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Doppler index and plasma level of atrial natriuretic hormone are improved by optimizing atrioventricular delay in atrioventricular block patients with implanted DDD pacemakers.

Doppler index is the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and has clinical value as an index of combined systolic and diastolic myocardial performance. This crossover study compared the Doppler index and atrial natriuretic hormone (atrial natriuretic peptide) [ANP] between optimal (AV) delay and prolonged AV delay in patients with DDD pacemakers. The study included 14 patients (6 men, 8 women, age 78.4+/-9.3 [SD] years) with AV block with an implanted DDD pacemaker. AV delay was prolonged in a 25-ms, stepwise fashion starting from 125 ms to 250 ms. Pacing rate was set at 70 beats/min. Cardiac output (CO) was assessed by pulsed Doppler echocardiography, and optimal AV delay was defined as the AV delay at which CO was maximum, and an AV delay setting of 250 ms as prolonged AV delay. Plasma level of ANP and Doppler index determined by echocardiography were measured 1 week after programming. AV delay was switched to another AV delay and measurements were repeated after 1 week. Optimal AV delay was 159+/-19 ms. Doppler index was significantly lower at optimal AV delay than at prolonged AV delay (0.68+/-0.26 vs 0.92+/-0.30, P < 0.05). The plasma ANP level was significantly lower at optimal AV delay than at prolonged AV delay (29.0+/-30.7 vs 52.6+/-44.9 pg/mL, P < 0.05). In conclusion, the Doppler index and the plasma ANP level were significantly lower at optimal AV delay than at prolonged AV delay. This study shows the importance of the optimal AV delay setting in patients with an implanted DDD pacemaker, the Doppler index and plasma ANP levels are good indicators for optimizing AV delay.

Aged↗

Determination of the optimal atrioventricular delay in DDD pacing. Comparison between echo and peak endocardial acceleration measurements.

The goal of this study was to compare two methods determining the optimal atrioventicular delay (AVD) in 19 patients implanted with the BEST-Living system for complete heart block. The definition of the optimal AVD was: the AVD with the echo method that provided the longest diastolic filling time without interruption of the A wave, and the AVD with the peak endocardial acceleration (PEA) method, corresponding to the knee of the PEA curve vs AV delay. The amplitude of the PEA was measured for every AVD programmed via an automatic scanner in steps of 60 to 300 ms (40 ms steps): in the VDD pacing mode with a low base rate, to obtain 100% sensed P waves; in DDD with a base rate = sinus rate + 20%, to obtain 100% paced P waves. Echocardiographic (Echo) measurement of the left ventricular filling time were performed in the same AV delay settings in VDD and DDD as the ones tested in the PEA method, which were manually programmed. The optimal AVDs obtained in DDD and those obtained in VDD were compared in the echo and the PEA tests by a paired Student's t-test. The optimal AVDs obtained by both Echo and by PEA were also compared by a paired Student's t-test in VDD and DDD. The r value of the correlation between the optimal AVDs obtained by Echo and those obtained by PEA was calculated. Similar values of optimal AVD were obtained with both methods. The optimal AVDs given by the Echo technique (179 +/- 25 ms in DDD and 124 +/- 18 ms in VDD) were slightly, but significantly shorter than the ones obtained with the PEA method (202 +/- 21 ms in DDD and 145 +/- 18 ms in VDD, P < 0.05). A highly significant difference between AVD VDD and AVD DDD was found with both methods (P < 0.001). The correlation between the AVDs obtained with the echo and the PEA methods was highly significant (r = 0.78, P < 0.01). Pacemaker software could be modified to determine automatically the optimal AVDs to be applied throughout the heart rate range.

Atrioventricular Node↗

Optimal atrioventricular delay setting determined by evoked QT interval in patients with implanted stimulus-T-driven DDDR pacemakers.

