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PubMed2005

Optimism and immunity: do positive thoughts always lead to positive effects?

The effects of dispositional optimism, as defined by generalized positive expectations for the future, on physical health are mixed, especially in diseases that can be immunologically mediated such as HIV and cancer. Both experimental and naturalistic studies show that optimism is negatively related to measures of cellular immunity when stressors are difficult (e.g., complex, persistent, and uncontrollable) but positively related when stressors are easy (e.g., straightforward, brief, and controllable). Although the negative relationship between optimism and immunity has been attributed to the violation of optimists' positive expectancies and subsequent disappointment, empirical evidence suggests that it is more likely to be a consequence of optimists' greater engagement during difficult stressors. For example, negative mood does not account for the effect, but conscientiousness, a personality facet related to engagement, does. The mixed immunological correlates of optimism may explain why it does not consistently predict better disease outcomes.

Adaptation, Psychological↗

PubMed2003

Lactic acid bacteria as prime candidates for codon optimization.

In species having a strong correlation of expressivity and codon bias it has been shown that heterologous expression can be optimized by changing codons of the introduced gene towards the set of codons that the host organism naturally uses in its highly expressed genes. Even though two lactic acid bacteria are fully sequenced, there are no reports on attempts of codon optimization in the literature. In this report it is demonstrated that codons used in highly expressed genes tend to differ from the codons in lowly expressed genes, and that there is a strong correlation of codon bias and empirical expressivity (codon adaptation index) in Lactococcus lactis and Lactobacillus plantarum. This strongly suggests that codon optimization strategies could be applied to expression systems with lactic acid bacteria as producer strains. A good example of a candidate for codon optimization is the mouse interleukin-2 gene, which in its natural form has an extremely low codon adaptation index for expression in Lc. lactis.

Algorithms↗

PubMed2004

High-level expression of a codon optimized recombinant dust mite allergen, Blo t 5, in Chinese hamster ovary cells.

Blo t 5 is a major allergen from house dust mite Blomia tropicalis. Purification of native Blo t 5 (nBlo t 5) from whole dust mite extract is tedious and gave low yield. In this study, we demonstrated that codon optimization facilitated high-level expression of Blo t 5 in Chinese hamster ovary (CHO)-K1 cells and thus allows production of sufficient recombinant cBlo t 5 for specific immunotherapy. A codon optimized Blo t 5 gene was synthesized by PCR and the codon optimized or wild-type Blo t 5 gene in pcDNA3.0 was transfected into CHO-K1 cells and stably selected with Geneticin (G418). Western-immunoblot analysis of spent culture media detected a positive band at 14kDa for the codon optimized but not wild-type gene transfectants. In addition, a stable CHO-K1 clone produced up to 13 mg/L of the cBlo t 5 protein having a high correlation of human IgE reactivities and allergenicity to the native Blo t 5, thus indicating proper conformation of this recombinant form.

Allergens↗

PubMed2004

Optimization of submerged culture condition for the production of mycelial biomass and exopolysaccharides by Agrocybe cylindracea.

The optimization of submerged culture conditions and nutritional requirements was studied for the production of exopolysaccharide (EPS) from Agrocybe cylindracea ASI-9002 using the statistically based experimental design in a shake flask culture. Both maximum mycelial biomass and EPS were observed at 25 degrees C. The optimal initial pH for the production of mycelial biomass and EPS were found to be pH 4.0 and pH 6.0, respectively. Subsequently, optimum concentration of each medium component was determined using the orthogonal matrix method. The optimal combination of the media constituents for mycelial growth was as follows: maltose 80 g/l, Martone A-1 6 g/l, MgSO4 x 7H2O 1.4 g/l, and CaCl2 1.1 g/l; for EPS production: maltose 60 g/l, Martone A-1 6 g/l, MgSO4 x 7H2O 0.9 g/l, and CaCl2 1.1 g/l. Under the optimal culture condition, the maximum EPS concentration achieved in a 5-l stirred-tank bioreactor indicated 3.0 g/l, which is about three times higher than that at the basal medium.

Agaricales↗

PubMed2005

Optimization of pH controlled liquid hot water pretreatment of corn stover.

