Multiscale modeling in biology

The 1966 science-fction film Fantastic Voyage captured the public imagination with a clever idea: what fantastic things might we see and do if we could minaturize ourselves and travel through the bloodstream as corpuscles do? (This being Hollywood, the answer was that we'd save a fellow scientist from evildoers.

Financial integration, banking supervision and sustainability of the Western Balkan countries

Purpose: This paper examines the need of financial integration of Western Balkan countries as the main indicator of the region’s economic growth. Design/Methodology/Approach: We provide an overview in order to explain what the financial system in the region is. Primarily we concentrate in the banking sector and the nonperforming loans in the region. They require attention and standardization of regulatory classification. By establishing a regional platform it would be of additional value and would help overcome the limited visibility in some of the countries. Findings: Currently the challenges for financial stability in the Western Balkan area comprise non-performing loans, low capital adequacy and moderate growth of credit in the economy. The banking sector is reducing the debt due to required financial stability measures of the European banking authorities. As these countries integrate their financial institutions and markets into the European financial system, on the path towards harmonization of national and European legislation, cooperation between financial entities in the Western Balkans becomes very important. The Western Balkan countries are in a different stage of development of banking sustainability and supervision and because of that there is a need for more integration with the European Banks and the respective regulators to ensure an adequate banking regime. Practical Implications: The article highlights the fact that Western Balkan countries need to intensify their reforms to build banking sustainability in order to meet the criteria for EU membership. Originality/Value: With this article we show that the Western Balkan countries in their integration processes must first align their local and European legislation and requirements.peer-reviewe

Cultivation and anaerobic digestion of Scenedesmus spp. grown in a pilot-scale open raceway

Digestibility of a micro-algal mixture was evaluated by mesophilic anaerobic digestion in continuously-stirred tank reactors. The culture consisted primarily of Scenedesmus spp. continuously cultivated over a 6-month period in a 100 m2 raceway reactor instrumented to record pH, dissolved oxygen and temperature. The raceway received supplementary carbon in the form of flue gas from a diesel boiler (10% CO2) injected into a 1-m deep sump to control pH in the range 7.8–8.0. Dilution was optimised to biomass productivity and gave values of 10–15 and 20–25 g total suspended solids (TSS) m? 2 day? 1 in winter (December–February) and spring (April–May), respectively. The culture for the anaerobic digestion trial was harvested in February by centrifugation to give an algal paste containing 4.3% volatile solids (VS). Semi-continuous digestion at organic loading rates of 2.00, 2.75 and 3.50 g VS l? 1 day? 1 gave volumetric biogas productions of ~ 0.66, ~ 0.83 and ~ 0.99 l l? 1 day? 1, respectively. Specific methane yield ranged from 0.13 to 0.14 l CH4 g? 1 VSadded with biogas methane content ~ 62%. Overall the digestion process was stable, but only ~ 30% VS destruction was achieved indicating low biodegradability, due to the short retention times and the recalcitrant nature of this type of biomas

Sampling bias in systems with structural heterogeneity and limited internal diffusion

Complex systems research is becomingly increasingly data-driven, particularly in the social and biological domains. Many of the systems from which sample data are collected feature structural heterogeneity at the mesoscopic scale (i.e. communities) and limited inter-community diffusion. Here we show that the interplay between these two features can yield a significant bias in the global characteristics inferred from the data. We present a general framework to quantify this bias, and derive an explicit corrective factor for a wide class of systems. Applying our analysis to a recent high-profile survey of conflict mortality in Iraq suggests a significant overestimate of deaths

Liquid filled canyons on Titan

In May 2013 the Cassini RADAR altimeter observed channels in Vid Flumina, a drainage network connected to Titan’s second largest hydrocarbon sea, Ligeia Mare. Analysis of these altimeter echoes shows that the channels are located in deep (up to ~570 m), steep-sided, canyons and have strong specular surface reflections that indicate they are currently liquid filled. Elevations of the liquid in these channels are at the same level as Ligeia Mare to within a vertical precision of about 0.7 m, consistent with the interpretation of drowned river valleys. Specular reflections are also observed in lower order tributaries elevated above the level of Ligeia Mare, consistent with drainage feeding into the main channel system