Cardiac function is improved by optimizing the atrioventricular (AV) delay. An automatic optimizing function of AV delay may be necessary to achieve the most favourable haemodynamic state in paced patients. The QT interval may change when cardiac function is improved by optimizing the AV delay. The QT or stimulus-T interval is used as a sensor for rate-responsive pacemakers. Evoked (e) QT interval is measured as the time duration from the ventricular pace pulse (stimulus) and the T-sense point that is the steepest point of the intracardiac T wave (stimulus-T interval). The relationship between AV delay, eQT interval and cardiac function was studied in 10 patients (73 +/- 10 (SD) years old) with an implanted stimulus-T-driven DDDR pacemaker. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter. The AV delay was prolonged stepwise by 30 ms. Electrocardiogram event markers which indicated ventricular spike and sensed T wave were recorded, and the interval between two event markers was measured as eQT interval. When AV delay was changed from 240 ms to the AV delay at which CO was maximal (172 +/- 33 ms), eQT interval prolonged from 346 +/- 60 to 353 +/- 62 ms (P < 0.01). There was a significant positive correlation between the optimal AV delay at which CO was maximal (172 +/- 33 ms) and the optimal AV delay which was predicted from the maximum eQT interval (179 +/- 37 ms, r = 0.92, P < 0.001). When AV delay was changed from 240 ms to the predicted optimal AV delay, CO increased from 4.2 +/- 0.7 to 4.5 +/- 0.81.min-1 (P < 0.001) and PCWP was decreased from 7.1 +/- 4.0 to 5.7 +/- 3.1 mmHg (P < 0.05). In conclusion, the optimal AV delay can be predicted from the eQT interval which is sensed by an implanted pacemaker. Automatic setting of the optimal AV delay may be achieved by the QT sensor of an implanted pacemaker.

Aged↗

Optimal continuous positive airway pressure in patients with obstructive sleep apnoea: role of craniofacial structure.

Although nasal continuous positive airway pressure (CPAP) is effective in improving nocturnal obstructive apnoea, daytime sleepiness and well-being in patients with obstructive sleep apnoea syndrome (OSAS), not all patients tolerate this treatment. Since optimal CPAP titration is essential to maintain compliance, it is important to elucidate the factors that help to determine the optimal pressure. However, the determinants of the optimal CPAP level are controversial. The subjects comprised 27 Japanese male patients with OSAS who underwent standard polysomnography (PSG), pulmonary function tests, arterial blood gas analysis, cephalometry and CPAP titration. Twenty normal controls also underwent cephalometric analysis. The apnoea-hypopnoea index (AHI), mean oxygen saturation (mean SaO2) and the lowest SaO2 during sleep were found to be 54.7+/-22.6, 89.0+/-5.6%, and 69.7+/-9.0%, respectively by PSG. The mean optimal CPAP was 9.6+/-1.8 cmH2O. The cephalometric angles (SNA, SNB and NSBa) were similar to those found in the control subjects. but MP-H, and PNS-P were significantly longer than those in the control subjects as shown by cephalometry. The optimal CPAP was correlated with the mean SaO2 (P<0.0001), neck circumference (P<0.05) and three cephalometric variables (NSBa: P<0.01, MP-H: P<0.05, PNS-P: P<0.05). Multiple, step-wise, regression analysis showed that the mean SaO2 and NSBa were independent variables that best predicted the optimal CPAP. These variables accounted for 57.5% of the total variance (R2=0.575, P<0.001). Optimal CPAP was closely correlated with oxygen desaturation during sleep. However, the craniofacial structure had additional effects such as an independent factor in determining the optimal CPAP level.

Adult↗

Learning from the acquired optimized pulse shapes about the isotope selective ionization of potassium dimers.

Selective optimization of the 39,39K2 and 39,41K2 isotopomers in a three-photon ionization process is presented by applying evolution strategies on shaped fs pulses in a feedback loop. The optimizations at different center wavelengths show considerably large enhancements of one isotope compared to the other and reversed. We compare the acquired optimized pulse shapes for combined phase and amplitude with pure amplitude modulation. Particularly from their spectra we are able to extract information about the optimally chosen differing ionization paths via the involved vibrational states. Furthermore, a comparison of the temporal shape of the optimized pulse forms for combined phase and amplitude with pure phase optimization is given. The presented pulse form analysis demonstrates the potential of restricted optimization to gain insight into the underlying dynamical processes. Our approach reveals how the optimization algorithm precisely addresses the vibrational wave functions both spectrally and temporally.

