Finite element model of stresses in the anterior lens capsule of the eye

Continuum biomechanics continues to aid in the design of clinical procedures and biomedical devices. Such design requires detailed information on the biomechanical properties of the tissues of interest as well as appropriate methods of analysis. In this paper, we use a fully nonlinear, virtual work based finite element method to study the normal stress field in the anterior lens capsule of the porcine eye. The analysis shows that recently measured regional variations in material symmetry may combine with regional variations in membrane thickness to yield a nearly uniform and equibiaxial stress field in normalcy. These findings are discussed in terms of potential implications to the underlying mechanobiology and in particular, in terms of perturbations in stress that result from cataract surgery, the most commonly performed surgical procedure in North America.     

Three-dimensional mathematical model analysis of the patellofemoral joint

This paper is concerned with a mathematical model analysis of the patellofemoral joint in the human knee, taking into account the articular surface geometry and mechanical properties of the ligament. It was made by the application of a computer-aided design theory (previously studied) and it was possible to express the articular surface geometries in a mathematical formulation and hence elucidate the joint movement mechanics. This method was then applied to a three-dimensional geometrical model of the patellofemoral joint. For the modelling of tendofemoral contact at large angles of knee flexion, the geodestic line theory was adopted. Applying the Newton-Raphson method and the Runge-Kutta Gil method to the model, variables such as patellar attitudes, patellofemoral contact force and tensile force of the patellar ligament for various knee flexion angles were computed. Applying the Hertzian elastic theory, contact stress was also computed. These results showed good agreement with the previously reported experimental results. As an application for the model, some parameter analyses were performed in terms of the contact stress variations and compared with those of the normal knee. The simulation results indicated that both the Q-angle increase and decrease increased contact stress, the patella alta showed undulating variations of stress while the patella infera showed little change of stress, and the tibial tuberositas elevation showed 20-30% reduction of stress.     

Measuring antioxidants in tree species in the natural environment: from sampling to data evaluation

Biochemical measurements of antioxidants and protective pigments have been successfully introduced as markers of environmental stress in field studies (mainly forest studies). A guideline for field sampling and analysis methods is required to allow better comparison of data from different studies. The present review paper recommends HPLC methods for the analysis of ascorbate and glutathione (in oxidized and reduced form), tocopherols, and chloroplast pigments. Methodological variations are substantially lower (coefficients of variance of repeated extractions typically 4-9%) than biological variations of field samples (typical variation coefficients 8-36%), hence special emphasis is put on considerations of sampling standardization in the field with respect to sample time (seasonal and diurnal) and representative sampling of individuals and tissues. Following the suggestions in this paper would enable researchers to produce results that could be compared with those of several forest studies on conifers published in recent years. A larger data-set available for multivariate statistical evaluations (e.g. principal component analysis and cluster analysis) will enhance the diagnostic value of such investigations.     

Three-dimensional quantitative structure–activity relationship study on paullones as CDK inhibitors using CoMSIA and CoMFA

3D-QSAR studies were conducted on a series of paullones as CDK inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR) methods. Two methods were compared: the widely used comparative molecular field analysis (CoMFA) and the recently reported comparative molecular similarity indices analysis (CoMSIA). Systematic variations of some parameters in CoMSIA and CoMFA were performed to search for the best 3D-QSAR model. The computed results showed that the 3D-QSAR models from CoMSIA were clearly superior to those from CoMFA. Using the best model from CoMSIA analysis, a significant cross-validated q² was obtained and the predicted biological activities of the five compounds in the test set were in good agreement with the experimental values. The correlation results obtained from CoMSIA were graphically interpreted in terms of field contribution maps allowing physicochemical properties relevant for binding to be easily mapped back onto molecular structures. The features in the CoMSIA contour maps intuitively suggested where to modify a molecular structure in terms of physicochemical properties and functional groups in order to improve its binding affinity, which is very important for improving our understanding of the ligand-receptor interactions and in helping to design compounds with improved activity.     

