Noninvasive In Vivo Determination of Residual Strains and Stresses

2015 ◽  
Vol 137 (6) ◽  
Author(s):  
Samir Donmazov ◽  
Senol Piskin ◽  
Kerem Pekkan
Keyword(s):  
Experimental Data ◽  
Residual Stress ◽  
Residual Strain ◽  
Analytical Approach ◽  
Measurement Techniques ◽  
Data Sets ◽  
Residual Strains ◽  
Loading And Unloading

Vascular growth and remodeling during embryonic development are associated with blood flow and pressure induced stress distribution, in which residual strains and stresses play a central role. Residual strains are typically measured by performing in vitro tests on the excised vascular tissue. In this paper, we investigated the possibility of estimating residual strains and stresses using physiological pressure–radius data obtained through in vivo noninvasive measurement techniques, such as optical coherence tomography or ultrasound modalities. This analytical approach first tested with in vitro results using experimental data sets for three different arteries such as rabbit carotid artery, rabbit thoracic artery, and human carotid artery based on Fung’s pseudostrain energy function and Delfino’s exponential strain energy function (SEF). We also examined residual strains and stresses in the human swine iliac artery using the in vivo experimental ultrasound data sets corresponding to the systolic-to-diastolic region only. This allowed computation of the in vivo residual stress information for loading and unloading states separately. Residual strain parameters as well as the material parameters were successfully computed with high accuracy, where the relative errors are introduced in the range of 0–7.5%. Corresponding residual stress distributions demonstrated global errors all in acceptable ranges. A slight discrepancy was observed in the computed reduced axial force. Results of computations performed based on in vivo experimental data obtained from loading and unloading states of the artery exhibited alterations in material properties and residual strain parameters as well. Emerging noninvasive measurement techniques combined with the present analytical approach can be used to estimate residual strains and stresses in vascular tissues as a precursor for growth estimates. This approach is also validated with a finite element model of a general two-layered artery, where the material remodeling states and residual strain generation are investigated.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

MondoA Drives B-ALL Malignancy through Enhanced Adaptation to Metabolic Stress

Blood ◽  
2021 ◽  
Author(s):  
Alexandra Sipol ◽  
Erik Hameister ◽  
Busheng Xue ◽  
Julia Hofstetter ◽  
Maxim Barenboim ◽  
...  
Keyword(s):  
Stress Responses ◽  
Lymphoblastic Leukemia ◽  
Metabolic Stress ◽  
Tca Cycle ◽  
Underlying Mechanism ◽  
Patient Data ◽  
Data Sets ◽  
Dependent Manner

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired anti-metabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is to reprogram gene expression in a metabolism-dependent manner. MondoA (also known as MLXIP), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets we found that MondoA overexpression is associated with a worse survival in pediatric common acute lymphoblastic leukemia (B-ALL). Using CRISPR/Cas9 and RNA interference approaches, we observed that MondoA depletion reduces transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid (TCA) cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced PDH activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give a novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.

scholarly journals Exploring the effect of biological delays in kinetic models of influenza within a host or cell culture

2021 ◽  
Author(s):  
Benjamin P Holder ◽  
Catherine A. A. Beauchemin
Keyword(s):  
Differential Equation ◽  
Experimental Data ◽  
Influenza Infection ◽  
Biologically Relevant ◽  
Differential Equation Models ◽  
Viral Yield ◽  
Infection Parameters ◽  
Delay Differential

Background For a typical influenza infection in vivo, viral titers over time are characterized by 1–2 days of exponential growth followed by an exponential decay. This simple dynamic can be reproduced by a broad range of mathematical models which makes model selection and the extraction of biologically-relevant infection parameters from experimental data difficult. Results We analyze in vitro experimental data from the literature, specifically that of single-cycle viral yield experiments, to narrow the range of realistic models of infection. In particular, we demonstrate the viability of using a normal or lognormal distribution for the time a cell spends in a given infection state (e.g., the time spent by a newly infected cell in the latent state before it begins to produce virus), while exposing the shortcomings of ordinary differential equation models which implicitly utilize exponential distributions and delay-differential equation models with fixed-length delays. Conclusions By fitting published viral titer data from challenge experiments in human volunteers, we show that alternative models can lead to different estimates of the key infection parameters.

scholarly journals Three-dimensional residual strain in midanterior canine left ventricle

1997 ◽  
Vol 273 (4) ◽  
pp. H1968-H1976 ◽  
Author(s):  
Kevin D. Costa ◽  
Karen May-Newman ◽  
Dyan Farr ◽  
Walter G. O’Dell ◽  
Andrew D. McCulloch ◽  
...  
Keyword(s):  
Residual Stress ◽  
Left Ventricle ◽  
Residual Strain ◽  
Three Dimensional ◽  
Element Analysis ◽  
Primary Mechanism ◽  
Dimensional Measurements ◽  
Residual Strains ◽  
Shear Strains ◽  
Pressure State