Genetic factors in risk assessment for the development of type 2 diabetes mellitus in a small case series

Abstract. Objective: This study aimed to investigate the role of genetic biomarkers in assessing risk for the eventual development of type 2 diabetes mellitus (T2DM). Methods: Three Maltese women with a history of previous severe GDM and with apparent similar clinical risk factors underwent anthropomorphic and metabolic reassessment 4–7 years post-partum. They were further genotyped for four specific genetic single nucleotide polymorphisms (SNPs) using the qPCR technique for the alleles of SLC2A2 (rs5393A/C), FTO (rs9939609A/T), PCK (rs2071023C/G) and CDKAL1 (rs10946398A/C). Results: While the previous obstetric history of all the caseswas similar, the biological statuswas characterized by an increasing degree of obesity correlating to increasing severity of current carbohydrate intolerance. Genotyping showed that all the tested SNPs were homozygous mutant in the T2DM woman and heterozygous in the impaired glucose tolerance woman. The woman with normal glucose tolerance was shown to be wild type for SLC2A2 (rs5393A/C). Conclusions: There appeared to be an interrelationship between eventual severity of carbohydrate metabolism abnormalities and the genetic allele status. It would appear that the specific allele-scoring can be used to identify further the potential risk of developing T2DM.peer-reviewe

Connective tissue disease-associated interstitial lung disease

BACKGROUND: Connective tissue diseases (CTD) are frequently associated with interstitial lung disease (ILD), significantly impacting their morbidity and mortality. AIM: Analyze the experience of an autoimmune specialized unit on treating CTD-ILD and characterize the population based on most frequent diseases, imaging patterns, lung function tests results, serology and treatment. Assess mortality and mortality predictors in these patients. METHODS: Retrospective, descriptive and statistical analysis of the CTD-ILD patients followed up at an autoimmune diseases unit during a 6-year period. RESULTS: Over the study period, 75 patients with CTD-ILD were treated with a mean follow-up of 49 ± 31 months. The most frequent CTD were systemic sclerosis and rheumatoid arthritis. ILD was diagnosed prior to CTD in 8% of patients and concomitantly in 35%. Nonspecific interstitial pneumonia was the CT pattern in 60% and 35% had an isolated diminished DLCO on lung function tests. Pulmonary hypertension was present in 12% and it was the single most important mortality predictor (OR 14.41, p = 0.006). Corticosteroids are the mainstay of treatment but biologics were prescribed in 39% of the patients (mostly tocilizumab and rituximab). Two scleroderma patients were recently treated with nintedanib. CONCLUSIONS: ILD is a potential complication of every CTD and can impose a dramatic burden on these patients. The clinical relevance of ILD together with their early expression in the course of the disease underlines the importance of the presence of chest physicians in these units.info:eu-repo/semantics/publishedVersio

Connective tissue disease-associated interstitial lung disease

Background: Connective tissue diseases (CTD) are frequently associated with interstitial lung disease (ILD), significantly impacting their morbidity and mortality. Aim: Analyze the experience of an autoimmune specialized unit on treating CTD-ILD and characterize the population based on most frequent diseases, imaging patterns, lung function tests results, serology and treatment. Assess mortality and mortality predictors in these patients. Methods: Retrospective, descriptive and statistical analysis of the CTD-ILD patients followed up at an autoimmune diseases unit during a 6-year period. Results: Over the study period, 75 patients with CTD-ILD were treated with a mean follow-up of 49 ± 31 months. The most frequent CTD were systemic sclerosis and rheumatoid arthritis. ILD was diagnosed prior to CTD in 8% of patients and concomitantly in 35%. Nonspecific interstitial pneumonia was the CT pattern in 60% and 35% had an isolated diminished DLCO on lung function tests. Pulmonary hypertension was present in 12% and it was the single most important mortality predictor (OR 14.41, p = 0.006). Corticosteroids are the mainstay of treatment but biologics were prescribed in 39% of the patients (mostly tocilizumab and rituximab). Two scleroderma patients were recently treated with nintedanib. Conclusions: ILD is a potential complication of every CTD and can impose a dramatic burden on these patients. The clinical relevance of ILD together with their early expression in the course of the disease underlines the importance of the presence of chest physicians in these units.publishersversionpublishe