Controlled pH, liquid hot water pretreatment of corn stover has been optimized for enzyme digestibility with respect to processing temperature and time. This processing technology does not require the addition of chemicals such as sulfuric acid, lime, or ammonia that add cost to the process because these chemicals must be neutralized or recovered in addition to the significant expense of the chemicals themselves. Second, an optimized controlled pH, liquid hot water pretreatment process maximizes the solubilization of the hemicellulose fraction as liquid soluble oligosaccharides while minimizing the formation of monomeric sugars. The optimized conditions for controlled pH, liquid hot water pretreatment of a 16% slurry of corn stover in water was found to be 190 degrees C for 15 min. At the optimal conditions, 90% of the cellulose was hydrolyzed to glucose by 15FPU of cellulase per gram of glucan. When the resulting pretreated slurry, in undiluted form, was hydrolyzed by 11FPU of cellulase per gram of glucan, a hydrolyzate containing 32.5 g/L glucose and 18 g/L xylose was formed. Both the xylose and the glucose in this undiluted hydrolyzate were shown to be fermented by recombinant yeast 424A(LNH-ST) to ethanol at 88% of theoretical yield.

Cellulase↗

PubMed2005

Bouquet brachytherapy: feasibility and optimization of conically spaced implants.

PURPOSE: To examine the dosimetric feasibility of a conical implantation approach to robotic-assisted prostate brachytherapy. METHODS AND MATERIALS: An in-house inverse planning software based on the genetic algorithm (GA) was used to optimize the needle angulations and the seed positions along needles that form one or two bouquets. Volume data from 20 prostate seed implant patients (six 125I and 14 103Pd) previously treated using the conventional rectilinear template approach were used. The dosimetry outcomes of the optimized treatment plan in the conical approach were compared with those from the original treatment plans based on the conventional rectilinear template approach. RESULTS: When seed spacing is restricted to nominal 1 cm center-to-center spacing, dosimetry results in the conical approach suffer from a higher urethra dose and higher dose heterogeneity compared with the original rectilinear template plans. When the seed loading patterns are optimized as part of inverse planning, the resulting dosimetry plans exhibit adequate dose coverage and uniformity through the target volume, as well as satisfactory sparing of the urethra and rectum. CONCLUSIONS: Conically spaced implantation for prostate brachytherapy with 125I and 103Pd seeds is feasible in terms of dosimetry outcomes. Techniques for optimized inverse planning for this approach have been developed.

Brachytherapy↗

PubMed2005

Process evaluation for optimization of EDTA use and recovery for heavy metal removal from a contaminated soil.

This study aimed to establish an optimized, closed loop application of ethylenediaminetetraacetic acid (EDTA) in heavy metal removals from a contaminated soil through integrating EDTA recovery/regeneration and metal precipitation processes in the treatment train. Three divalent heavy metals were investigated, namely, Pb, Cd, and Ni. The extractability of the metals by EDTA followed the decreasing order of CdPb>>Ni. The first part of this study was to search for the optimal use of the fresh EDTA in removing these heavy metals from the contaminated soil. The second part of this study was devoted to the recovery/regeneration of the spent EDTA which followed the sequential processes involving (1) complex destabilization by adding ferric ion (Fe(III)) to liberate Pb, Cd, and Ni, (2) precipitation of the liberated Pb, Cd, and Ni in phosphate (PO4(3-)) forms, and (3) precipitation of the excess Fe(III) which eventually produced free EDTA for reuse. The process variables were dosages of Fe(III) and PO4(3-), pH and reaction times. Laborious trial experiments would be needed in searching for the optimum conditions for the above processes. To expedite this exercise, a geochemical equilibrium model, MINTEQA2, was used to find the thermodynamically favorable conditions for recoveries of both EDTA and heavy metals. This was then followed by experimental examination of the process kinetics to observe for the optimal reaction time for each thermodynamically favorable process. This study revealed that 2 h of reaction time each for the complex destabilization reaction and the metal phosphate precipitation reaction was sufficient to achieve equilibrium. With the optimized process condition identified in this study, a total of 95%, 89% and 90% of the extracted Pb, Cd and Ni, respectively, could be precipitated from the spent EDTA solution, with 84% EDTA recovery. The reused EDTA maintained more than 90% of its preceding extraction power in each cycle of reuse.

Chelating Agents↗

PubMed2005

Optimizing the specific surface area of fly ash-based sorbents for flue gas desulfurization.

High performance sorbents for flue gas desulfurization can be synthesized by hydration of coal fly ash, calcium sulfate, and calcium oxide. In general, higher desulfurization activity correlates with higher sorbent surface area. Consequently, a major aim in sorbent synthesis is to maximize the sorbent surface area by optimizing the hydration conditions. This work presents an integrated modeling and optimization approach to sorbent synthesis based on statistical experimental design and two artificial intelligence techniques: neural network and genetic algorithm. In the first step of the approach, the main and interactive effects of three hydration variables on sorbent surface area were evaluated using a full factorial design. The hydration variables of interest to this study were hydration time, amount of coal fly ash, and amount of calcium sulfate and the levels investigated were 4-32 h, 5-15 g, and 0-12 g, respectively. In the second step, a neural network was used to model the relationship between the three hydration variables and the sorbent surface area. A genetic algorithm was used in the last step to optimize the input space of the resulting neural network model. According to this integrated modeling and optimization approach, an optimum sorbent surface area of 62.2m(2)g(-1) could be obtained by mixing 13.1g of coal fly ash and 5.5 g of calcium sulfate in a hydration process containing 100ml of water and 5 g of calcium oxide for a fixed hydration time of 10 h.

