A multiscale hybrid mathematical model of epidermal-dermal interactions during skin wound healing.

Following injury, skin activates a complex wound healing programme. While cellular and signalling mechanisms of wound repair have been extensively studied, the principles of epidermal-dermal interactions and their effects on wound healing outcomes are only partially understood. To gain new insight into the effects of epidermal-dermal interactions, we developed a multiscale, hybrid mathematical model of skin wound healing. The model takes into consideration interactions between epidermis and dermis across the basement membrane via diffusible signals, defined as activator and inhibitor. Simulations revealed that epidermal-dermal interactions are critical for proper extracellular matrix deposition in the dermis, suggesting these signals may influence how wound scars form. Our model makes several theoretical predictions. First, basal levels of epidermal activator and inhibitor help to maintain dermis in a steady state, whereas their absence results in a raised, scar-like dermal phenotype. Second, wound-triggered increase in activator and inhibitor production by basal epidermal cells, coupled with fast re-epithelialization kinetics, reduces dermal scar size. Third, high-density fibrin clot leads to a raised, hypertrophic scar phenotype, whereas low-density fibrin clot leads to a hypotrophic phenotype. Fourth, shallow wounds, compared to deep wounds, result in overall reduced scarring. Taken together, our model predicts the important role of signalling across dermal-epidermal interface and the effect of fibrin clot density and wound geometry on scar formation. This hybrid modelling approach may be also applicable to other complex tissue systems, enabling the simulation of dynamic processes, otherwise computationally prohibitive with fully discrete models due to a large number of variables

Multiscale modeling of layer formation in epidermis

The mammalian skin epidermis is a stratified epithelium composed of multiple layers of epithelial cells that exist in appropriate sizes and proportions, and with distinct boundaries separating each other. How the epidermis develops from a single layer of committed precursor cells to form a complex multilayered structure of multiple cell types remains elusive. Here, we construct stochastic, three-dimensional, and multiscale models consisting of a lineage of multiple cell types to study the control of epidermal development. Symmetric and asymmetric cell divisions, stochastic cell fate transitions within the lineage, extracellular morphogens, cell-to-cell adhesion forces, and cell signaling are included in model. A GPU algorithm was developed and implemented to accelerate the simulations. These simulations show that a balance between cell proliferation and differentiation during lineage progression is crucial for the development and maintenance of the epidermal tissue. We also find that selective intercellular adhesion is critical to sharpening the boundary between layers and to the formation of a highly ordered structure. The long-range action of a morphogen provides additional feedback regulations, enhancing the robustness of overall layer formation. Our model is built upon previous experimental findings revealing the role of Ovol transcription factors in regulating epidermal development. Direct comparisons of experimental and simulation perturbations show remarkable consistency. Taken together, our results highlight the major determinants of a well-stratified epidermis: balanced proliferation and differentiation, and a combination of both short- (symmetric/asymmetric division and selective cell adhesion) and long-range (morphogen) regulations. These underlying principles have broad implications for other developmental or regenerative processes leading to the formation of multilayered tissue structures, as well as for pathological processes such as epidermal wound healing

Effects of knee joint angle on global and local strains within human triceps surae muscle: MRI analysis indicating in vivo myofascial force transmission between synergistic muscles

Purpose Mechanical interactions between muscles have been shown for in situ conditions. In vivo data for humans is unavailable. Global and local length changes of calf muscles were studied to test the hypothesis that local strains may occur also within muscle for which global strain equals zero. Methods For determination of globally induced strain in m. gastrocnemius in dissected human cadavers several knee joint angles were imposed, while keeping ankle joint angle constant and measuring its muscle-tendon complex length changes. In vivo local strains in both gastrocnemius and soleus muscles were calculated using MRI techniques in healthy human volunteers comparing images taken at static knee angles of 173° and 150°. Results Imposed global strains on gastrocnemius were much smaller than local strains. High distributions of strains were encountered, e.g. overall lengthened muscle contains locally lengthened, as well as shortened areas within it. Substantial strains were not limited to gastrocnemius, but were found also in synergistic soleus muscle, despite the latter muscle-tendon complex length remaining isometric (constant ankle angle: i.e. global strain = 0), as it does not cross the knee. Based on results of animal experiments this effect is ascribed to myofascial connections between these synergistic muscles. The most likely pathway is the neurovascular tract within the anterior crural compartment (i.e. the collagen reinforcements of blood vessels, lymphatics and nerves). However, direct intermuscular transmission of force may also occur via the perimysium shared between the two muscles. Conclusions Global strains imposed on muscle (joint movement) are not good estimators of in vivo local strains within it: differing in magnitude, as well as direction of length change. Substantial mechanical interaction occurs between calf muscles, which is mediated by myofascial force transmission between these synergistic muscles. This confirms conclusions of previous in situ studies in experimental animals and human patients, for in vivo conditions in healthy human subjects. © 2011 Springer-Verlag

