SEARCH · PubMed Health

Results for “Optimization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources

PubMed2004

Codon optimization of the tat antigen of human immunodeficiency virus type 1 generates strong immune responses in mice following genetic immunization.

DNA vaccines have been successful in eliciting potent immune responses in mice. Their efficiency, however, is restricted in larger animals. One reason for the limited performance of the DNA vaccines is the lack of molecular strategies to enhance immune responses. Additionally, genes directly cloned from pathogenic organisms may not be efficiently translated in a heterologous host expression system as a consequence of codon bias. To evaluate the influence of codon optimization on the immune response, we elected to use the Tat antigens of human immunodeficiency virus type 1 (HIV-1) (subtype C) and HIV-2, as these viral antigens are poorly immunogenic in natural infection and in experimental immunization and they are functionally important in viral infectivity and pathogenesis. Substituting codons that are optimally used in the mammalian system, we synthetically assembled Tat genes and compared them with the wild-type counterparts in two different mouse strains. Codon-optimized Tat genes induced qualitatively and quantitatively superior immune responses as measured in a T-cell proliferation assay, enzyme-linked immunospot assay, and chromium release assay. Importantly, while the wild-type genes promoted a mixed Th1-Th2-type cytokine profile, the codon-optimized genes induced a predominantly Th1 profile. Using a pepscan strategy, we mapped an immunodominant T-helper epitope to the core and basic domains of HIV-1 Tat. We also identified cross-clade immune responses between HIV-1 subtype B and C Tat proteins mapped to this T-helper epitope. Developing molecular strategies to optimize the immunogenicity of DNA vaccines is critical for inducing strong immune responses, especially to antigens like Tat. Our identification of a highly conserved T-helper epitope in the first exon of HIV-1 Tat of subtype C and the demonstration of a cross-clade immune response between subtypes B and C are important for a more rational design of an HIV vaccine.

AIDS Vaccines↗

PubMed2005

Mycobacterial codon optimization enhances antigen expression and virus-specific immune responses in recombinant Mycobacterium bovis bacille Calmette-Guérin expressing human immunodeficiency virus type 1 Gag.

Although its potential for vaccine development is already known, the introduction of recombinant human immunodeficiency virus (HIV) genes to Mycobacterium bovis bacille Calmette-Guérin (BCG) has thus far elicited only limited responses. In order to improve the expression levels, we optimized the codon usage of the HIV type 1 (HIV-1) p24 antigen gene of gag (p24 gag) and established a codon-optimized recombinant BCG (rBCG)-p24 Gag which expressed a 40-fold-higher level of p24 Gag than did that of nonoptimized rBCG-p24 Gag. Inoculation of mice with the codon-optimized rBCG-p24 Gag elicited effective immunity, as evidenced by virus-specific lymphocyte proliferation, gamma interferon ELISPOT cell induction, and antibody production. In contrast, inoculation of animals with the nonoptimized rBCG-p24 Gag induced only low levels of immune responses. Furthermore, a dose as small as 0.01 mg of the codon-optimized rBCG per animal proved capable of eliciting immune responses, suggesting that even low doses of a codon-optimized rBCG-based vaccine could effectively elicit HIV-1-specific immune responses.

AIDS Vaccines↗

PubMed2005

Therapeutic optimism in the consent forms of phase 1 gene transfer trials: an empirical analysis.

BACKGROUND: "Therapeutic misconception" arises when human subjects interpret a clinical trial as aimed primarily at therapy rather than producing knowledge. Therapeutic misconceptions may be more prevalent in trials enrolling gravely ill subjects or involving novel and well publicized investigational agents. OBJECTIVE: To examine the extent to which investigators express therapeutic optimism in phase 1 human gene transfer consent documents, whether highly active gene transfer researchers are more prone to expressing therapeutic optimism, and whether consent forms have grown more optimistic in their descriptions of personal benefit over the last decade. DESIGN: Content analysis was performed on 277 consent documents to measure the number of sentences describing possibility of benefit, terminology used for experimental agents, the proportion of statements describing personal versus societal benefits, and whether investigators attempted to thwart therapeutic misconceptions. RESULTS: Consent forms generally used therapeutic terminology to describe study agents, devoted more sentences to describing possible personal benefits than to describing benefits to society, and infrequently explained that a particular benefit was unlikely. Consent documents used by highly active gene transfer researchers tended to portray significantly greater optimism about personal benefit than less active investigators, though they were also significantly more cautious with agent terminology. Finally, therapeutic optimism expressed in consent forms has declined over the past decade. CONCLUSIONS: Consent documents used in phase 1 gene transfer trials, although increasingly attentive to possible therapeutic misconceptions, are inappropriately optimistic about direct benefits of trial participation. Such optimism is expressed more emphatically in trials involving highly active gene transfer researchers as principal investigators.

