Physiological Models

The aim of the present study was to evaluate the penetration of paclitaxel in normal as well as cancerous human cervical monolayer membranes and to compare these results with the paclitaxel penetration in a model dipalmitoylphosphatidylcholine (DPPC) monolayer. At physiologically relevant surface pressures of 30 mN/m, equilibrium drug penetration was observed in DPPC model membrane, whereas in cervical lipid model membranes exclusion of the drug and destabilization of the membrane was observed. The maximum surface pressure increment due to penetration ( π max ) of 600 nM paclitaxel, for DPPC monolayer was found to be 3.6, 5.4 and 5.0 times higher than those for penetration in the cancerous monolayer at surface pressures 10, 20 and 30 mN/m, respectively. At initial surface pressure 10 mN/m, the maximum surface pressure increment, for 600 nM paclitaxel penetration, of normal cervical lipid membrane was double that of the cancerous cervical lipid membrane. At 30 mN/m initial surface pressure the representative IC 50 concentration of the drug produced negligible drug penetration and significant membrane destabilization in cervical lipid model membranes. The difference in penetration profile could be due to differences in composition of the model membranes. The cholesterol level in cancerous cervical membrane was 1.5-folds higher than that in the normal cervical membrane. Apart from PC, another constituent present in 20-32% in cancerous and normal membranes is sphingomyelin (SM). Introduction of 70% SM to the DPPC monolayer decreased the π max from 4.7 to 1.1 mN/m, revealing the rigidifying effect of SM which was directly proportional to the amount of SM added. Modulation of fluidity of the membranes can alter the penetration of paclitaxel in biological membranes and hence its toxicity profile.

the simplified steady-state equations is essentially the same with that obtained with PBPK models. Overall, this study suggests that no adult-children differences in the parent chemical concentrations of the VOCs are likely to be observed during inhalation exposures. The physiological-model-based approaches used in the present study to estimate the UF HH-PK and UF HC-PK provide a scientific basis for their magnitude. They can replace the currently used empirical default approaches to provide chemical-specific UF HH-PK in future risk assessments.

This paper addresses the problem of nonlinear system stabilization using hybrid control. Its main contribution is the derivation of a new methodology to solve the problem of global stabilization of a specific class of nonlinear systems. Using classical Lyapunov techniques and some recent results on switching design of hybrid controllers, it is shown how a locally asymptotically stabilizing controller can be suitably modified to yield global asymptotic stability. The resulting control laws avoid chattering and capture the interplay between the original locally stabilizing control loop and an outer control loop that comes into effect when the system trajectories deviate too much from the origin. The methodology proposed is used to derive a simple control design method for global stabilization of a particular class of single input single output (SISO) nonlinear systems coupled by a given term. Simulation results are presented and discussed.

Although mast cell secretion has been intensively studied because of its pivotal role in allergic reactions and its advantages as a physiologic model, the molecular composition of the secretory machine is virtually unknown. In view of the guanine-nucleotide dependency of mast cell exocytosis and the participation of Rab3 proteins in synaptic vesicle release, we hypothesized that a Rab3 isoform regulates mast cell secretion. Fragments of Rab3A, 3B, and 3D were cloned from RBL-2H3 mast cells by reverse transcriptionpolymerase chain reaction (RT-PCR). Northern blot analysis revealed Rab3D transcripts to be relatively abundant, Rab3B substantially less so, and Rab3A and 3C undetectable. By ribonuclease (RNase) protection assay, Rab3D transcripts were at least 10-fold more abundant than those of other isoforms, and by immunoblot analysis, Rab3D protein was at least 60-fold more abundant than that of Rab3B. Rab3D was more abundant in RBL cells than in brain, but the total mass of Rab3 proteins in RBL cells was 10-fold less than in brain. Rab3D only partly colocalized with secretory granules in RBL cells, but fully colocalized in mature peritoneal mast cells. There was a descending concentration gradient of Rab3D from peripheral to central granules, and no cytoplasmic pool was detectable in resting mast cells. Following exocytotic degranulation, Rab3D translocated to the plasma membrane and remained there for at least 15 min. These studies suggest that Rab3D is a component of the regulated exocytotic machine of mast cells, and identify differences between mast cells and neurons in Rab3 expression and trafficking. Tuvim, M.

We have previously reported, via the ARS forum, on simulation results for modelling the function of the cardiovascular system in disease and drug responses, decision support and its validation in simulation [1]: we now propose to describe the development of the associated realtime decision support system.