Specificity in carcinogen-DNA interaction: a theoretical exploration of the factors involved in the effect of neighboring bases on N-methyl-N-nitrosourea alkylation of DNA

Recent experimental studies indicate that in a polynucleotide chain neighboring bases have a significant effect on the relative alkylation of O6 or N7 of guanine by N-methyl-N-nitrosourea (MNU). This paper provides a theoretical exploration of this phenomenon in terms of an appropriate index of reactivity, called accessible surface integrated field (ASIF), introduced recently for the very sake of accounting for specificity or selectivity in drug-macromolecule interaction. The detailed analysis indicates that in the present case the observed variations in relative reactivity are attributable essentially to parallel variations in the accessibilities to the target atoms.     

Bioelectrorheological model of the cell. 3. Viscoelastic shear deformation of the membrane.

An analytical electromechanical model of a spherical cell exposed to an alternating electric field was used to calculate shear stress generated in the cellular membrane. Shape deformation of Neurospora crassa (slime) spheroplasts was measured. Statistical analysis permitted empirical evaluation of creep of the cellular membrane within the range of infinitesimal stress. Final results were discussed in terms of various rheological models.     

Quantum chemical analysis explains hemagglutinin peptide-MHC Class II molecule HLA-DRbeta1*0101 interactions

We present a new method to explore interactions between peptides and major histocompatibility complex (MHC) molecules using the resultant vector of the three principal multipole terms of the electrostatic field expansion. Being that molecular interactions are driven by electrostatic interactions, we applied quantum chemistry methods to better understand variations in the electrostatic field of the MHC Class II HLA-DRbeta1*0101-HA complex. Multipole terms were studied, finding strong alterations of the field in Pocket 1 of this MHC molecule, and weak variations in other pockets, with Pocket 1>Pocket 4>Pocket 9 approximately Pocket 7>Pocket 6. Variations produced by "ideal" amino acids and by other occupying amino acids were compared. Two types of interactions were found in all pockets: a strong unspecific one (global interaction) and a weak specific interaction (differential interaction). Interactions in Pocket 1, the dominant pocket for this allele, are driven mainly by the quadrupole term, confirming the idea that aromatic rings are important in these interactions. Multipolar analysis is in agreement with experimental results, suggesting quantum chemistry methods as an adequate methodology to understand these interactions.     

The implant thread as a retention element in cortical bone: the effect of thread size and thread profile: a finite element study

Assuming that high stress peaks in the bone can trigger bone resorption a screw-shaped bone implant should be given such a design that the peak stresses arising in the bone, as a result of a certain load, are minimized. Using idealized assumptions the aim of the study was to analyse the effect of variations of the size and the profile of the thread of an axially loaded, screw-shaped, bone implant upon the magnitude of the stress peaks in cortical bone. The investigation was performed by means of axisymmetric finite element analysis. It was found that the shape of the thread profile has a profound effect upon the magnitude of the stresses in the bone and that very small threads of a favourable profile can be quite effective.     

Decreased glucose tolerance but normal blood glucose levels in the field in the caviomorph rodent Ctenomys talarum: the role of stress and physical activity

Hystricomorph rodents have a divergent insulin molecule with only 1-10% of the biological activity in comparison to other mammalian species. In this study, we used the subterranean rodent Ctenomys talarum as a model and performed blood glucose tolerance tests (GTTs) with trained and untrained individuals to evaluate blood glucose regulation and the possible role of physical activity as a compensatory mechanism. Additionally, we evaluated the variations in blood glucose during acute and chronic stress and gathered data in the field to evaluate natural-occurring variations in blood glucose levels. The GTTs showed that C. talarum have a diminished capacity of regulating blood glucose levels in comparison to other mammals and suggest that unexplored differences in the compensatory mechanisms, insulin structure and/or glucose transporters exist within species of hystricomorph rodents. However, blood glucose levels in the field stayed within the normal mammalian range. Physical activity did not prove to be a compensatory mechanism for blood glucose regulation. The individuals did not display important increases in blood glucose after acute stressors and managed to adequately regulate blood glucose during chronic stress. We suggest that the species may not face a selective pressure favoring a more tightly, mammalian like, capacity of regulating blood glucose levels.     