Adsorption↗

PubMed2004

Optimizing control of simulated moving beds--linear isotherm.

A new optimization based adaptive control strategy for simulated moving beds (SMBs) is proposed. A linearized reduced order model, which accounts for the periodic nature of the SMB process, is used for online optimization and control. The manipulated variables are the four inlet flow rates, the outputs are the raffinate and extract concentrations. Concentration measurements at the raffinate and extract outlets are used as the feedback information. The state estimate from the periodic Kalman filter is used for the prediction of the outlet concentrations over a chosen horizon. Predicted outlet concentrations are the basis for the calculation of the optimal input adjustments, which maximize the productivity and minimize the desorbent consumption subject to constraints on product purities. The realization of this concept is discussed and the implementation on a virtual eight column SMB platform is assessed, in the case of binary linear systems. For a whole series of typical plant disturbances it is shown that the proposed approach is effective in minimizing off-spec products and in achieving optimal SMB operation, also in the case where there are significant model uncertainties.

Models, Theoretical↗

PubMed2005

Orthogonal array designs for the optimization of liquid-liquid-liquid microextraction of nonsteroidal anti-inflammatory drugs combined with high-performance liquid chromatography-ultraviolet detection.

Orthogonal array designs (OADs) were applied for the first time to optimize liquid-liquid-liquid microextraction (LLLME) conditions for the analysis of three nonsteroidal anti-inflammatory drug residues (2-(4-chlorophenoxy)-2-methylpropionic acid, ketoprofen, and naproxen) in wastewater samples. Six relevant factors were investigated: type of organic solvent, composition of donor phase and acceptor phase, stirring speed, extraction time and salt concentration. In the first stage, mixed-level orthogonal array design, an OA16 (4(1) x 2(12)) matrix was employed to study the effect of six factors, by which the effect of each factor was estimated using individual contributions as response functions. Based on the results of the first stage, 1-octanol was chosen as organic solvent for extraction. The other five factors were selected for further optimization using an OA16 (4(5)) matrix and a 4 x 4 table to locate more exact levels for each variable. The relative standard deviations for the reproducibility of optimized LLLME varied from 6.2 to 7.1%. The coefficients of determination for calibration curves were higher than 0.9950. The method detection limits for drugs spiked in ultrapure water were in the range of 0.03-0.3 ng/mL. The final optimized conditions were applied to the analysis of drug residues in three wastewater samples in Singapore.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Musculoskeletal parameters of muscles crossing the shoulder and elbow and the effect of sarcomere length sample size on estimation of optimal muscle length.

BACKGROUND: Knowledge of musculoskeletal parameters is essential to understanding and modeling a muscle's force generating capability. A study of musculoskeletal parameters was conducted in two parts: (I) Empirical measurement of upper extremity musculoskeletal parameters. (II) Computational bootstrap simulation to examine statistical power of detecting optimal muscle length as a function of sarcomere length sample size and effect size. METHODS: Parameters were determined with a cadaver model. Sarcomere lengths were measured for 120 samples per muscle using laser diffraction and the mean sarcomere length used to estimate optimal muscle length. A bootstrap computational simulation was conducted to estimate variance in mean sarcomere length as a function of sample size. Statistical power for detecting optimal muscle length as a function of sample size and effect size was then determined. FINDINGS: Parameters are reported in tabular format. Power is 80% at approximately 85, 50, 40 and 25 samples for effect sizes of 0.5, 0.75, 1.0 and 1.5 mm respectively. INTERPRETATION: Musculoskeletal parameters for predicting muscle forces can be adequately measured in a cadaver model. Measurement of 40-60 sarcomere lengths per muscle is sufficient to calculate mean sarcomere length for estimating optimal muscle length with power of 80% for an effect size of 0.75-1.0 mm.

Adult↗

PubMed2006

Stimulation parameter optimization for functional electrical stimulation assisted gait in human spinal cord injury using response surface methodology.

