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Design and initial performance of PlanTIS: a high-resolution positron emission tomograph for plants
(2010)
Positron emitters such as 11C, 13N and 18F and their labelled compounds are widely used in clinical diagnosis and animal studies, but can also be used to study metabolic and physiological functions in plants dynamically and in vivo. A very particular tracer molecule is 11CO2 since it can be applied to a leaf as a gas. We have developed a Plant Tomographic Imaging System (PlanTIS), a high-resolution PET scanner for plant studies. Detectors, front-end electronics and data acquisition architecture of the scanner are based on the ClearPET™ system. The detectors consist of LSO and LuYAP crystals in phoswich configuration which are coupled to position-sensitive photomultiplier tubes. Signals are continuously sampled by free running ADCs, and data are stored in a list mode format. The detectors are arranged in a horizontal plane to allow the plants to be measured in the natural upright position. Two groups of four detector modules stand face-to-face and rotate around the field-of-view. This special system geometry requires dedicated image reconstruction and normalization procedures. We present the initial performance of the detector system and first phantom and plant measurements.
Mechano-pharmacological testing of L-Type Ca²⁺ channel modulators via human vascular celldrum model
(2020)
Background/Aims: This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. Methods: The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca²⁺ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). Results: It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5% and 50nM verapamil by 2,8%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. Conclusion: The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.
Hypertension describes the pathological increase of blood pressure, which is most commonly associated with the increase of vascular wall stiffness [1]. Referring to the “Deutsche Bluthochdruck Liga” this pathology shows a growing trend in our aging society. In order to find novel pharmacological and probably personalized treatments, we want to present a functional approach to study biomechanical properties of a human aortic vascular model.
In this method review we will give an overview of recent studies which were carried out with the CellDrum technology [2] and underline the added value to already existing standard procedures known from the field of physiology.
Herein described CellDrum technology is a system to measure functional mechanical properties of cell monolayers and thin tissue constructs in-vitro. Additionally, the CellDrum enables to elucidate the mechanical response of cells to pharmacological drugs, toxins and vasoactive agents. Due to its highly flexible polymer support, cells can also be mechanically stimulated by steady and cyclic biaxial stretching.
Background
Minor changes in protein structure induced by small organic and inorganic molecules can result in significant metabolic effects. The effects can be even more profound if the molecular players are chemically active and present in the cell in considerable amounts. The aim of our study was to investigate effects of a nitric oxide donor (spermine NONOate), ATP and sodium/potassium environment on the dynamics of thermal unfolding of human hemoglobin (Hb). The effect of these molecules was examined by means of circular dichroism spectrometry (CD) in the temperature range between 25°C and 70°C. The alpha-helical content of buffered hemoglobin samples (0.1 mg/ml) was estimated via ellipticity change measurements at a heating rate of 1°C/min.
Results
Major results were:
1) spermine NONOate persistently decreased the hemoglobin unfolding temperature T u irrespectively of the Na + /K + environment,
2) ATP instead increased the unfolding temperature by 3°C in both sodium-based and potassium-based buffers and
3) mutual effects of ATP and NO were strongly influenced by particular buffer ionic compositions. Moreover, the presence of potassium facilitated a partial unfolding of alpha-helical structures even at room temperature.
Conclusion
The obtained data might shed more light on molecular mechanisms and biophysics involved in the regulation of protein activity by small solutes in the cell.
As a deduction from these results, we can conclude that proteins mainly in vitro, denaturate totally at a temperature between 57°C -62°C, and they also affected by NO and different ions types. In which mainly, NO cause earlier protein denaturation, which means that, NO has a destabilizing effect on proteins, and also different ions will alter the protein denaturation in which, some ions will cause earlier protein denaturation while others not.
The importance of the availability of stored blood or blood cells, respectively, for urgent transfusion cannot be overestimated. Nowadays, blood storage becomes even more important since blood products are used for epidemiological studies, bio-technical research or banked for transfusion purposes. Thus blood samples must not only be processed, stored, and shipped to preserve their efficacy and safety, but also all parameters of storage must be recorded and reported for Quality Assurance. Therefore, blood banks and clinical research facilities are seeking more accurate, automated means for blood storage and blood processing.
Cement augmentation is an emerging surgical procedure in which bone cement is used to infiltrate and reinforce osteoporotic vertebrae. Although this infiltration procedure has been widely applied, it is performed empirically and little is known about the flow characteristics of cement during the injection process. We present a theoretical and experimental approach to investigate the intertrabecular bone permeability during the infiltration procedure. The cement permeability was considered to be dependent on time, bone porosity, and cement viscosity in our analysis. In order to determine the time-dependent permeability, ten cancellous bone cores were harvested from osteoporotic vertebrae, infiltrated with acrylic cement at a constant flow rate, and the pressure drop across the cores during the infiltration was measured. The viscosity dependence of the permeability was determined based on published experimental data. The theoretical model for the permeability as a function of bone porosity and time was then fit to the testing data. Our findings suggest that the intertrabecular bone permeability depends strongly on time. For instance, the initial permeability (60.89 mm4/N.s) reduced to approximately 63% of its original value within 18 seconds. This study is the first to analyze cement flow through osteoporotic bone. The theoretical and experimental models provided in this paper are generic. Thus, they can be used to systematically study and optimize the infiltration process for clinical practice.
This paper presents a two-dimensional-in-space mathematical model of biosensors based on an array of enzyme microreactors immobilised on a single electrode. The modeling system acts under amperometric conditions. The microreactors were modeled by particles and by strips. The model is based on the diffusion equations containing a nonlinear term related to the Michaelis-Menten kinetics of the enzymatic reaction. The model involves three regions: an array of enzyme microreactors where enzyme reaction as well as mass transport by diffusion takes place, a diffusion limiting region where only the diffusion takes place, and a convective region, where the analyte concentration is maintained constant. Using computer simulation, the influence of the geometry of the microreactors and of the diffusion region on the biosensor response was investigated. The digital simulation was carried out using the finite difference technique.
The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study.
On the basis of bivariate data, assumed to be observations of independent copies of a random vector (S,N), we consider testing the hypothesis that the distribution of (S,N) belongs to the parametric class of distributions that arise with the compound Poisson exponential model. Typically, this model is used in stochastic hydrology, with N as the number of raindays, and S as total rainfall amount during a certain time period, or in actuarial science, with N as the number of losses, and S as total loss expenditure during a certain time period. The compound Poisson exponential model is characterized in the way that a specific transform associated with the distribution of (S,N) satisfies a certain differential equation. Mimicking the function part of this equation by substituting the empirical counterparts of the transform we obtain an expression the weighted integral of the square of which is used as test statistic. We deal with two variants of the latter, one of which being invariant under scale transformations of the S-part by fixed positive constants. Critical values are obtained by using a parametric bootstrap procedure. The asymptotic behavior of the tests is discussed. A simulation study demonstrates the performance of the tests in the finite sample case. The procedure is applied to rainfall data and to an actuarial dataset. A multivariate extension is also discussed.
Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients.
In a special paired sample case, Hotelling’s T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given.
The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.