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Parameters of control when facing stochastic demand: a DEA approach applied to Bangladeshi vaccination sites.

An aim of vaccination programs is near-complete coverage. One method for achieving this is for health facilities providing these services to operate frequently and for many hours during each session. However, if vaccine vials are not fully used, the remainder is often discarded, considered as waste. Without an active appointment schedule process, there is no way for facility staff to control the stochastic demand of potential patients, and hence reduce waste. And yet reducing the hours of operation or number of sessions per week could hinder access to vaccination services. In lieu of any formal system of controlling demand, we propose to model the optimal number of hours and sessions in order to maximize outputs, the number and type of vaccines provided given inputs, using Data Envelopment Analysis (DEA). Inputs are defined as the amount of vaccine wastage and the number of full-time equivalent staff, size of the facility, number of hours of operation and the number of sessions. Outputs are defined as the number and type of vaccines aimed at children and pregnant women. This analysis requires two models: one DEA model with possible reallocations between the number of hours and the number of sessions but with the total amount of time fixed and one model without this kind of reallocation in scheduling. Comparing these two scores we can identify the "gain" that would be possible were the scheduling of hours and sessions modified while controlling for all other types of inefficiency. By modeling an output-based model, we maintain the objective of increasing coverage while assisting decision-makers determining optimal operating processes.

Bangladesh↗

[Biotechnology using modified microorganisms].

Few microorganisms, as compare to their high diversity, are used for human needs. They can produce molecules of interest, process fermentation, protect crops, treat wastes or clean environment. Molecular technics and genetic engineering are new tools offer to geneticists which breed microorganisms for years. Using them, it is now possible, theoretically, to introduce any gene in any organism. Some examples are given concerning genetic modifications in yeasts and lactic acid bacteria to optimize agrofood processes and to improve nutritive and flavour characteristics of fermented products like bread, beer, wine, cheese, meat, vegetable juices... In spite of scientific and industrial interest of the new technologies, limiting factors can explain that genetically modified microorganisms are not routinely used in agrofood yet. First, risks assessment on human health and environment are still in debate, but their is a consensus, within the scientific community, to consider that new characteristics of improved microorganisms are more important than the technics used for their construction. Second, regulations turn out to impose constraints susceptible to discourage technological innovations. At least, the public perception about the new technologies appears, actually, as the major factor to limit their development.

Genetic Engineering↗

[Recovery of platinum with immobilized Citrobacter freudii XP05 biomass].

The objective of this work was to develop a valuable adsorbent for recovery of platinum by studying the properties of Pt4+ -adsorption with immobilized Citrobacter freudii XP05 biomass. Five methods for immobilization of Citrobacter freudii XP05 biomass were compared. The method with gelatin-alginate sodium as entrapment matrix was considered to be the optimal. Spherical and uniform beads were produced and the SEM micrograph indicated that the cell of strain XP08 were uniformly dispersed within the matrix. The adsorption of Pt4+ by immobilized XP05 biomass was affected with adsorptive time, pH value of the solution, immobilized biomass concentration, Pt4+ initial concentration The adsorption was a rapid process. The optimal pH value for Pt4+ adsorption was 1.5, and its adsorptive capacity increased linearly with increasing Pt4+ initial concentrations in the range of 50 - 250 mg/L. The experimental data could be fitted to Langmuir and Freundlich models of adsorption isotherm. The adsorptive capacity reached 35.2 mg/g under the conditions of 250 Pt4+ mg/L, 2.0 g/L immobilized biomass, pH 1.5 and 30 degrees C for 60 min. 98.7% of Pt4+ adsorbed on immobilized biomass could be desorbed with 0.5 mol HC1/L. The characteristics of dynamic adsorption and desorption of immobilized XP05 biomass in packed-bed reactor were investigated. The saturation uptake was 24.66 mg Pt4+ /g under the conditions of flow rate 1.2 mL/min, pH 1.5, 50 mg Pt4+/L and 1.85 g biomass(dry weight) . Adsorptive efficiency of Pt4 + by the immobilized XP05 biomass was above 78% for 4 cycles of adsorption and desorption. The recovery of platinum from waste platinum catalyst was studied. The adsorptive capacity was 20.94 mg Pt4+/g immobilized biomass under the conditions of 4.0 g/L immobilized XP05 biomass, 117.76 mg Pt4+/L and pH 1.5 for 60 min. The immobilized XP05 biomass is potentially applicable to the recovery of platinum from waste and wastewater containing platinum.