All previous studies of residual strain in the ventricular wall have been based on one- or two-dimensional measurements. Transmural distributions of three-dimensional (3-D) residual strains were measured by biplane radiography of columns of lead beads implanted in the midanterior free wall of the canine left ventricle (LV). 3-D bead coordinates were reconstructed with the isolated arrested LV in the zero-pressure state and again after local residual stress had been relieved by excising a transmural block of tissue. Nonhomogeneous 3-D residual strains were computed by finite element analysis. Mean ± SD ( n = 8) circumferential residual strain indicated that the intact unloaded myocardium was prestretched at the epicardium (0.07 ± 0.06) and compressed in the subendocardium (−0.04 ± 0.05). Small but significant longitudinal shortening and torsional shear residual strains were also measured. Residual fiber strain was tensile at the epicardium (0.05 ± 0.06) and compressive in the subendocardium (−0.01 ± 0.04), with residual extension and shortening, respectively, along structural axes parallel and perpendicular to the laminar myocardial sheets. Relatively small residual shear strains with respect to the myofiber sheets suggest that prestretching in the plane of the myocardial laminae may be a primary mechanism of residual stress in the LV.

Mapping of Intervertebral Disk Annulus Fibrosus Compressive Properties Is Sensitive to Specimen Boundary Conditions

2019 ◽  
Vol 141 (4) ◽  
Author(s):  
Sarah E. Duclos ◽  
Arthur J. Michalek
Keyword(s):  
Residual Strain ◽  
Annulus Fibrosus ◽  
Intervertebral Disk ◽  
Transverse Plane ◽  
The State ◽  
Compressive Properties ◽  
Spatial Homogeneity ◽  
Matrix Deposition ◽  
Residual Strains

Predicting the mechanical behavior of the intervertebral disk (IVD) in health and in disease requires accurate spatial mapping of its compressive mechanical properties. Previous studies confirmed that residual strains in the annulus fibrosus (AF) of the IVD, which result from nonuniform extracellular matrix deposition in response to in vivo loads, vary by anatomical regions (anterior, posterior, and lateral) and zones (inner, middle, and outer). We hypothesized that as the AF is composed of a nonlinear, anisotropic, viscoelastic material, the state of residual strain in the transverse plane would influence the apparent values of axial compressive properties. To test this hypothesis, axial creep indentation tests were performed, using a 1.6 mm spherical probe, at nine different anatomical locations on bovine caudal AFs in both the intact (residual strain present) and strain relieved states. The results showed a shift toward increased spatial homogeneity in all measured parameters, particularly instantaneous strain. This shift was not observed in control AFs, which were tested twice in the intact state. Our results confirm that time-dependent axial compressive properties of the AF are sensitive to the state of residual strain in the transverse plane, to a degree that is likely to affect whole disk behavior.

Curing Residual Strain Monitoring of Carbon Fiber Reinforced Polymer Composite Using Notched Long-Period Fiber Grating

2018 ◽  
Vol 26 (1) ◽  
pp. 27-34
Author(s):  
Ke-Ping Ma ◽  
Chao-Wei Wu ◽  
Bo-Lan Fang ◽  
Chia-Chin Chiang
Keyword(s):  
Residual Stress ◽  
Composite Materials ◽  
Residual Strain ◽  
Structural Engineering ◽  
Fiber Grating ◽  
Long Period Fiber Grating ◽  
Long Period ◽  
Strain Monitoring ◽  
Residual Strains ◽  
Period Fiber Grating

Composite materials are widely used in the aerospace industry and structural engineering owing to their advantageous mechanical properties. The curing monitoring of composite material is important to ensure the quality of the curing process, especially for the characterization of residual strains after manufacturing. In this study, we present a notched long-period fiber grating (NLPFG) with a period of 650 μm and a diameter of 66 μm that can be used in the curing monitoring of composite materials. This NLPFG was embedded into the middle layers of composite materials in order to determine the curing residual stress exhibited by the materials. The experimental results showed that the residual stress was about 107 MPa and the axial residual strain was 1490 με. Therefore, the proposed NLPFG has potential as a strain sensor for composite materials.

scholarly journals The Role of Dimensionality in Understanding Granuloma Formation

Computation ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 58 ◽  
Author(s):  
Simeone Marino ◽  
Caitlin Hult ◽  
Paul Wolberg ◽  
Jennifer Linderman ◽  
Denise Kirschner
Keyword(s):  
Experimental Data ◽  
Large Scale ◽  
Bacterial Load ◽  
Computational Cost ◽  
Granuloma Formation ◽  
In Silico Studies ◽  
Cellular Recruitment ◽  
2D And 3D