Quillaja saponaria is a valuable commercial and ecological Chilean native species that has suffered considerably degradation countrywide; however, the determination of the optimum characteristics of the planting stock, an important aspect in restoration projects, has receive little attention. The aim of this study was to evaluate the effect of container size and dose of fertilizer on morphological and physiological responses of Q. saponaria seedlings cultivated in a nursery under well-watered and water restricted conditions. After 27 days growing under contrasting watering regimes, growth, biomass allocation, and gas exchange were measured in 6-month-old seedlings. We found that survival, height and diameter increment, and root dry weight were higher in the water stressed seedlings cultivated in large containers. The water stressed seedlings cultivated in large containers also had superior stomatal conductance, however when the fertilizer dose was decreased, this trait decreased considerably. Thus, a superior performance in a water-restricted environment could be expected in those seedlings cultivated in larger containers with low fertilizer.

Various models of HIV infection and evolution have been considered in the literature. This paper considers a variant of the Wodarz and Nowak mathematical model, adding "aggressiveness" as a new state variable in order to quantify the strength of the virus and its response to drugs. Although the model proposed is relatively simple, simulation results suggest that it may be useful in predicting the impact of the effectiveness of therapy on HIV dynamics.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO 2 ) during physiological and pathological conditions remains a subject of debate. We have developed a physiological model for oxygen delivery and metabolism, which allows the estimation of net oxygen diffusibility at the capillary level, termed ''effective oxygen diffusibility (EOD).'' The results of PET in monkeys showed dynamic changes in EOD in response to changes in oxygen delivery and consumption. EOD is defined as capillary volume and permeability product, but its change mainly reflects the pericapillary oxygen gradient as long as capillary architecture is preserved. EOD may have sufficient predictability to represent the tissue oxygen demand and application of the model to PET data. In the future, EOD may give us further insight to understand the physiological regulatory system for oxygen demand in the brain. D 2004 Published by Elsevier B.V.

This study investigates individuals' cognitive load processing abilities while engaged on a decision-making task in serious games, to explore how a substantial cognitive load dominates over the physiological arousal effect on pupil diameter. A serious game was presented to the participants, which displayed the on-line biofeedback based on physiological measurements of arousal. In such dynamic decision-making environment, the pupil diameter was analyzed in relation to the heart rate, to evaluate if the former could be a useful measure of cognitive abilities of individuals. As pupil might reflect both cognitive activity and physiological arousal, the pupillary response will show an arousal effect only when the cognitive demands of the situation are minimal. Evidence shows that in a situation where a substantial level of cognitive activity is required, only that activity will be observable on the pupil diameter, dominating over the physiological arousal effect indicated by the pupillary response. It is suggested that it might be possible to design serious games tailored to the cognitive abilities of an individual player, using the proposed physiological measurements to observe the moment when such dominance occurs.

Increasing availability of multi-scale and multi-channel physiological data opens new horizons for quantitative modeling in medicine. However, practical limitations of existing approaches include both the low accuracy of the simplified analytical models and empirical expert-defined rules and the insufficient interpretability and stability of the pure data-driven models. Such challenges are typical for automated diagnostics from high-resolution image data and multi-channel temporal physiological information available in modern clinical settings. In addition, increasing number of portable and wearable systems for collection of physiological data outside medical facilities provide an opportunity for express and remote diagnostics as well as early detection of irregular and transient patterns caused by developing abnormalities or subtle initial effects of new treatments. However, quantitative modeling in such applications is even more challenging due to obvious limitations on the number of data channels, increased noise and non-stationary nature of considered tasks. Methods from nonlinear dynamics (NLD) are natural modeling tools for adaptive biological systems with multiple feedback loops and are capable of inferring essential dynamic properties from just one or a small number of data channels. However, most NLD indicators require long periods of data for stable calculation which significantly limits their practical value. Many of these challenges in biomedical modeling could be overcome by boosting and similar ensemble learning techniques that are capable of discovering robust multi-component meta-models from existing simplified models and other incomplete empirical knowledge. Here we describe an application of this approach to a practical system for express diagnostics and early detection of treatment responses from short beat-to-beat heart rate (RR) time series. The proposed system could play a key role in many applications relevant to e-healthcare, personalized medicine, express and remote web-enabled diagnostics, decision support systems, treatment optimization and others.