Biomass↗

Surface modification of magnetic nanoparticles with alkoxysilanes and their application in magnetic bioseparations.

A versatile and inexpensive method for the introduction of amine groups onto the surface of silica-coated magnetite composite nanoparticles has been established based on the condensation of (aminopropyl)triethoxysilane (APTS). The process was observed to be sensitive to a range of variables, and a range of silane surface-modified nanoparticles was synthesized under various reaction conditions, that is, solvent systems [water, tetrahydrofuran (THF), ethanol, or 1:1 mixtures of them], reaction times (from 1 to 24 h), and temperatures (18, 50, and 70 degrees C), with water as the catalyst and silane at either 0.2% or 2% (w/v) in an attempt to optimize the process. The products of the various reactions were characterized in terms of their possession of surface -NH2 groups, morphologies, and properties with respect to DNA binding and elution before being modified with a single-stranded oligonucleotide capture sequence. It was observed that careful manipulation of temperature, time, and solvent conditions was important for optimal silanization of the nanoparticles, and in our experiments best results were obtained when silanization of the particles in suspension involved use of water as the solvent and APTS at 0.2% (w/v) and when the reaction was conducted at room temperature for 5 h and was preceded by ultrasonication of the particle suspension. The materials produced were used in experiments to selectively capture complementary nucleic acid sequences by hybridization after grafting with an oligonucleotide. The efficiency of the oligonucleotide-modified particles in the capture experiments was observed to be directly related to the original density of amine groups present at the surface of the support. The results indicate that surface engineering of the nanoparticles was possible by silanization under defined, optimized conditions. This approach could be extended to the activation of such surfaces and other materials with other functional groups.

Kinetics↗

Systematic approach to life support system analyses and integration.

This paper is devoted to the consideration of possible viewpoint on CELSS development and design. If the aim to create practically applicable CELSS is accepted then the task to optimize the process of CELSS research and development in terms of minimum cost, hours, maximum applicability, scientific contribution, etc. becomes actual. Requirements of applicability and scientific significance are synergetic since understanding of general properties of CELSS gives an ability to create CELSS for different applications. To accomplish the task three main groups of parameters have to be optimized: i) configuration and operating parameters of developing CELSS itself; ii) organizational management of research and development of CELSS; iii) features of an area where CELSS is planned to be used (space missions, terrestrial applications, or biosphere investigation) and where requirements to CELSS characteristic come from. Given paper is a brief review presented some attempts to arrange mentioned above into some set of formalized and interacting criteria, and some progression of research stages derived from these criteria.

Ecological Systems, Closed↗

Encapsulation of a lipid precursor, the eicosapentaenoic acid, to study the development of the Crassostrea gigas oyster flavours.

The present study is part of a larger project whose aim is to understand how the oyster Crassostrea gigas develops its aromas from a lipid precursor, the eicosapentaenoic acid (EPA), in glyceride form. The objective of this study is, therefore, to prepare an encapsulation process that will enable the bivalve to be supplied with this lipid precursor. The complex coacervation method was chosen as it gave the best compatible microcapsules with respect to the nutritional aspects of oyster (i.e. digestibility) and the environmental constraints (i.e. behaviour and stability in seawater). The aim of this study is to manufacture and optimize a process of complex coacervation, to obtain capsules made of gelatin and acacia gum with a size under 100 microm in diameter and containing very small drops of cod liver oil (rich in EPA). The preservation of these microcapsules in seawater has been confirmed.

Acacia↗

MINLP models for the synthesis of optimal peptide tags and downstream protein processing.

