scholarly journals Modelling the effects of bacterial cell state and spatial location on tuberculosis treatment: Insights from a hybrid multiscale cellular automaton model

2016 ◽  
Author(s):  
Ruth Bowness ◽  
Mark A. J. Chaplain ◽  
Gibin G. Powathil ◽  
Stephen H. Gillespie
Keyword(s):  
Cellular Automaton ◽  
Bacterial Cell ◽  
Temporal Dynamics ◽  
Treatment Success ◽  
Spatial Location ◽  
Multiscale Model ◽  
Host Cells ◽  
Phenotypic Switching ◽  
Cell State ◽  
The Individual

AbstractIf improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of different compounds into lesions. Treatment success therefore depends critically on the responses of the individual bacteria that constitute the infection.We propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the cellular level, linking the behaviour of individual bacteria and host cells with the macroscopic behaviour of the microenvironment. The individual elements (bacteria, macrophages and T cells) are modelled using cellular automaton (CA) rules, and the evolution of oxygen, drugs and chemokine dynamics are incorporated in order to study the effects of the microenvironment in the pathological lesion. We allow bacteria to switch states depending on oxygen concentration, which affects how they respond to treatment. This is the first multiscale model of its type to consider both oxygen-driven phenotypic switching of theMycobacterium tuberculosisand antibiotic treatment. Using this model, we investigate the role of bacterial cell state and of initial bacterial location on treatment outcome. We demonstrate that when bacteria are located further away from blood vessels, less favourable outcomes are more likely, i.e. longer time before infection is contained/cleared, treatment failure or later relapse. We also show that in cases where bacteria remain at the end of simulations, the organisms tend to be slower-growing and are often located within granulomas, surrounded by caseous material.

scholarly journals Design of Personalized Devices—The Tradeoff between Individual Value and Personalization Workload

2020 ◽  
Vol 11 (1) ◽  
pp. 241
Author(s):  
Juliane Kuhl ◽  
Andreas Ding ◽  
Ngoc Tuan Ngo ◽  
Andres Braschkat ◽  
Jens Fiehler ◽  
...  
Keyword(s):  
Customer Value ◽  
Early Stage ◽  
Treatment Success ◽  
Product Family ◽  
Flow Diverter ◽  
New Method ◽  
Product Families ◽  
Wide Range ◽  
The Individual ◽  
Individual Value

Personalized medical devices adapted to the anatomy of the individual promise greater treatment success for patients, thus increasing the individual value of the product. In order to cater to individual adaptations, however, medical device companies need to be able to handle a wide range of internal processes and components. These are here referred to collectively as the personalization workload. Consequently, support is required in order to evaluate how best to target product personalization. Since the approaches presented in the literature are not able to sufficiently meet this demand, this paper introduces a new method that can be used to define an appropriate variety level for a product family taking into account standardized, variant, and personalized attributes. The new method enables the identification and evaluation of personalizable attributes within an existing product family. The method is based on established steps and tools from the field of variant-oriented product design, and is applied using a flow diverter—an implant for the treatment of aneurysm diseases—as an example product. The personalization relevance and adaptation workload for the product characteristics that constitute the differentiating product properties were analyzed and compared in order to determine a tradeoff between customer value and personalization workload. This will consequently help companies to employ targeted, deliberate personalization when designing their product families by enabling them to factor variety-induced complexity and customer value into their thinking at an early stage, thus allowing them to critically evaluate a personalization project.

Perceived Causal Problem Networks: Reliability, Central Problems, and Clinical Utility for Depression

Assessment ◽  
2021 ◽  
pp. 107319112110392
Author(s):  
Lars Klintwall ◽  
Martin Bellander ◽  
Matti Cervin
Keyword(s):  
Clinical Utility ◽  
Treatment Success ◽  
Centrality Measures ◽  
Retest Reliability ◽  
Causal Relations ◽  
Future Studies ◽  
Causal Networks ◽  
Novel Method ◽  
The Individual ◽  
Test Retest Reliability

Personalized case conceptualization is often regarded as a prerequisite for treatment success in psychotherapy for patients with comorbidity. This article presents Perceived Causal Networks, a novel method in which patients rate perceived causal relations among behavioral and emotional problems. First, 231 respondents screening positive for depression completed an online Perceived Causal Networks questionnaire. Median completion time (including repeat items to assess immediate test–retest reliability) was 22.7 minutes, and centrality measures showed excellent immediate test–retest reliability. Networks were highly idiosyncratic, but worrying and ruminating were the most central items for a third of respondents. Second, 50 psychotherapists rated the clinical utility of Perceived Causal Networks visualizations. Ninety-six percent rated the networks as clinically useful, and the information in the individual visualizations was judged to contain 47% of the information typically collected during a psychotherapy assessment phase. Future studies should individualize networks further and evaluate the validity of perceived causal relations.

