Model Reduction for the Chemical Master Equation: an Information-Theoretic Approach

The complexity of mathematical models in biology has rendered model reduction an essential tool in the quantitative biologist's toolkit. For stochastic reaction networks described using the Chemical Master Equation, commonly used methods include time-scale separation, the Linear Mapping Approximation and state-space lumping. Despite the success of these techniques, they appear to be rather disparate and at present no general-purpose approach to model reduction for stochastic reaction networks is known. In this paper we show that most common model reduction approaches for the Chemical Master Equation can be seen as minimising a well-known information-theoretic quantity between the full model and its reduction, the Kullback-Leibler divergence defined on the space of trajectories. This allows us to recast the task of model reduction as a variational problem that can be tackled using standard numerical optimisation approaches. In addition we derive general expressions for the propensities of a reduced system that generalise those found using classical methods. We show that the Kullback-Leibler divergence is a useful metric to assess model discrepancy and to compare different model reduction techniques using three examples from the literature: an autoregulatory feedback loop, the Michaelis-Menten enzyme system and a genetic oscillator

Training deep neural density estimators to identify mechanistic models of neural dynamics

Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators-- trained using model simulations-- to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features, and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin-Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics

An evaluation of energy efficiency measures in a Turkish campus building for thermal comfort and economic risk

As new and retrofitted Turkish buildings adopt stateof-the-art energy efficiency measures, hidden risks associated with compromised thermal comfort and disappointing returns on investment could go unnoticed unless a building is subjected to an uncertainty and risk analysis. Standard deterministic predictions are not sufficient, as they do not capture the effects of uncertainty and variability with regard to local microclimate conditions, physical parameters, and discrepancies in the model formulations, also known as “model form uncertainties”. In this paper, we analyze the impact of uncertainty on the performance of a Turkish campus building. We examine the risk that an energy efficient design that is accepted because of the positive results of a conventional energy simulation, causes unacceptable discomfort and unsatisfactory returns on investment. The results of a comprehensive uncertainty analysis shows that these risks exist in certain areas and not in others. The predicted annual output of PV panels is relatively stable with only minor variability, which justifies the investment in Istanbul. Same with shading devices, which lead to a satisfactory internal rate of return under uncertainty. However, with regard to comfort we find that risks could be substantial. We find that relying completely on occupants opening and closing windows for fresh air with fan coil units maintaining the indoor temperature may lead to an insufficient supply of outdoor air for occupants and a substantial risk of overheating. Overall, the results of the analysis demonstrate that understanding risks is in some cases crucial to make an informed design decision regarding various energy saving design strategies.NSF ; Georgia Institute of Technology ; European Commission ; CEE

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Industry financial ratios-application of factor analysis in Turkish construction industry

Turkish economy has been hit by various economical crises between the years 1998 and 2001 and the economic stagnation still continues. Past experiences in various countries show that it is vitally important to encourage construction activities in order to get out of stagnation, as construction output directly affects about 200 other sectors and industry financial ratio analysis is a means to provide a basis for the governments to undertake corrective action. However, there are over 50 financial ratios that can be used during analysis and some are more important than the others for different industries. Previous research has shown that there are about 25 factors that are important for the construction companies. This, in turn, requires elimination of unrelated data. Factor analysis is a data reduction and classification technique, which can be applied in financial analysis. Factor analysis was thus applied to the financial data collected from Turkish construction companies for a 5-year period in order to determine the financial indicators that can be used to analyse the financial trend of the industry. Five independent factors, i.e. liquidity, capital structure and profitability, activity efficiency, profit margin and growth, and assets structure were identified to be sensitive to the economical changes in the country. The results of the factor-based analysis can be used both by the government to analyse the changes in the industry with respect to time and by the construction companies to analyse their financial state with respect to their rivals. © 2005 Elsevier Ltd. All rights reserved

Remifentanil produces vasorelaxation in isolated rat thoracic aorta strips

PubMedID: 12492799Background: Remifentanil can cause transient instability in hemodynamic variables. However this change may not be solely the result of autonomic or central nervous system inhibition or of centrally mediated vagal stimulation. In this study, the aim was to examine the direct effects of remifentanil on isolated thoracic aorta strips in vitro. Methods: Forty-five Wistar rat thoracic aorta rings were isolated, and contraction-relaxation responses were recorded. Results: In aortic rings precontracted with phenylephrine or potassium chloride, remifentanil produced concentration-dependent relaxation in both endothelium-intact and denuded rings (P<0.001). Remifentanil induced significantly greater relaxation in intact rings than in those denuded of endothelium, regardless of whether they were precontracted with phenylephrine hydrochloride or KCl (P<0.001). When the endothelium was present, remifentanil produced greater relaxation in KCl-contracted rings than in PE-contracted rings at lower concentrations (10-9 and 10-8), and similar relaxation at higher concentrations (10-7 and 10-6). However, when the endothelium was removed, relaxation was similar in both solutions, at all concentrations (10-9 to 10-6). In intact rings, pretreatment with L-NO-ARG or indomethacin reduced the degree of remifentanil-induced relaxation. In Ca+ ± free media, calcium-dependent KCl contractions were inhibited in a dose-dependent manner by remifentanil (P<0.001). Conclusion: Remifentanil vasodilates by an endothelium-dependent mechanism, involving prostacyclin and nitric oxide released from the endothelium. Its endothelium-independent vasodilation probably occurs via the suppression of voltage-sensitive Ca++ channels. © Acta Anaesthesiologica Scandinavica 47 (2003)

Nuclear power risk perception in serbia: Fear of exposure to radiation vs. social benefits

Nuclear power remains one of the most accessible choices in addressing environmental and social concerns due to the continuously increasing energy needs around the world. While it remains an excellent source of energy due to its low price and low level of emissions, potential accidents remain a serious problem. An example of such is the most recent accident in the Fukushima Daiichi Nuclear Power Plant (2011), which reminded the world of the potential risks of nuclear energy and the consequences of which continue to have a lasting effect. There is no nuclear power plant in Serbia, but there are about 15 nuclear power stations scattered within its neighboring countries. Therefore, the Serbian Government decided to study how the Serbian public perceives the risks related to the potential construction of nuclear power stations in the country, nuclear energy in general, and its possible benefits and risks. The objective of this paper is to present the results of this assessment along with a literature overview on the (environmental) risk of nuclear power. A pilot study consisted of a series of 270 randomized face-to-face interviews that took place in the public square of Belgrade in March 2019. Logistic regression was used to examine the cumulative effects of the different risk factors. The results showed that the majority of the respondents are skeptical and do not support the construction of nuclear power stations in Serbia. Furthermore, this research identified several additional important correlations that have a significant impact on the public perception of risk

Remifentanil produces vasorelaxation in isolated rat thoracic aorta strips [7]

PubMedID: 15243971[No abstract available

Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group

Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey, and 48 unrelated healthy volunteers from different geographic regions of Turkey, were included in this study. Methylation status of the promoter region of the EGFR gene was detected by methylation-specific-polymerase chain reaction (MS-PCR). The correlation between EGFR gene promoter methylation profiles and clinical characteristics were examined using the χ2 test. Methylation was observed in 79.0% of HNSCC patients, whereas this ratio was 90.0% in healthy individuals. The results show that promoter region methylation of the EGFR gene was not associated with HNSCC development in the studied Turkish patient group. In addition, the methylation status of the EGFR gene promoter was not found to be related to age, gender or tumor stage