A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of p H and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups.

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: Relevance to the diagnosis of neuroblastoma.

BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. CONCLUSIONS: A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. Pediatr Blood Cancer 2015;62:587-593. © 2015 Wiley Periodicals, Inc.

A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: Proton binding of carboxylated latex particles as a case study

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of pH and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups. © 2011 American Institute of Physics.

Impact of the Femoral Head Position on Moment Arms in Total Hip Arthroplasty: A Parametric Finite Element Study.

BACKGROUND: Although the importance of accurate femoral reconstruction to achieve a good functional outcome is well documented, quantitative data on the effects of a displacement of the femoral center of rotation on moment arms are scarce. The purpose of this study was to calculate moment arms after nonanatomical femoral reconstruction. METHODS: Finite element models of 15 patients including the pelvis, the femur, and the gluteal muscles were developed. Moment arms were calculated within the native anatomy and compared to distinct displacement of the femoral center of rotation (leg lengthening of 10 mm, loss of femoral offset of 20%, anteversion ±10°, and fixed anteversion at 15°). Calculations were performed within the range of motion observed during a normal gait cycle. RESULTS: Although with all evaluated displacements of the femoral center of rotation, the abductor moment arm remained positive, some fibers initially contributing to extension became antagonists (flexors) and vice versa. A loss of 20% of femoral offset led to an average decrease of 15% of abductor moment. Femoral lengthening and changes in femoral anteversion (±10°, fixed at 15°) led to minimal changes in abductor moment arms (maximum change of 5%). Native femoral anteversion correlated with the changes in moment arms induced by the 5 variations of reconstruction. CONCLUSION: Accurate reconstruction of offset is important to maintaining abductor moment arms, while changes of femoral rotation had minimal effects. Patients with larger native femoral anteversion appear to be more susceptible to femoral head displacements.

Estudo químico-computacional da reatividade de aziridinona e diaziridinona através de cálculos semi-empíricos

The results of semiempirical molecular orbital calculations performed on aziridinone and diaziridinone employing the MNDO, AM1, and PM3 molecular models are presented. The AM1 method, which best reproduces ground-state molecular properties, is used to calculate electronic parameters and the use of these parameters for the evaluation of reactivity is discussed.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

Experimental poisoning by Senecio brasiliensis in calves: quantitative and semi-quantitative study on changes in the hepatic extracellular matrix and sinusoidal cells

Extracellular matrix plays an important role in chronic hepatic lesions and has been studied in experimental intoxication models. However in cattle, studies on chronic disease have focused on the hepatocellular damage and extracellular matrix (ECM) changes are usually overlooked. There are no specific studies on the hepatic ECM in either normal or chronically damaged bovine liver. Thus an experimental model of hepatic toxicity model using Senecio brasiliensis poisoned calves was designed. Senecio brasiliensis contains pyrrolizidine alkaloids which cause either acute or chronic progressive dose dependent liver damage. Five calves were orally fed with 0.38g of dry leaves of S. brasiliensis/kg/day for 24 days. Liver needle biopsy specimens were obtained every 15 days for 60 days. Clinical signs of digestive complications appeared at 3rd week. One calf died on 45th day and four were evaluated up to 60th day. Biopsy samples were processed for routine light microscopy, immuno-histochemistry and transmission electron microscopy. From 30th day on progressive liver damage characterized by hepatocellular ballooning, necrosis, apoptosis and megalocytosis, centrilobular, pericellular and portal fibrosis were seen by light microscopy. Quantitative and semi-quantitative measurements of hepatic ECM components were performed before and after the onset of lesions. Morphometric analysis of total collagen and elastic fiber system was conducted. Total collagen and I and III collagen types progressively increased in throughout the liver of affected calves. Changes in location, amount and disposition of the elastic fiber system were also observed. Then numbers of Kupffer cells were significantly increased at 30th day and total numbers of sinusoidal cells were significantly increased at 45th and 60th days. Liver damage was progressive and irreversible even after the exposure to the plant was discontinued. Severe fibrotic lesions occurred mainly in portal tracts, followed by veno-occlusive and pericellular fibrosis. Collagen types I and III s were present in every normal and damaged liver, with predominance of type I. In affected calves the increase of total collagen and elastic fibers system paralleled the number of total sinusoidal cells.

