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PubMedDate not supplied

[A low-frequency magnetic field and regeneration of bony tissue of the jaw: optimization of exposure parameters (experimental research)].

The optimal parameters of exposure to low-frequency magnetic field were chosen in experiments with 132 rats, using a simplex method of the extreme exposure. These parameters are as follows: 22 mT induction, length of exposure 20 min, pulse regimen. Exposure in such conditions provides the most effective influence of magnetic field on the reparative osteogenesis and mineralization processes and on the subsequent organic restructuring of the bone at the site of the mandibular standard defect.

Animals↗
PubMed1990

Optimal design parameters of the bicycle-rider system for maximal muscle power output.

The purpose of this study was to find the optimal values of design parameters for a bicycle-rider system (crank length, pelvic inclination, seat height, and rate of crank rotation) which maximize the power output from muscles of the human lower limb during bicycling. The human lower limb was modelled as a planar system of five rigid bodies connected by four smooth pin joints and driven by seven functional muscle groups. The muscles were assumed to behave according to an adapted form of Hill's equation. The dependence of the average power on the design parameters was examined. The instantaneous power of each muscle group was studied and simultaneous activity of two seemingly antagonistic muscle groups was analyzed. Average peak power for one full pedal revolution was found to be around 1100 W. The upper body position corresponding to this peak power output was slightly reclined, and the pedalling rate was 155 rpm for a nominal crank length of 170 mm.

Bicycling↗
PubMed2024

optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material.

Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.

Humans↗
PubMed1988

Optimizing electroporation parameters for a variety of human hematopoietic cell lines.

The parameters affecting electroporation of four human hematopoietic cell lines were investigated. The optimal conditions for electroporation are described for both transient and stable expression of foreign genes. A correlation exists between the levels of transient gene expression and stable transfection frequency. In addition, linear DNA yields higher stable transfection frequencies than supercoiled DNA. The cumulative results indicate that electroporation is a simple and useful method for obtaining transient and stable expression of foreign genes in human hematopoietic cells.

Cell Line↗
PubMedDate not supplied

Optimization of parameters for fitting linear accelerator photon beams using a modified CBEAM model.

Measured beam profiles and central-axis depth-dose data for 6- and 25-MV photon beams are used to generate a dose matrix which represents the full beam. A corresponding dose matrix is also calculated using the modified CBEAM model. The calculational model uses the usual set of three parameters to define the intensity at beam edges and the parameter that accounts for collimator transmission. An additional set of three parameters is used for the primary profile factor, expressed as a function of distance from the central axis. An optimization program has been adapted to automatically adjust these parameters to minimize the chi 2 between the measured and calculated data. The average values of the parameters for small (6 X 6 cm2), medium (10 X 10 cm2), and large (20 X 20 cm2) field sizes are found to represent the beam adequately for all field sizes. The calculated and the measured doses at any point agree to within 2% for any field size in the range 4 X 4 to 40 X 40 cm2.

Humans↗
PubMed1986

Optimization of parameters for maximization of plateletpheresis and lymphocytapheresis yields on the Haemonetics Model V50.

Automated apheresis techniques afford the opportunity of tailoring collection parameters for each donor's hematologic profile. This study investigated the effect of various settings of the volume offset parameter as utilized in the Haemonetics Model V50 instrumentation during platelet- and lymphocytapheresis to optimize product yield, purity, and collection efficiency. In both types of procedures, increased product yield could be obtained by using an increased volume offset for donors having lower hematocrits. This improvement was related to an increase in collection efficiency. Platelet products also contained fewer contaminating lymphocytes with this approach. Adjustment of the volume offset parameter can be utilized to make the most efficient use of donors and provide higher-quality products.

Automation↗
PubMed1992

Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells.

