to be faster for development purposes. Here we propose the advantageous use of cloud computing to perform a large data-mining analysis of public domain 3' arrays

Software to compute infinitesimal symmetries of exterior differenial systems, with applications

A description is given of a software package to compute symmetries of partial differential equations, using computer algebra. As an application, the computation of higher-order symmetries of the classical Boussinesq equation is given leading to the recursion operator for symmetries in a straightforward way. Nonlocal symmetries for the Federbush model are obtained yielding the linearization of the model

Electronic Visualisation in Chemistry: From Alchemy to Art

Chemists now routinely use software as part of their work. For example, virtual chemistry allows chemical reactions to be simulated. In particular, a selection of software is available for the visualisation of complex 3-dimensional molecular structures. Many of these are very beautiful in their own right. As well as being included as illustrations in academic papers, such visualisations are often used on the covers of chemistry journals as artistically decorative and attractive motifs. Chemical images have also been used as the basis of artworks in exhibitions. This paper explores the development of the relationship of chemistry, art, and IT. It covers some of the increasingly sophisticated software used to generate these projections (e.g., UCSF Chimera) and their progressive use as a visual art form

On Multiphase-Linear Ranking Functions

Multiphase ranking functions ($\mathit{M{\Phi}RFs}$) were proposed as a means to prove the termination of a loop in which the computation progresses through a number of "phases", and the progress of each phase is described by a different linear ranking function. Our work provides new insights regarding such functions for loops described by a conjunction of linear constraints (single-path loops). We provide a complete polynomial-time solution to the problem of existence and of synthesis of $\mathit{M{\Phi}RF}$ of bounded depth (number of phases), when variables range over rational or real numbers; a complete solution for the (harder) case that variables are integer, with a matching lower-bound proof, showing that the problem is coNP-complete; and a new theorem which bounds the number of iterations for loops with $\mathit{M{\Phi}RFs}$. Surprisingly, the bound is linear, even when the variables involved change in non-linear way. We also consider a type of lexicographic ranking functions, $\mathit{LLRFs}$, more expressive than types of lexicographic functions for which complete solutions have been given so far. We prove that for the above type of loops, lexicographic functions can be reduced to $\mathit{M{\Phi}RFs}$, and thus the questions of complexity of detection and synthesis, and of resulting iteration bounds, are also answered for this class.Comment: typos correcte

From quantum fusiliers to high-performance networks

Our objective was to design a quantum repeater capable of achieving one million entangled pairs per second over a distance of 1000km. We failed, but not by much. In this letter we will describe the series of developments that permitted us to approach our goal. We will describe a mechanism that permits the creation of entanglement between two qubits, connected by fibre, with probability arbitrarily close to one and in constant time. This mechanism may be extended to ensure that the entanglement has high fidelity without compromising these properties. Finally, we describe how this may be used to construct a quantum repeater that is capable of creating a linear quantum network connecting two distant qubits with high fidelity. The creation rate is shown to be a function of the maximum distance between two adjacent quantum repeaters.Comment: 2 figures, Comments welcom

Widening mismatch between UK seafood production and consumer demand: a 120-year perspective

This is the final version. Available from Springer via the DOI in this record. Data availability: The datasets generated and used for the UK seafood production and trade analyses and to produce Figs. 1–6 are available on GitHub at https://github.com/lukeo jharrison/UKSeafoodProductionConsumerDemandPaper (Harrison et al. 2023).Developed countries are increasingly dependent on international trade to meet seafood requirements, which has important social, environmental, and economic implications. After becoming an independent coastal state following Brexit, the UK faces increased trade barriers and changes in seafood availability and cost. We compiled a long-term (120-year) dataset of UK seafood production (landings and aquaculture), imports, and exports, and assessed the influence of policy change and consumer preference on domestic production and consumption. In the early twentieth century, distant-water fisheries met an increasing demand for large, flaky fish such as cod and haddock that are more abundant in northerly waters. Accordingly, from 1900 to 1975, the UK fleet supplied almost 90% of these fish. However, policy changes in the mid-1970s such as the widespread establishment of Exclusive Economic Zones and the UK joining the European Union resulted in large declines in distant-water fisheries and a growing mismatch between seafood production versus consumption in the UK. While in 1975, UK landings and aquaculture accounted for 89% of seafood consumed by the British public, by 2019 this was only 40%. The combination of policy changes and staunch consumer preferences for non-local species has resulted in today’s situation, where the vast majority of seafood consumed in the UK is imported, and most seafood produced domestically is exported. There are also health considerations. The UK public currently consumes 31% less seafood than is recommended by government guidelines, and even if local species were more popular, total domestic production would still be 73% below recommended levels. In the face of climate change, global overfishing and potentially restrictive trade barriers, promoting locally sourced seafood and non-seafood alternatives would be prudent to help meet national food security demands, and health and environmental targets.UK Research and Innovatio

Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

Platelet responses to agonists in a cohort of highly characterised platelet donors are consistent over time.

BACKGROUND AND OBJECTIVES: Platelet function shows significant inheritance that is at least partially genetically controlled. There is also evidence that the platelet response is stable over time, but there are few studies that have assessed consistency of platelet function over months and years. We aimed to measure platelet function in platelet donors over time in individuals selected from a cohort of 956 donors whose platelet function had been previously characterised. MATERIALS AND METHODS: Platelet function was assessed by flow cytometry, measuring fibrinogen binding and P-selectin expression after stimulation with either cross-linked collagen-related peptide or adenosine 5'-diphosphate. Eighty-nine donors from the Cambridge Platelet Function Cohort whose platelet responses were initially within the lower or upper decile of reactivity were retested between 4 months and five and a half years later. RESULTS: There was moderate-to-high correlation between the initial and repeat platelet function results for all assays (P ≤ 0·007, r2 0·2961-0·7625); furthermore, the range of results observed in the initial low and high responder groups remained significantly different at the time of the second test (P ≤ 0·0005). CONCLUSION: Platelet function remains consistent over time. This implies that this potential influence on quality of donated platelet concentrates will remain essentially constant for a given donor

Diverse Functions of Retinoic Acid in Brain Vascular Development

As neural structures grow in size and increase metabolic demand, the CNS vasculature undergoes extensive growth, remodeling, and maturation. Signals from neural tissue act on endothelial cells to stimulate blood vessel ingression, vessel patterning, and acquisition of mature brain vascular traits, most notably the blood–brain barrier. Using mouse genetic and in vitro approaches, we identified retinoic acid (RA) as an important regulator of brain vascular development via non-cell-autonomous and cell-autonomous regulation of endothelial WNT signaling. Our analysis of globally RA-deficient embryos (Rdh10 mutants) points to an important, non-cell-autonomous function for RA in the development of the vasculature in the neocortex. We demonstrate that Rdh10 mutants have severe defects in cerebrovascular development and that this phenotype correlates with near absence of endothelial WNT signaling, specifically in the cerebrovasculature, and substantially elevated expression of WNT inhibitors in the neocortex. We show that RA can suppress the expression of WNT inhibitors in neocortical progenitors. Analysis of vasculature in non-neocortical brain regions suggested that RA may have a separate, cell-autonomous function in brain endothelial cells to inhibit WNT signaling. Using both gain and loss of RA signaling approaches, we show that RA signaling in brain endothelial cells can inhibit WNT-β-catenin transcriptional activity and that this is required to moderate the expression of WNT target Sox17. From this, a model emerges in which RA acts upstream of the WNT pathway via non-cell-autonomous and cell-autonomous mechanisms to ensure the formation of an adequate and stable brain vascular plexus