This letter analyzes the oscillation onset-offset conditions of the vocal folds as a function of laryngeal size. A version of the two-mass model of the vocal folds is used, coupled to a two-tube approximation of the vocal tract in configuration for the vowel ∕a∕. The standard male configurations of the laryngeal and vocal tract models are used as reference, and their dimensions are scaled using a single factor. Simulations of the vocal fold oscillation and oral output are produced for varying values of the scaling factor. The results show that the oscillation threshold conditions become more restricted for smaller laryngeal sizes, such as those appropriate for females and children.

In this study we use a low-dimensional laryngeal model to reproduce temporal variations in oral airflow produced by speakers in the vicinity of an abduction gesture. It attempts to characterize these temporal patterns in terms of biomechanical parameters such as glottal area, vocal fold stiffness, subglottal pressure, and gender differences in laryngeal dimensions. A two-mass model of the vocal folds coupled to a two-tube approximation of the vocal tract is fitted to oral airflow records measured in men and women during the production of /aha/ utterances, using the subglottal pressure, glottal width, and Q factor as control parameters. The results show that the model is capable of reproducing the airflow records with good approximation. A nonlinear damping characteristics is needed, to reproduce the flow variation at glottal abduction. Devoicing is achieved by the combined action of vocal fold abduction, the decrease of subglottal pressure, and the increase of vocal fold tension. In...

A two-dimensional, seven link, nine degrees of freedom biped model was developed to investigate the dynamic characteristics of normal and transfemoral amputee locomotion during the entire gait cycle. The equations of motion were derived using the Lagrange method and the stance foot-ground contact was simulated using a five-point penetration model. The joint driving torques were obtained using forward dynamic optimization of the normal human gait and applied to the intact joints of the amputee. Three types of motion controllers; frictional, elastic and hydraulic were considered for the prosthetic joints of the amputee and their design parameters were optimized to achieve the closest kinematics to that of the normal gait. It was found that, if optimally designed, all three passive controllers could reasonably reproduce a normal kinematical pattern in the swing phase. However, the stance phase kinematics could only be replicated by the hydraulic and elastic controllers; the performance...

Fecal incontinence affects people of all ages and social backgrounds and can have devastating psychological and economic consequences. This disorder is largely attributed to decreased mechanical efficiency of the internal anal sphincter (IAS), yet little is known about the pathophysiological mechanisms responsible for the malfunction of sphincteric smooth muscle at the cellular level. The object of this study was to develop a three-dimensional (3-D) physiological model of the IAS bioengineered in vitro from isolated smooth muscle cells. Smooth muscle cells isolated from the IAS of rabbits were seeded in culture on top of a loose fibrin gel, where they migrated and self-assembled in circumferential alignment. As the cells proliferated, the fibrin gel contracted around a 5-mm-diameter SYLGARD mold, resulting in a 3-D cylindrical ring of sphincteric tissue. We found that 1) the bioengineered IAS rings generated a spontaneous basal tone, 2) stimulation with 8-bromo-cAMP (8-Br-cAMP) caus...

In this study, formulae for predicting projected area factors and view factors of individual body parts of standing and sedentary humans for detailed radiation analysis were developed. For this purpose, detailed geometry models of the human body were generated representing an average subject with a height of 1.75 m and a DuBois' area of 1.83 m 2. Thermal analysis software incorporating advanced, voxel-based ray tracing techniques and regression analysis were deployed to model the local projected area factors of humans exposed to direct and diffuse solar radiation. A method was developed to predict view factors of individual body parts based on the projected area factor calculations. This technique makes it possible to predict view factors between individual body parts and surrounding surfaces for almost any arbitrary geometrical configurations of the radiation envelope. The predicted view factors were validated and showed good agreement with experimental data available in the literature.

We present the elements of a mathematical computational model that reflects the experimental finding that the timescale of a neuron is not fixed; but rather varies with the history of its stimulus. Unlike most physiological models, there are no predetermined rates associated with transitions between states of the system nor are there predetermined constants associated with adaptation rates; instead, the model is a kind of ''modulating automata'' where the rates emerge from the history of the system itself. We focus in this paper on the temporal dynamics of a neuron and show how a simple internal structure will give rise to complex temporal behavior. The internal structure modeled here is an abstraction of a reasonably well-understood physiological structure. We also suggest that this behavior can be used to transform a ''rate'' code into a ''temporal one''.