BACKGROUND: The aims of this study were to identify the reflex moment induced by flexion withdrawal reflex and to optimize stimulation parameters for restoring swing motion with respect to initial kinematic conditions in human with spinal cord injury. METHODS: The influence of hip position and passive movement in the reflex moment were tested in six subjects with chronic spinal cord injury. The two-dimensional dynamic models consisted of thigh, shank and foot segments were developed to compute the swing-phase response and the response surface method was also used to optimize stimulation parameters for restoration of gait by functional electrical stimulation. FINDINGS: At three different hip positions, significant linear relationship was found between the reflex moment and hip angle (P < 0.05) and hip movement also increased the reflex moment compare to isometric conditions. The hip and knee flexion velocities significantly contributed to the hip and knee flexion angle during the swing-phase (P < 0.05) and increase of initial joint velocity resulted in a decrease of the burst frequency and duration time for optimal swing motion in spinal cord injured patients. INTERPRETATION: From dynamic simulation, we concluded that optimal solutions of pulse amplitude, frequency and duration time of burst for electrical stimulation assisted gait were influenced by initial kinematic conditions at toe-off. The reflex model and the results of this study can be applied to the design and control strategies of neuroprosthetic devices using functional electrical stimulation for spinal cord injured patients.

Adult↗

PubMed2005

A diagnostic reasoning and optimal treatment model for bacterial infections with fuzzy information.

This study proposes an optimization model for optimal treatment of bacterial infections. Using an influence diagram as the knowledge and decision model, we can conduct two kinds of reasoning simultaneously: diagnostic reasoning and treatment planning. The input information of the reasoning system are conditional probability distributions of the network model, the costs of the candidate antibiotic treatments, the expected effects of the treatments, and extra constraints regarding belief propagation. Since the prevalence of the pathogens and infections are determined by many site-by-site factors, which are not compliant with conventional approaches for approximate reasoning, we introduce fuzzy information. The output results of the reasoning model are the likelihood of a bacterial infection, the most likely pathogen(s), the suggestion of optimal treatment, the gain of life expectancy for the patient related to the optimal treatment, the probability of coverage associated with the antibiotic treatment, and the cost-effect analysis of the treatment prescribed.

Anti-Bacterial Agents↗

PubMed2006

An optimized assay for transcription factor NF-kappaB with dsDNA-coupled microplate.

To develop an EMSA-free assay approach for analyzing the sequence-specific DNA-binding proteins (DBPs), an easy cost-effective dsDNA-coupled plate (dcPlate) was developed in our lab for this purpose. In this paper, the assay conditions of such dcPlate were fully optimized for detecting an important transcription factor, NF-kappaB. The optimized parameters of dcPlate for assay of NF-kappaB were as follows: immobilized DNA probe at the concentration of 25 pmol/100 microL-well, incubation time of 90 min for NF-kappaB binding to dcPlate, primary and secondary antibody concentration of 0.1 microL/100 microL dilution, incubation time of 90 min for primary antibody binding to NF-kappaB, temperature of 25 degrees C for the above process, colorimetric developing time for 30 min. After optimization, the signal was improved three times higher than that from not optimized conditions. The linear colorimetric detection ranges of the purified recombinant NF-kappaB p50 and the cell nuclear extract were from 0.59 to 75 ng/well and 0.313 to 10 microg/well, respectively.

Colorimetry↗

PubMed2006

Release modulating hydrophilic matrix systems of losartan potassium: optimization of formulation using statistical experimental design.

The aim of the present research work was to systemically device a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the amount of the release retardant polymers - HPMC K15M (X(1)), HPMC K100M (X(2)) and sodium carboxymethyl cellulose (X(3)). The dependent variables were the burst release in 15 min (Y(1)), cumulative percentage release of drug after 60 min (Y(2)) and hardness (Y(3)) of the tablets with constraints on the Y(2)=31-35%. Statistical validity of the polynomials was established. In vitro release and swelling studies were carried out for the optimized formulation and the data were fitted to kinetic equations. The polynomial mathematical relationship obtained Y(2)=32.91-2.30X(1)-5.69X(2)-0.97X(3)-0.41X(1)X(2)+0.21X(1)X(3)-0.92X(1)(2)-1.89X(2)(2) (r(2)=0.9944) explained the main and quadratic effects, and the interactions of factors influencing the drug release from matrix tablets. The adjusted (0.9842) and predicted values (0.9893) of r(2) for Y(2) were in close agreement. Validation of the optimization study indicated high degree of prognostic ability of response surface methodology. Tablets showed an initial burst release preceding a more gradual sustained release phase following a non-fickian diffusion process. The Box-Behnken experimental design facilitated the formulation and optimization of sustained release hydrophilic matrix systems of losartan potassium.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Microspheres method for ocular blood flow measurement in rats: size and dose optimization.