Plastic responses in the metabolome and functional traits of maize plants to temperature variations

Environmentally inducible phenotypic plasticity is a major player in plant responses to climate change. However, metabolic responses and their role in determining the phenotypic plasticity of plants that are subjected to temperature variations remain poorly understood. The metabolomic profiles and metabolite levels in the leaves of three maize inbred lines grown in different temperature conditions were examined with a nuclear magnetic resonance metabolomic technique. The relationship of functional traits to metabolome profiles and the metabolic mechanism underlying temperature variations were then explored. A comparative analysis showed that during heat and cold stress, maize plants shared common plastic responses in biomass accumulation, carbon, nitrogen, sugars, some amino acids and compatible solutes. We also found that the plastic response of maize plants to heat stress was different from that under cold stress, mainly involving biomass allocation, shikimate and its aromatic amino acid derivatives, and other non‐polar metabolites. The plastic responsiveness of functional traits of maize lines to temperature variations was low, while the metabolic responsiveness in plasticity was high, indicating that functional and metabolic plasticity may play different roles in maize plant adaptation to temperature variations. A linear regression analysis revealed that the maize lines could adapt to growth temperature variations through the interrelation of plastic responses in the metabolomes and functional traits, such as biomass allocation and the status of carbon and nitrogen. We provide valuable insight into the plastic response strategy of maize plants to temperature variations that will permit the optimisation of crop cultivation in an increasingly variable environment.     

Modeling normal and altered human erythrocyte shapes by a new parametric equation: application to the calculation of induced transmembrane potentials

We present simple parametric equations in terms of Jacobi elliptic functions that provide a realistic model of abnormal variations in size which maintain the biconcave shape of a normal erythrocyte (anisocytosis) and abnormal variations in shape which maintain the original volume of the erythrocyte (poikilocytosis), as well as continuous deformations from the normal to the altered shapes. We illustrate our results with parameterizations of microcytes, macrocytes, and stomatocytes, and we apply these parameterizations to the numerical calculation of the induced transmembrane voltage in microcytes, macrocytes, and stomatocytes exposed to an external electromagnetic field of 1800 MHz.     

Study of the velocity and strain fields in the flow through prosthetic heart valves

A comparative experimental study of the velocity field and the strain field produced down-stream of biological and mechanical artificial valves is presented. In order to determine the spatial and temporal distributions of these fields, a phase-locked stereoscopic particle image velocimetry (or 3D-PIV) technique was implemented. Emphasis was placed on the identification of the fundamental differences between the extensional and the shear components of the strain tensor. The analysis of the characteristic flows reveal that the strains in every direction may reach high values at different times during the cardiac cycle. It was found that elevated strain levels persist throughout the cardiac cycle as a result of all these contributions. Finally, it is suggested that the frequency with which the strain variations occur at particular instants and locations could be associated to the cumulative damage process of the blood constituents and should be taken into account in the overall assessment of existing valve types, as well as in future design efforts.     

Local variations in the micromechanical properties of mouse femur: the involvement of collagen fiber orientation and mineralization

In this study we sought to understand the material level basis for local variations in the uniaxial micromechanical properties of mouse cortical bone. It was hypothesized that the opposing anterior and posterior quadrants will significantly differ in terms of their mechanical function, such that, the anterior portion will be stronger in tension whereas the posterior quadrant will be stronger in compression. Mechanical properties were assessed via microtensile and microcompressive tests of standardized coupon-shaped specimens from femurs of Swiss Webster mice (9 weeks). The mineralization and mineral quality was assessed via Raman spectroscopy and the overall collagen orientation was investigated with quantitative polarized imaging. Micromechanical tests demonstrated that the modulus, yield stress, maximum stress and fracture energy of the posterior quadrant was 66%, 53%, 42% and 31% of anterior quadrant; however, the compressive properties did not differ between the two quadrants. Raman microspectroscopic analysis indicated that the mineral matrix ratio, mineral crystallinity and carbonation did not vary between the quadrants. However, the collagen fibers in the anterior quadrant were significantly (p<0.05) more oriented along the longer axis of the diaphyseal shaft than the collagen fibers of the posterior quadrant. Therefore, we concluded that the orientation of collagen fibers with respect to the anatomical loading axis has a profound effect on the uniaxial mechanical function of murine bone. It will be a matter of further research to reveal the role of local variations in the mode of stress on this material level dichotomy in tissue organization and mechanical function.     

