scholarly journals MultIscale MultiObjective Systems Analysis (MIMOSA): an advanced metabolic modeling framework for complex systems

2019 ◽  
Author(s):  
Joseph J. Gardner ◽  
Bri-Mathias S. Hodge ◽  
Nanette R. Boyle
Keyword(s):  
Systems Analysis ◽  
Metabolic Modeling ◽  
Natural Environments ◽  
Complex Cell ◽  
Proof Of Concept ◽  
Modeling Framework ◽  
Trichodesmium Erythraeum ◽  
Pure Cultures ◽  
High Degree ◽  
Degree Of Heterogeneity

ABSTRACTIn natural environments, cells live in complex communities and experience a high degree of heterogeneity internally and in the environment. Unfortunately, most of the metabolic modeling approaches that are currently used assume ideal conditions and that each cell is identical, limiting their application to pure cultures in well-mixed vessels. Here we describe our development of MultIscale MultiObjective Systems Analysis (MIMOSA), a metabolic modeling approach that can track individual cells in both space and time, track the diffusion of nutrients and light and the interaction of cells with each other and the environment. As a proof-of concept study, we used MIMOSA to model the growth of Trichodesmium erythraeum, a filamentous diazotrophic cyanobacterium which has cells with two distinct metabolic modes. The use of MIMOSA significantly improves our ability to predictively model metabolic changes and phenotype in more complex cell cultures.

scholarly journals Multiscale Multiobjective Systems Analysis (MiMoSA): an advanced metabolic modeling framework for complex systems

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joseph J. Gardner ◽  
Bri-Mathias S. Hodge ◽  
Nanette R. Boyle
Keyword(s):  
Systems Analysis ◽  
Metabolic Modeling ◽  
Natural Environments ◽  
Complex Cell ◽  
Proof Of Concept ◽  
Modeling Framework ◽  
Trichodesmium Erythraeum ◽  
Pure Cultures ◽  
High Degree ◽  
Degree Of Heterogeneity

AbstractIn natural environments, cells live in complex communities and experience a high degree of heterogeneity internally and in the environment. Even in ‘ideal’ laboratory environments, cells can experience a high degree of heterogeneity in their environments. Unfortunately, most of the metabolic modeling approaches that are currently used assume ideal conditions and that each cell is identical, limiting their application to pure cultures in well-mixed vessels. Here we describe our development of Multiscale Multiobjective Systems Analysis (MiMoSA), a metabolic modeling approach that can track individual cells in both space and time, track the diffusion of nutrients and light and the interaction of cells with each other and the environment. As a proof-of concept study, we used MiMoSA to model the growth of Trichodesmium erythraeum, a filamentous diazotrophic cyanobacterium which has cells with two distinct metabolic modes. The use of MiMoSA significantly improves our ability to predictively model metabolic changes and phenotype in more complex cell cultures.

scholarly journals A 3D hydrodynamic flow-focusing device for cell sorting

2021 ◽  
Vol 25 (3) ◽  
Author(s):  
Xiaofei Yuan ◽  
Andrew Glidle ◽  
Hitoshi Furusho ◽  
Huabing Yin
Keyword(s):  
Cell Sorting ◽  
Control Strategies ◽  
Three Dimensional ◽  
Hydrodynamic Flow ◽  
Proof Of Concept ◽  
Flow Focusing ◽  
Hydrodynamic Focusing ◽  
Cell Handling ◽  
Fluid Flow Control ◽  
High Degree

AbstractOptical-based microfluidic cell sorting has become increasingly attractive for applications in life and environmental sciences due to its ability of sophisticated cell handling in flow. The majority of these microfluidic cell sorting devices employ two-dimensional fluid flow control strategies, which lack the ability to manipulate the position of cells arbitrarily for precise optical detection, therefore resulting in reduced sorting accuracy and purity. Although three-dimensional (3D) hydrodynamic devices have better flow-focusing characteristics, most lack the flexibility to arbitrarily position the sample flow in each direction. Thus, there have been very few studies using 3D hydrodynamic flow focusing for sorting. Herein, we designed a 3D hydrodynamic focusing sorting platform based on independent sheath flow-focusing and pressure-actuated switching. This design offers many advantages in terms of reliable acquisition of weak Raman signals due to the ability to precisely control the speed and position of samples in 3D. With a proof-of-concept demonstration, we show this 3D hydrodynamic focusing-based sorting device has the potential to reach a high degree of accuracy for Raman activated sorting.

scholarly journals Precision radiogenomics: fusion biopsies to target tumour habitats in vivo

2021 ◽  
Author(s):  
Mireia Crispin-Ortuzar ◽  
Evis Sala
Keyword(s):  
Ovarian Cancer ◽  
Ct Scans ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
High Degree ◽  
Degree Of Heterogeneity

SummaryHigh-grade serous ovarian cancer lesions display a high degree of heterogeneity on CT scans. We have recently shown that regions with distinct imaging profiles can be accurately biopsied in vivo using a technique based on the fusion of CT and ultrasound scans.