Within the first 2–3 months of a Mycobacterium tuberculosis (Mtb) infection, 2–4 mm spherical structures called granulomas develop in the lungs of the infected hosts. These are the hallmark of tuberculosis (TB) infection in humans and non-human primates. A cascade of immunological events occurs in the first 3 months of granuloma formation that likely shapes the outcome of the infection. Understanding the main mechanisms driving granuloma development and function is key to generating treatments and vaccines. In vitro, in vivo, and in silico studies have been performed in the past decades to address the complexity of granuloma dynamics. This study builds on our previous 2D spatio-temporal hybrid computational model of granuloma formation in TB (GranSim) and presents for the first time a more realistic 3D implementation. We use uncertainty and sensitivity analysis techniques to calibrate the new 3D resolution to non-human primate (NHP) experimental data on bacterial levels per granuloma during the first 100 days post infection. Due to the large computational cost associated with running a 3D agent-based model, our major goal is to assess to what extent 2D and 3D simulations differ in predictions for TB granulomas and what can be learned in the context of 3D that is missed in 2D. Our findings suggest that in terms of major mechanisms driving bacterial burden, 2D and 3D models return very similar results. For example, Mtb growth rates and molecular regulation mechanisms are very important both in 2D and 3D, as are cellular movement and modulation of cell recruitment. The main difference we found was that the 3D model is less affected by crowding when cellular recruitment and movement of cells are increased. Overall, we conclude that the use of a 2D resolution in GranSim is warranted when large scale pilot runs are to be performed and if the goal is to determine major mechanisms driving infection outcome (e.g., bacterial load). To comprehensively compare the roles of model dimensionality, further tests and experimental data will be needed to expand our conclusions to molecular scale dynamics and multi-scale resolutions.

scholarly journals Computational toxicology

2015 ◽  
Vol 34 (12) ◽  
pp. 1304-1309 ◽  
Author(s):  
RT Naven ◽  
S Louise-May
Keyword(s):  
Critical Role ◽  
Pharmaceutical Research ◽  
In Vitro Models ◽  
New Drugs ◽  
Data Sets ◽  
Predictive Toxicology ◽  
Drug Induced ◽  
Chemical Toxicology

Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These ‘outliers’ and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them.

scholarly journals Modeling Amantadine Treatment of Inuenza A Virus In Vitro

2021 ◽  
Author(s):  
Catherine A. A. Beauchemin ◽  
James J. McSharry ◽  
George L. Drusano ◽  
Jack T. Nguyen ◽  
Gregory T. Went ◽  
...  
Keyword(s):  
Experimental Data ◽  
Viral Infection ◽  
Mathematical Models ◽  
Influenza A ◽  
Mdck Cells ◽  
Rapid Development ◽  
Human Model ◽  
Parameter Estimates

We analyzed the dynamics of an influenza A/Albany/1/98 (H3N2) viral infection, using a set of mathematical models highlighting the differences between in vivo and in vitro infection. For example, we found that including virion loss due to cell entry was critical for the in vitro model but not for the in vivo model. Experiments were performed on influenza virus-infected MDCK cells in vitro inside a hollow-fiber (HF) system, which was used to continuously deliver the drug amantadine. The HF system captures the dynamics of an influenza infection, and is a controlled environment for producing experimental data which lend themselves well to mathematical modeling. The parameter estimates obtained from fitting our mathematical models to the HF experimental data are consistent with those obtained earlier for a primary infection in a human model. We found that influenza A/Albany/1/98 (H3N2) virions under normal experimental conditions at 37°C rapidly lose infectivity with a half-life of ~ 6.6 ± 0.2 h, and that the lifespan of productively infected MDCK cells is ~ 13 h. Finally, using our models we estimated that the maximum efficacy of amantadine in blocking viral infection is ~ 74%, and showed that this low maximum efficacy is likely due to the rapid development of drug resistance.

scholarly journals Various Knee Model Measurement Techniques to Find the Knee Geometries

2016 ◽  
Vol 3 (3) ◽  
pp. 4-6
Author(s):  
Kavinaya C ◽  
Ashuthoshkumar L
Keyword(s):  
Computational Models ◽  
Measurement Techniques ◽  
Knee Kinematics ◽  
Load Measurement ◽  
Knee Simulator ◽  
Subject Specific ◽  
The Subject ◽  
Model Measurement

Computation of knee modeling is a subject-specific techniquethatdefining the zero-load measurements of the cruciate and indemnity ligaments.The dynamic knee simulator was used to test the three carcass knees. The carcass knees also experiencedphysicalsachet of motion testing to discovery their inactivesort of motion in order to regulate the zero-load measurements for everymuscle bundle. Compotation multibody knee representations were shaped for each knee and classical kinematics were likened to investigational kinematics for a replicated walk series. Simple-minded non-linear mechanisminhibition elements were used to characterize cruciate and deposited particles in musclepackages in the knee representations. This learningoriginate that knee kinematics was enormously sensitive to changing of the zero-load measurement. The domino effects also recommendoptimum methods for describing each of the muscle bundle zero-load measurements, irrespective of the subject. These consequencesvalidate the significance ofthe zero-load length when modeling the knee united and verify that physicalcloak of motion dimensions can be usedto determine the passive range of motion of the knee joint. It is also supposed that the method defined here forresponsible zero-load measurement can be used for in vitro or in vivo subject-specific computational models.

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