scholarly journals Levitation of non-magnetizable droplet inside ferrofluid

2018 ◽  
Vol 857 ◽  
pp. 398-448 ◽  
Author(s):  
Chamkor Singh ◽  
Arup K. Das ◽  
Prasanta K. Das
Keyword(s):  
Magnetic Field ◽  
Steady State ◽  
Viscosity Ratio ◽  
Temporal Dynamics ◽  
Liquid Droplet ◽  
Droplet Surface ◽  
Two Dimensions ◽  
Projection Algorithm ◽  
The Stability ◽  
The Individual

The central theme of this work is that a stable levitation of a denser non-magnetizable liquid droplet, against gravity, inside a relatively lighter ferrofluid – a system barely considered in ferrohydrodynamics – is possible, and exhibits unique interfacial features; the stability of the levitation trajectory, however, is subject to an appropriate magnetic field modulation. We explore the shapes and the temporal dynamics of a plane non-magnetizable droplet levitating inside a ferrofluid against gravity due to a spatially complex, but systematically generated, magnetic field in two dimensions. The coupled set of Maxwell’s magnetostatic equations and the flow dynamic equations is integrated computationally, utilizing a conservative finite-volume-based second-order pressure projection algorithm combined with the front-tracking algorithm for the advection of the interface of the droplet. The dynamics of the droplet is studied under both the constant ferrofluid magnetic permeability assumption as well as for more realistic field-dependent permeability described by Langevin’s nonlinear magnetization model. Due to the non-homogeneous nature of the magnetic field, unique shapes of the droplet during its levitation, and at its steady state, are realized. The complete spatio-temporal response of the droplet is a function of the Laplace number $La$ , the magnetic Laplace number $La_{m}$ and the Galilei number $Ga$ ; through detailed simulations we separate out the individual roles played by these non-dimensional parameters. The effect of the viscosity ratio, the stability of the levitation path and the possibility of existence of multiple stable equilibrium states is investigated. We find, for certain conditions on the viscosity ratio, that there can be developments of cusps and singularities at the droplet surface; we also observe this phenomenon experimentally and compare with the simulations. Our simulations closely replicate the singular projection on the surface of the levitating droplet. Finally, we present a dynamical model for the vertical trajectory of the droplet. This model reveals a condition for the onset of levitation and the relation for the equilibrium levitation height. The linearization of the model around the steady state captures that the nature of the equilibrium point goes under a transition from being a spiral to a node depending upon the control parameters, which essentially means that the temporal route to the equilibrium can be either monotonic or undulating. The analytical model for the droplet trajectory is in close agreement with the detailed simulations.

scholarly journals Nonlinear visuoauditory integration in the mouse superior colliculus

2021 ◽  
Author(s):  
Shinya Ito ◽  
Yufei Si ◽  
Alan M. Litke ◽  
David A. Feldheim
Keyword(s):  
Superior Colliculus ◽  
Sensory Integration ◽  
Large Scale ◽  
Temporal Dynamics ◽  
Critical Role ◽  
Sensory Information ◽  
Population Level ◽  
Object Identification ◽  
Response Properties ◽  
The Individual

AbstractSensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.

Polyacrylamide gel electrophoresis of exoenzymes produced by Pseudomonas fluorescens strain W

1971 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Harvey Winters ◽  
W. A. Corpe
Keyword(s):  
Pseudomonas Fluorescens ◽  
Bacterial Cell ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Deae Cellulose ◽  
Complex Mixture ◽  
Gram Negative ◽  
Coomassie Blue ◽  
The Individual ◽  
Cell Envelopes

Culture filtrates from strain W of Pseudomonas fluorescens that cause lysis of gram-negative bacterial cell envelopes were examined for specific hydrolases. The enzymes were concentrated by ammonium sulfate fractionation and by column fractionation on Sephadex G-100. Attempts to separate the individual hydrolases quantitatively by elution from DEAE-cellulose failed because of the formation of aggregates. Resolution of the individual hydrolases was accomplished by disc gel electrophoresis using polyacrylamide (7.5%) gels buffered at pH 8.9 with Tris-glycine. The enzyme mixture was separated into 13 distinct protein bands which were stained with Coomassie blue. The individual hydrolases were detected either directly on the gels or by assay after elution from gel segments and included four proteinases, three phosphatases, two β-glucosidases, one ribonuclease, one lipase, one esterase, and one catalase. These methods provide a rapid, sensitive technique for the detection of many individual hydrolases in a complex mixture.