Journal Article↗

The clinical value of non-coplanar photon beams in biologically optimized intensity modulated dose delivery on deep-seated tumours.

The aim of the present study is to compare the merits of different radiobiologically optimized treatment techniques using few-field planar and non-coplanar dose delivery on an advanced cancer of the cervix, with rectum and bladder as principal organs at risk. Classically, the rational for using non-coplanar beams is to minimize the overlap of beam entrance and exit regions and to find new beam directions avoiding organs at risk, in order to reduce damage to sensitive normal tissues. Two four-beam configurations have been extensively studied. The first consists of three evenly spaced coplanar beams and a fourth non-coplanar beam. A second tetrahedral-like configuration, with two symmetric non-coplanar beams at the same gantry angle and two coplanar beams, with optimized beam directions, was also tested. The present study shows that when radiobiologically optimized intensity modulated beams are applied to such a geometry, only a marginal increase in the treatment outcome can be achieved by non-coplanar beams compared to the optimal coplanar treatment. The main reason for this result is that the high dose in the beam-overlap regions is already optimally reduced by biologically optimized intensity modulation in the plane. The large number of degrees of freedom already incorporated in the treatment by the use of intensity modulation and radiobiological optimization, leads to the saturation of the benefit acquired by a further increase in the degrees of freedom with non-coplanar beams. In conclusion, the use of coplanar radiobiologically optimized intensity modulation simplifies the dose delivery, reducing the need for non-coplanar beam portals.

Female↗

Evaluation of geometrically optimized single- and double-plane interstitial high dose rate implants with respect to conformality and homogeneity.

The use of a stepping source in high dose rate brachytherapy supported with dwell-time optimization makes it possible to deviate from the classical dosimetry systems. Dose distributions of single- and double-plane implants were analysed for conformality and homogeneity at idealized target volumes. The Paris system was used for catheter positioning and target volume determination. Geometric optimization and individual dose prescription were applied. Volumetric indices and dose parameters were calculated at optimal active length, which was found to be equal to target volume length. The mean conformality, homogeneity, external volume and overdose volume indices were 0.78, 0.67, 0.22 and 0.13, respectively. The average minimum target and reference doses were 69% and 86%, respectively. Comparisons between the volumetric indices of geometrical optimized and non-optimized implants were also performed, and a significant difference was found regarding any index. The geometrical optimization resulted in superior conformality and slightly inferior homogeneity. At geometrically optimized implants, the active length can be reduced compared to non-optimized implants. Volumetric parameters and dose-volume histogram-based individual dose prescription are recommended for quantitative assessment of interstitial implants.

Brachytherapy↗

'Optimal' participation: a reflective look.

PURPOSE: There is mounting interest by professionals working in the rehabilitation sciences related to the concept of participation, especially given the increasing numbers of individuals worldwide living with chronic illnesses. It is now internationally agreed that participation level is influenced by both personal and environmental factors. The question arises as to the meaning of 'optimal' participation. The main objective of this article is to provide a reflective look at the concept of participation and the meaning of 'optimality' for individuals with and without disability and to explore both in relation to response shift. METHOD: Similarities in definitions of participation are first examined. Normal participation level is discussed leading to an 'optimal' level based on normality. Cases are used to illustrate normality as well as how 'optimal' participation can be achieved through a transition period despite disabilities caused by a health condition such as a stroke. RESULTS: 'Optimal' participation would rely on a perfect fit between an individual's reality (how activities and roles are actually realised) and expectations of how activities and roles should be accomplished. A transition period, including a response shift, following an acute event or onset of a chronic condition can lead to an optimal participation level despite persisting disabilities. CONCLUSIONS: A better understanding of the meaning of optimal participation and its association to response shift is important to clinical practice. Interventions aimed at optimizing participation through assisting clients who are experiencing a response shift can then be designed to maximize participation and concomitantly, quality of life in those with chronic health conditions.

