Optimized Baxter Model of Protein Solutions: Electrostatics versus Adhesion

A theory is set up of spherical proteins interacting by screened electrostatics and constant adhesion, in which the effective adhesion parameter is optimized by a variational principle for the free energy. An analytical approach to the second virial coefficient is first outlined by balancing the repulsive electrostatics against part of the bare adhesion. A theory similar in spirit is developed at nonzero concentrations by assuming an appropriate Baxter model as the reference state. The first-order term in a functional expansion of the free energy is set equal to zero which determines the effective adhesion as a function of salt and protein concentrations. The resulting theory is shown to have fairly good predictive power for the ionic-strength dependence of both the second virial coefficient and the osmotic pressure or compressibility of lysozyme up to about 0.2 volume fraction.Comment: 40 pages, 9 figure

Collective diffusion coefficient of proteins with hydrodynamic, electrostatic and adhesive interactions

A theory is presented for lambda_C, the coefficient of the first-order correction in the density of the collective diffusion coefficient, for protein spheres interacting by electrostatic and adhesive forces. An extensive numerical analysis of the Stokesian hydrodynamics of two moving spheres is given so as to gauge the precise impact of lubrication forces. An effective stickiness is introduced and a simple formula for lambda_C in terms of this variable is put forward. A precise though more elaborate approximation for lambda_C is also developed. These and numerically exact expressions for lambda_C are compared with experimental data on lysozyme at pH 4.5 and a range of ionic strengths between 0.05 M and 2 M.Comment: 8 pages, 3 figures, 1 tabl

Deep residual learning in CT physics: scatter correction for spectral CT

Recently, spectral CT has been drawing a lot of attention in a variety of clinical applications primarily due to its capability of providing quantitative information about material properties. The quantitative integrity of the reconstructed data depends on the accuracy of the data corrections applied to the measurements. Scatter correction is a particularly sensitive correction in spectral CT as it depends on system effects as well as the object being imaged and any residual scatter is amplified during the non-linear material decomposition. An accurate way of removing scatter is subtracting the scatter estimated by Monte Carlo simulation. However, to get sufficiently good scatter estimates, extremely large numbers of photons is required, which may lead to unexpectedly high computational costs. Other approaches model scatter as a convolution operation using kernels derived using empirical methods. These techniques have been found to be insufficient in spectral CT due to their inability to sufficiently capture object dependence. In this work, we develop a deep residual learning framework to address both issues of computation simplicity and object dependency. A deep convolution neural network is trained to determine the scatter distribution from the projection content in training sets. In test cases of a digital anthropomorphic phantom and real water phantom, we demonstrate that with much lower computing costs, the proposed network provides sufficiently accurate scatter estimation

Application of the Optimized Baxter Model to the hard-core attractive Yukawa system

We perform Monte Carlo simulations on the hard-core attractive Yukawa system to test the Optimized Baxter Model that was introduced in [P.Prinsen and T. Odijk, J. Chem. Phys. 121, p.6525 (2004)] to study a fluid phase of spherical particles interacting through a short-range pair potential. We compare the chemical potentials and pressures from the simulations with analytical predictions from the Optimized Baxter Model. We show that the model is accurate to within 10 percent over a range of volume fractions from 0.1 to 0.4, interaction strengths up to three times the thermal energy and interaction ranges from 6 to 20 % of the particle diameter, and performs even better in most cases. We furthermore establish the consistency of the model by showing that the thermodynamic properties of the Yukawa fluid computed via simulations may be understood on the basis of one similarity variable, the stickiness parameter defined within the Optimized Baxter Model. Finally we show that the Optimized Baxter Model works significantly better than an often used, naive method determining the stickiness parameter by equating the respective second virial coefficients based on the attractive Yukawa and Baxter potentials.Comment: 11 pages, 8 figure

Fluid-crystal coexistence for proteins and inorganic nanocolloids: dependence on ionic strength

We investigate theoretically the fluid-crystal coexistence of solutions of globular charged nanoparticles like proteins and inorganic colloids. The thermodynamic properties of the fluid phase are computed via the optimized Baxter model. This is done specifically for lysozyme and silicotungstates for which the bare adhesion parameters are evaluated via the experimental second virial coefficients. The electrostatic free energy of the crystal is approximated by supposing the cavities in the interstitial phase between the particles are spherical in form. In the salt-free case a Poisson-Boltzmann equation is solved to calculate the effective charge on a particle and a Donnan approximation is used to derive the chemical potential and osmotic pressure in the presence of salt. The coexistence data of lysozyme and silicotungstates are analyzed within this scheme, especially with regard to the ionic-strength dependence of the chemical potentials. The latter agree within the two phases provided some upward adjustment of the effective charge is allowed for.Comment: 15 pages, 9 figure

Exercise Stress Testing in Children with Metabolic or Neuromuscular Disorders

The role of exercise as a diagnostic or therapeutic tool in patients with a metabolic disease (MD) or neuromuscular disorder (NMD) is relatively underresearched. In this paper we describe the metabolic profiles during exercise in 13 children (9 boys, 4 girls, age 5–15 yrs) with a diagnosed MD or NMD. Graded cardiopulmonary exercise tests and/or a 90-min prolonged submaximal exercise test were performed. During exercise, respiratory gas-exchange and heart rate were monitored; blood and urine samples were collected for biochemical analysis at set time points. Several characteristics in our patient group were observed, which reflected the differences in pathophysiology of the various disorders. Metabolic profiles during exercises CPET and PXT seem helpful in the evaluation of patients with a MD or NMD

Exercise Stress Testing in Children with Metabolic or Neuromuscular Disorders

The role of exercise as a diagnostic or therapeutic tool in patients with a metabolic disease (MD) or neuromuscular disorder (NMD) is relatively underresearched. In this paper we describe the metabolic profiles during exercise in 13 children (9 boys, 4 girls, age 5–15 yrs) with a diagnosed MD or NMD. Graded cardiopulmonary exercise tests and/or a 90-min prolonged submaximal exercise test were performed. During exercise, respiratory gas-exchange and heart rate were monitored; blood and urine samples were collected for biochemical analysis at set time points. Several characteristics in our patient group were observed, which reflected the differences in pathophysiology of the various disorders. Metabolic profiles during exercises CPET and PXT seem helpful in the evaluation of patients with a MD or NMD

Impaired Cognitive Functioning in Patients with Tyrosinemia Type I Receiving Nitisinone

ObjectiveTo examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet.Study designWe performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development.ResultsAverage total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 ± 13 vs 91 ± 13; P = .008). Both verbal and performance IQ subscores differed (77 ± 14 vs 95 ± 11; P < .05 and 70 ± 11 vs 87 ± 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 ± 15 to 69 ± 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration.ConclusionPatients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein-restricted diet

How to select outcome measurement instruments for outcomes included in a "Core Outcome Set" - a practical guideline

BackgroundIn cooperation with the Core Outcome Measures in Effectiveness Trials (COMET) initiative, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative aimed to develop a guideline on how to select outcome measurement instruments for outcomes (i.e., constructs or domains) included in a "Core Outcome Set" (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population.MethodsInformed by a literature review to identify potentially relevant tasks on outcome measurement instrument selection, a Delphi study was performed among a panel of international experts, representing diverse stakeholders. In three consecutive rounds, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments, to justify their choices, and to add other relevant tasks. Consensus was defined as being achieved when 70 % or more of the panelists agreed and when fewer than 15 % of the panelists disagreed.ResultsOf the 481 invited experts, 120 agreed to participate of whom 95 (79 %) completed the first Delphi questionnaire. We reached consensus on four main steps in the selection of outcome measurement instruments for COS: Step 1, conceptual considerations; Step 2, finding existing outcome measurement instruments, by means of a systematic review and/or a literature search; Step 3, quality assessment of outcome measurement instruments, by means of the evaluation of the measurement properties and feasibility aspects of outcome measurement instruments; and Step 4, generic recommendations on the selection of outcome measurement instruments for outcomes included in a COS (consensus ranged from 70 to 99 %).ConclusionsThis study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS. This guideline can be used by COS developers in defining how to measure core outcomes