Investigating the robustness of the classical enzyme kinetic equations in small intracellular compartments

<p>Abstract</p> <p>Background</p> <p>Classical descriptions of enzyme kinetics ignore the physical nature of the intracellular environment. Main implicit assumptions behind such approaches are that reactions occur in compartment volumes which are large enough so that molecular discreteness can be ignored and that molecular transport occurs via diffusion. Though these conditions are frequently met in laboratory conditions, they are not characteristic of the intracellular environment, which is compartmentalized at the micron and submicron scales and in which active means of transport play a significant role.</p> <p>Results</p> <p>Starting from a master equation description of enzyme reaction kinetics and assuming metabolic steady-state conditions, we derive novel mesoscopic rate equations which take into account (i) the intrinsic molecular noise due to the low copy number of molecules in intracellular compartments (ii) the physical nature of the substrate transport process, i.e. diffusion or vesicle-mediated transport. These equations replace the conventional macroscopic and deterministic equations in the context of intracellular kinetics. The latter are recovered in the limit of infinite compartment volumes. We find that deviations from the predictions of classical kinetics are pronounced (hundreds of percent in the estimate for the reaction velocity) for enzyme reactions occurring in compartments which are smaller than approximately 200 nm, for the case of substrate transport to the compartment being mediated principally by vesicle or granule transport and in the presence of competitive enzyme inhibitors.</p> <p>Conclusion</p> <p>The derived mesoscopic rate equations describe subcellular enzyme reaction kinetics, taking into account, for the first time, the simultaneous influence of both intrinsic noise and the mode of transport. They clearly show the range of applicability of the conventional deterministic equation models, namely intracellular conditions compatible with diffusive transport and simple enzyme mechanisms in several hundred nanometre-sized compartments. An active transport mechanism coupled with large intrinsic noise in enzyme concentrations is shown to lead to huge deviations from the predictions of deterministic models. This has implications for the common approach of modeling large intracellular reaction networks using ordinary differential equations and also for the calculation of the effective dosage of competitive inhibitor drugs.</p

Effects of Heat-Producing Elements on the Stability of Deep Mantle Thermochemical Piles

©2020. American Geophysical Union. All Rights Reserved. Geochemical observations of ocean island and mid-ocean ridge basalts suggest that abundances of heat-producing elements (HPEs: U, Th, and K) vary within the mantle. Combined with bulk silicate Earth models and constraints on the Earth's heat budget, these observations suggest the presence of a more enriched (potentially deep and undepleted) reservoir in the mantle. Such a reservoir may be related to seismically observed deep mantle structures known as large low shear velocity provinces (LLSVPs). LLSVPs might represent thermochemical piles of an intrinsically denser composition, and many studies have shown such piles to remain stable over hundreds of Myr or longer. However, few studies have examined if thermochemical piles can remain stable if they are enriched in HPEs, a necessary condition for them to constitute an enriched HPE reservoir. We conduct a suite of mantle convection simulations to examine the effect of HPE enrichment up to 25× the ambient mantle on pile stability. Model results are evaluated against present-day pile morphology and tested for resulting seismic signatures using self-consistent potential pile compositions. We find that stable piles can form from an initial basal layer of dense material even if the layer is enriched in HPEs, depending on the density of the layer and degree of HPE enrichment, with denser basal layers requiring increased HPE enrichment to form pile-like morphology instead of a stable layer. Thermochemical piles or LLSVPs may therefore constitute an enriched reservoir in the deep mantle