Arguing Using Opponent Models

Peer reviewedPostprin

T1ρ-based fibril-reinforced poroviscoelastic constitutive relation of human articular cartilage using inverse finite element technology

BackgroundMapping of T1ρ relaxation time is a quantitative magnetic resonance (MR) method and is frequently used for analyzing microstructural and compositional changes in cartilage tissues. However, there is still a lack of study investigating the link between T1ρ relaxation time and a feasible constitutive relation of cartilage which can be used to model complicated mechanical behaviors of cartilage accurately and properly.MethodsThree-dimensional finite element (FE) models of ten in vitro human tibial cartilage samples were reconstructed such that each element was assigned by material-level parameters, which were determined by a corresponding T1ρ value from MR maps. A T1ρ-based fibril-reinforced poroviscoelastic (FRPE) constitutive relation for human cartilage was developed through an inverse FE optimization technique between the experimental and simulated indentations.ResultsA two-parameter exponential relationship was obtained between the T1ρ and the volume fraction of the hydrated solid matrix in the T1ρ-based FRPE constitutive relation. Compared with the common FRPE constitutive relation (i.e., without T1ρ), the T1ρ-based FRPE constitutive relation indicated similar indentation depth results but revealed some different local changes of the stress distribution in cartilages.ConclusionsOur results suggested that the T1ρ-based FRPE constitutive relation may improve the detection of changes in the heterogeneous, anisotropic, and nonlinear mechanical properties of human cartilage tissues associated with joint pathologies such as osteoarthritis (OA). Incorporating T1ρ relaxation time will provide a more precise assessment of human cartilage based on the individual in vivo MR quantification

In the early global fight against COVID-19, quick mask mandates were most effective

Before the development of an effective vaccine, policymakers had to use other approaches such as mask mandates and stay-at-home orders to slow the spread of COVID-19. In new research covering 164 countries, Brian An, Simon Porcher, Shui-Yan Tang, and Eunji Emily Kim examine the effectiveness of these measures aimed at stopping the spread of COVID-19, finding that mask mandates, if adopted early, were the most effective. They also find that countries with less individualistic cultures, and those with better healthcare capacity prior to the pandemic, were more likely to adopt early mask mandates

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to the mouse lumbar intervertebral disc

A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries

An Experimental Investigation of Humidity and Temperature Effects on the Mechanical Properties of Persfluorosulfonic Acid Membrane

The mechanical properties of a perfluorosulfonic acid (PFSA) membrane have been investigated at different humidities and temperatures in a custom-designed environmental chamber. Tensile tests were conducted to determine Young’s modulus, the proportional limit stress (“yield strength”), break stress, and break strain. In-plane dimensional changes of the membrane at different temperature and humidities were also determined. The results indicate that Young’s modulus and the proportional limit stress of the PFSA membrane decrease as humidity and temperature increase. Higher temperature leads to lower break stress and higher break strain. However, humidity has little effect on the break stress and break strain. A nonparametric statistical analysis, Kruskal–Wallis test, is applied to the experimental results, which shows that the effects of temperature and humidity on Young’s modulus and proportional limit stress are statistically significant

An Experimental Investigation of Humidity and Temperature Effects on the Mechanical Properties of Persfluorosulfonic Acid Membrane

The mechanical properties of a perfluorosulfonic acid (PFSA) membrane have been investigated at different humidities and temperatures in a custom-designed environmental chamber. Tensile tests were conducted to determine Young’s modulus, the proportional limit stress (“yield strength”), break stress, and break strain. In-plane dimensional changes of the membrane at different temperature and humidities were also determined. The results indicate that Young’s modulus and the proportional limit stress of the PFSA membrane decrease as humidity and temperature increase. Higher temperature leads to lower break stress and higher break strain. However, humidity has little effect on the break stress and break strain. A nonparametric statistical analysis, Kruskal–Wallis test, is applied to the experimental results, which shows that the effects of temperature and humidity on Young’s modulus and proportional limit stress are statistically significant

Towards controlling activity of a peptide asparaginyl ligase (PAL) by lumazine synthetase compartmentalization

Peptide asparaginyl ligases (PALs) hold significant potential in protein bioconjugation due to their excellent kinetic properties and broad substrate compatibility. However, realizing their full potential in biocatalytic applications requires precise control of their activity. Inspired by nature, we aimed to compartmentalize a representative PAL, OaAEP1-C247A, within protein containers to create artificial organelles with substrate sorting capability. Two encapsulation approaches were explored using engineered lumazine synthases (AaLS). The initial strategy involved tagging the PAL with a super-positively charged GFP(+36) for encapsulation into the super-negatively charged AaLS-13 variant, but it resulted in undesired truncation of the enzyme. The second approach involved genetic fusion of the OaAEP1-C247A with a circularly permutated AaLS variant (cpAaLS) and its co-production with AaLS-13, which successfully enabled compartmentalization of the PAL within a patch-work protein cage. Although the caged PAL retained its activity, it was significantly reduced compared to the free enzyme (~30-40-fold), likely caused by issues related to OaAEP1-C247A stability and folding. Nevertheless, these findings demonstrated feasibility of the AaLS encapsulation approach and encourages further optimization in the design of peptide-ligating artificial organelle in E. coli, aiming for a more effective and stable system for protein modifications