The National Renewable Energy Laboratory (NREL) has developed a suite of thermal comfort tools to assist in the development of smaller and more efficient climate control systems in automobiles. These tools, which include a 126-segment sweating manikin, a finite element physiological model of the human body, and a psychological model based on human subject testing, are designed to predict human thermal comfort in transient nonuniform thermal environments such as automobiles. The manikin measures the heat loss from the human body in the vehicle environment and sends the heat flux from each segment to the physiological model. The physiological model predicts the body's response to the environment, determines 126 segment skin temperatures, sweat rates, and breathing rate, and transmits the data to the manikin. The psychological model uses temperature data from the physiological model to predict the local and global thermal comfort as a function of local skin and core temperatures and their rates of change. Results of initial integration testing show the thermal response of a manikin segment to transient environmental conditions.

Musculoskeletal disorder of the lower limb is one of the most common health burdens that may lead to functional impairment in an individual. Although various operative management options are available, there seems no unanimity on a particular procedure that serves the best. To objectively assess disorders and effectively plan surgeries, it is essential to understand lower limb biomechanics under physiological loading conditions. With that motivation, this PhD aims to develop a comprehensive finite element based musculoskeletal modeling framework of the lower limb. The first phase of the PhD focuses on the development and evaluation of subject-specific finite element models under passive flexion. Novel approaches are proposed and evaluated for fast model development focusing on geometry and ligament properties. In the second phase, a novel finite element based approach for soft tissue artifact compensation is proposed and evaluated. This contribution allowed to effectively compensate...

We present an eco-physiological model reproducing the growth of eight foraminifer species (Neogloboquadrina pachyderma, Neogloboquadrina incompta, Neogloboquadrina dutertrei, Globigerina bulloides, Globigerinoides ruber, Globigerinoides sacculifer, Globigerinella siphonifera and Orbulina universa). By using the main physiological rates of foraminifers (nutrition, respiration, symbiotic photosynthesis), this model estimates their growth as a function of temperature, light availability, and food concentration. Model parameters are directly derived or calibrated from experimental observations and only the influence of food concentration (estimated via Chlorophyll-a concentration) was calibrated against field observations. Growth rates estimated from the model show positive correlation with observed abundance from plankton net data suggesting close coupling between individual growth and population abundance. This observation was used to directly estimate potential abundance from the model-derived growth. Using satellite data, the model simulate the dominant foraminifer species with a 70.5% efficiency when compared to a data set of 576 field observations worldwide. Using outputs of a biogeochemical model of the global ocean (PISCES) instead of satellite images as forcing variables gives also good results, but with lower efficiency (58.9%). Compared to core tops observations, the model also correctly reproduces the relative worldwide abundance and the diversity of the eight species when using either satellite data either PISCES

The development of human cardiovascular systems physiology is inhibited by the lack of multiscale functional physiological data, which represents human heart physiology at the molecular, cellular, tissue, organ, and system levels. We have developed an experimental approach to study explanted human hearts in vitro at multiple physiological scales with a wide array of imaging modalities. This approach has already yielded data indicating significant differences between animal models of diseases and actual human heart disease. Our data provides a quantitative foundation for multiscale physiological models of the cardiovascular system and will allow improvement in translation of medical technology and pharmacology from animal models to therapy.

The authors have created an interactive multimedia computer simulator "GOLEM" for learning diagnostics and therapy of clinical disorders. It allows students to solve various critical situations in the form of simulation games. The simulator is based on mathematical simulation models of body-fluid balance, respiration, circulation and renal function. The mathematical description consists of 39 non-linear differential and algebraic equations of more than 200 variables. General aspects of large-scale model design and deployment are discussed. Typical usage of the simulator in medical training is described and its pedagogical benefits are highlighted.

RGB snapshot triple-spectral-line imaging 3 monochromatic spectral images from a single-snapshot RGB image data can be extracted if object is illuminated simultaneously at 3 laser wavelengths, and the RGB-band sensitivities of the image sensor are known  corrected R-, G-and B-band images*. 3 *) WO 2013135311 (A1). Method and device for imaging of spectral reflectance at several wavelength bands.

Introduction Perthes’ disease is one of the most common hip disorders in young children characterized by malformation of the femoral head. Several studies have investigated the biomechanical alterations of Perthes’ disease using Finite Element Analysis (FEA), however, most of them were 2D models and lack patient-specific details of the cartilage and necrotic bone. Thus, the objective of this study was to investigate the altered biomechanics of a Perthes’ hip joint by finite element contact modeling using MRI to develop the patient-specific model of the cartilages and bones. Methods The MRI data of both hips of a unilateral Perthes’ case was obtained to segment the bones and cartilages using Simpleware. A 3D point cloud data of the segmented parts were exported to SolidWorks to build the 3D models. FEA was performed using Comsol 4.3b. The same Poisson’s ratio 0.30 was set for the femoral, pelvic and necrotic bones. The Poisson’s ratio 0.35 was set for the femoral and acetabular carti...

