Stacking transgenic event DAS-Ø15Ø7-1 alters maize composition less than traditional breeding.

The impact of crossing ('stacking') genetically modified (GM) events on maize-grain biochemical composition was compared with the impact of generating nonGM hybrids. The compositional similarity of seven GM stacks containing event DAS-Ø15Ø7-1, and their matched nonGM near-isogenic hybrids (iso-hybrids) was compared with the compositional similarity of concurrently grown nonGM hybrids and these same iso-hybrids. Scatter plots were used to visualize comparisons among hybrids and a coefficient of identity (per cent of variation explained by line of identity) was calculated to quantify the relationships within analyte profiles. The composition of GM breeding stacks was more similar to the composition of iso-hybrids than was the composition of nonGM hybrids. NonGM breeding more strongly influenced crop composition than did transgenesis or stacking of GM events. These findings call into question the value of uniquely requiring composition studies for GM crops, especially for breeding stacks composed of GM events previously found to be compositionally normal.

Levodopa inhibits habit-learning in Parkinson's disease.

Mixed dopaminergic medication, comprising dopamine agonists and levodopa, may affect habit-learning in patients with Parkinson's disease (PD). However, the specific impact of levodopa on this effect is unknown. We assessed habit-learning in 20 non-demented PD-patients both with and without levodopa. We observed intact habit-learning in PD-patients OFF-medication. In contrast, the administration of 200 mg of levodopa impaired habit-learning. We conclude that potential deficits in habit-learning in PD may be attributed to the intake of levodopa.

Correlation of self-assessed fatigue and alertness in multiple sclerosis.

BACKGROUND: Fatigue is the most common symptom in multiple sclerosis patients, but is difficult to measure; quantification thus relies on self-assessed questionnaires. OBJECTIVE: To evaluate a battery of neuropsychological tests regarding their capacity to objectify self-reported fatigue. METHODS: We assessed the correlation between age, gender, education, Kurtzke's Expanded Disability Status Scale, depression, fatigue and neuropsychological testing using a cross-sectional approach in 110 multiple sclerosis patients. Fatigue was measured with the Fatigue Severity Scale. Cognition was measured using a series of neuropsychological tests including three subtests of the Test of Attentional Performance, the Brief Repeatable Battery of Neuropsychological Tests and the Faces Symbol Test. RESULTS: According to the Fatigue Severity Scale 51.4% of the cohort were fatigued (scores > or =4). Age, education and depression showed a significant correlation with the Fatigue Severity Scale. Only 5.5% of the cohort exhibited cognitive impairment in the Brief Repeatable Battery of Neuropsychological Tests scores. After correction for age, education, Expanded Disability Status Scale and depression, Fatigue Severity Scale scores were an independent predictor of performance in the alertness subtest of the Test of Attentional Performance (standardized coefficient beta = 0.298, p = 0.014). CONCLUSION: The alertness subtest of the Test of Attentional Performance may offer an objective method of evaluating self-reported fatigue, and may therefore - in addition to the Fatigue Severity Scale - be a suitable tool for the assessment of multiple sclerosis patients complaining of fatigue.

Evaluation of logistic and polynomial models for fitting sandwich-ELISA calibration curves.

Appropriately modeled calibration curves are important for accurately estimating the concentrations of proteins in samples evaluated in sandwich-format enzyme-linked immunosorbent assay (ELISA). Calibration curves are commonly fit using polynomial or logistic models. We compared the fit of a quadratic, cubic and 4-parameter logistic model for highly-replicated calibration curves across seven assays used for quantifying transgenic proteins in commercial crops. Results indicate that it is typically undesirable to include zero-concentration data when modeling these curves over the quantitative range, and simple polynomial models are typically preferable to the commonly recommended 4-parameter logistic model. These results are applicable to assays where precision constraints preclude interpolating results from the flat portions of the calibration curve, and it is under these conditions that the moderate improvements in accuracy described here will have impact.

Cognitive screening in multiple sclerosis.

Cognitive screening tests in multiple sclerosis (MS) are time- and cost-saving test instruments. In the case of a positive test result (alert function) a comprehensive cognitive test procedure should be administered. This paper explains what cognitive screening in MS means and presents several screening instruments used in MS with their statistical test characteristics, e. g. sensitivity and specificity.