scholarly journals A Novel Kinetic Modeling Framework for the Polycondensation of Sugars Using Monte Carlo and the Method of Moments

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 745
Author(s):  
Dimitrios Meimaroglou ◽  
Sandrine Hoppe ◽  
Baptiste Boit
Keyword(s):  
Monte Carlo ◽  
Kinetic Modeling ◽  
Method Of Moments ◽  
Kinetic Monte Carlo ◽  
Kinetic Scheme ◽  
Modeling Framework ◽  
Industrial Sectors ◽  
The Monte Carlo Method ◽  
Reacting Systems ◽  
High Degree

The kinetics of the hydrolysis and polycondensation reactions of saccharides have made the subject of numerous studies, due to their importance in several industrial sectors. The present work, presents a novel kinetic modeling framework that is specifically well-suited to reacting systems under strict moisture control that favor the polycondensation reactions towards the formation of high-degree polysaccharides. The proposed model is based on an extended and generalized kinetic scheme, including also the presence of polyols, and is formulated using two different numerical approaches, namely a deterministic one in terms of the method of moments and a stochastic kinetic Monte Carlo approach. Accordingly, the most significant advantages and drawbacks of each technique are clearly demonstrated and the most fitted one (i.e., the Monte Carlo method) is implemented for the modeling of the system under different conditions, for which experimental data were available. Through these comparisons it is shown that the model can successfully follow the evolution of the reactions up to the formation of polysaccharides of very high degrees of polymerization.

scholarly journals Prevalence and Impact of Atrial Fibrillation in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2490
Author(s):  
Giulio Francesco Romiti ◽  
Bernadette Corica ◽  
Gregory Y. H. Lip ◽  
Marco Proietti
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Meta Analysis ◽  
Geographical Location ◽  
Treatment Strategies ◽  
Cardiovascular Complications ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
High Degree ◽  
Degree Of Heterogeneity

Background: In patients with COVID-19, cardiovascular complications are common and associated with poor prognosis. Among these, an association between atrial fibrillation (AF) and COVID-19 has been described; however, the extent of this relationship is unclear. The aim of this study is to investigate the epidemiology of AF in COVID-19 patients and its impact on all-cause mortality. Methods: A systematic review and meta-analysis were performed and reported according to PRISMA guidelines, and a protocol for this study was registered on PROSPERO (CRD42021227950). PubMed and EMBASE were systematically searched for relevant studies. A random-effects model was used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Results: Overall, 31 studies were included in the analysis, with a total number of 187,716 COVID-19 patients. The prevalence of AF was found to be as high as 8% of patients with COVID-19 (95% CI: 6.3–10.2%, 95% prediction intervals (PI): 2.0–27.1%), with a high degree of heterogeneity between studies; a multiple meta-regression model including geographical location, age, hypertension, and diabetes showed that these factors accounted for more than a third of the heterogeneity. AF COVID-19 patients were less likely to be female but more likely older, hypertensive, and with a critical status than those without AF. Patients with AF showed a significant increase in the risk of all-cause mortality (OR: 3.97, 95% CI: 2.76–5.71), with a high degree of heterogeneity. A sensitivity analysis focusing on new-onset AF showed the consistency of these results. Conclusions: Among COVID-19 patients, AF is found in 8% of patients. AF COVID-19 patients are older, more hypertensive, and more likely to have a critical status. In COVID-19 patients, AF is associated with a 4-fold higher risk of death. Further studies are needed to define the best treatment strategies to improve the prognosis of AF COVID-19 patients.

scholarly journals Similarly Lethal Strains of Extraintestinal Pathogenic Escherichia coli Trigger Markedly Diverse Host Responses in a Zebrafish Model of Sepsis

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Amelia E. Barber ◽  
Brittany A. Fleming ◽  
Matthew A. Mulvey
Keyword(s):  
The United States ◽  
Host Responses ◽  
Inflammatory Condition ◽  
Therapeutic Approaches ◽  
Zebrafish Model ◽  
Life Threatening ◽  
High Degree ◽  
Care Costs ◽  
Variable Impact ◽  
Degree Of Heterogeneity