Recent clinical trials have shown that for some cancers, high-intensity alternating chemotherapy does not significantly improve either survival times or response rates compared with nonalternating therapy. The current study uses optimal control to determine the best way to treat a tumor that contains drug-resistant cells that cannot be destroyed. The delivery of two non-cross-resistant chemotherapeutic agents is limited by bounds on the drug concentration and the dose intensity. This ensures that the drug toxicity stays within a tolerable range. The aim of the therapy is to maximize the host survival time, defined as the time over which the tumor burden can be kept below a fixed bound. The model is posed as a free terminal time, optimal parameter selection problem in which the constraints are continuously parametrized by time and the number of courses of therapy is free to vary. New theory is developed so that the optimal parameter selection problem can be solved as a sequence of fixed terminal time problems using existing optimal control software. Numerical simulations of Gompertz tumor growth showed that a treatment maintaining a high tumor burden doubled and sometimes tripled with survival time under aggressive therapy. When these simulations were repeated using exponential and logistic tumor growth models, the tumor burden during treatment had little influence upon survival time. In all simulations, survival time was not extended by delivering the anticancer drugs concurrently instead of staggering the treatment arms.

Animals↗
PubMed2026

SNP genotyping in Pseudotsuga menziesii and Pinus radiata using targeted genotyping-by-sequencing (GBS): improved Bayesian SNP calling using a beta-binomial distribution and other optimized input parameters.

BACKGROUND: Single-nucleotide polymorphism markers (SNPs) have important applications in gene conservation, breeding, and fundamental genetics research. Our long-term goal is to develop routine approaches for SNP genotyping in forest trees. Ideally, these approaches would be inexpensive, able to accommodate a wide range of samples and SNPs, available through commercial providers, and produce high-quality SNP data. RESULTS: Using targeted genotyping-by-sequencing (GBS), we developed SNP assays for two highly heterozygous tree species, Douglas-fir (Pseudotsuga menziesii) and radiata pine (Pinus radiata). Using Douglas-fir haploid and diploid data, we optimized Bayesian SNP calling by testing four input parameters: (1) allele and genotype prior probabilities, (2) Rho, the beta-binomial dispersion parameter, (3) estimated read error (BayesReadError), and (4) the logPO cutoff used to filter low confidence SNP calls. logPO is the Bayesian posterior odds ratio for a called SNP. Compared to assuming a binomial distribution of read counts (Rho = 0), the beta-binomial distribution (Rho = 0.33) substantially reduced call error and heterozygote undercalling. Compared to the other Bayesian parameters, genotype priors had little effect on genotyping success. For Douglas-fir, we tested 5,360 SNP assays, and then studied the performance of the best 4,000. For radiata pine, we tested 6,000 SNP assays, and then studied the performance of the best 4,570. In Douglas-fir and radiata pine, our Bayesian approach resulted in median call rates of 95% to 98% for the top-ranked SNPs, with an estimated call error of 1.60% for known homozygous genotypes and 2.27% for known heterozygotes. In radiata pine, median and mean call rates were above 91% for GBS and SNP genotyping using an Axiom fixed genotyping array. Additionally, the median correspondence between the GBS and Axiom genotypes was about 98% overall (mean 96%). CONCLUSIONS: By optimizing Bayesian SNP calling, selecting the best 4-5 K SNPs, and excluding samples with low DNA amounts, we substantially reduced call error and heterozygote undercalling, resulting in SNP genotypes that were nearly identical to genotypes obtained using the Axiom array. Furthermore, genotyping performance should increase even further if our SNP rankings were used to develop less complex probe pools that target fewer SNPs.

Pinus↗
PubMed1990

Hyaluronic acid determinations: optimizing assay parameters.

Assay conditions for determining hyaluronic acid levels in cultured cells have been examined. In cultures labeled with [3H]glucosamine, hyaluronic acid is measured by digestion with a highly specific hyaluronidase from Streptomyces hyaluronlyticus. Products obtained in the presence and absence of preliminary enzyme digestion are precipitated with cetylpyridinium chloride. The precipitation step has been optimized for ion concentration, glycosaminoglycan carrier and for cetylpyridinium chloride levels. Chondroitin sulfate is an effective carrier in the precipitation of radiolabeled product, while unlabeled hyaluronic acid is not. Addition of sulfate to the mixture yields a flocculent precipitate that facilitates subsequent steps of the determination. Optimizing these steps in hyaluronic acid determination can generate two- to three-fold increases in apparent levels of deposition in cultured cells.