Fit of four curve-linear models to decay profiles for pest control substances in soil.

Experiments that investigate the pattern of degradation of pest control substances in soil are often undertaken to estimate the persistence of compounds in the environment. Mathematical models are typically fit to decay data to facilitate the interpretation of the results and make predictions concerning the environmental fate of xenobiotics in soil. Four mathematical models were fit to 61 data sets to compare their performance in conforming to empirical patterns of degradation of pest control substances in soil. The use of composite residual plots allowed comparisons of the performance of the different models over many data sets. While an exponential model, estimated using nonlinear regression, fit many data sets very well, a shift-log, biexponential, and Monod equation appears superior in many cases, and systematic deviations from data sets are often less evident with the latter models. A knowledge of the patterns of bias typically exhibited by each model across many data sets may be useful for selecting models with reduced bias when fitting individual data sets.

Subthalamic stimulation differentially modulates declarative and nondeclarative memory.

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems.

Comparison of linear and nonlinear regression for modeling the first-order degradation of pest-control substances in soil.

First-order kinetic models are often used to profile the degradation of pest-control compounds in soil. This approach is based on enzyme theory and is often favored due to its simplicity and its requirement by regulatory agencies. Here, linear and nonlinear regression approaches to modeling first-order decay are compared. Composite residual plots of many soil degradation data sets are presented on a normalized scale. These plots illustrate the general error structure for the data and are useful for detecting common mis-specifications of the models. Results indicate that a nonlinear regression approach to modeling first-order decay of compounds in soil more accurately describes most data sets when compared with a linear approach. Specifically, the observed error structure does not support the broad use of a logarithmic transformation to stabilize the variance. In addition, models generated using the linear approach generally exhibit more dramatic systematic deviations from the observations as compared with models generated using the nonlinear approach. The analysis methods described here may be useful for comparing alternative models in this and other research areas.

Binary insecticidal crystal protein from Bacillus thuringiensis, strain PS149B1: effects of individual protein components and mixtures in laboratory bioassays.

A family of novel binary insecticidal crystal proteins, with activity against western corn rootworm, Diabrotica virgifera virgifera LeConte, was identified from Bacillus thuringiensis Berliner. A binary insecticidal crystal protein (bICP) from B. thuringiensis strain PS149B1 is composed of a 14-kDa protein (Cry34Abl) and a 44-kDaprotein (Cry35Ab1). These proteins have been co-expressed in transgenic maize plants, Zea mays L., and effectively control western corn rootworm larvae under field conditions. Laboratory experiments were conducted to better understand the contribution of each component protein to the in vivo activity of the bICP. The 14-kDa protein is active alone against southern corn rootworm, Diabrotica undecimpunctata howardi Barber, and was synergized by the 44-kDa protein. In mixtures, the concentration of the 14-kDa protein had a greater impact on efficacy than the 44-kDa component. Although both proteins are clearly required for maximal insecticidal activity, laboratory results did not support the formation of a stable, fixed-ratio complex of the two component proteins.

Safe composition levels of transgenic crops assessed via a clinical medicine model.

Substantial equivalence has become established as a foundation concept in the safety evaluation of transgenic crops. In the case of a food and feed crop, no single variety is considered the standard for safety or nutrition, so the substantial equivalence of transgenic crops is investigated relative to the array of commercial crop varieties with a history of safe consumption. Although used extensively in clinical medicine to compare new generic drugs with brand-name drugs, equivalence limits are shown to be a poor model for comparing transgenic crops with an array of reference crop varieties. We suggest an alternate model, also analogous to that used in clinical medicine, where reference intervals are constructed for a healthy heterogeneous population. Specifically, we advocate the use of distribution-free tolerance intervals calculated across a large amount of publicly available compositional data such as is found in the International Life Sciences Institute Crop Composition Database.

Modeling inspiratory and expiratory steady-state velocity fields in the Sprague-Dawley rat nasal cavity.