This study modified the microspheres method by optimizing the dose and size of microspheres (MS) to enable accurate ocular blood flow measurement in rats. Fluorescent MS, either 6, 8, 10 or 15 microm diameter, were administered into the left ventricle of anesthetized adult Brown Norway rat in a dose of either 10(6), 5x10(6), or 10(7). The total number of MS entrapped in retina, choroid and optic nerve (Ntissue) was quantified and compared between size and dose groups. The MS distribution in the retina and their reentry into systemic circulation were evaluated for different sized MS. The results showed that at the 5x10(6) dose, the Ntissue of 8 microm MS was significantly more than either 6 or 10 microm MS in the retina (P<0.02) and optic nerve (P<0.03). The 10 microm MS produced the highest Ntissue for the choroid, as compared with either 8 or 6 microm MS (P<0.03). At the 10(6) dose, no difference of N(tissue) was found between 8, 10, and 15 microm MS in the retina. The 10 microm MS yielded the highest Ntissue in the choroid as compared to 8 and 15 microm MS (P<0.003). The Ntissue for 8 microm MS was higher than both 10 and 15 microm (P<0.01) MS in the optic nerve. No MS (>or=8 microm) reentered the systemic circulation. The 15 microm MS tended to lodge in pre-capillary arterioles and caused significant blood pressure increase during the injection. The blood flow measured with the optimal size MS (mean+/-SE) were 19+/-3.4 and 170+/-35 microl/min in the retina and choroid, respectively; and 0.18+/-0.03 microl/min per mm optic nerve. It is concluded that the 8 microm MS are the optimal size for both retinal and optic nerve blood flow estimation; the 10 microm for the choroid. The optimal dose for the retina was approximately 2.5x10(6), 0.5x10(6) for the choroid, and 5x10(6) approximately 10(7) for the optic nerve. The 15 microm MS are inappropriate for ocular blood flow measurements in rats.

Animals↗

PubMed2005

Synthesis of standing-up trajectories using dynamic optimization.

Dynamic optimization as a tool to compute standing-up trajectories was investigated. Sit-to-stand manoeuvres in five intact persons and five trans-femoral amputees were measured. Movements and ground reaction forces acting on the body were recorded. A five-segment 3D dynamic model of standing-up was developed. In each particular subject, the optimization criterion which yielded trajectories that best resemble the measured standing-up movement was determined. Since the intact persons used considerably different criteria in choosing the standing-up trajectories than the amputees, the optimal trajectories were computed by minimizing cost functionals (CF) with distinctive structures for each group of individuals. In intact persons, a unique cost functional was found which yielded realistic standing-up manoeuvres. In amputees, subject-specific sets of parameters indicating slightly different preferences in optimizing the effort of particular muscle groups were used.

Adult↗

PubMed2005

Optimizing sequential biventricular pacing using radionuclide ventriculography.

BACKGROUND: Biventricular pacemakers are usually programmed with the default setting of synchronous biventricular pacing, although the ventricles may be paced sequentially. Whether this parameter is important for optimizing resynchronization therapy is not clear. OBJECTIVES: The purpose of this study was to investigate whether sequential pacing acutely improves left ventricular ejection fraction (LVEF) and dyssynchrony and to assess the feasibility of nuclear ventriculography for device optimization. METHODS: Twenty-seven patients implanted with a biventricular pacemaker or implantable cardioverter-defibrillator for heart failure were studied. LVEF was measured using planar radionuclide ventriculography during simultaneous biventricular pacing and during sequential pacing at four different interventricular intervals ranging from LV-40 (preexciting the left ventricle by 40 ms) to LV+40 (preexciting the right ventricle). Interventricular and intraventricular dyssynchrony were analyzed by phase analysis at each setting. RESULTS: There was great heterogeneity in individual response to VV interval programming. Twenty-four of 27 patients (89%) had significant changes (both favorable and unfavorable) in LVEF at different interventricular delays, with variations of up to 10% in absolute terms. Simultaneous biventricular pacing yielded maximal LVEF in 9 of 27 patients (33%), with a relative increase in LVEF of 18 +/- 14% by optimized sequential pacing in the remaining patients. Interventricular dyssynchrony varied significantly, with least dyssynchrony at the LV-20 setting (P = .024). There were no significant differences in intraventricular dyssynchrony at the different settings. CONCLUSION: Programming VV intervals has considerable impact on LVEF. However, there is a great degree of variation between patients in response to these settings, requiring individual assessment for device optimization.

Aged↗