A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching

Lovastatin is an anti-cholesterol lactone drug indicated for the treatment of hyperlipidemia and to reduce the risk of coronary heart disease. It is converted to the β-hydroxy acid form (lovastatin acid) in vivo, which is the major pharmacologically active metabolite. Here, we describe the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method utilizing polarity switching for the simultaneous quantification of lovastatin and lovastatin acid in human plasma. Simple protein precipitation extraction and direct injection of the extracted samples without drying/reconstitution showed good recoveries of both analytes (~70%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The interconversion between lovastatin and lovastatin acid during sample preparation and storage was minimal (< 1.9%). The lower limits of quantification were 0.5 and 0.2 nM (or 0.2 and 0.084 ng/mL) for lovastatin and lovastatin acid, respectively, using only 50 μL of plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving lovastatin

The impact of income level on skeletal muscle health in rural Chinese older residents: a study of mediating effects based on dietary knowledge

China’s rural residents have basically solved the problem of subsistence, but due to aging, the prevalence of sarcopenia (abbreviated as sarcopenia) has been increasing year by year, especially the skeletal muscle health of the rural older residents has not been sufficiently paid attention to, so analyses of the impact of income level on the skeletal muscle health of the older people in rural areas of China are of great practical significance. Based on the annual data of the China Health and Nutrition Survey (CHNS) in 2006, 2009, and 2011, we introduced the mediator variable of dietary knowledge and used the Probit model regression, mediation effect model, and instrumental variable regression to assess the skeletal muscle health status of the rural older people in China and explore the mechanism of the influence of the income level on the skeletal muscle health of the rural older residents in China. The primary objectives of this study were to evaluate the impact of income level on the skeletal muscle health status of older adults living in rural areas of China and to investigate the underlying mechanisms. By analyzing the findings of this study, our aim is to establish a correlation between the economic status and skeletal muscle health of older adults in rural communities, as well as elucidate the influence of income level and dietary knowledge on their skeletal muscle health. Through the attainment of these objectives, we hope to provide valuable insights and recommendations for enhancing skeletal muscle health among the rural older population in China. Based on our research findings, it can be inferred that there was a significant association between the financial status of rural older adults and their skeletal muscle health. Additionally, the prevalence of sarcopenia was lower among individuals with higher income levels, and there was a negative correlation between the prevalence of sarcopenia and the level of dietary knowledge among rural older individuals. The knowledge of dietary knowledge level of rural older people plays a mediating role in the income level and the prevalence of sarcopenia. Moreover, with the change in income level and the increase in age, the change in skeletal muscle health status showed obvious heterogeneity, in which the effect on the relatively younger (65–70 years old) samples was greater. Therefore, sustained income growth remains an effective way to improve the skeletal muscle health of older rural residents. At the same time, improving dietary knowledge and dietary quality among the older people is important in preventing a decline in muscle strength and physical function and in preventing the onset of sarcopenia

Effects of growth on geometry of gastrocnemius muscle in children: a three-dimensional ultrasound analysis