Many producers and consumers of legacy training simulator and game environments are beginning to envision a new era where psycho-socio-physiologic models could be interoperated to enhance their environments' simulation of human agents. This paper explores whether we could embed our behavior modeling framework (described in the companion paper, Part 1) behind a legacy first person shooter 3D game environment to recreate portions of the Black Hawk Down scenario. Section 1 amplifies the interoperability needs and challenges confronting the field, presents the questions that are examined, and describes the test scenario. Sections 2 and 3 review the software and knowledge engineering methodology, respectively, needed to create the system and populate it with bots. Results (Section 4) and discussion (Section 5) reveal that we were able to generate plausible and adaptive recreations of Somalian crowds, militia, women acting as shields, suicide bombers, and more. Also, there are specific lessons learned about ways to advance the field so that such interoperabilities will become more affordable and widespread.

groups revealed that, compared to individuals with sustained virological response and with a similar post-treatment followup period, nonresponders had consistently elevated levels of IL-8, ISG15 and OAS by 6-20 fold. The reverse was true however for IFNa and IFNg. In addition, pre-treatment HCV RNA loads in PBMC of nonresponders were 6-fold greater than those who responded. Conclusions: The overall significantly higher levels of IL-8, ISG15 and OAS in PBMC of nonresponders compared to those detected in responders implicates a role for these genes in IFN/RBV therapy failure and HCV persistence in the lymphoid cell compartment. In addition, the fact that the post-treatment levels of IFNa and IFNg were lower in PBMC of nonresponders than responders could be interpreted as a reaffirmation of a vital role of these cytokines in purging HCV from this compartment.

The Lesser Black-backed Gull Larus fuscus is a large gull species (135-150 cm wingspan) found in coastal regions of the North Atlantic, including the Belgian Coast, where it arrives in summer to breed. These gulls exploit different food sources: discarded fish from demersal trawlers, human (urban and industrial) food waste, and soil dwellers such as earthworms, insects and small mammals mainly at agricultural fields and urban parks. Each of these food sources is exploited with different frequencies by each individual bird and in each period of the breeding season. We are studying what drivers lead a breeding gull to forage on a particular food source, and whether certain foraging strategies are more advantageous than others. From the chick’s point of view, an ideal diet has to meet all energetic and nutritional requirements for development from hatching until fledging. Depending on the origin of the food provided, a chick’s diet will have different energy densities and nutrient cont...

The first procedures have been established for in vitro micropropagation and plant regeneration of the desiccation-tolerant plant Ramonda myconi (L.) Rchb. An integrated optimisation of salt, antioxidant and growth regulator composition, and potassium-phosphate buffer-mediated pH stabilisation of culture media resulted in an effective tissue culture system that prevented the undesirable hyperhydricity and tissue necrosis typical of Ramonda tissue cultures. We examined whether there is any similarity in tissue culturing between the two resurrection plants Craterostigma plantagineum and R. myconi as a consequence of their common physiological specialisation. The fact that regenerated plants developed on dedifferentiated cell cultures, which is a precondition of Agrobacterium-mediated gene transfer, could mean an applicable basis for the optimisation of the genetic transformation of Ramonda species.

The first procedures have been established for in vitro micropropagation and plant regeneration of the desiccation-tolerant plant Ramonda myconi (L.) Rchb. An integrated optimisation of salt, antioxidant and growth regulator composition, and potassium-phosphate buffer-mediated pH stabilisation of culture media resulted in an effective tissue culture system that prevented the undesirable hyperhydricity and tissue necrosis typical of Ramonda tissue cultures. We examined whether there is any similarity in tissue culturing between the two resurrection plants Craterostigma plantagineum and R. myconi as a consequence of their common physiological specialisation. The fact that regenerated plants developed on dedifferentiated cell cultures, which is a precondition of Agrobacterium-mediated gene transfer, could mean an applicable basis for the optimisation of the genetic transformation of Ramonda species.