Animals↗
PubMed1979

Optimization of parameters in protein nitrogen unit precipitation procedure for allergenic extracts.

This work establishes the optimum conditions for the protein nitrogen unit (PNU) phosphotungstic acid (PTA) precipitation procedure for allergenic extracts. The volume of extract analyzed, the dilution of the extract prior to precipitation, the percent PTA in the precipitating solution, the washing of the precipitate, and the volume of concentrated HCl initially added to the extract were optimized, as they were found to be the factors which affected the amount of PTA precipitate obtained. Varying the digestion time, the digestion temperature, and the percent HCl in the 15% PTA precipitating solution did not cause detectable differences in the PNU values of the extracts studied.

Allergens↗
PubMed1992

Design and optimization of a micropump-based electrospray device for preparation of nitrocellulose substrates for plasma desorption time-of-flight mass spectrometry.

Details of a nitrocellulose (NC) substrate preparation technique in 252Cf plasma desorption time-of-flight mass spectrometry were investigated using an electrospray device, in which a micropump was employed for solution delivery. The molecular ion yields for three standard proteins (porcine insulin, chicken-egg lysozyme and chymotrypsinogen A) were studied as a function of the electrosprayed NC layer thickness, spray rate, NC solution concentration and some other parameters. Optimal parameters of the NC substrate preparation procedure were determined, which include deposition of a layer of 250-750 micrograms cm-2 at up to 15 microliters min-1 spray rate and up to 15 micrograms microliters-1 solution concentration.

Animals↗
PubMed1991

Multiparameter optimizations in micellar liquid chromatography using the iterative regression optimization strategy.

An extension of the iterative regression optimization strategy to multi-parameter optimizations is described and applied to the separation of ionic compounds (amino acids and peptides) by means of micellar liquid chromatography. The parameters examined are the concentration of surfactant, the concentration of 2-propanol and pH. Fairly regular (linear, weakly curved) retention behaviour of the compounds as a function of the parameters results in an efficient optimization using a relatively small number of initial experiments.

Amino Acids↗
PubMed1990

Electric field-mediated gene transfer into K562 cells: optimization of parameters affecting efficiency.

Since hemopoietic cells are refractory to transfection by conventional chemical means, we have developed a reliable and efficient gene transfer system for K562 cells which uses electric field-mediated gene transfer (EFMGT). EFMGT involves the exposure of cells in suspension to an electric field which transiently allows the entry of DNA into the cell and its subsequent integration and expression. Plasmids bearing the neo gene were used to identify and select transfected clonogenic cells manifested by geneticin resistance in semisolid medium. Transfection efficiency is significantly affected by the following variables: voltage, capacitance, time constant, number of pulses, buffer type and temperature, DNA concentration, configuration, and promoter type. Cell cycle status also appears to be critical as shown in studies employing aphidicolin synchronization. Using optimal conditions, we have consistently achieved a transfection efficiency of 0.3-0.4% of clonogenic cells per microgram DNA. Stability of neo gene expression was also demonstrated after 4 months in nonselective culture conditions. This level of efficiency compares favorably with other reports of gene transfer into human hemopoietic progenitor cells.

Blast Crisis↗
PubMed1992

[Contact cyclophotocoagulation with the continuous wave Nd:YAG laser with quartz fiber. Optimizing coagulation parameters].

Transscleral cyclo-photocoagulation with a cw-Nd:YAG-laser was studied in enucleated porcine eyes with application times of between 10 ms and 1.5 s. Contact coagulation via a quartz fiber (core 600 microns) required about 32% less power to create visible ciliary body coagulation compared to non-contact coagulation via a focusing handpiece. Application of focusing fiber tips led to a further reduction in the coagulation threshold by a factor of 0.6. The energy per laser application required for ciliary body coagulation increased with application time. During contact coagulation using plane fiber tips a pronounced temperature rise was sometimes observed at the fiber tip due to deposits of carbonized tissue with the subsequent risk of scleral damage. In a pilot study five eyes with secondary glaucoma were treated under coagulation conditions found to be optimal (8 W at 0.2 s).