ABSTRACT Sepsis is a life-threatening systemic inflammatory condition that is initiated by the presence of microorganisms in the bloodstream. In the United States, sepsis due to ExPEC and other pathogens kills well over a quarter of a million people each year and is associated with tremendous health care costs. A high degree of heterogeneity in the signs and symptomology of sepsis makes this disease notoriously difficult to effectively diagnose and manage. Here, using a zebrafish model of sepsis, we find that similarly lethal but genetically distinct ExPEC isolates can elicit notably disparate host responses. These variances are in part due to differences in the levels and types of flagellin that are expressed by the infecting ExPEC strains. A better understanding of the variable impact that bacterial factors like flagellin have on host responses during sepsis could lead to improved diagnostic and therapeutic approaches to these often deadly infections. In individuals with sepsis, the infecting microbes are commonly viewed as generic inducers of inflammation while the host background is considered the primary variable affecting disease progression and outcome. To study the effects of bacterial strain differences on the maladaptive immune responses that are induced during sepsis, we employed a novel zebrafish embryo infection model using extraintestinal pathogenic Escherichia coli (ExPEC) isolates. These genetically diverse pathogens are a leading cause of sepsis and are becoming increasingly dangerous because of the rise of multidrug-resistant strains. Zebrafish infected with ExPEC isolates exhibit many of the pathophysiological features seen in septic human patients, including dysregulated inflammatory responses (cytokine storms), tachycardia, endothelial leakage, and progressive edema. However, only a limited subset of ExPEC isolates can trigger a sepsis-like state and death of the host when introduced into the bloodstream. Mirroring the situation in human patients, antibiotic therapy reduced ExPEC titers and improved host survival rates but was only effective within limited time frames that varied, depending on the infecting pathogen. Intriguingly, we find that phylogenetically distant but similarly lethal ExPEC isolates can stimulate markedly different host transcriptional responses, including disparate levels of inflammatory mediators. These differences correlate with the amounts of bacterial flagellin expression during infection, as well as differential activation of Toll-like receptor 5 by discrete flagellar serotypes. Altogether, this work establishes zebrafish as a relevant model of key aspects of human sepsis and highlights the ability of genetically distinct ExPEC isolates to induce divergent host responses independently of baseline host attributes. IMPORTANCE Sepsis is a life-threatening systemic inflammatory condition that is initiated by the presence of microorganisms in the bloodstream. In the United States, sepsis due to ExPEC and other pathogens kills well over a quarter of a million people each year and is associated with tremendous health care costs. A high degree of heterogeneity in the signs and symptomology of sepsis makes this disease notoriously difficult to effectively diagnose and manage. Here, using a zebrafish model of sepsis, we find that similarly lethal but genetically distinct ExPEC isolates can elicit notably disparate host responses. These variances are in part due to differences in the levels and types of flagellin that are expressed by the infecting ExPEC strains. A better understanding of the variable impact that bacterial factors like flagellin have on host responses during sepsis could lead to improved diagnostic and therapeutic approaches to these often deadly infections. Podcast: A podcast concerning this article is available.

scholarly journals Application of the polygon method to analyze the differentiation of the regions of the Volga federal district by the level of e-business development

2021 ◽  
Vol 270 ◽  
pp. 01025
Author(s):  
Marina Bikeeva ◽  
Evgeniya Sysoeva
Keyword(s):  
Federal District ◽  
Software Tools ◽  
Business Development ◽  
Special Software ◽  
The Republic ◽  
Integral Assessment ◽  
High Degree ◽  
Polygon Method ◽  
Nizhny Novgorod Region ◽  
Degree Of Heterogeneity

The materials of the article contain an integral assessment of the level of development of e-business on the example of the regions of the Volga Federal District (VFD). As a result of calculating the private and local ranks of the values of the selected criteria, fourteen polygons of the level of e-business development were built by the number of regions in the district. The results obtained make it possible to ascertain the existence of a high degree of heterogeneity of the VFD regions in terms of the level of e-business development. The leading regions include the Republic of Tatarstan, the Perm Territory, and the Nizhny Novgorod Region. The outsider regions - the Republic of Mari El, the Republic of Mordovia and the Kirov region - are characterized by a low share of organizations that used the capabilities of the Intranet and Extranet in their activities, the lack of special software tools for managing sales of goods (works, services), limited use of software, in particular, ERP-, CRM and SCM-systems.

scholarly journals Accountability and Reporting in the Fight against Corruption: Preliminary Evidences from the Italian Setting

2017 ◽  
Vol 12 (4) ◽  
pp. 1
Author(s):  
Rosanna Spanò ◽  
Luca Ferri ◽  
Clelia Fiondella ◽  
Marco Maffei
Keyword(s):  
Content Analysis ◽  
Research Question ◽  
National Context ◽  
Reporting Practices ◽  
High Degree ◽  
Poor Reporting ◽  
Degree Of Heterogeneity ◽  
Regional Governments

This paper aims to explain how Italian Regional Governments reacted to the introduction of the Anti-Corruption Plans in order to understand the degree of thoroughness. To answer the research question 20 Anti-Corruption Plans prepared by Italian Regional Governments for the years 2013-2016. The plans were examined using a meaning-oriented content analysis. This analysis allows us to detect the degree of compliance with the National Anticorruption Plan (NAP). Also we investigated the characteristics of the information, as well as the degree of thoroughness of the reports. Our findings highlight the existence of high degree of heterogeneity in the Anti corruption plans that characterises the national context. Also, our findings reveal the existence of a wide presence of regions employing poor reporting practices.

scholarly journals Intraclonal polymorphism in the bacterium Streptomyces ambofaciens ATCC23877: evidence for a high degree of heterogeneity of the wild type clones

1999 ◽  
Vol 430 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Patricia Martin ◽  
Annie Dary ◽  
Axelle André ◽  
Gilles Fischer ◽  
Pierre Leblond ◽  
...  
Keyword(s):  
Wild Type ◽  
Streptomyces Ambofaciens ◽  
High Degree ◽  
Degree Of Heterogeneity
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