Bisphosphonate Treatment Modifies Canine Bone Mineral and Matrix Properties and their Heterogeneity

Bone loss and alterations in bone quality are major causes leading to bone fragility in postmenopausal women. Although bisphosphonates are well known to reduce bone turnover and prevent bone loss in postmenopausal osteoporosis, their effects on other bone properties are not fully characterized. Changes in bone mineral and matrix properties may contribute to the anti-fracture efficacy observed with bisphosphonate treatments. The aim of this work was to analyze the effect of a 1-year treatment with either alendronate or risedronate, at low and high doses, on spatially resolved bone material and compositional properties that could contribute to the fracture efficacy of these agents. Distal tibias from 30 normal beagles that had been treated daily for 1 year with oral doses of vehicle (Veh), alendronate (Aln) at 0.2 or 1 mg/kg, and risedronate (Ris) at 0.1 or 0.5 mg/kg were analyzed by Fourier Transform Infrared imaging (FTIRI) to assess the changes in both mineral and matrix properties in discrete bone areas. The widths at half maximum of the pixel histograms for each FTIRI parameter were used to assess the heterogeneity of the bone tissue. Aln and Ris increased the mineral content and the collagen maturity mainly in cancellous bone and at the endocortical surface. Significant differences were observed in the mineral content and in the hydroxyapatite crystallinity distribution in bone tissue, which can contribute to reduced ductility and micro-crack accumulation. No significant differences were observed between low and high dose nor between Aln and Ris treatments. These results show that pharmacologic suppression of bone turnover increases the mineral and matrix bone tissue maturity in normal cancellous and endocortical bone areas where bone turnover is higher. These positive effects for decreased fracture risk are also associated with a loss of bone heterogeneity that could be one factor contributing to increased bone tissue brittleness and micro-crack accumulation

Rapid determination of internal strains in soft tissues using an experimentally calibrated finite element model derived from magnetic resonance imaging

Background: Finite element models (FEMs) of medical images can provide information about the underlying tissue that cannot be obtained from the original images. Preforming an accurate simulation requires the careful experimental calibration of boundary conditions. Here we describe a method for deriving a geometric mesh for soft biological materials using a magnetic resonance imaging (MRI) system, and an experimental workflow for calibrating the boundary conditions and optimizing the mesh density in these simulations. Methods: A three-dimensional image stack of a ballistic sphere gel, a bovine caudal intervertebral disc (IVD), and a human lumbar IVD were generated using a positional MRI system. These images were then segmented using a semi-automated process, converted to a tetrahedral mesh, and then modeled as a linear elastic solid. The mesh density was optimized based on simulation time and convergence with the experimental results. The modulus of the ballistic gel was determined experimentally, while the material properties for the nucleus pulposus (NP) and the annulus fibrosus (AF) within the bovine and human IVDs were assigned from literature. The simulation for the spherical gel and the bovine IVD matched the reaction forces determined experimentally in compression. We then simulated a 0.3 MPa compressive load on the human lumbar IVD at the optimal mesh density and material properties determined from the bovine model and then examined the resultant internal strains. Results: The scaled mesh density demonstrated excellent correspondence with the experimental results, confirming that accuracy was not compromised. Both the ballistic gel and the IVD samples exhibited a wide range of internal strains. The NP of the IVD underwent greater deformation than the AF under loading. Conclusions: This study validated a strategy for mesh optimization and FEM of soft biological materials from data generated from MRI scans. This calibrated approach allows for the rapid examination of internal strain distributions medical images that can be performed on the order of minutes

Multimodel uncertainty changes in simulated river flows induced by human impact parameterizations

Human impacts increasingly affect the global hydrological cycle and indeed dominate hydrological changes in some regions. Hydrologists have sought to identify the human-impact-induced hydrological variations via parameterizing anthropogenic water uses in global hydrological models (GHMs). The consequently increased model complexity is likely to introduce additional uncertainty among GHMs. Here, using four GHMs, between-model uncertainties are quantified in terms of the ratio of signal to noise (SNR) for average river flow during 1971–2000 simulated in two experiments, with representation of human impacts (VARSOC) and without (NOSOC). It is the first quantitative investigation of between-model uncertainty resulted from the inclusion of human impact parameterizations. Results show that the between-model uncertainties in terms of SNRs in the VARSOC annual flow are larger (about 2% for global and varied magnitude for different basins) than those in the NOSOC, which are particularly significant in most areas of Asia and northern areas to the Mediterranean Sea. The SNR differences are mostly negative (-20% to 5%, indicating higher uncertainty) for basin-averaged annual flow. The VARSOC high flow shows slightly lower uncertainties than NOSOC simulations, with SNR differences mostly ranging from -20% to 20%. The uncertainty differences between the two experiments are significantly related to the fraction of irrigation areas of basins. The large additional uncertainties in VARSOC simulations introduced by the inclusion of parameterizations of human impacts raise the urgent need of GHMs development regarding a better understanding of human impacts. Differences in the parameterizations of irrigation, reservoir regulation and water withdrawals are discussed towards potential directions of improvements for future GHM development. We also discuss the advantages of statistical approaches to reduce the between-model uncertainties, and the importance of calibration of GHMs for not only better performances of historical simulations but also more robust and confidential future projections of hydrological changes under a changing environment