Clinical Trials, Phase I as Topic↗

PubMed2005

Optimal conditions and specific characteristics of Vent exo- DNA polymerase in ligation-mediated polymerase chain reaction protocols.

An optimized procedure for the ligation-mediated polymerase chain reaction (PCR) technique using Thermococcus litoralis exo- DNA polymerase (Vent exo-) was developed. The optimal dosage of Vent exo- at the primer extension and PCR amplification steps as well as the optimal DNA quantity to use were established. We showed that Vent exo- can efficiently create the blunt-ended termini required for subsequent linker ligation. Vent exo- proves to be more efficient than Pyrococcus furiosus exo- (Pfu exo-) for this task. Vent exo- resolves highly GC-rich sequence substantially better than Thermus aquaticus DNA polymerase (Taq) and with a similar efficiency as Pfu exo-. The DNA/DNA polymerase activity ratio is significantly higher for Vent exo- than for Pfu exo-, which is reflected by the sensibility of Vent exo- in efficiently amplifying genomic DNA. Furthermore, the range of efficiency of Vent exo- demonstrates the importance of conducting evaluative testing to identify the optimal dosage of use of this polymerase to obtain successful PCR amplification. Optimal MgSO4 concentrations to use with Vent exo- were established. Our results show that Vent exo- DNA polymerase produces bands of uniform and strong intensity and can efficiently be used for the analysis of DNA in living cells by ligation-mediated PCR.

DNA↗

PubMed1996

Hardware prototypes of a Boolean neural network and the simulated annealing optimization method.

Boolean Neural Network is a neural network that operates with binary weight values of "1" and "0". Otherwise it is formally analogous to the Multilayer Perceptron (MLP). Simulated Annealing is a stochastic optimization methods that is suitable for performing nonlinear multivariable optimization tasks. Training a Boolean Neural Network is a well-suited problem to this algorithm. However, the Simulated Annealing method is computationally heavy, which makes the training procedure slow. The training speed can be improved by using custom designed hardware for the whole system including the optimization method and the neural network. Hardware prototypes of a Boolean Neural Network and the Simulated Annealing optimization method have been designed using discrete components. The Boolean Neural Network implementation is basically a dynamically configurable feedforward network of Boolean logic gates of two inputs. The Simulated Annealing implementation is a general purpose hardware tool for multivariable optimization tasks. Here it is applied to do supervised training of the Boolean Neural Network hardware.

Algorithms↗

PubMed1985

Pulse sequence optimization for MR imaging using a paramagnetic hepatobiliary contrast agent.

Paramagnetic agents enhance contrast between tissues in magnetic resonance (MR) imaging by altering tissue relaxation times. The effect of these changes on MR image intensity depends in part on the choice of operator-controlled pulse sequence parameters. With the newly described paramagnetic hepatobiliary contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine), Fe(EHPG)-, an in vivo experimental analysis of pulse sequence optimization was performed on the rat. We compared the enhancement of the liver divided by background noise, EL/N, of standard inversion-recovery (IR) and spin-echo (SE) T1-weighted pulse sequences and several pulse sequences theoretically predicted to have improved EL/N. Optimization of the echo time (TE = TEmin) gave a substantial (greater than 60%) increase in EL/N over the standard IR and SE pulse sequences. Images obtained with optimized repetition rate and inversion time gave only a slight additional improvement. Within the uncertainties of our relaxation measurements, the measured changes in EL/N with pulse sequence optimization corresponded well with theoretical predictions. With the experimental and theoretical data, the importance of using a short echo time to obtain maximal T1 contrast in contrast-enhanced MR imaging and the relative merits of optimized SE versus IR pulse sequences for contrast-enhanced MR imaging are discussed.

Animals↗

PubMed1989

Optimal hematocrit for canine gastric oxygenation.