The development of systematic methods for the synthesis of downstream protein processing operations has seen growing interest in recent years, as purification is often the most complex and costly stage in biochemical production plants. The objective of the work presented here is to develop mathematical models based on mixed integer optimization techniques, which integrate the selection of optimal peptide purification tags into an established framework for the synthesis of protein purification processes. Peptide tags are comparatively short sequences of amino acids fused onto the protein product, capable of reducing the required purification steps. The methodology is illustrated through its application on two example protein mixtures involving up to 13 contaminants and a set of 11 candidate chromatographic steps. The results are indicative of the benefits resulting by the appropriate use of peptide tags in purification processes and provide a guideline for both optimal tag design and downstream process synthesis.

Amino Acid Sequence↗

Accelerated process development for protease production in continuous multi-stage cultures.

A fermentation process was developed and optimized for the production of a specific protease from Bacillus licheniformis PWD-1. Media formulations were constructed and crucial environmental parameters were optimized to enhance growth and product formation. Process dynamics of substrate consumption, biomass-, product-, as well as by-product formation were determined under controlled conditions in a bioreactor. Using kinetic data from batch- and continuous-culture experiments, a fed-batch process was developed producing proteolytic activities 10 times those found during regular batch culture. In one stage continuous stirred tank culture protease formation was completely decoupled from sporulation. Shift experiments in one-stage continuous cultures led to the development of a two-stage continuous stirred tank fermentation process using optimized conditions for growth in the first stage and protease formation in the second stage. Accordingly, the basis for a continuous production of the enzyme on a pilot scale was accomplished.

Bacillus↗

Bioprocess development for the production of an antifungal molecule by Bacillus licheniformis BC98.

The optimization of process parameters for the production of an antifungal molecule produced by Bacillus licheniformis BC98 was carried out using novel statistical tools. The parameters studied were pH, temperature and agitation rate. Fed batch cultivations were carried out since the maximum production of the molecule was observed in the late log phase. The statistical design used allows the evaluation of the effects of several different process variables in a single batch. Data from several batches indicated that while the effects of two of the variable factors, viz., temperature and agitation rate, were significant at 95% confidence intervals, the agitation rate was most critical for the production of the molecule, and pH had no significant effect. The cultivation of the bacterium under optimized conditions (fed batch, 150 rpm, 32 degrees C, pH 5.8) resulted in a 30-fold increase compared with that under unoptimized conditions (shake flask, 100 rpm, 29 degrees C, pH 5.8) in the production of the antifungal molecule.

Journal Article↗

SYNOPSIS: SYNthesize and OPtimize System in Silico.

We present a de novo design program called SYNOPSIS, that includes a synthesis route for each generated molecule. SYNOPSIS designs novel molecules by starting from a database of available molecules and simulating organic synthesis steps. This way of generating molecules imposes synthetic accessibility on the molecules. In addition to a starting database, a fitness function is needed that calculates the value of a desired property for an arbitrary molecule. The values obtained from this function guide the design process in optimizing the molecules toward an optimal value of the calculated property. Two applications are described. The first uses an electric dipole moment calculation to generate molecules possessing a strong dipole moment. The second makes use of the three-dimensional structure of a viral enzyme in order to generate high affinity ligands. Twenty eight compounds designed with the program resulted in 18 synthesized and tested compounds, 10 of which showed HIV inhibitory activity in vitro.

Anti-HIV Agents↗

Hydrolysis of animal manure lignocellulosics for reducing sugar production.

Converting animal manure into value-added products provides a potential alternative for treatment and disposal of such materials. Lignocellulosics are a major component of animal manure and represent an undeveloped bioresource. In this work, a process was developed for hydrolyzing manure lignocellulosics into fermentable sugars. When raw dairy manure was pre-treated with 3% sulfuric acid at 110 degrees C for 1 h, hemicellulose was completely degraded into mainly arabinose, galactose and xylose. The pretreated materials were then treated with cellulolytic enzymes, Celluclast-1.5L and Novozyme-188, to hydrolyze the cellulose. The optimal enzyme loadings were identified as 13 FPU cellulase/g substrate and 5 IU beta-glucosidase/g substrate. The optimal temperature and pH were determined to be 46 degrees C and 4.8, respectively. A substrate concentration of 50 g/l favored both glucose concentration (in hydrolysate) and glucose yield (based on per 100 g manure). It was also found that a reduced particle size of 590-mum resulted in a high glucose yield with further decreases in particle size not increasing the yield. For each particle size investigated, the addition of 2% tween-80 resulted in at least 20% improvement in glucose yield. The optimized hydrolysis process achieved a glucose yield of 11.32 g/100 g manure, which corresponded to about 40% cellulose conversion.

