Application of dried blood spot sampling combined with LC-MS/MS for genotyping and phenotyping of CYP450 enzymes in healthy volunteers

An early clinical development study (phase I) was conducted to determine the usefulness of dried blood spot (DBS) sampling as an alternative to venous sampling for phenotyping and genotyping of CYP450 enzymes in healthy volunteers. Midazolam (MDZ) was used as a substrate for phenotyping CYP3A4 activity; the concentrations of MDZ and its main metabolite 1'-hydroxymidazolam (1-OH MDZ) were compared between the DBS method from finger punctures, plasma and whole blood (WB), drawn by venipuncture, whereby several methodological parameters were studied (i.e. punch width, amount of dots analyzed and storage time stability). Genotyping between DBS and venous WB samples was compared for CYP2D6 (*3, *4, *6), CYP2C19 (*2, *3), CYP3A4 (*1B) and CYP3A5 (*3C). In addition, the subject's and phlebotomist's satisfaction with venous blood sampling compared with the DBS method was evaluated using a standardized questionnaire. An LC-MS/MS method for the quantification of the MDZ and 1-OH MDZ concentrations in DBS samples was developed and validated in the range of 0.100-100 ng/mL. No compromises were made for the limits of quantification of the DBS-LC-MS/MS method vs the authentic plasma and WB methods.     

Polymer nanocomposite coatings based on polyhedral oligosilsesquioxanes: route for industrial manufacturing and barrier properties

A route to a large variety of functionalized POSS compounds by a two-step procedure has been developed. Up-scaling to high volume industrial applications is feasible. In the first step, an amino-functionalized silane such as 3-aminopropyltriethoxy silane is converted to amino-functionalized POSS (amine-POSS) by a sol–gel process. In the second step, the amine groups of amine-POSS are converted by state-of-the-art amine chemistry. A large number of reactants including carboxylic acids, esters, anhydrides, isocyanates, carbonates, epoxides, and acrylates as well as reactants suitable for nucleophilic substitution can be applied. Conversion of an amine-POSS with hexanoic acid leads to an amide-POSS. Amine chemistry can usually be performed under mild conditions, which suppresses degradation and/or cross-linking reactions of the amine-POSS during the conversion. MALDI-TOF mass spectroscopy and dynamic light scattering (particle size: 3–6 nm) have been applied to prove the conversion of an amine-POSS to an amide-POSS. ¹H-NMR and TGA-MS prove the presence of amide-POSS and its thermal stability. Gas barrier properties of nanocomposite coatings based on functionalized POSS are characterized.     

Dominant parameters for maximum velocity induced by body-force models for plasma actuators

This study investigates the relationship between body-force fields and maximum velocity induced in quiescent air for development of a simple body-force model of a plasma actuator. Numerical simulations are conducted with the body force near a wall. The spatial distribution and temporal variation of the body force are a Gaussian distribution and steady actuation, respectively. The dimensional analysis is performed to derive a reference velocity and Reynolds number based on the body-force distribution. It is found that the derived Reynolds number correlates well with the nondimensional maximum velocity induced in quiescent conditions when the center of the Gaussian distribution is fixed at the wall. Additionally, two flow regimes are identified in terms of the Reynolds number. Considering the variation of the center of gravity of force fields, another Reynolds number is defined by introducing a new reference length. The nondimensional maximum velocity is found to be scaled with the latter Reynolds number, i.e., the maximum induced velocity in quiescent conditions is determined from three key parameters of the force field: the total induced momentum per unit time, the height of the center of gravity, and the standard deviation from it. This scaling turns out to be applicable to existing body-force models of the plasma actuator, despite the force distributions different from the Gaussian distribution. Comparisons of velocity profiles with experimental data validate the results and show that the flow induced by a plasma actuator can be simulated with simple force distributions by adjustment of the key body-force parameters.     

Raman and photoluminescence signal separation in Raman hyperspectral imagery including noise reduction

Raman hyperspectral imaging (RHSI) is a valuable tool for gaining crucial information about the chemical composition of materials. However, obtaining clear Raman signals is not always a trivial task. Raw Raman signals can be susceptible to photoluminescence interference and noise. Hence, the preprocessing of RHSI is a required step for an effective and reliable chemical analysis. The main challenge is splitting the measured RHSI into separate Raman photoluminescence signals. Since no golden-standard exists, it is non-trivial to validate the correctness of the separated signals. While current state-of-the-art preprocessing methods are effective, they require expert knowledge and involve unintuitive hyperparameters. Current approaches also lack generalizability, requiring extensive hyperparameter tuning on a case-by-case basis, while even then results are not always as expected. To this end, this work proposes a novel iterative RHSI preprocessing pipeline for splitting raw Raman signals and noise removal based on linear spline and radial basis function regression (IlsaRBF). The proposed method involves hyperparameters based on the physical properties of Raman spectroscopy, making them intuitive to use. This leads to more robust and stable hyperparameters, reducing the necessity for extensive hyperparameter tuning. A thorough evaluation shows that the proposed method outperforms the current state-of-the-art. Additionally, a cosmic ray identification and removal algorithm (CRIR) and dynamic PCA for noise reduction are introduced. A standalone tool containing our proposed methods is provided, making RHSI preprocessing available to a broader audience, aiding further research and advancements in the field of Raman spectroscopy.