Exploring business models for medical games: Key components and challenges

The costs of health care are going up in many countries. In order to provide affordable and effective health care solutions, new technologies and approaches are constantly being developed. In this research, video games are presented as a possible solution to the problem. Video games are fun, and nowadays most people like to spend time on them. In addition, recent studies have pointed out that video games can have notable health benefits. Health games have already been developed, used in practice, and researched. However, the bulk of health game studies have been concerned with the design or the effectiveness of the games; no actual business studies have been conducted on the subject, even though health games often lack commercial success despite their health benefits. This thesis seeks to fill this gap. The specific aim of this thesis is to develop a conceptual business model framework and empirically use it in explorative medical game business model research. In the first stage of this research, a literature review was conducted and the existing literature analyzed and synthesized into a conceptual business model framework consisting of six dimensions. The motivation behind the synthesis is the ongoing ambiguity around the business model concept. In the second stage, 22 semi-structured interviews were conducted with different professionals within the value network for medical games. The business model framework was present in all stages of the empirical research: First, in the data collection stage, the framework acted as a guiding instrument, focusing the interview process. Then, the interviews were coded and analyzed using the framework as a structure. The results were then reported following the structure of the framework. In the results, the interviewees highlighted several important considerations and issues for medical games concerning the six dimensions of the business model framework. Based on the key findings of this research, several key components of business models for medical games were identified and illustrated in a single figure. Furthermore, five notable challenges for business models for medical games were presented, and possible solutions for the challenges were postulated. Theoretically, these findings provide pioneering information on the untouched subject of business models for medical games. Moreover, the conceptual business model framework and its use in the novel context of medical games provide a contribution to the business model literature. Regarding practice, this thesis further accentuates that medical games can offer notable benefits to several stakeholder groups and offers advice to companies seeking to commercialize these games.

Multibody models for examination of touchdown bearing systems

Increased rotational speed brings many advantages to an electric motor. One of the benefits is that when the desired power is generated at increased rotational speed, the torque demanded from the rotor decreases linearly, and as a consequence, a motor of smaller size can be used. Using a rotor with high rotational speed in a system with mechanical bearings can, however, create undesirable vibrations, and therefore active magnetic bearings (AMBs) are often considered a good option for the main bearings, as the rotor then has no mechanical contact with other parts of the system but levitates on the magnetic forces. On the other hand, such systems can experience overloading or a sudden shutdown of the electrical system, whereupon the magnetic field becomes extinct, and as a result of rotor delevitation, mechanical contact occurs. To manage such nonstandard operations, AMB-systems require mechanical touchdown bearings with an oversized bore diameter. The need for touchdown bearings seems to be one of the barriers preventing greater adoption of AMB technology, because in the event of an uncontrolled touchdown, failure may occur, for example, in the bearing’s cage or balls, or in the rotor. This dissertation consists of two parts: First, touchdown bearing misalignment in the contact event is studied. It is found that misalignment increases the likelihood of a potentially damaging whirling motion of the rotor. A model for analysis of the stresses occurring in the rotor is proposed. In the studies of misalignment and stresses, a flexible rotor using a finite element approach is applied. Simplified models of cageless and caged bearings are used for the description of touchdown bearings. The results indicate that an increase in misalignment can have a direct influence on the bending and shear stresses occurring in the rotor during the contact event. Thus, it was concluded that analysis of stresses arising in the contact event is essential to guarantee appropriate system dimensioning for possible contact events with misaligned touchdown bearings. One of the conclusions drawn from the first part of the study is that knowledge of the forces affecting the balls and cage of the touchdown bearings can enable a more reliable estimation of the service life of the bearing. Therefore, the second part of the dissertation investigates the forces occurring in the cage and balls of touchdown bearings and introduces two detailed models of touchdown bearings in which all bearing parts are modelled as independent bodies. Two multibody-based two-dimensional models of touchdown bearings are introduced for dynamic analysis of the contact event. All parts of the bearings are modelled with geometrical surfaces, and the bodies interact with each other through elastic contact forces. To assist in identification of the forces affecting the balls and cage in the contact event, the first model describes a touchdown bearing without a cage, and the second model describes a touchdown bearing with a cage. The introduced models are compared with the simplified models used in the first part of the dissertation through parametric study. Damages to the rotor, cage and balls are some of the main reasons for failures of AMB-systems. The stresses in the rotor in the contact event are defined in this work. Furthermore, the forces affecting key bodies of the bearings, cage and balls can be studied using the models of touchdown bearings introduced in this dissertation. Knowledge obtained from the introduced models is valuable since it can enable an optimum structure for a rotor and touchdown bearings to be designed.

Finite-Sample Simulation-Based Inference in VAR Models with Applications to Order Selection and Causality Testing

Statistical tests in vector autoregressive (VAR) models are typically based on large-sample approximations, involving the use of asymptotic distributions or bootstrap techniques. After documenting that such methods can be very misleading even with fairly large samples, especially when the number of lags or the number of equations is not small, we propose a general simulation-based technique that allows one to control completely the level of tests in parametric VAR models. In particular, we show that maximized Monte Carlo tests [Dufour (2002)] can provide provably exact tests for such models, whether they are stationary or integrated. Applications to order selection and causality testing are considered as special cases. The technique developed is applied to quarterly and monthly VAR models of the U.S. economy, comprising income, money, interest rates and prices, over the period 1965-1996.

Bivariate semi-Pareto distributions and processes

A bivariate semi-Pareto distribution is introduced and characterized using geometric minimization. Autoregressive minification models for bivariate random vectors with bivariate semi-Pareto and bivariate Pareto distributions are also discussed. Multivariate generalizations of the distributions and the processes are briefly indicated.

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Performance of Gabion Faced Reinforced Earth Retaining Walls

Gabion faced re.taining walls are essentially semi rigid structures that can generally accommodate large lateral and vertical movements without excessive structural distress. Because of this inherent feature, they offer technical and economical advantage over the conventional concrete gravity retaining walls. Although they can be constructed either as gravity type or reinforced soil type, this work mainly deals with gabion faced reinforced earth walls as they are more suitable to larger heights. The main focus of the present investigation was the development of a viable plane strain two dimensional non linear finite element analysis code which can predict the stress - strain behaviour of gabion faced retaining walls - both gravity type and reinforced soil type. The gabion facing, backfill soil, In - situ soil and foundation soil were modelled using 20 four noded isoparametric quadrilateral elements. The confinement provided by the gabion boxes was converted into an induced apparent cohesion as per the membrane correction theory proposed by Henkel and Gilbert (1952). The mesh reinforcement was modelled using 20 two noded linear truss elements. The interactions between the soil and the mesh reinforcement as well as the facing and backfill were modelled using 20 four noded zero thickness line interface elements (Desai et al., 1974) by incorporating the nonlinear hyperbolic formulation for the tangential shear stiffness. The well known hyperbolic formulation by Ouncan and Chang (1970) was used for modelling the non - linearity of the soil matrix. The failure of soil matrix, gabion facing and the interfaces were modelled using Mohr - Coulomb failure criterion. The construction stages were also modelled.Experimental investigations were conducted on small scale model walls (both in field as well as in laboratory) to suggest an alternative fill material for the gabion faced retaining walls. The same were also used to validate the finite element programme developed as a part of the study. The studies were conducted using different types of gabion fill materials. The variation was achieved by placing coarse aggregate and quarry dust in different proportions as layers one above the other or they were mixed together in the required proportions. The deformation of the wall face was measured and the behaviour of the walls with the variation of fill materials was analysed. It was seen that 25% of the fill material in gabions can be replaced by a soft material (any locally available material) without affecting the deformation behaviour to large extents. In circumstances where deformation can be allowed to some extents, even up to 50% replacement with soft material can be possible.The developed finite element code was validated using experimental test results and other published results. Encouraged by the close comparison between the theory and experiments, an extensive and systematic parametric study was conducted, in order to gain a closer understanding of the behaviour of the system. Geometric parameters as well as material parameters were varied to understand their effect on the behaviour of the walls. The final phase of the study consisted of developing a simplified method for the design of gabion faced retaining walls. The design was based on the limit state method considering both the stability and deformation criteria. The design parameters were selected for the system and converted to dimensionless parameters. Thus the procedure for fixing the dimensions of the wall was simplified by eliminating the conventional trial and error procedure. Handy design charts were developed which would prove as a hands - on - tool to the design engineers at site. Economic studies were also conducted to prove the cost effectiveness of the structures with respect to the conventional RCC gravity walls and cost prediction models and cost breakdown ratios were proposed. The studies as a whole are expected to contribute substantially to understand the actual behaviour of gabion faced retaining wall systems with particular reference to the lateral deformations.

A study on fuzzy semi inner product spaces

Mathematical models are often used to describe physical realities. However, the physical realities are imprecise while the mathematical concepts are required to be precise and perfect. Even mathematicians like H. Poincare worried about this. He observed that mathematical models are over idealizations, for instance, he said that only in Mathematics, equality is a transitive relation. A first attempt to save this situation was perhaps given by K. Menger in 1951 by introducing the concept of statistical metric space in which the distance between points is a probability distribution on the set of nonnegative real numbers rather than a mere nonnegative real number. Other attempts were made by M.J. Frank, U. Hbhle, B. Schweizer, A. Sklar and others. An aspect in common to all these approaches is that they model impreciseness in a probabilistic manner. They are not able to deal with situations in which impreciseness is not apparently of a probabilistic nature. This thesis is confined to introducing and developing a theory of fuzzy semi inner product spaces.

Stochastic processes and their applications semi-markov analysis of some inventory and queuing problems

This thesis analyses certain problems in Inventories and Queues. There are many situations in real-life where we encounter models as described in this thesis. It analyses in depth various models which can be applied to production, storag¢, telephone traffic, road traffic, economics, business administration, serving of customers, operations of particle counters and others. Certain models described here is not a complete representation of the true situation in all its complexity, but a simplified version amenable to analysis. While discussing the models, we show how a dependence structure can be suitably introduced in some problems of Inventories and Queues. Continuous review, single commodity inventory systems with Markov dependence structure introduced in the demand quantities, replenishment quantities and reordering levels are considered separately. Lead time is assumed to be zero in these models. An inventory model involving random lead time is also considered (Chapter-4). Further finite capacity single server queueing systems with single/bulk arrival, single/bulk services are also discussed. In some models the server is assumed to go on vacation (Chapters 7 and 8). In chapters 5 and 6 a sort of dependence is introduced in the service pattern in some queuing models.