Matthew Poole

Bio: Matthew Poole is an academic researcher from University of Portsmouth. The author has contributed to research in topics: Particle swarm optimization & Swarm intelligence. The author has an hindex of 10, co-authored 20 publications receiving 338 citations. Previous affiliations of Matthew Poole include Swansea University & University of Leeds.

The molecular basis of the chemosensitivity of metastatic cutaneous melanoma to chemotherapy

Abstract: Background Chemotherapy benefits relatively few patients with cutaneous melanoma. The assessment of tumour chemosensitivity by the ATP-based tumour chemosensitivity assay (ATP-TCA) has shown strong correlation with outcome in cutaneous melanoma, but requires fresh tissue and dedicated laboratory facilities. Aim To examine whether the results of the ATP-TCA correlate with the expression of genes known to be involved in resistance to chemotherapy, based on the hypothesis that the molecular basis of chemosensitivity lies within known drug resistance mechanisms. Method The chemosensitivity of 47 cutaneous melanomas was assessed using the ATP-TCA and correlated with quantitative expression of 93 resistance genes measured by quantitative reverse transcriptase PCR (qRT-PCR) in a Taqman Array after extraction of total RNA from formalin-fixed paraffin-embedded tissue. Results Drugs susceptible to particular resistance mechanisms showed good correlation with genes linked to these mechanisms using signatures of up to 17 genes. Comparison of these signatures for DTIC, treosulfan and cisplatin showed several genes in common. HSP70 , at least one human epidermal growth factor receptor, genes involved in apoptosis ( IAP2 , PTEN ) and DNA repair ( ERCC1 , XPA , XRCC1 , XRCC6 ) were present for these agents, as well as genes involved in the regulation of proliferation ( Ki67 , p21, p27). The combinations tested included genes represented in the single agent signatures. Conclusions These data suggest that melanoma chemosensitivity is influenced by known resistance mechanisms, including susceptibility to apoptosis. Use of a candidate gene approach may increase understanding of the mechanisms underlying chemosensitivity to drugs active against melanoma and provide signatures with predictive value.

Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy

Abstract: BACKGROUND : Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro . This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients’ tumours. METHODS : The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene ( PBGD), and assessed by multiple linear regression. RESULTS : Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin þgemcitabine and treosulfan þgemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan þgemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved. CONCLUSION : The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.

Hierarchical reconstructions of cardiac tissue

Abstract: We consider the general problem of comparing and integrating computational models of cardiac tissue at different levels of physiological detail. We use a general theory of synchronous concurrent algorithms to model spatially extended biological systems, and expand the theory to create hierarchical models by relating observable behaviour at different levels. The general concepts and methods are illustrated by a detailed case study of electrical behaviour in cardiac tissue, in which models based on coupled systems of ordinary differential equations, partial differential equations (PDEs) and cellular automata (CAs) are compared and combined.

An algorithmic model of the mammalian heart: propagation, vulnerability, re-entry and fibrillation

Abstract: The theory of synchronous concurrent algorithms is outlined and applied to the construction of an anisotropic coupled map lattice model of electrical activity in the mammalian cardiac ventricles, derived from anatomical measurements of geometry and fibre orientation. The model is used to illustrate propagation, vulnerability, re-entry and fibrillation.

Reconstructing the heart

Abstract: The electrical activity of the heart can be reconstructed at different levels and time scales; for example, its global rhythmicity and irregularity, propagating action potentials and wave fronts, membrane action potentials and ionic currents, and single channel currents. Various different types of mathematical model are used, including eikonal equations, partial and ordinary differential equations, and coupled lattices of maps or ordinary differential equations. These phenomena and models form a hierarchy in which the organ and tissue physiology results from the cellular biophysics. On making discrete approximations of continuous spaces and times, the range of diverse models of cardiac excitation are all examples of synchronous concurrent algorithms (SCAs) and, as such, they may be studied in a unified way from the point of view of parallel deterministic computation. The theory of SCAs provides mathematical methods that may be used for the decomposition, combination and comparison of different types of model in the reconstruction of a hierarchical model of electrical activity in the heart.

Inertia Weight strategies in Particle Swarm Optimization

Abstract: Particle Swarm Optimization is a popular heuristic search algorithm which is inspired by the social learning of birds or fishes. It is a swarm intelligence technique for optimization developed by Eberhart and Kennedy [1] in 1995. Inertia weight is an important parameter in PSO, which significantly affects the convergence and exploration-exploitation trade-off in PSO process. Since inception of Inertia Weight in PSO, a large number of variations of Inertia Weight strategy have been proposed. In order to propose one or more than one Inertia Weight strategies which are efficient than others, this paper studies 15 relatively recent and popular Inertia Weight strategies and compares their performance on 05 optimization test problems.

A survey of stream processing

Abstract: Stream processing is a term that is used widely in the literature to describe a variety of systems. We present an overview of the historical development of stream processing and a detailed discussion of the different languages and techniques for programming with streams that can be found in the literature. This includes an analysis of dataflow, specialized functional and logic programming with streams, reactive systems, signal processing systems, and the use of streams in the design and verification of hardware.

Epigenetic Resensitization to Platinum in Ovarian Cancer

Abstract: Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P < 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine-cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P < 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P < 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS.

Introductory programming: a systematic literature review

Abstract: As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research.

Purinergic signalling and cancer

Abstract: Receptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer.