An extracellular stochastic model of early HIV infection and the formulation of optimal treatment policy

The problem of scheduling optimal treatment strategies for patients at the early stage of human immunodeficiency virus (HIV) infection is investigated. Unlike patients with an established HIV infection, complete eradication of the infection is still possible at this stage and treatment can further increase the probability of eradication. However, high dosages of drugs should be avoided, if possible, because of toxic side effects. Stochastic simulation is capable of determining the infection establishment probability at the early infection stage. Consequently, to obtain acceptable treatment strategies, an optimization problem was formulated, employing a stochastic model to predict the response of an average patient to treatment. Optimal treatment strategies for prompt and also a few days latency in treatment initiation were computed. These strategies were compared with constant treatment strategies and were shown to be more beneficial in silico, i.e., they either decreased the infection establishment probability or the dosage of the drugs.     

Magnetic separations: From steel plants to biotechnology

Magnetic separations have for decades been essential processes in diverse industries ranging from steel production to coal desulfurization. In such settings magnetic fields are used in continuous flow processes as filters to remove magnetic impurities. High gradient magnetic separation (HGMS) has found even broader use in wastewater treatment and food processing. Batch scale magnetic separations are also relevant in industry, particularly biotechnology where fixed magnetic separators are used to purify complex mixtures for protein isolation, cell separation, drug delivery, and biocatalysis. In this review, we introduce the basic concepts behind magnetic separations and summarize a few examples of its large scale application. HGMS systems and batch systems for magnetic separations have been developed largely in parallel by different communities. However, in this work we compare and contrast each approach so that investigators can approach both key areas. Finally, we discuss how new advances in magnetic materials, particularly on the nanoscale, as well as magnetic filter design offer new opportunities for industries that have challenging separation problems.     

Effectiveness factor for spatial gradient sensing in living cells

We consider the steady-state pattern of messenger molecules produced in the membrane of a cell perceiving and responding to an extracellular gradient of chemoattractant, which directs cell movement towards the chemoattractant source. Specifically, we analyze the undesirable effect of lateral diffusion in blurring the intracellular messenger profile. The concept of an effectiveness factor, akin to the analysis of reactions in porous catalysts, is applied to the spatial gradient sensing problem, with the distinction that slow, not fast, diffusion is required for effective gradient sensing. Analytical effectiveness factor expressions are derived for ideal geometries and then generalized to arbitrary cell shapes. In the case of mouse fibroblasts responding to gradients of platelet-derived growth factor, we conclude that the cell morphology and orientation with respect to the gradient can dictate whether messenger diffusion obliterates gradient sensing or has very little effect. The analysis outlined here allows the effect of intracellular messenger diffusion on spatial gradient sensing to be quantified for individual cells.     

A Thermo-Hydro-Mechanics Bidirectional Coupling Mathematical Model for Drying of Biological Porous Medium

Based on Fickian diffusion theory, Fourier's law of heat conduction and thermoelasticity mechanics, a thermo-hydro-mechanics bidirectional coupling mathematical model has been developed to simulate the hot air convective drying of biological porous media. The transient model, composed of a system of partial differential equations, was solved by finite difference methods. The numerical results were compared with available experimental data obtained during the drying of potatoes. The numerical results obtained using the mathematical model were in good agreement with the experimental data. Numerical simulations of the drying curve variations and the spatio-temporal distributions of moisture, temperature, and drying stresses and strains were evaluated.     

Kinetic model for the hydrolysis of sterilized palm press fibre

In this study, a kinetic model for enzymatic hydrolysis of oil palm residues considering the effect of sterilization was proposed and validated. Experiments were performed in batch reactor using palm oil mill effluent (POME) supplemented with sterilized and non-sterilized pressed pericarp fibers (PPF) as substrates. Kinetic parameters were estimated by fitting the experimental data to the models. It was found that the sterilization process as well as the variety in substrate particle size exerted an effect on the apparent rate constant (k), but no effect on the apparent Michaelis constant (K_M) and apparent competitive inhibition constant (K_I). When compared with the experimental data, the kinetic model provided good prediction to the oil palm residues hydrolysis with mean square error less than 10%.     

A Kinetic Study of In Vitro Lysis of Mycobacterium smegmatis

The traditional diagnostic tests for tuberculosis consist of an acid fast stain and a culture test from a sputum sample. With the emergence of drug resistant strains of tuberculosis, nucleic acid amplification has become the diagnostic test of choice. The nucleic acid amplification test consists of four steps: sputum sample collection, lysis of bacilli to release DNA, DNA amplification by PCR and detection of PCR products. The DNA extraction step has been largely overlooked and this study describes a systematic approach to measure the kinetics of cell lysis in a Tris-EDTA buffer. Mycobacterium smegmatis is a saphorytic, fast-growing mycobacterium that is often used as a surrogate of Mycobacterium tuberculosis in laboratory studies. M. smegmatis cells have been transformed with green fluorescent protein (GFP) genes. Transformed cells are lysed in a temperature-controlled cuvette that is equipped with optical input/output. The fluorescence signal increases when the GFP is released from lysed cells, and the extent of lysis of the loaded cells can be followed in real time. The experimental results are complemented by two theoretical models. The first model is based on a Monte Carlo simulation of the lysis process and the accompanying probability density function, as described by the Fokker-Planck equation. The second model follows a chemical reaction engineering approach: the cell wall is modeled as layers, where each layer is made up of “blocks”. Blocks can only be removed if they are exposed to the lysis solution and the model describes the rate of block exposure and removal. Both models are consistent with the experimental results. The main findings are: (1) the activation energy for M. smegmatis lysis in Tris-EDTA buffer is 22.1 kcal/mol, (2) cells lyse on the average after 14-17% loss in cell wall thickness locally, (3) with the help of the models, the initial distribution in cell wall thickness of the population can be resolved and (4) near complete lysis of the cells is accomplished in 200 s at 80 °C (90 s at 90 °C). The results can be used to design an optimal lysis protocol that compromises between shorter processing times at higher temperature and reduced thermal damage to DNA at lower temperature.     

A Mathematical Model for Prediction of Pore Size Distribution Development during Activated Carbon Preparation

A new modeling approach was introduced for the prediction of pore size distribution development during activated carbon preparation. The mathematical model is based on the modification of a single-pore model for pore growth rate estimation using a population balance and applying a variable structural parameter random-pore model. The model predictions were compared with experimental pore size distributions and conversions at various times for pistachio shell char activation by steam between 800° and 950°C, and the kinetic parameters were estimated.     

Validation of a population balance model for olivine dissolution

The dissolution of silicate minerals, among them olivine, in water enables its subsequent reaction with carbon dioxide to form magnesium carbonate, a process called aqueous mineral carbonation. A general model for the dissolution of olivine, based on a population balance approach, has been developed. For this purpose, the dissolution rate of olivine has been measured as a function of varying particle size and pH at . Three separate particle populations in three different size ranges were used: a sub 90, a 90-180, and a 180- size fraction. The pH was varied between 2 and 4.75 using HCl. Experiments were carried out in a flow-through reactor under a nitrogen atmosphere of 20 bar. The dissolution extent varied from 12% up to complete dissolution, depending on experimental conditions. Particle size distributions of the different size fractions were measured with a Coulter Multisizer^®. Using the assumption of a surface controlled reaction, the solution to the population balance equation was coupled with a reactor model. Data were fitted to the model to obtain a shape modulated dissolution rate, , combining the volume shape factor k_v with the dissolution rate D, which has the dimensions of a velocity. Including earlier published dissolution experiments an overall correlation for the dissolution rate was regressed. Using the general model, the limitations of the simplified model employed in an earlier publication are illustrated.     

Performance Study of a Closed-Type Heat Pump Tumble Dryer Using a Simulation Model and an Experimental Set-Up

In the interests of competitiveness, manufactures of tumble dryers are seeking to reduce both their electricity use and the drying time. This study examines how the cylinder volume of the compressor and the total heat transfer of the condenser influence the drying time and electricity use in a heat pump tumble dryer. A transient simulation model was developed and compared to an experimental set-up with good similarity. The simulations show that increasing the cylinder volume of the compressor by 50% decreases the drying time by 14% without using more electricity.     

Biosynthesis of 4-hydroxyphenylpyruvic acid from l-tyrosine using recombinant Escherichia coli cells expressing membrane bound l-amino acid deaminase

4-Hydroxyphenylpyruvic acid(4-HPPA), a kind of α-keto acid, is an intermediate in the metabolism of tyrosine and has a wide range of application in food, pharmaceutical and chemical industry. Using amino acids as raw material to produce the corresponding α-keto acid is thought to be both economic and efficient. Among the enzymes that convert amino acid to α-keto acid, membrane bound L-amino acid deaminase(mL-AAD), which is anchored to the outer side of the cytomembrane, becomes an ideal enzyme to prepare α-keto acid since there is no cofactors needed and H_2 O_2 production during the reaction. In this study, the mL-AAD from Proteus vulgaris was used to prepare whole-cell catalysts to produce 4-HPPA from L-tyrosine. The secretory efficiency of mL-AAD conducted by its own twin-arginine signal peptide(twin-arginine translocation pathway, Tat) and integrated pelB(the general secretory pathway, Sec)-Tat signal peptide was determined and compared firstly, using two pET systems(pET28 a and pET20 b). It was found that the Tat pathway(pET28 a-mlaad) resulted in higher cell-associated mL-AAD activity and cell biomass, and was more beneficial to prepare biocatalyst. In addition, expression hosts B121(DE3) and 0.05 mmol ·L~(-1) IPTG were found to be suitable for mL-AAD expression. The reaction conditions for mL-AAD were optimized and 72.72 mmol·L~(-1) 4-HPPA was obtained from 100 mmol·L~(-1) tyrosine in 10 h under the optimized conditions. This bioprocess, which is more eco-friendly and economical than the traditional chemical synthesis ways, has great potential for industrial application.     

Theoretical performance of countercurrent reactors for production of enantiopure compounds

Irreversible reactions are being applied in enzymatic kinetic resolution to obtain enantiomerically pure compounds from racemic mixtures. Using model calculations for situations without mass transfer limitation, we show that reversible reactions might also be useful for enzymatic kinetic resolution, provided that countercurrent systems are used rather than batch or cocurrent systems. The required reaction time or enzyme amount in a countercurrent system is much lower than in an analogous cocurrent system or its batch equivalent. More importantly, often the calculated yield and enantiomeric excess are better in countercurrent systems. Racemization can also be favorably used in countercurrent systems. Consequently, to achieve with a reversible reaction a particular enantiomeric excess and yield, a countercurrent system needs less dilution or activated co-reactant and less enantioselective enzyme than a cocurrent system.     

Development of a unified framework for calculating molecular weight distribution in diffusion controlled free radical bulk homo-polymerization

In the present work, two different approaches to model diffusion controlled free radical polymerization, namely the free volume model and the entanglement theory are compared. These approaches are applied to methyl methacrylate bulk polymerization in a batch reactor to calculate the conversion, total radical concentration, the number and weight average molecular weights as well as the entire molecular weight distribution as a function of the polymerization time and the process conditions. All the diffusion-controlled phenomena were taken into account, including gel, glass and cage effects as well as residual termination. The molecular weight distribution is calculated by direct numerical integration of a large system of non-linear ordinary differential equations describing the conservation of the mass of macromolecular species in the batch reactor. Model predictions are in good agreement with available experimental data for conversion, number and weight average molecular weights as well as the entire molecular weight distribution, thus justifying the ability of these models to describe the main issues of the diffusion-controlled free radical polymerization.     

A protein diffusion model of the sealing effect

Water transport across the arterial endothelium is believed primarily to occur through breaks in the tight junction strands at the cell periphery between neighboring cells. Additional proteins arriving at the tight junction can close these breaks, thereby attenuating this water flux. Motivated by evidence that the diffusion of presynthesized protein from the interior of the cell to and incorporation into the cell border is the mechanism of endothelial tight junctional sealing, we develop a diffusion-limited mathematical model of intercellular gap sealing. A single endothelial cell is represented as a thin, axisymmetric disk, initially containing a uniform distribution of junctional protein that does not interact with the apical or basal cell surfaces. Upon application of a transmural pressure gradient, water flows through the junctional cleft, and tight junction remodeling begins. We assume that proteins at the junction are instantaneously incorporated into its strand, dropping the free protein concentration at the cell periphery to zero. This sets the diffusion of intracellular proteins toward the junction in motion. The solution of this one-dimensional initial value problem provides excellent fits to current and previously published experimental data over a wide variety of conditions. It yields three physically meaningful parameters for each fit, including a protein diffusivity in the cytoplasm that varies little within experimental treatments. Statistical variation of these parameters allows rational comparison of experimental runs and identification of outlier runs.     

Experimental design for the joint model discrimination and precise parameter estimation through information measures

Experimental design procedures for model discrimination and for estimation of precise model parameters are usually treated as independent techniques. In order to conciliate the objectives of both experimental design procedures, the present paper proposes the use of experimental design criteria that are based on measures of the information gain when new experiments are carried out. The proposed criterion depends on the volumes of the confidence regions of the model parameters and presents a number of advantageous aspects, such as the conciliation of the usual experimental design objectives and the fact that the obtained criterion values can be easily interpreted in terms of the information eliminated after carrying out additional experiments. Besides, the proposed design criterion can easily accommodate multiobjective experimental design approaches, as shown in the examples.     

Experimental campaign,modeling, and sensitivity analysis for the molecular distillation of petroleum residues 673.15 K+

This research activity proposes a sensitivity analysis of the molecular distillation process by focusing the attention on the response of the overall distillate flow rate under several conditions of distillation temperature and feed flow rate. Specific equations to characterize physicochemical properties of petroleum residues have been formulated by means of ASTM-based experimental campaigns combined with specific optimization techniques.     

Mathematical modelling of Sec pathway mechanism in Escherichia coli: a case study for periplasmic translocation of maltose binding protein-glucose isomerase fusion protein

Within the framework of reported information on the Sec pathway mechanism, a mathematical model for the periplasmic translocation of fusion proteins in bacteria was developed. The mathematical model includes all stages of the targeting stage and assume that the ATP-driven translocation stage is completed in a single step. The equations for the targeting stage involved cytoplasmic folding rate and SecB binding kinetics. Rate equations for the translocation stage were derived using King-Altman and network reduction techniques. Experimental data for maltose binding protein-glucose isomerase fusion protein (MBP-GI) translocation and reported data for MBP translocation were used to estimate the parameters. The simulation results show that the model fits well to the experimental data of cytoplasmic and periplasmic MBP-GI distributions. When the values of the targeting stage parameters, k₁ and k₃ or the concentration of SecB are changed, the model correctly predicts the expected changes in the MBP-GI distribution to the cytoplasmic and periplasmic spaces. The SecB complex and the preprotein concentrations predicted attain steady state immediately, within seconds, and their amounts are very low when compared to MBP-GI in either compartment. The model can be made applicable to any protein that uses the Sec pathway, and with ATP and Sec pathway protein limitations.     

Large-Scale Experimental Validation of a Model for the Kinetics of Ozone and Hydroxyl Radicals with Natural Organic Matter

A unified model for the kinetics of O₃ and ^?OH with NOM was proposed, calibrated and validated based on large experimental data sets. Single-phase batch experiments were done on 11 water samples from seven resources. Seasonal variations were studied on three resources. Effects of reaction time with ozone, ozone dose, pH, temperature, radical scavenger adding, and NOM dilution were studied. The experiments represented more than 1200 and 900 concentration measurements, respectively, for ozone and pCBA (^?OH tracer). Mechanistic models were used for ozone self-decomposition and carbonate species kinetics. Results showed that the proposed model is robust and can handle different water characteristics and different experimental conditions: 75% of the experiments were modeled satisfactorily (for ozone and pCBA). Next, the domain of validity was determined: 6 ≤ pH ≤ 8; 1 meq.L^?1 ≤ alkalinity ≤ 6 meq.L^?1; 0–0.5 mgC.L^?1 ≤ TOC ≤ 3.1 mgC.L^?1. Only water samples with high organic (TOC > 2.4 mg.L^?1) and low inorganic contents (alkalinity < 0.3 meq.L^?1) could not be modeled adequately. Seasonal comparisons showed that the quality of the predictions decreases only for pCBA when having calibrated the model at another season. The model gave good results when using only 6 single batch experiments for calibration.     

Valid parameter range analyses for chemical reaction kinetic models

The present work quantifies the relations between the structure of a chemical reaction kinetic model, its valid parameter range, and the truncation error tolerance of the model. General methods are presented to solve the three important problems of valid parameter range analysis: (1) identification of the valid parameter range of a kinetic model, (2) estimation of the error tolerance required when applying a kinetic model over a specified parameter range, and (3) improvement of existing model generation algorithms to construct more robust models. Finally, the relationship between a model's structure, its valid parameter range, and the truncation error tolerance are illustrated by the flexibility-tolerance-model graph. The new methods are applied to pyrolysis of methane/ethane mixtures.