Activities of Daily Living↗

An optimal model and its application for the management of municipal solid waste from regional small cities in China.

Based on the basic characteristics of municipal solid waste (MSW) from regional small cities in China, some optimal management principles have been put forward: regional optimization, long-term optimization, and integrated treatment/disposal optimization. According to these principles, an optimal MSW management model for regional small cities is developed and provides a useful method to manage MSW from regional small cities. A case study application of the optimal model is described and shows that the optimal management scenarios in the controlling region can be gained, adequately validating and accounting for the advantages of the optimal model.

China↗

A Monte Carlo study of grid performance in diagnostic radiology: task-dependent optimization for digital imaging.

A Monte Carlo computational model has been used to optimize grid design in digital radiography. The optimization strategy involved finding grid designs that, for a constant signal-to-noise ratio, resulted in the lowest mean absorbed dose in the patient. Different examinations were simulated to explore the dependence of the optimal scatter-rejection technique on the imaging situation. A large range of grid designs was studied, including grids with both aluminium and fibre interspaces and covers, and compared to a 20 cm air gap. The results show that the optimal tube potential in each examination does not depend strongly on the scatter-rejection technique. There is a significant dose reduction associated with the use of fibre-interspaced grids, particularly in paediatric radiography. The optimal grid ratio and strip width increase with increasing scattering volume. With increasing strip density, the optimal strip width decreases, and the optimal grid ratio increases. Optimal grid ratios are higher than those used today, particularly for grids with large strip density. It is, however, possible to identify grids of good performance for a range of strip densities and grid ratios provided the strip width is selected accordingly. The computational method has been validated by comparison with measurements with a caesium iodide image receptor.

Algorithms↗

Optimization of multiple spin-echo sequences for 3D polymer gel dosimetry.

The overall performance of polymer gel dosimeters for three-dimensional radiation dosimetry is determined by the temporal and spatial stability of the gels, dose sensitivity and image quality with respect to both systematic and stochastic deviations. The dose resolution (D(p)delta) is determined by the dose sensitivity and the signal-to-noise ratio (SNR) in the dose images. The dose sensitivity can be altered by changing the chemical composition of the polymer gel. The SNR is determined by the scanner and the imaging sequence. In the dose verification of conformal radiotherapy treatments the chosen number of slices may reach a number of 10-20. For these experiments, to obtain a sufficient SNR within a reasonable measurement time using a certain MR scanner, the imaging sequence should be optimized. A few other studies have emphasized the importance of optimizing the imaging sequence with respect to dose resolution (D(p)delta) or SNR but do not give quantitative values for the optimal sequence parameters for scanning a polymer gel dosimeter in three dimensions. In this paper, it is proved that a multiple spin-echo sequence is preferable to a single spin-echo sequence. It is also shown that when using a multiple spin-echo sequence it is not the inter-echo time that should be optimized but the number of echoes. An algebraical expression is derived for the dose resolution in terms of sequence parameters. A mathematical formalism and look-up tables are provided that can be used to optimize both a single and a slice-selective multiple spin-echo sequence to acquire a set of dose images at various locations. The use of the optimization protocol is illustrated by some examples. The optimization protocol enables the user to derive the optimal sequence parameters to acquire a set of dose maps obtained by quantitative T2 imaging for each polymer gel dosimeter within the shortest time possible.

Acrylic Resins↗

Optimizer convergence and local minima errors and their clinical importance.