scholarly journals P03.11 Finding a predictive marker for compliance to TTFields therapy - the comptune study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii27-iii27
Author(s):  
M A Proescholdt ◽  
A Haj ◽  
C Doenitz ◽  
A Brawanski ◽  
A Mühlberger ◽  
...  
Keyword(s):  
Psychological Assessment ◽  
Medical Center ◽  
Treatment Success ◽  
Compliance Rate ◽  
Treatment Compliance ◽  
Observation Time ◽  
Continuous Exposure ◽  
Psychological Profile ◽  
Assessment Battery ◽  
The Individual

Abstract BACKGROUND Tumor Treating Fields (TTFields) imply the administration of alternating electric fields to induce mitotic arrest in Glioblastoma (GBM) cells. Based on the specific mode of action, which requires continuous exposure of the malignant cell pool to TTFields, compliance to TTFields treatment is a crucial parameter for treatment success. Correspondingly, a recent post hoc analysis of the EF-14 trial has demonstrated a strong correlation between TTFields compliance rate and treatment success. However, there is currently no data regarding predictive factors for individual compliance rate. We are therefore performing a prospective study designed to analyze specific parameters potentially influencing compliance to TTFields treatment employing a standardized psychological assessment battery in GBM patients who choose or not choose to undergo TTFields treatment in a longitudinal fashion. The results of the psychological profile will be correlated to the compliance rates of the individual patients. MATERIAL AND METHODS Forty adult patients treated for newly diagnosed GBM at the University Regensburg Medical Center will be recruited. The psychological assessment battery aims at assessing four categories relevant for treatment compliance: 1. Lack of communicative skills, 2. depressive and anxiety disorders, 3. interpersonal factors (e.g. social support), and 4. intrapersonal factors, (e.g. beliefs about benefit, self-efficacy). The study endpoints are: 1. willingness to undergo TTFields therapy and 2. compliance rate of the individual patient, provided by the technical support team. The first interview takes place after treatment consultation (T0), 2 weeks after diagnosis (T1), at the initiation of TTFields treatment (T2) and every 4 weeks during treatment either until second disease progression or after maximal 8 months observation time per patient. Additionally, demographic (gender, age, marital status), clinical (KPI, extent of resection) and biological factors (MGMT promoter status, IDH1 mutation) will be assessed. RESULTS The study has been approved by the local ethics committee and has recruited the first 23 patients within 8 months since initiation of the study. The most updated results will be presented at the meeting. CONCLUSION One of the most challenging aspects in the application of TTFields in clinical practice is the identification of influencing factors increasing patients’ compliance. This study is designed to provide a psychological profile predictive for high treatment compliance.

scholarly journals Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 707 ◽  
Author(s):  
Susan Realegeno ◽  
Lalita Priyamvada ◽  
Amrita Kumar ◽  
Jessica B. Blackburn ◽  
Claire Hartloge ◽  
...  
Keyword(s):  
Viral Entry ◽  
Membrane Trafficking ◽  
Gene Knockout ◽  
Host Cells ◽  
Viral Fusion ◽  
Genetic Screens ◽  
Viral Spread ◽  
Cog Complex ◽  
Conserved Oligomeric Golgi ◽  
The Individual

Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1–COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure. In this study, we investigated the role of the COG complex in OPXV infection using cell lines with individual COG gene knockout (KO) mutations. COG KO cells infected with MPXV and vaccinia virus (VACV) produced small plaques and a lower virus yield compared to wild type (WT) cells. In cells where the KO phenotype was reversed using a rescue plasmid, the size of virus plaques increased demonstrating a direct link between the decrease in viral spread and the KO of COG genes. KO cells infected with VACV displayed lower levels of viral fusion and entry compared to WT suggesting that the COG complex is important for early events in OPXV infection. Additionally, fewer actin tails were observed in VACV-infected KO cells compared to WT. Since COG complex proteins are required for cellular trafficking of glycosylated membrane proteins, the disruption of this process due to lack of individual COG complex proteins may potentially impair the virus-cell interactions required for viral entry and egress. These data validate that the COG complex previously identified in our genetic screens plays a role in OPXV infection.