To determine whether an optimal hematocrit exists at which gastric tissue is maximally oxygenated, chambered segments of resting canine stomach were perfused at a constant pressure while hematocrit was decreased in steps from 60 to 10%. The two groups of animals used were a control group and a second group given pentagastrin to elevate metabolic activity. Total blood flow was inversely related to hematocrit in both the control and pentagastrin-treated animals, and arteriovenous oxygen difference was directly related to hematocrit. Consequently, the relationship between gastric oxygen consumption and hematocrit was parabolic in both groups. Therefore, the oxygen uptake vs. hematocrit data from each experiment were fit to a quadratic equation that was used to calculate the maximal oxygen uptake and the optimal hematocrit for each preparation. Both the maximum oxygen uptake and the optimal hematocrit in the pentagastrin-treated group (2.1 +/- 0.4 ml.min-1.100 g-1 and 45.7 +/- 1.4%, respectively) were significantly greater than in the control group (1.5 +/- 0.4 ml.min-1.100 g-1 and 38.2 +/- 0.7%, respectively). We conclude that an optimal hematocrit exists for the oxygenation of gastric tissue and that it is within the normal hematocrit range under resting conditions. However, the optimal hematocrit is slightly higher than normal during periods of increased metabolic activity.

Animals↗

PubMed1981

Optimized blood sampling protocols and sequential design of kinetic experiments.

Design of optimal blood sampling protocols for kinetic experiments is discussed and evaluated, with the aid of several examples--including an endocrine system case study. The criterion of optimality is maximum accuracy of kinetic model parameter estimates. A simple example illustrates why a sequential experiment approach is required; optimal designs depend on the true model parameter values, knowledge of which is usually a primary objective of the experiment, as well as the structure of the model and the measurement error (e.g., assay) variance. The methodology is evaluated from the results of a series of experiments designed to quantify the dynamics of distribution and metabolism of three iodothyronines, T3, T4, and reverse-T3. This analysis indicates that 1) the sequential optimal experiment approach can be effective and efficient in the laboratory, 2) it works in the presence of reasonably controlled biological variation, producing sufficiently robust sampling protocols, and 3) optimal designs can be highly efficient designs in practice, requiring for maximum accuracy a number of blood samples equal to the number of independently adjustable model parameters, no more or less.

Animals↗

PubMed1985

Multiple-objective criteria for optimal experimental design: application to ferrokinetics.

Optimal experimental design is used to predict the experimental conditions that will allow the "best" estimates of model parameters. A variety of criteria must be considered before an optimal design is chosen. Maximizing the determinant of the information matrix (D optimality), which tends to produce the most precise simultaneous estimates of all parameters, is commonly considered as the primary criterion. To complement this criterion, we present another whose effect is to reduce the interaction among the parameter estimates so that changes in any one parameter can be more distinct. This new criterion consists of maximizing the determinant of an appropriately scaled information matrix (M optimality). These criteria are applied jointly in a multiple-objective function. To illustrate the use of these concepts, we develop an optimal experimental design of blood sampling schedules using a detailed ferrokinetic model.

Humans↗

PubMed2001

Optimized suspension culture: the rotating-wall vessel.

Suspension culture remains a popular modality, which manipulates mechanical culture conditions to maintain the specialized features of cultured cells. The rotating-wall vessel is a suspension culture vessel optimized to produce laminar flow and minimize the mechanical stresses on cell aggregates in culture. This review summarizes the engineering principles, which allow optimal suspension culture conditions to be established, and the boundary conditions, which limit this process. We suggest that to minimize mechanical damage and optimize differentiation of cultured cells, suspension culture should be performed in a solid-body rotation Couette-flow, zero-headspace culture vessel such as the rotating-wall vessel. This provides fluid dynamic operating principles characterized by 1) solid body rotation about a horizontal axis, characterized by colocalization of cells and aggregates of different sedimentation rates, optimally reduced fluid shear and turbulence, and three-dimensional spatial freedom; and 2) oxygenation by diffusion. Optimization of suspension culture is achieved by applying three tradeoffs. First, terminal velocity should be minimized by choosing microcarrier beads and culture media as close in density as possible. Next, rotation in the rotating-wall vessel induces both Coriolis and centrifugal forces, directly dependent on terminal velocity and minimized as terminal velocity is minimized. Last, mass transport of nutrients to a cell in suspension culture depends on both terminal velocity and diffusion of nutrients. In the transduction of mechanical culture conditions into cellular effects, several lines of evidence support a role for multiple molecular mechanisms. These include effects of shear stress, changes in cell cycle and cell death pathways, and upstream regulation of secondary messengers such as protein kinase C. The discipline of suspension culture needs a systematic analysis of the relationship between mechanical culture conditions and biological effects, emphasizing cellular processes important for the industrial production of biological pharmaceuticals and devices.