What determines the specific pattern of activation of primary motor cortex (M1) neurons in the context of a given motor task? In order to address this question, we develop a system level physiological model and compare its predictions with experimental data related to the caudal part of M1, during voluntary trained tasks. Our model describes the transformation from the neural activity in M1, through the motor control signal, into joint torques and down to endpoint force and movement. The redundancy of the system is resolved by adding a biologically plausible optimization criterion. We compare the predictions of our model to the experimental results and reproduce the observed activity in M1 during a variety of tasks. Using our model we were able to explain, for the first time, many basic experimental observations in a mechanistically explicit way.

The BOLD signal provided by the functional MRI medical modality measures the ratio of oxy-to deoxyhaemoglobin at each location inside the brain. The detection of activated regions upon the application of an external stimulus, e.g., visual or auditive, is based on the comparison of the mentioned ratios of a rest condition (pre-stimulus) and of a stimulated condition (post-stimulus). Therefore, an accurate knowledge of the impulse response of the BOLD signal to neural stimulus in a given region is needed to design robust detectors that discriminate, with a high level of confidence activated from non activated regions. Usually, in the literature, the hemodynamic response has been modeled by known functions, e.g., gamma functions, fitting them, or not, to the experimental data. In this paper we present a different approach based on the physiologic behavior of the vascular and neural tissues. Here, a linear model based on reasonable physiological assumptions about oxygen consumption and vasodilatation processes are used to design a linear model from which a transfer function is derived. The estimation of the model parameters is performed by using the minimum square error (MSE) by forcing the adjustment of the stimulus response to the observations. Experimental results using real data have shown that the proposed model successfully explains the observations allowing to achieve small values for the fitting error.

Drepanopus forcipatus and Calanus australis are key planktonic copepods on the southern Patagonian shelf. Their feeding and reproductive patterns and population status were investigated during late summer, when environmental conditions may be critical. The presence of food in the gut and food-pellet length were recorded in adult females and the most abundant copepodite stages. Diet composition was also studied in adult females. Female reproductive status was evaluated by gonad staging. Despite generally low feeding conditions and decreasing seasonal temperature, both copepods fed to some degree. The most numerous copepodites and adult females of both species showed similarly low feeding activity. About half of the adult females of the two species and C5s of C. australis contained food in their guts, but the proportion of fed C4-females of D. forcipatus was much lower. All copepods were generally feeding at low or intermediate levels. Gonad stage distribution and population structure...

A new insulin and nutrition control method for tight glycaemic control in critical care is presented from concept to clinical trials to clinical practice change. The primary results show that the method can provide very tight glycaemic control in critical care for a very critically ill cohort. More specifically, the final clinical practice change protocol provided 2100 hours of control with average blood glucose of 5.8 +/-0.9 mmol/L for an initial 10 patient pilot study. It also used less insulin, while providing the same or greater nutritional input, as compared to retrospective hospital control for a relatively very critically ill cohort with high insulin resistance.

Designing orthopedic implants with a long lifespan is essential for improving patients’ quality of life. It is necessary to develop new products with a high degree of personalization for the human body. Physicians and engineers analyzed the geometry and behavior of healthy joints’ motion under specific load conditions as well as the behavior over time and lifetime of orthopedic implants fitted to patients to improve their quality. The paper presents the way in which three-dimensional modeling techniques using specialized software (Catia, SolidWorks) can be combined with reverse engineering techniques (3D scanning) to optimize the design of orthopedic implants. The design of an implant consists of its three-dimensional modeling, as well as simulation of its integration into the human body, in order to analyze its behavior during motion. Therefore, it is necessary not only to 3D model the parts that make up the implant itself, but also to 3D model the bone to which the implant will be...

The authors present their way of designing multimedia educational software to support the teaching of pathological and clinical physiology, taking advantage of interactive simulation games. Simulation models, created using Matlab/Simulink® from MathWorks, are decomposed to so-called simulation chips suitable for interdisciplinary cooperation during design-time. Interactive animations utilize Flash and Director from Macromedia, the user interfaces of the simulators are implemented in Control Web from Moravian Instruments, all integrated by Microsoft Visual Studio .NET. The authors also give their arguments concerning their preference for industrial development tools over academic "open source" tools.