Commercial microwave links in urban rainfall-runoff modelling: Two different approaches to removing the bias

2020 ◽  
Author(s):  
Jaroslav Pastorek ◽  
Martin Fencl ◽  
Jörg Rieckermann ◽  
Vojtěch Bareš
Keyword(s):  
Wave Attenuation ◽  
Temporal Dynamics ◽  
Estimation Methods ◽  
Rainfall Runoff ◽  
Geophysical Research ◽  
Urban Catchment ◽  
Individual Level ◽  
The Individual ◽  
Commercial Microwave Links ◽  
Heavy Rainfalls

<p>Commercial microwave links (CMLs) are point-to-point radio connections widely used as cellular backhaul and thus very well covering urbanized areas. They can provide path-integrated quantitative precipitation estimates (QPEs) as they operate at frequencies where radio wave attenuation caused by raindrops is almost proportional to rainfall intensity. Pastorek et al. (2019b) demonstrated the feasibility of using CML QPEs to predict rainfall-runoff in a small urban catchment. Unfortunately, runoff volumes were highly biased, mostly for QPEs from short CMLs, although the temporal runoff dynamics were predicted very well, especially during heavy rainfall events. It was also shown that, for the heavy rainfalls, reducing the bias by adjusting the CML QPEs to traditional rainfall measurements (Fencl et al., 2017) leads to less accurate reproduction of the runoff temporal dynamics.</p><p>Current understanding is that the bias in CML QPEs is often caused by imprecise estimation of wet antenna attenuation (WAA), which is a complex process influenced by many physical phenomena, including radome hardware or positioning of the outdoor unit. However, traditional WAA estimation methods are typically unable to take into account all the individual-level factors. We proposed (Pastorek et al., 2019a) to estimate WAA separately for each of the examined CMLs by using discharge measurements at the outlet of a small urban catchment and showed that this approach can reduce the bias in CML QPEs, leading to generally satisfying performance of rainfall-runoff models, mainly for heavy rainfalls.</p><p>In the presented study, we evaluate the effect of the method proposed in Pastorek et al. (2019a) (method i) on rainfall-runoff modelling in more detail and compare it to the method of Fencl et al. (2017) (method ii). For a case study in Prague-Letňany, Czech Rep., a calibrated rainfall-runoff model is used to predict discharges at the outlet of the small urban catchment (1.3 km<sup>2</sup>) using QPEs from 16 CMLs. First results confirm that minimizing the bias in CML QPEs using method i is convenient mainly for heavy rainfalls, as Nash-Sutcliffe efficiency is considerably higher in this case for all but one CML (on average 0.65; only 0.40 for method ii). Moreover, method i preserves the information about the rainfall temporal dynamics during heavy rainfalls better than method ii for most of the individual CMLs (correlation coefficient with observed runoffs on average 0.83 for method i and 0.78 for method ii). Next steps should include generalization for other case studies, including an exploratory analysis of the potential mismatches.</p><p> </p><p>References</p><p>Fencl, M., Dohnal, M., Rieckermann, J., Bareš, V., 2017. Gauge-adjusted rainfall estimates from commercial microwave links. Hydrol. Earth Syst. Sci. 21, 617–634.</p><p>Pastorek, J., Fencl, M., Rieckermann, J. and Bareš, V., 2019b. Commercial microwave links for urban drainage modelling: The effect of link characteristics and their position on runoff simulations. Journal of environmental management 251, 109522.</p><p>Pastorek, J., Fencl, M., and Bareš, V., 2019a. Calibrating microwave link rainfall retrieval model using runoff observations. Geophysical Research Abstracts 21, EGU2019-10072.</p><p> </p><p>This study was supported by the project no. 20-14151J of the Czech Science Foundation and by the project of the Czech Technical University in Prague no. SGS19/045/OHK1/1T/11.</p>

scholarly journals A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Melisa Hendrata ◽  
Janti Sudiono
Keyword(s):  
Differential Equations ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Multiscale Model ◽  
Cellular Migration ◽  
Phenotypic Switching ◽  
Tumor Growth Rate ◽  
Discrete Equations ◽  
Pathological Conditions ◽  
Avascular Tumor

Apoptosis is a programmed cell death that occurs naturally in physiological and pathological conditions. Defective apoptosis can trigger the development and progression of cancer. Experiments suggest the ability of secretome derived from mesenchymal stem cells (MSC) to induce apoptosis in cancer cells. We develop a hybrid discrete-continuous multiscale model to further investigate the effect of MSC-derived secretome in tumor growth. The model encompasses three biological scales. At the molecular scale, a system of ordinary differential equations regulate the expression of proteins involved in apoptosis signaling pathways. At the cellular scale, discrete equations control cellular migration, phenotypic switching, and proliferation. At the extracellular scale, a system of partial differential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. The simulation is able to produce both avascular tumor growth rate and phenotypic patterns as observed in the experiments. In addition, we obtain good quantitative agreements with the experimental data on the apoptosis of HeLa cancer cells treated with MSC-derived secretome. We use this model to predict the growth of avascular tumor under various secretome concentrations over time.

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