Two of the errors common in the inverse treatment planning optimization have been investigated. The first error is the optimizer convergence error, which appears because of non-perfect convergence to the global or local solution, usually caused by a non-zero stopping criterion. The second error is the local minima error, which occurs when the objective function is not convex and/or the feasible solution space is not convex. The magnitude of the errors, their relative importance in comparison to other errors as well as their clinical significance in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP) were investigated. Two inherently different optimizers, a stochastic simulated annealing and deterministic gradient method were compared on a clinical example. It was found that for typical optimization the optimizer convergence errors are rather small, especially compared to other convergence errors, e.g., convergence errors due to inaccuracy of the current dose calculation algorithms. This indicates that stopping criteria could often be relaxed leading into optimization speed-ups. The local minima errors were also found to be relatively small and typically in the range of the dose calculation convergence errors. Even for the cases where significantly higher objective function scores were obtained the local minima errors were not significantly higher. Clinical evaluation of the optimizer convergence error showed good correlation between the convergence of the clinical TCP or NTCP measures and convergence of the physical dose distribution. On the other hand, the local minima errors resulted in significantly different TCP or NTCP values (up to a factor of 2) indicating clinical importance of the local minima produced by physical optimization.

Algorithms↗

Multiobjective inverse planning for intensity modulated radiotherapy with constraint-free gradient-based optimization algorithms.

We consider the behaviour of the limited memory L-BFGS algorithm as a representative constraint-free gradient-based algorithm which is used for multiobjective (MO) dose optimization for intensity modulated radiotherapy (IMRT). Using a parameter transformation, the positivity constraint problem of negative beam fluences is entirely eliminated: a feature which to date has not been fully understood by all investigators. We analyse the global convergence properties of L-BFGS by searching for the existence and the influence of possible local minima. With a fast simulated annealing (FSA) algorithm we examine whether the L-BFGS solutions are globally Pareto optimal. The three examples used in our analysis are a brain tumour, a prostate tumour and a test case with a C-shaped PTV. In 1% of the optimizations global convergence is violated. A simple mechanism practically eliminates the influence of this failure and the obtained solutions are globally optimal. A single-objective dose optimization requires less than 4 s for 5400 parameters and 40000 sampling points. The elimination of the problem of negative beam fluences and the high computational speed permit constraint-free gradient-based optimization algorithms to be used for MO dose optimization. In this situation, a representative spectrum of possible solutions is obtained which contains information such as the trade-off between the objectives and range of dose values. Using simple decision making tools the best of all the possible solutions can be chosen. We perform an MO dose optimization for the three examples and compare the spectra of solutions, firstly using recommended critical dose values for the organs at risk and secondly, setting these dose values to zero.

Algorithms↗

Optimization of beam orientations and beam weights for conformal radiotherapy using mixed integer programming.

An algorithm for optimizing beam orientations and beam weights for conformal radiotherapy has been developed. The algorithm models the optimization of beam orientations and beam weights as a problem of mixed integer linear programming (MILP), and optimizes the beam orientations and beam weights simultaneously. The application process of the algorithm has four steps: (a) prepare a pool of beam orientation candidates with the consideration of avoiding any patient-gantry collision and avoiding direct irradiation of organs at risk with quite low tolerances (e.g., eyes). (b) Represent each beam orientation candidate with a binary variable, and each beam weight with a continuous variable. (c) Set up an optimization problem according to dose prescriptions and the maximum allowed number of beam orientations. (d) Solve the optimization problem with a ready-to-use MILP solver. After optimization, the candidates with unity binary variables remain in the final beam configuration. The performance of the algorithm was tested with clinical cases. Compared with standard treatment plans, the beam-orientation-optimized plans had better dose distributions in terms of target coverage and avoidance of critical structures. The optimization processes took less than 1 h on a PC with a Pentium IV 2.4 GHz processor.

Algorithms↗

Intensity-modulated radiotherapy optimization with gEUD-guided dose-volume objectives.