Animals↗

PubMed1998

High-frequency oscillatory ventilation in neonatal RDS: initial volume optimization and respiratory mechanics.

To determine whether initial lung volume optimization influences respiratory mechanics, which could indicate the achievement of optimal volume, we studied 17 premature infants with respiratory distress syndrome (RDS) assisted by high-frequency oscillatory ventilation. The continuous distending pressure (CDP) was increased stepwise from 6-8 cmH2O up to optimal CDP (OCDP), i.e., that allowing good oxygenation with the lowest inspired O2 fraction. Respiratory system compliance (Crs) and resistance were concomitantly measured. Mean OCDP was 16.5 +/- 1.2 cmH2O. Inspired O2 fraction could be reduced from an initial level of 0.73 +/- 0.17 to 0.33 +/- 0.07. However, Crs (0.45 +/- 0.14 ml . cmH2O-1 . kg-1 at starting CDP point) remained unchanged through lung volume optimization but appeared inversely related to OCDP. Similarly, respiratory system resistance was not affected. We conclude that there is a marked dissociation between oxygenation improvement and Crs profile during the initial phase of lung recruitment by early high-frequency oscillatory ventilation in infants with RDS. Thus optimal lung volume cannot be defined by serial Crs measurement. At the most, low initial Crs suggests that higher CDP will be needed.

High-Frequency Ventilation↗

PubMed1998

Optimal maternal weight gain during singleton pregnancy.

The aim of this study was to determine optimal maternal weight gain in a singleton pregnancy and evaluate the current recommendations. We used a historical prospective design to evaluate the association between pregnancy weight gain and perinatal outcome. All singleton pregnancies without congenital anomalies delivered between 1987 and 1993 at a single institution in New York City were analyzed. After adjusting for the prepregnancy body mass index, we determined the weight gain associated with optimal perinatal outcome. During this 6-year study period, 20,971 pregnant women met the inclusion criteria. Among them, 1,975 (9.4%) had adverse perinatal outcome. Prepregnancy weight and weight gain during pregnancy were strongly associated with adverse outcome. For women of average size, optimal outcome was found in those who gained between 31 and 40 pounds. For women underweight prior to pregnancy, optimal outcome occurred in those who gained 36-40 pounds. For women who were overweight or obese, a gain of 26-30 pounds was associated with optimal outcome. Weight gain during pregnancy is strongly associated with perinatal outcome, independent of important confounding factors, and should be carefully monitored during pregnancy. A randomized controlled trial is required to determine if perinatal and maternal outcome can be improved by advising pregnant women to gain weight using these new ranges rather than the Institute of Medicine's recommendations.

Adolescent↗

PubMed2004

Can optimal primary cytoreduction be predicted in advanced stage epithelial ovarian cancer? Role of preoperative serum CA-125 level.

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease 500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.

Adenocarcinoma↗

PubMed2006

Optimal diet for glycemia and lipids.

Concentrations of glucose and lipids in the blood have important health implications and are influenced by dietary intake. Dietary intake and energy expenditure regulate body weight, which is also an important determinant of health. Thus it would be important to determine the optimal diet for affecting blood glucose and lipids and body weight. Many professional health organizations in different countries have made dietary recommendations that include caloric restriction when needed to prevent or reverse overweight or obesity, limitation of saturated and trans fat, and emphasis on fruits and vegetables. These professional groups have not recommended extremely low carbohydrate or extremely low fat diets, despite much popular interest and recent research in these approaches. In several clinical trials, diet and exercise interventions prevented or delayed the development of type-2 diabetes. These trials showed the value of diet interventions, but did not attempt to determine which dietary approach was optimal. Clinical trials attempting to determine the optimal diet suffer from small sample sizes, short follow-up, and poor follow-up of participants. Therefore, the optimal balance between the total fat and carbohydrate contents and the optimal types of fats and carbohydrates remain unknown.