Surface energy balance is a major determinant of land surface temperature and the Earth's climate. To date, there is no approach that can produce effective, physically consistent, global and multi-decadal energy-water flux data over land. Net radiation (R n) can be quantified regionally using satellite retrievals of surface reflectance and thermal emittance with errors b10%. However, consistent, useful retrieval of latent heat flux (λE) from remote sensing is not yet possible. In theory, λE could be inferred as a residual of R n , ground heat (G) and sensible heat (H) fluxes (R n-H-G). However, large uncertainties in remote sensing of both H and G result in low accuracies for λE. Where vegetation is the dominant surface cover, λE is largely driven by transpiration of intercellular water through leaf stomata during the photosynthetic uptake of carbon. In these areas, satellite retrievals of photosynthesis (GPP) could be used to quantify transpiration rates through stomatal conductance. Here, we demonstrate how remote sensing of GPP could be applied to obtain λE from passive optical measurements of vegetation leaf reflectance related to the photosynthetic rate independent of knowledge of H, R n and G. We validate the algorithm using five structurally and physiologically diverse eddy flux sites in western and central Canada. Results show that transpiration and H were accurately predicted from optical data and highly significant relationships were found between the energy budget obtained from eddy flux measurements and remote sensing (0.64 ≤ r 2 ≤ 0.85). We conclude that spaceborne estimates of GPP could significantly improve not only estimates of the carbon balance but also the energy balance over land.

No accurate quantitative information currently exists on how water use of apple (Malus domestica) orchards varies from planting to full-bearing age, leading to poor irrigation and water allocation decision making. This study sought to address this knowledge gap by investigating how the water use and tree water status vary with canopy cover, cultivar, and climatic conditions in 12 orchards growing in prime apple-producing regions in South Africa. The orchards were planted to the Golden Delicious/Golden Delicious Reinders cultivars which are widely planted in South Africa and the Cripps’ Pink/Cripps’ Red/Rosy Glow which are high-value late-season cultivars. The performance of two transpiration reduction coefficients, one based on sap flow (Ksf) and the other based on soil water depletion (Ks) (FAO approach) were evaluated against the midday stem water potential (MSWP) in all the orchards. While canopy cover had a clear effect on the whole-tree sap flow rates, there were no significant...

To produce large volumes of biomass for implementing its green energy policy, the Government of Indonesia has issued a short rotation energy plantation program for a number of tree species including Calliandra calothyrsus (Meissn.). Optimum density and prompt harvesting are needed to maximise productivity, but information regarding both factors is insufficient. This study aimed to investigate the optimum growth spacing and ideal felling age to produce the largest volumes of biomass both economically and sustainably. Experiments were arranged on one hectare of land, which was divided into four plots with different plant spacing treatments (1 Â 1.5 m; 1.5 Â 1.5 m; 2 Â 1.5 m; and 2 Â 2 m). Growth and yield observations were carried out on plants aged 12, 18, and 24 months in each plot, with 30 sample trees left for growth observations and ten sample trees cut at each of the three ages after planting. This resulted in a total of 240 samples from the 2,710 trees planted. Trees were felled at 50 cm from the soil surface, and the resulting stools were left to regrow. A year after felling, resulting coppices, were observed and cut. Growth, productivity and calorific value were studied for both 'primary' and 'coppiced' wood. Study results demonstrate that competition between plants strongly determines the growth and productivity of 'primary' wood. The plot with the densest plant spacing had the lowest nutrient content for almost all soil nutrients. Higher plant density showed higher competition index values, and resulted in fewer and smaller diameter stems emerging from stools, and lower biomass productivity. Competition index values, which increased with plant age, can be used as an indicator for determining harvest timing. Productivity increased by up to 15% following development as a coppice plantation. Optimum wood productivity and greatest economy came from parent stands with plant spacing of 2 Â 2 m, harvested at 18 months old and coppiced. This treatment yielded an average biomass/tree of primary wood 7.2 kg and coppice wood 8.22 kg, respectively, with lignin content of approximately 22%, and calorific value of around 18,807 kJ. These values match biomass energy requirements for feedstock for electricity generation. Harvesting at 24 months showed no significant increases in productivity, lignin content, or calorific value.

G αq/11 activation with cellular differentation. In summary, we identified and characterized a novel G αq/11 agonist molecule acting at the TSHR and which showed a marked anti-proliferative ability. Hence, Gq biased activation of the TSHR is capable of ameliorating the proliferative signals from its orthosteric ligand and may offer a therapeutic option for thyroid growth modulation.