Bioelectrorheological model of the cell. 1. Analysis of stresses and deformations

An electrorheological model of a cell in alternating electric field is proposed. The model relates changes in the spherical cell's shape to the field conditions, electric parameters of cytoplasm, cell membrane and external medium, and to the rheological parameters of the membrane. Stresses were determined using Maxwell's stress tensor for isotropic media. Shear stresses in the cell membrane were analyzed. Predictions of the model for variations of shear stress in cellular membranes subjected to an external periodic electric field are presented and related to the conditions prevailing in electrobiological research.     

Computational model of the fluid dynamics of a cannula inserted in a vessel: incidence of the presence of side holes in blood flow

Vascular access methods, performed by the insertion of cannulae into vessels, may disturb the physiological flow of blood, giving rise to non-physiological pressure variations and shear stresses. To date, the hydrodynamic behaviour of the cannulae has been evaluated comparing their pressure loss–flow rate relationships, as obtained from in vitro experiments using a monodimensional approach; this methodology neither furnish information about the local fluid dynamics nor the established flow field in specific clinical work conditions. Since the shear stress is a critical factor in the design of artificial circulatory devices, more knowledge should be necessary about the local values assumed by the haemodynamic parameters during cannulation. An alternative way to investigate the fluid dynamic as accurately as possible is given by numeric studies. A 3D model of cannula concentrically placed in a rigid wall vessel is presented, with the finite element methodology used to numerically simulate the steady-state flow field in two different venous cannulation case studies, with two cannulae having a central hole and two or four side holes, respectively, with the same boundary conditions. Lower velocity and shear stress peak values have been computed for the model with four side holes upstream of the central hole, in the region of the cannula where the inlet flows meet and towards cannula's outlet, due to the increased flow symmetry and inlet area with respect to the model with two side holes. Starting from the investigation of different cannula designs, numerically assessing the local fluid dynamics, indications can be drawn to support both the design phase and the device optimal clinical use, in order to limit risks of biomechanical origin. Thus the presence of four side holes implied, as a consequence of the greater inlet area and of the increased symmetry, a less disturbed blood flow, together with reduced shear stress values. Furthermore, results show that the numerical simulations furnished useful informations on the interaction between vessel and cannula, e.g. on the fluid dynamics establishing in the free luminal space left, in the vessel, by the inserted cannula.     

Morpho–physiological responses of Rocket (<Emphasis Type="Italic">Eruca sativa</Emphasis> L.) varieties to sodium sulfate (Na<Subscript>2</Subscript>SO<Subscript>4</Subscript>) stress: an experimental approach

Rocket (Eruca sativa L.) is a medicinal plant that belongs to the Brassicaceae family and was reported to be a tolerant plant under soil salinity as well as high genetic diversity among its varieties. Since morphological and physiological changes to sodium sulfate stress toward this plant have not been investigated yet, the present study was implemented to assess the response of rocket (Eruca sativa L.) varieties to sodium sulfate (Na2SO4) stress as well as the relationship among these traits. Two varieties of rocket plants, the Iranian and Italian ones, were subjected to four salinity (Na₂SO₄) treatments [0 (control), 15, 30 and 60 mM of Na₂SO₄ solution] and three growth stages (49, 65, and 74 days) in factorial experiment with completely randomized design and three replications were considered. Some morphologic traits such as grain yield were measured during the growth period. The results of the analysis of variances between the mentioned variables indicated a significant difference between the varieties in terms of K⁺, Na⁺, Na⁺/K⁺, leaf length, grain yield, organic and mineral matter. The results of correlation and regression of the amounts of K⁺ showed a linear relationship with the grain yield and its variations were not independent from the variations of grain yield. Eventually, it seems that the Italian variety was more tolerant and having better performance in comparison with the Iranian variety, in response to salt stress.     