Anesthesia, Local↗
PubMed1976

Augmented immunogenicity of tumor cell membranes produced by surface budding viruses: parameters of optimal immunization.

Membranes prepared from tumor cells infected with surface budding viruses are much more immunogenic than membranes from uninfected tumor cells. Factors affecting immunization with membranes from virus-infected tumor cells were studied. Preparations made with influenza virus were clearly superior to those prepared with vesicular stomatitis virus (VSV). Membranes infected with VSV were maximally immunogenic at a dose equivalent to a 10% cell pack whereas influenza-virus-infected membranes were immunogenic at 1/100th of this dose. Subcutaneous inoculation was better than other routes of administration. Maximum protection against challenge with viable tumor cells was afforded by two inoculations of VSV-infected membranes spaced 3 days apart or a single inoculation with influenza-virus-infected membranes. Administration of membranes in complete Freund's adjuvant either had no effect of induced a slight degree of tumor enhancement. Immunization with influenza-virus-infected membranes significantly reduced tumor size and incidence even at a challenge dose of tumor cells which was 50 times the LD100.

Animals↗
PubMed1989

Computational issues of importance to the inverse recovery of epicardial potentials in a realistic heart-torso geometry.

In vitro data from a realistic-geometry electrolytic tank were used to demonstrate the consequences of computational issues critical to the ill-posed inverse problem in electrocardiography. The boundary element method was used to discretize the relationship between the body surface potentials and epicardial cage potentials. Variants of Tikhonov regularization were used to stabilize the inversion of the body surface potentials in order to reconstruct the epicardial surface potentials. The computational issues investigated were (1) computation of the regularization parameter; (2) effects of inaccuracy in locating the position of the heart; and (3) incorporation of a priori information on the properties of epicardial potentials into the regularization methodology. Two methods were suggested by which a priori information could be incorporated into the regularization formulation: (1) use of an estimate of the epicardial potential distribution everywhere on the surface and (2) use of regional bounds on the excursion of the potential. Results indicate that the a posteriori technique called CRESO, developed by Colli Franzone and coworkers, most consistently derives the regularization parameter closest to the optimal parameter for this experimental situation. The sensitivity of the inverse computation in a realistic-geometry torso to inaccuracies in estimating heart position are consistent with results from the eccentric spheres model; errors of 1 cm are well tolerated, but errors of 2 cm or greater result in a loss of position and amplitude information. Finally, estimates and bounds based on accurate, known information successfully lower the relative error associated with the inverse and have the potential to significantly enhance the amplitude and feature position information obtainable from the inverse-reconstructed epicardial potential map.

Animals↗
PubMed1990

Perioperative assessment of cardiac energy metabolism by means of arterio-coronary venous difference in lactate concentration (acDL). A parameter for optimizing ventricular function of the postcardioplegic myocardium.

Fourty-three patients undergoing open heart surgery were subjected to extended hemodynamic and metabolic monitoring (arterial and coronary sinus (CS) lactate concentration). In 95% of patients investigated, a significant increase in CS lactate concentration above the arterial lactate concentration was established at the beginning of reperfusion (RPT). In these cases, a decrease in the CS lactate below the arterial concentration occurs within the RPT creating a cross-over point (COP) from negative to positive lactate extraction values. Whereas the initial rise in CS lactate is an expression of the expected ischemia-induced acceleration of anaerobic glycolysis, the onset of a positive lactate extraction can be related to reconsolidation of mitrochondrial oxidative phosphorylation. We found two groups with an early and late COP at 7.2 +/- 0.8 min (ECOP) and 42.5 +/- 5.2 min (LCOP) (P less than 0.005). Whereas a short cross-over time was associated with a normal postoperative outcome, cardiac recovery was delayed in the LCOP group. With the aid of metabolic monitoring it is possible to identify the COP and cardiac overload situations and so to optimize the perioperative outcome, especially in selected patients (NYHA stage III/IV, re-operation, high-risk operation).

Adenosine Triphosphate↗