Carbohydrates↗

Immunomagnetic isolation of islets from the rat pancreas.

Islets were selectively isolated from rat pancreatic digests using magnetic microspheres coated with anti-islet monoclonal antibodies. The isolation process was optimized as a function of bead concentration and time of incubation with the tissue digest. Apparent and normalized islet yields of 92 +/- 6% and 81 +/- 7%, respectively, were obtained by incubating the digests with 10(7) beads/mL for 40 min followed by isolation of the bead-coated islets under a magnetic field. While some fragmentation occurred, the isolation process did not alter islet functionality as demonstrated by an insulin secretion response to glucose stimulation equivalent to that of handpicked controls. The technique is fast, reproducible, and potentially scaleable to larger pancreases as a secondary purification step.

Animals↗

Perceptual learning in clear displays optimizes perceptual expertise: learning the limiting process.

Human operators develop expertise in perceptual tasks by practice or perceptual learning. For noisy displays, practice improves performance by learned external-noise filtering. For clear displays, practice improves performance by improved amplification or enhancement of the stimulus. Can these two mechanisms of perceptual improvement be trained separately? In an orientation task, we found that training with clear displays generalized to performance in noisy displays, but we did not find the reverse to be true. In noisy displays, the noise in the stimulus limits performance. In clear displays, performance is limited by noisiness of internal representations and processes. Our results suggest that training in one display condition optimizes the limiting factor(s) in performance in that condition and that noise filtering is also improved by exposure to the stimulus in clear displays. The asymmetric pattern of transfer implies the existence of two independent mechanisms of perceptual learning, which may reflect channel re-weighting in adult visual system. These results also suggest that training operators with clear stimuli may suffice to improve performance in a range of clear and noisy environments by simultaneous learning by two mechanisms.

Humans↗

Evolutionary optimization of the catalytic efficiency of enzymes.

1. The rate equation for a generalized Michaelian type of enzymic reaction mechanism has been analyzed in order to establish how the mechanism should be kinetically designed in order to optimize the catalytic efficiency of the enzyme for a given average magnitude of true and apparent first-order rate constants in the mechanism at given concentrations of enzyme, substrate and product. 2. As long as on-velocity constants for substrate and product binding to the enzyme have not reached the limiting value for a diffusion-controlled association process, the optimal state of enzyme operation will be characterized by forward (true and apparent) first-order rate constants of equal magnitude and reverse rate constants of equal magnitude. The drop in free energy driving the catalysed reaction will occur to an equal extent for each reaction step in the mechanism. All internal equilibrium constants will be of equal magnitude and reflect only the closeness of the catalysed reaction to equilibrium conditions. 3. When magnitudes of on-velocity constants for substrate and product binding have reached their upper limits, the optimal kinetic design of the reaction mechanism becomes more complex and has to be established by numerical methods. Numerical solutions, calculated for triosephosphate isomerase, indicate that this particular enzyme may or may not be considered to exhibit close to maximal efficiency, depending on what value is assigned to the upper limit for a ligand association rate constant. 4. Arguments are presented to show that no useful information on the evolutionary optimization of the catalytic efficiency of enzymes can be obtained by previously taken approaches that are based on the application of linear free-energy relationships for rate and equilibrium constants in the reaction mechanism.

Biological Evolution↗

Assessing cellular proliferation: what's worth measuring?