Distribution patterns of odorant molecules in the rat nasal olfactory region depend in large part on the detailed airflow patterns in the nasal cavity, which in turn depend on the anatomical structure. To investigate these flow patterns, we constructed an anatomically accurate finite element model of the right nasal cavity of the Sprague-Dawley rat based on horizontal (anterior-posterior) nasal cast cross sections. By numerically solving the fluid mechanical momentum and continuity equations using the finite element method, we studied the flow distribution and the complete velocity field for both inspiration and expiration throughout the nasal cavity under physiological flow rates of resting breathing and sniffing. Detailed velocity profiles, volumetric flow distributions, and streamline patterns for quasi-steady airflow are presented. S-shaped streamlines passing through the olfactory region are found to be less prevalent during expiratory than inspiratory flow leading to trapping and an increase in odorant molecule retention in the olfactory region during sniffing. The rat nasal velocity calculations will be used to study the distribution of odorant uptake onto the rat olfactory mucosa and compare it with the known anatomic location of some types of rat olfactory receptors.

Numerical modeling of odorant uptake in the rat nasal cavity.

An anatomically accurate 3-dimensional numerical model of the right rat nasal cavity was developed and used to compute low, medium, and high flow rate inspiratory and expiratory mucosal odorant uptake (imposed patterning) for 3 odorants with different mucus solubilities. The computed surface mass flux distributions were compared with anatomic receptor gene expression zones identified in the literature. In general, simulations predicted that odorants that were highly soluble in mucus were absorbed dorsally and medially, corresponding roughly to receptors from one of the gene expression zones. Insoluble odorants tended to be absorbed more peripherally in the rat olfactory region corresponding to the other 2 zones. These findings also agreed in general with the electroolfactogram measurements and the voltage-sensitive dye measurements reported in the literature. This numerical approach is the first to predict detailed odorant flux information across the olfactory mucosa in the rat nasal cavity during inspiratory and expiratory flow and to relate it to anatomic olfactory receptor location, physiological function, and biochemical experiment. This numerical technique can allow us to separate the contributions of imposed and inherent patterning mechanisms on the rat olfactory mucosa.

Numerical modeling of turbulent and laminar airflow and odorant transport during sniffing in the human and rat nose.

Human sniffing behavior usually involves bouts of short, high flow rate inhalation (>300 ml/s through each nostril) with mostly turbulent airflow. This has often been characterized as a factor enabling higher amounts of odorant to deposit onto olfactory mucosa than for laminar airflow and thereby aid in olfactory detection. Using computational fluid dynamics human nasal cavity models, however, we found essentially no difference in predicted olfactory odorant flux (g/cm2 s) for turbulent versus laminar flow for total nasal flow rates between 300 and 1000 ml/s and for odorants of quite different mucosal solubility. This lack of difference was shown to be due to the much higher resistance to lateral odorant mass transport in the mucosal nasal airway wall than in the air phase. The simulation also revealed that the increase in airflow rate during sniffing can increase odorant uptake flux to the nasal/olfactory mucosa but lower the cumulative total uptake in the olfactory region when the inspired air/odorant volume was held fixed, which is consistent with the observation that sniff duration may be more important than sniff strength for optimizing olfactory detection. In contrast, in rats, sniffing involves high-frequency bouts of both inhalation and exhalation with laminar airflow. In rat nose odorant uptake simulations, it was observed that odorant deposition was highly dependent on solubility and correlated with the locations of different types of receptors.

Numerical modeling of nasal obstruction and endoscopic surgical intervention: outcome to airflow and olfaction.

BACKGROUND: Mechanical obstruction of odorant flow to the olfactory neuroepithelium may be a primary cause of olfactory loss in nasal-sinus disease patients. Surgical removal of nasal obstruction may facilitate the recovery of olfactory ability. Unfortunately, quantifying the functional impact of nasal obstruction and subsequent surgical outcomes using acoustic rhinometry, rhinomanometry, or CT scans is inadequate. METHODS: Using computational fluid dynamics (CFD) techniques, we can convert patient CT scans into anatomically accurate 3D numerical nasal models that can be used to predict nasal airflow and odorant delivery rates. These models also can be rapidly modified to reflect anatomic changes, e.g., surgical removal of polyps. RESULTS: CFD modeling of one patient's nose pre- and postsurgery showed significant improvement in postsurgical ortho- and retronasal airflow and odorant delivery rate to olfactory neuroepithelium (> 1000 times), which correlated well with olfactory recovery. CONCLUSION: This study has introduced a novel technique (CFD) to calculate nasal airflow dynamics and its effects on olfaction, nasal obstruction, and sinus disease. In the future, such techniques may provide a quantitative evaluation of surgical outcome and an important preoperative guide to optimize nasal airflow and odorant delivery.

Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction.

Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (

Isometric force kinetics upon rapid activation and relaxation of mouse, guinea pig and human heart muscle studied on the subcellular myofibrillar level.

The kinetics of force development and relaxation upon rapid application and removal of Ca2+ was measured in bundles of few myofibrils isolated from triton X-100 skinned left ventricular trabeculae of mice (M), guinea pigs (G) and humans (H). Upon rapidly switching from relaxing solution (pCa 7.5) to activating solution (pCa 4.5) at 10 degrees C, force rose by a single exponential with a rate constant k(act) of 5.2 s(-1) (M), 1.7 s(-1) (G) and 0.3 s(-1) (H) to a plateau of 0.14 microN/microm2 (M), 0.16 microN/microm2 (G) and 0.15 microN/microm2 (H). A rapid release followed by a rapid restretch to the original length applied during steady-state Ca2+ activation at pCa 4.5 induced an exponential force redevelopment with a rate constant k(redev) that was indistinguishable from k(act), indicating that k(act) is limited by cross-bridge turnover kinetics rather than by the Ca2+-induced activation of the regulatory system. Upon rapidly switching from pCa 4.5 to pCa 7.5, force decayed in a pronounced biphasic manner. Thus a slow initial, almost linear decay with a rate constant k(lin) of 1.8 s(-1) (M), 0.6 s(-1) (G) and 0.15 s(-1) (H) and a duration t(lin) of 0.06 s (M), 0.11 s (G) and 0.3 s (H) was followed by a rapid exponential decay with a rate constant k(rel) of 18 s(-1) (M), 11 s(-1) (G) and 4.6 s(-1) (H). The pronounced biphasic shapes of the force decays determined here for the first time in cardiac myofibrils differs from the force decays that had been reported for multicellular skinned trabeculae in which relaxation was induced by rapid removal of Ca2+ by flash photolysis of caged Ca2+ chelators. In the skinned trabeculae, no pronounced initial slow phase was observed. The force decays shown here are much more similar to those reported for single skeletal myofibrils. The kinetics of isometric relaxation of skinned trabeculae (i.e., multicellular preparations), therefore, do not reflect the kinetics of force relaxation at the cardiac myofibrillar level.

Experimental and numerical determination of odorant solubility in nasal and olfactory mucosa.

Odorant deposition in the nasal and olfactory mucosas is dependent on a number of factors including local air/odorant flow distribution patterns, odorant mucosal solubility and odorant diffusive transport in the mucosa. Although many of these factors are difficult to measure, mucosal solubility in the bullfrog mucus has been experimentally determined for a few odorants. In the present study an experimental procedure was combined with computational fluid dynamic (CFD) techniques to further describe some of the factors that govern odorant mucosal deposition. The fraction of odorant absorbed by the nasal mucosa (eta) was experimentally determined for a number of odorants by measuring the concentration drop between odorant 'blown' into one nostril and that exiting the contralateral nostril while the subject performed a velopharyngeal closure. Odorant concentrations were measured with a photoionization detector. Odorants were delivered to the nostrils at flow rates of 3.33 and 10 l/min. The velopharyngeal closure nasal air/odorant flows were then simulated using CFD techniques in a 3-D anatomically accurate human nose modeland the mucosal odorant uptake was numerically calculated. The comparison between the numerical simulations and the experimental results lead to an estimation of the human mucosal odorant solubility and the mucosal effective diffusive transport resistance. The results of the study suggest that the increase in diffusive resistance of the mucosal layer over that of a thin layer of water seemed to be general and non-odorant-specific; however, the mucosa solubility was odorant specific and usually followed the trend that odorants with lower water solubility were more soluble in the mucosa than would be predicted from water solubility alone. The ability of this approach to model odorant movement in the nasal cavity was evaluated by comparison of the model output with known values of odorant mucosa solubility.