Blood Glucose↗

PubMed1998

Constrained optimization for neural map formation: a unifying framework for weight growth and normalization.

Computational models of neural map formation can be considered on at least three different levels of abstraction: detailed models including neural activity dynamics, weight dynamics that abstract from the neural activity dynamics by an adiabatic approximation, and constrained optimization from which equations governing weight dynamics can be derived. Constrained optimization uses an objective function, from which a weight growth rule can be derived as a gradient flow, and some constraints, from which normalization rules are derived. In this article, we present an example of how an optimization problem can be derived from detailed nonlinear neural dynamics. A systematic investigation reveals how different weight dynamics introduced previously can be derived from two types of objective function terms and two types of constraints. This includes dynamic link matching as a special case of neural map formation. We focus in particular on the role of coordinate transformations to derive different weight dynamics from the same optimization problem. Several examples illustrate how the constrained optimization framework can help in understanding, generating, and comparing different models of neural map formation. The techniques used in this analysis may also be useful in investigating other types of neural dynamics.

Animals↗

PubMed2002

A methodology for missile countermeasures optimization under uncertainty.

The missile countermeasures optimization problem is a complex strategy optimization problem that combines aircraft maneuvers with additional countermeasures in an attempt to survive attack from a single surface-launched, anti-aircraft missile. Classic solutions require the evading aircraft to execute specific sequences of maneuvers at precise distances from the pursuing missile and do not effectively account for uncertainty about the type and/or current state of the missile. This paper defines a new methodology for solving the missile countermeasures optimization problem under conditions of uncertainty. The resulting genetic programming system evolves programs that combine maneuvers with such countermeasures as chaff, flares, and jamming to optimize aircraft survivability. This methodology may be generalized to solve strategy optimization problems for intelligent, autonomous agents operating under conditions of uncertainty.

Aircraft↗

PubMed2004

An orthogonal multi-objective evolutionary algorithm for multi-objective optimization problems with constraints.

In this paper, an orthogonal multi-objective evolutionary algorithm (OMOEA) is proposed for multi-objective optimization problems (MOPs) with constraints. Firstly, these constraints are taken into account when determining Pareto dominance. As a result, a strict partial-ordered relation is obtained, and feasibility is not considered later in the selection process. Then, the orthogonal design and the statistical optimal method are generalized to MOPs, and a new type of multi-objective evolutionary algorithm (MOEA) is constructed. In this framework, an original niche evolves first, and splits into a group of sub-niches. Then every sub-niche repeats the above process. Due to the uniformity of the search, the optimality of the statistics, and the exponential increase of the splitting frequency of the niches, OMOEA uses a deterministic search without blindness or stochasticity. It can soon yield a large set of solutions which converges to the Pareto-optimal set with high precision and uniform distribution. We take six test problems designed by Deb, Zitzler et al., and an engineering problem (W) with constraints provided by Ray et al. to test the new technique. The numerical experiments show that our algorithm is superior to other MOGAS and MOEAs, such as FFGA, NSGAII, SPEA2, and so on, in terms of the precision, quantity and distribution of solutions. Notably, for the engineering problem W, it finds the Pareto-optimal set, which was previously unknown.

Algorithms↗

PubMed1999

Enabling occupational performance: optimal experiences in therapy.

Occupational therapists believe that engagement in occupation contributes to health through an individually balanced use of time, a positive focus for one's physical and mental energy, and the provision of a sense of purpose. Flow is a construct which describes optimal experiences or enjoyment in everyday activities. A review of the literature suggests that the theory of optimal experience is complementary to occupational therapy beliefs and that an understanding of the flow experience may contribute to our understanding of human occupation. Specifically, flow may be useful in understanding those aspects of the occupation, environment and person that contribute to a "just right" challenge, and to enabling occupational performance through enjoyable, structured and purposeful activity. Occupational therapists are encouraged to explore whether optimal experiences facilitate occupational performance for individuals with a disability. Future research could explore whether the occupational opportunities available to persons with a disability provide the degree of challenge required to elicit the optimal experience. Finally, research could explore whether the client-driven selection of meaningful occupation, and therapist enablement of the "just right" challenge, influences optimal experience, occupational performance, and life satisfaction for those with a disability.

Persons with Disabilities↗