Polytypic Genetic Programming

Program synthesis via heuristic search often requires a great deal of boilerplate code to adapt program APIs to the search mechanism. In addition, the majority of existing approaches are not type-safe: i.e. they can fail at runtime because the search mechanisms lack the strict type information often available to the compiler. In this article, we describe Polytope, a Scala framework that uses polytypic programming, a relatively recent advance in program abstraction. Polytope requires a minimum of boilerplate code and supports a form of strong-typing in which type rules are automatically enforced by the compiler, even for search operations such as mutation which are applied at run-time. By operating directly on language-native expressions, it provides an embeddable optimization procedure for existing code. We give a tutorial example of the specific polytypic approach we adopt and compare both runtime efficiency and required lines of code against the well-known EpochX GP framework, showing comparable performance in the former and the complete elimination of boilerplate for the latter

Evolving Gaussian Process Kernels for Translation Editing Effort Estimation

In many Natural Language Processing problems the combination of machine learning and optimization techniques is essential. One of these problems is estimating the effort required to improve, under direct human supervision, a text that has been translated using a machine translation method. Recent developments in this area have shown that Gaussian Processes can be accurate for post-editing effort prediction. However, the Gaussian Process kernel has to be chosen in advance, and this choice in- fluences the quality of the prediction. In this paper, we propose a Genetic Programming algorithm to evolve kernels for Gaussian Processes. We show that the combination of evolutionary optimization and Gaussian Processes removes the need for a-priori specification of the kernel choice, and achieves predictions that, in many cases, outperform those obtained with fixed kernels.TIN2016-78365-

The rolling problem: overview and challenges

In the present paper we give a historical account -ranging from classical to modern results- of the problem of rolling two Riemannian manifolds one on the other, with the restrictions that they cannot instantaneously slip or spin one with respect to the other. On the way we show how this problem has profited from the development of intrinsic Riemannian geometry, from geometric control theory and sub-Riemannian geometry. We also mention how other areas -such as robotics and interpolation theory- have employed the rolling model.Comment: 20 page

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

Evolving DNA motifs to predict GeneChip probe performance

Background: Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results: Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion: The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. © 2009 Langdon and Harrison; licensee BioMed Central Ltd

Hyper-parameter Optimisation by Restrained Stochastic Hill Climbing

Abstract. Machine learning practitioners often refer to hyper-parameter optimisation (HPO) as an art form and a skill that requires intuition and experience; Neuroevolution (NE) typically employs a combination of manual and evolutionary approaches for HPO. This paper explores the integration of a stochastic hill climbing approach for HPO within a NE algorithm. We empirically show that HPO by restrained stochastic hill climbing (HORSHC) is more effective than manual and pure evolutionary HPO. Empirical evidence is derived from a comparison of: (1) a NE algorithm that solely optimises hyper-parameters through evolution and (2) a number of derived algorithms with random search optimisation integration for optimising the hyper-parameters of a Neural Network. Through statistical analysis of the experimental results it has been revealed that random initialisation of hyper-parameters does not significantly affect the final performance of the Neural Networks evolved. However, HORSHC, a novel optimisation approach proposed in this paper has been proven to significantly out-perform the NE control algorithm. HORSHC presents itself as a solution that is computationally comparable in terms of both time and complexity as well as outperforming the control algorithm

The Toll-Like Receptor Signaling Molecule Myd88 Contributes to Pancreatic Beta-Cell Homeostasis in Response to Injury

Commensal flora and pathogenic microbes influence the incidence of diabetes in animal models yet little is known about the mechanistic basis of these interactions. We hypothesized that Myd88, an adaptor molecule in the Toll-like-receptor (TLR) pathway, regulates pancreatic β-cell function and homeostasis. We first examined β-cells histologically and found that Myd88−/− mice have smaller islets in comparison to C57Bl/6 controls. Myd88−/− mice were nonetheless normoglycemic both at rest and after an intra-peritoneal glucose tolerance test (IPGTT). In contrast, after low-dose streptozotocin (STZ) challenge, Myd88−/−mice had an abnormal IPGTT relative to WT controls. Furthermore, Myd88−/− mice suffer enhanced β-cell apoptosis and have enhanced hepatic damage with delayed recovery upon low-dose STZ treatment. Finally, we treated WT mice with broad-spectrum oral antibiotics to deplete their commensal flora. In WT mice, low dose oral lipopolysaccharide, but not lipotichoic acid or antibiotics alone, strongly promoted enhanced glycemic control. These data suggest that Myd88 signaling and certain TLR ligands mediate a homeostatic effect on β-cells primarily in the setting of injury

A tale of two stories: astrocyte regulation of synaptic depression and facilitation

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that changes of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the underlying mechanism is poorly understood. Here, we investigate the characteristics of short-term plasticity modulation by astrocytes using a biophysically realistic computational model. Mean-field analysis of the model unravels that astrocytes may mediate counterintuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally inhibit or potentiate the synapse: the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. But this global effect usually coexists with the opposite local effect on paired pulses: with release-decreasing astrocytes most paired pulses become facilitated, while paired-pulse depression becomes prominent under release-increasing astrocytes. Moreover, we show that the frequency of astrocytic intracellular Ca2+ oscillations controls the effects of the astrocyte on short-term synaptic plasticity. Our model explains several experimental observations yet unsolved, and uncovers astrocytic gliotransmission as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has deep implications on the processing of neuronal spikes and resulting information transfer at synapses.Comment: 93 pages, manuscript+supplementary text, 10 main figures, 11 supplementary figures, 1 tabl

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Non-destructive characterisation and classification of ceramic artefacts using pEDXRF and statistical pattern recognition

Background: Portable energy dispersive X-ray fluorescence (pEDXRF) spectrometry analysis was applied for the characterisation of archaeological ceramic findings from three Neolithic sites in Serbia. Two dimension reduction techniques, principal component analysis (PCA) and scattering matrices-based dimension reduction were used to examine the possible classification of those findings, and to extract the most discriminant features. Results: A decision-making procedure is proposed, whose goal is to classify unknown ceramic findings based on their elemental compositions derived by pEDXRF spectrometry. As a major part of decision-making procedure, the possibilities of two dimension reduction methods were tested. Scattering matrices-based dimension reduction was found to be the more efficient method for the purpose. Linear classifiers designed based on the desired output allowed for 7 of 8 unknown samples from the test set to be correctly classified. Conclusions: Based on the results, the conclusion is that despite the constraints typical of the applied analytical technique, the elemental composition can be considered as viable information in provenience studies. With a fully-developed procedure, ceramic artefacts can be classified based on their elemental composition and well-known provenance