Design optimization of scaffold microstructures using wall shear stress criterion towards regulated flow-induced erosion

Tissue scaffolds aim to provide a cell-friendly biomechanical environment for facilitating cell growth. Existing studies have shown significant demands for generating a certain level of wall shear stress (WSS) on scaffold microstructural surfaces for promoting cellular response and attachment efficacy. Recently, its role in shear-induced erosion of polymer scaffold has also drawn increasing attention. This paper proposes a bi-directional evolutionary structural optimization (BESO) approach for design of scaffold microstructure in terms of the WSS uniformity criterion, by downgrading highly-stressed solid elements into fluidic elements and/or upgrading lowly-stressed fluidic elements into solid elements. In addition to this, a computational model is presented to simulate shear-induced erosion process. The effective stiffness and permeability of initial and optimized scaffold microstructures are characterized by the finite element based homogenization technique to quantify the variations of mechanical properties of scaffold during erosion. The illustrative examples show that a uniform WSS is achieved within the optimized scaffold microstructures, and their architectural and biomechanical features are maintained for a longer lifetime during shear-induced erosion process. This study provides a mathematical means to the design optimization of cellular biomaterials in terms of the WSS criterion towards controllable shear-induced erosion.     

Genome-Wide Analysis of Genetic Variations and the Detection of Rich Variants of NBS-LRR Encoding Genes in Common Wild Rice Lines

Common wild rice (Oryza rufipogon Griff.) is invaluable genetic resource for rice resistance breeding. Whole-genome re-sequencing was conducted to systematically analyze the variations in two new inbred lines (Huaye 3 and Huaye 4) developed from a common wild rice. A total of 4,841,127 SNPs, 1,170,479 InDels, 24,080 structural variations (SVs), and 298 copy number variations (CNVs) were identified in three materials. Approximately 16.24 and 5.64% of the total SNPs and InDels of Huaye 3 and Huaye 4 were located in genic regions, respectively. Together, 12,486 and 15,925 large-effect SNPs, and 12,417 and 14,513 large-effect InDels, which affect the integrity of the encoded protein, were identified in Huaye 3 and Huaye 4, respectively. The distribution map of 194 and 245 NBS-LRR encoding homologs was constructed across 12 rice chromosomes. Further, GO enrichment analysis of the homologs with identical genotype variations in Huaye 3 and Huaye 4 revealed 67, 82, and 58 homologs involved in cell death, response to stress, and both terms, respectively. Comparative analysis displayed that 550 out of 652 SNPs and 129 out of 147 InDels were present in a widely used blast-susceptible rice variety (LTH). Protein-protein interaction analysis revealed a strong interaction between NBS-LRR candidates and several known R genes. One homolog of disease resistance protein (RPM1) was involved in the plant-pathogen interaction pathway. Artificial inoculation of disease/insect displayed resistance phenotypes against rice blast and brown planthopper in two lines. The results will provide allele-specific markers for rice molecular breeding.     

Effects of stents under asymmetric inflow conditions

Patient-to-patient variations in artery geometry may determine their susceptibility to stenosis formation. These geometrical variations can be linked to variations in flow characteristics such as wall shear stress through stents, which increases the risk of restenosis. This paper considers computer models of stents in non-symmetric flows and their effects on flow characteristics at the wall. This is a fresh approach from the point of view of identifying a stent design whose performance is insensitive to asymmetric flow. Measures of dissipated energy and power are introduced in order to discriminate between competing designs of stents.     

Design of the lac gene circuit revisited

The lactose (lac) operon of Escherichia coli serves as the paradigm for gene regulation, not only for bacteria, but also for all biological systems from simple phage to humans. The details of the systems may differ, but the key conceptual framework remains, and the original system continues to reveal deeper insights with continued experimental and theoretical study. Nearly as long lasting in impact as the pivotal work of Jacob and Monod is the classic experiment of Novick and Weiner in which they demonstrated all-or-none gene expression in response to an artificial inducer. These results are often cited in claims that normal gene expression is in fact a discontinuous bistable phenomenon. In this paper, I review several levels of analysis of the lac system and introduce another perspective based on the construction of the system design space. These represent variations on a theme, based on a simply stated design principle, that captures the key qualitative features of the system in a largely mechanism-independent fashion. Moreover, this principle can be readily interpreted in terms of specific mechanisms to make predictions regarding monostable vs. bistable behavior. The regions of design space representing bifurcations are compared with the corresponding regions identified through bifurcation analysis. I present evidence based on biological considerations as well as modeling and analysis to suggest that induction of the lac system in its natural setting is a monostable continuously graded phenomenon. Nevertheless, it must be acknowledged that the lac stability question remains unsettled, and it undoubtedly will remain so until there are definitive experimental results.