During development, muscle growth is usually finely adapted to meet functional demands in daily activities. However, how muscle geometry changes in typically developing children and how these changes are related to functional and mechanical properties is largely unknown. In rodents, longitudinal growth of the pennate m. gastrocnemius medialis (GM) has been shown to occur mainly by an increase in physiological cross-sectional area and less by an increase in fibre length. Therefore, we aimed to: (i) determine how geometry of GM changes in healthy children between the ages of 5 and 12years, (ii) test whether GM geometry in these children is affected by gender, (iii) compare normalized growth of GM geometry in children with that in rats at similar normalized ages, and (iv) investigate how GM geometry in children relates to range of motion of angular foot movement at a given moment. Thirty children (16 females, 14 males) participated in the study. Moment-angle data were collected over a range of angles by rotating the foot from plantar flexion to dorsal flexion at standardized moments. GM geometry in the mid-longitudinal plane was measured using three-dimensional ultrasound imaging. This geometry was compared with that of GM geometry in rats. During growth from 5 to 12years of age, the mean neutral footplate angle (0Nm) occurred at -5° (SD 7°) and was not a function of age. Measured at standardized moments (4Nm), footplate angles towards plantar flexion and dorsal flexion decreased by 25 and 40%, respectively. In both rats and children, GM muscle length increased proportionally with tibia length. In children, the length component of the physiological cross-sectional area and fascicle length increased by 7 and 5% per year, respectively. Fascicle angle did not change over the age range measured. In children, the Achilles tendon length increased by 6% per year. GM geometry was not affected by gender. We conclude that, whereas the length of GM in rat develops mainly by an increase in physiological cross-sectional area of the muscle, GM in children develops by uniform scaling of the muscle. This effect is probably related to the smaller fascicle angle in human GM, which entails a smaller contribution of radial muscle growth to increased GM muscle length. The net effect of uniform scaling of GM muscle belly causes it to be stiffer, explaining the decrease in range of motion of angular foot movement at 4Nm towards dorsal flexion during growth. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland

The Core/Shell Structure of CdSe/ZnS Quantum Dots Characterized by X-Ray Absorption Fine Spectroscopy

Understanding the chemical and physical properties of core/shell nanocrystal quantum dots (QDs) is key for their use in lightemission applications. In this paper, a single-step injection-free scalable synthetic method is applied to prepare high-quality core/shell QDs with emission wavelengths of 544 nm, 601 nm, and 634 nm. X-ray absorption fine structure spectra are used to determine the core/shell structure of CdSe/ZnS quantum dots. Moreover, theoretical XANES spectra calculated by FEFF.8.20 are used to determine the structure of Se and S compounds. The QD samples displayed nearly spherical shapes with diameters of approximately 3.4 ± 0.5 nm (634 nm), 4.5 ± 0.4 nm (601 nm), and 5.5 ± 0.5 nm (544 nm). With XANES results and MS calculations, it is indicated that sphalerite ZnS capped with organic sulfur ligands should be the shell structure. Wurtzite CdSe is the main core structure with a Cd-Se bond length of 2.3Å without phase shift. This means that different emission wavelengths are only due to the crystal size with single-step injection-free synthesis. Therefore, single-step injection-free synthesis could generate a nearly ideal core/shell structure of CdSe/ZnS QDs capped with an organic sulfur ligand

TripVista: Triple Perspective Visual Trajectory Analytics and its application on microscopic traffic data at a road intersection

In this paper, we present an interactive visual analytics system, Triple Perspective Visual Trajectory Analytics (TripVista), for exploring and analyzing complex traffic trajectory data. The users are equipped with a carefully designed interface to inspect data interactively from three perspectives (spatial, temporal and multidimensional views). While most previous works, in both visualization and transportation research, focused on the macro aspects of traffic flows, we develop visualization methods to investigate and analyze microscopic traffic patterns and abnormal behaviors. In the spatial view of our system, traffic trajectories with various presentation styles are directly interactive with user brushing, together with convenient pattern exploration and selection through ring-style sliders. Improved ThemeRiver, embedded with glyphs indicating directional information, and multiple scatterplots with time as horizontal axes illustrate temporal information of the traffic flows. Our system also harnesses the power of parallel coordinates to visualize the multi-dimensional aspects of the traffic trajectory data. The above three view components are linked closely and interactively to provide access to multiple perspectives for users. Experiments show that our system is capable of effectively finding both regular and abnormal traffic flow patterns.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000316816300021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Computer Science, Theory &amp; MethodsEngineering, Electrical &amp; ElectronicEICPCI-S(ISTP)2