The assessment of cellular proliferation is, in the main, carried out on histological material. Ideally, such methods should be applicable to routinely processed tissues, they should be relatively inexpensive and the results easily quantified and interpreted. A knowledge of what is 'normal' within the tissue from both a temporal and spatial point of view is essential. There is a burgeoning literature on novel markers of cell proliferation, usually these are immunohistochemically based, each method with its own unique set of conditions for optimal tissue processing. Some would argue this is simply a process of 'reinventing the wheel' since mitotic counting is a perfectly adequate indicator of proliferation, but we could justly counter that a labelling index (S-phase or growth fraction) is more likely to produce an accurate assessment when the sample size is small. In tumours, tissue heterogeneity is likely to render any single measurement meaningless. To date, there are no reliable validated immunohistochemical markers of the labelling index in animal tissues which visualise naturally occurring proliferation-associated molecules, though this may change shortly.

Animals↗

[Optimization of conservation regimes and processes of regeneration of organs and tissues in surgery and transplantology using mathematical methods of planning experiments].

The experience of using mathematical planning of an experiment in solving problems of multifactor optimisation in surgery and transplantology is discussed, including optimisation of heart and bone tissue preservation with low-dose aldehydes and antioxidants, study of the effects of retabolil on gastroenteroanastomosis regeneration, and optimisation of ischaemic damage prevention with low-dose aldehydes. In solving these problems, multifactor economical plans were initially applied to identify the optimal variants for several outputs. Second-order plans were further employed to specify the optimal regimes and construct models describing the optimum region. Recommendations on the choice of the most rational and time-saving regimes have been elaborated.

Humans↗

On the influence of oxygen and cell concentration in an SFPR whole cell biocatalytic Baeyer-Villiger oxidation process.

Efficient whole cell biotransformations, in particular microbial whole cell Baeyer-Villiger oxidation with molecular oxygen, demand comprehension and optimization of the process details involved. Optimal provision of oxygen and control of bioprocess parameters are pivotal for their success. The interrelation of cell density and oxygen supply in an in situ substrate feeding and product removal (SFPR) whole cell Baeyer-Villiger oxidation process was investigated in detail. Both parameters were optimized with respect to practical considerations. The outcome of this study supports a schematic process model, allows estimation of optimum process conditions and exploration of its limits.

Bioreactors↗

Dynamic organization of the somatosensory cortex induced by motor activity.

Intensive and long-lasting experience of altered sensory input induces permanent changes in the functional organization of the somatosensory cortex. In addition, an increasing body of evidence suggests the existence of dynamic, short-term and task-dependent adaptation of representational maps within somatosensory cortex. It is hypothesized that somatosensory maps can, not only, be acquired within a short period of time, but might also be set up during periods of training related to specific tasks and subsequently activated dynamically upon performance of that particular task. In order to test this hypothesis we studied the functional organization of somatosensory cortex for a heavily overlearned and frequently performed task for which no new acquisition of a sensory map had to be assumed. To this end, the functional organization of somatosensory cortex for handwriting was compared with the organization during rest in healthy humans. Functional organization of the somatosensory cortex was assessed using non-invasive, neuromagnetic source imaging based on tactile stimulation of the thumb (D1) and little finger (D5) during writing and rest. In different blocks, subjects wrote with their right, dominant and their left hand, respectively. During writing, D1 and D5 of the writing hand were stimulated. To test the reliability of our results all measurements were repeated after 1 week. It was found that amplitudes of somatosensory evoked magnetic fields with latencies of 45 ms were reduced during writing compared with rest. This finding is in accordance with the sensorimotor gating effect. Using source localization we could show that cortical representations of D1 and D5 are more distant during writing with either hand compared with rest. Our data suggest that somatosensory cortical maps undergo rapid modulation depending on task-specific involvement of sensory processing in daily-life overlearned movements. As it is unlikely that a new sensory map is always acquired when a frequently used task such as writing is performed, we suggest that somatosensory cortex switches between different, concurrently pre-existing maps depending on actual requirements. Task-dependent activation of pre-existing maps might be a powerful mechanism to optimize stimulus processing.

Adult↗