Currently, most intensity-modulated radiation therapy systems use dose-volume (DV)-based objectives. Although acceptable plans can be generated using these objectives, much trial and error is necessary to plan complex cases with many structures because numerous parameters need to be adjusted. An objective function that makes use of a generalized equivalent uniform dose (gEUD) was developed recently that has the advantage of involving simple formulae and fewer parameters. In addition, not only does the gEUD-based optimization provide the same coverage of the target, it provides significantly better protection of critical structures. However, gEUD-based optimization may not be superior once dose distributions and dose-volume histograms (DVHs) are used to evaluate the plan. Moreover, it is difficult to fine-tune the DVH with gEUD-based optimization. In this paper, we propose a method for combining the gEUD-based and DV-based optimization approaches to overcome these limitations. In this method, the gEUD optimization is performed initially to search for a solution that meets or exceeds most of the treatment objectives. Depending on the requirements, DV-based optimization with a gradient technique is then used to fine-tune the DVHs. The DV constraints are specified according to the gEUD plan, and the initial intensities are obtained from the gEUD plan as well. We demonstrated this technique in two clinical cases: aprostate cancer and ahead and neck cancer case. Compared with the DV-optimized plan, the gEUD plan provided better protection of critical structures and the target coverage was similar. However, homogeneities were slightly poorer. The gEUD plan was then fine-tuned with DV constraints, and the resulting plan was superior to the other plans in terms of the dose distributions. The planning time was significantly reduced as well. This technique is an effective means of optimizing individualized treatment plans.

Adenocarcinoma↗

Beam orientation optimization for intensity-modulated radiation therapy using mixed integer programming.

The purpose of this study is to extend an algorithm proposed for beam orientation optimization in classical conformal radiotherapy to intensity-modulated radiation therapy (IMRT) and to evaluate the algorithm's performance in IMRT scenarios. In addition, the effect of the candidate pool of beam orientations, in terms of beam orientation resolution and starting orientation, on the optimized beam configuration, plan quality and optimization time is also explored. The algorithm is based on the technique of mixed integer linear programming in which binary and positive float variables are employed to represent candidates for beam orientation and beamlet weights in beam intensity maps. Both beam orientations and beam intensity maps are simultaneously optimized in the algorithm with a deterministic method. Several different clinical cases were used to test the algorithm and the results show that both target coverage and critical structures sparing were significantly improved for the plans with optimized beam orientations compared to those with equi-spaced beam orientations. The calculation time was less than an hour for the cases with 36 binary variables on a PC with a Pentium IV 2.66 GHz processor. It is also found that decreasing beam orientation resolution to 10 degrees greatly reduced the size of the candidate pool of beam orientations without significant influence on the optimized beam configuration and plan quality, while selecting different starting orientations had large influence. Our study demonstrates that the algorithm can be applied to IMRT scenarios, and better beam orientation configurations can be obtained using this algorithm. Furthermore, the optimization efficiency can be greatly increased through proper selection of beam orientation resolution and starting beam orientation while guaranteeing the optimized beam configurations and plan quality.

Algorithms↗

Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy.

Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

Algorithms↗

Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice.

Codon usage optimization of human immunodeficiency virus type 1 (HIV-1) structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo; however, all optimized genes reported thus far are derived from HIV-1 (group M) subtype B viruses. Here, we report the generation and biological characterization of codon usage-optimized gag, pol, env (gp160, gp140, gp120), and nef genes from a primary (nonrecombinant) HIV-1 subtype C isolate. After transfection into 293T cells, optimized subtype C genes expressed one to two orders of magnitude more protein (as determined by immunoblot densitometry) than the corresponding wild-type constructs. This effect was most pronounced for gp160, gp140, Gag, and Pol (>250-fold), but was also observed for gp120 and Nef (45- and 20-fold, respectively). Optimized gp160- and gp140-derived glycoproteins were processed, incorporated into virus particles, and mediated virus entry when expressed in trans to complement an env-minus HIV-1 provirus. Mice immunized with optimized gp140 DNA developed antibody as well as CD4+ and CD8+ T cell immune responses that were orders of magnitude greater than those of mice immunized with wild-type gp140 DNA. These data confirm and extend previous studies of codon usage optimization of HIV-1 genes to the most prevalent group M subtype. Our panel of matched optimized and wild-type subtype C genes should prove valuable for studies of protein expression and function, the generation of subtype-specific immunological reagents, and the production of DNA-based sub-unit vaccines directed against a broader spectrum of viruses.

AIDS Vaccines↗