This paper examines long-term eddy covariance data from 18 European and 17 North American and Asian forest, wetland, tundra, grassland, and cropland sites under nonwater-stressed conditions with an empirical rectangular hyperbolic light response model and a single layer two light-class carboxylase-based model. Relationships according to ecosystem functional type are demonstrated between empirical and physiological parameters, suggesting linkages between easily estimated parameters and those with greater potential for process interpretation. Relatively sparse documentation of leaf area index

Introduction This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women aVected with the disease. Methods In women suVering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology as well as clinical aspects. The relevant molecular biologic aspects were compared to those of tissue injury and repair (TIAR) mechanisms reported in literature. Results and conclusions Circumstantial evidence suggests that endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatizations with the activation of the mechanism of 'tissue injury and repair' (TIAR). This results in tion of the TIAR mechanism followed by inWltrative growth and chronic inXammation, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principle the same pathophysiology. In conclusion, endometriosis and adenomyosis result from the physiological mechanism of 'tissue injury and repair' (TIAR) involving local estrogen production in an estrogen-sensitive environment normally controlled by the ovary.

Trans-and cis-1,2-dichloroethylene (DCE) isomers inhibit their own metabolism in vivo by inactivation of the metabolizing enzyme, presumably the cytochrome P450 isoform, CYP2E1. In this study, we examined cytochrome P450 isoform-speci®c inhibition by three chloroethylenes, cis-DCE, trans-DCE, and trichloroethylene (TCE), and evaluated several kinetic mechanisms of enzyme inhibition with physiological models of inhibition. Trans-DCE was more potent than cis-DCE, and both were much more eective than TCE in inhibiting CYP2E1. The kinetics of in vitro loss of p-nitrophenol hydroxylase (pNP-OH) activity (a marker of CYP2E1) in microsomal incubations and of the in vivo gas uptake results were most consistent with a mechanism in which inhibition of the metabolizing enzyme (CYP2E1) was presumed to be related to interaction of a reactive DCE metabolite with remaining substrate-bound, active CYP2E1. The kinetics of inhibition by TCE, a weak inhibitor in vitro, were very dierent from that of the dichloroethylenes. With TCE, parent compound concentrations in¯uenced enzyme loss. Trans-DCE was a more potent inhibitor of CYP2E1 than cis-DCE based on both in vivo and in vitro studies. Quantitative dierences in the inhibitory properties of the 1,2-DCE isomers may be due to the dierent stability of epoxides formed from bioactivation by CYP2E1. Epoxide intermediates of DCE metabolism, reacting by water addition, would yield dialdehyde, a potent cross-linking reagent.

This paper addresses the simulation of the dynamics of complex systems by using hierarchical graph and multi-agent system. A complex system is composed of numerous interacting parts that can be described recursively. First we summarize the hierarchical aspect of the complex system. We then present a de- scription of hierarchical graph as a data structure for structural modeling in parallel

The important requirement that COST Action 730 demanded of the physiological model to be used for the Universal Thermal Climate Index was its capability of accurate simulation of the human thermophysiological responses across a wide range of relevant environmental conditions, such as conditions corresponding to the selection of all habitable climates and their seasonal changes, and transient conditions representing temporal variation of outdoor conditions. In the first part of this study available heat budget/two-node models and multi-node thermophysiological models were evaluated by direct comparison over the wide spectrum of climatic conditions. The UTCI-Fiala model predicted most reliably the average human thermal response which was showed by least deviations from physiologically plausible responses when compared to other models. In the second part of the study, this model was, therefore, subjected to extensive validation using results of human subject experiments for a range of relevant (steady-state and transient) environmental conditions. The UTCI-Fiala multi-node model proved its ability to predict adequately the human physiological response for a variety of moderate and extreme conditions represented in the COST 730 database. The mean skin and core temperatures were predicted with average root-meansquare deviations of 1.35 ± 1.00 °C and 0.32 ± 0.20 °C, respectively.

Blood pressure laboratory. Simulation and experiment results proved the usefulness of Guyton's model in control system design which can present the dynamical response of blood pressure in the circulation under and after hypotensive control. The results also indicated the safety and stability of the controller.

Blood velocity and pressure fields in large arteries are greatly influenced by the deformability of the vessel. However, computational methods for simulating blood flow in three-dimensional models of arteries have either considered a rigid wall assumption for the vessel or significantly simplified or reduced geometries. Computing blood flow in deformable domains using standard techniques like the ALE method remains a formidable problem for large, realistic anatomic and physiologic models of the cardiovascular system. We have developed a new method to simulate blood flow in three-dimensional deformable models of arteries. The method couples the equations of the deformation of the vessel wall at the variational level as a boundary condition for the fluid domain. We consider a strong coupling of the degrees-of-freedom of the fluid and the solid domains. The effect of the vessel wall boundary is therefore added in a monolithic way to the fluid equations, resulting in a remarkably robust...