Stability studies of clonazepam, diazepam, haloperidol, and doxepin with diverse polarities in an acidic environment

Stability of clonazepam, diazepam, haloperidol, and doxepin was determined in acidic solutions. In addition, determination of the kinetic and thermodynamic properties of this stability was carried out. Reaction rate constants (k), half-life times (t(0.1) and t(0.5)), and activation energy (Ea) were estimated for the drugs, which differed in polarity expressed with log P values. It was observed that estimated Ea values increased from 42.13 to 125.03 kJ/mol with an increase of lipophilicity (log P) beginning from the most hydrophilic drug (clonazepam, 2.70 log P) to the most lipophilic drug (doxepin, 4.10 log P). All degradation products were studied using an HPLC/electrospray ionization-MS technique in the positive ionization mode.     

Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent

Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance imaging (MRI) contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after deamination by recombinant CDase, the CEST contrast disappears. In addition, expression of the enzyme in three different cell lines exhibiting different expression levels of CDase shows good agreement with the CDase activity measured with CEST MRI. Consequently, CDase activity was imaged with high-resolution CEST MRI. These data demonstrate the ability to detect enzyme activity based on proton exchange. Consequently, CEST MRI has the potential to follow the kinetics of multiple enzymes in real time in living tissue.     

Classification of genomic data: some aspects of feature selection

Feature selection, while working with genomic data sets, is of particular interest, not only for classification (diagnostics) improvement, but also for the data interpretability. Application of the multivariate feature selection approaches allows an efficient reduction of data dimensionality, but as demonstrated in our study, sets of the selected variables depend on the objective function of the classifier. It is possible to select different subset of genes for classification due to the correlation of genes but their interpretation ought to be cautiously made.     

Magnesium azaphthalocyanines: an emerging family of excellent red-emitting fluorophores

Magnesium(II), zinc(II), and metal-free phthalocyanines (Pcs) and azaphthalocyanines (AzaPcs) containing alkylsulfanyl, aryloxy, and dialkylamino peripheral substituents have been synthesized. The complexation of magnesium(II) by metal-free Pcs and AzaPcs has been studied in detail to determine the optimal reaction conditions necessary to ensure a complete conversion. Photophysical and photochemical measurements in tetrahydrofuran showed that magnesium(II) AzaPcs with aryloxy and alkylsulfanyl substituents have excellent fluorescent properties (Φ(F) up to 0.73) and that the corresponding zinc(II) Pcs are efficient singlet oxygen producers (Φ(Δ) up to 0.68). The presence of dialkylamino substituents causes intramolecular charge transfer within the molecule that competes with fluorescence and singlet oxygen formation. Alkylsulfanyl MgAzaPc and ZnAzaPc were the most photostable compounds among the series of studied derivatives. In addition, high molar absorption coefficients (ε ～ 300,000 M(-1) cm(-1)), absorption (λ(max) ～ 650 nm), and emission (λ(em) ～ 660 nm, high Φ(F)) in the red region suggest that these molecules are potential fluorescent probes that are superior to the commercial red cyanine dye Cy5. MgAzaPc, when incorporated into lipidic bilayers of liposomes, maintains excellent fluorescence properties (Φ(F) = 0.64). Water-soluble MgAzaPc with quaternary ammonium peripheral substituents retained a high fluorescence quantum yield even in water (Φ(F) = 0.25). The described properties show that magnesium(II) AzaPcs are excellent red-emitting fluorophores with potential applications as fluorescent probes in sensing or in vitro imaging applications.     

Implementation of the nonlinear imperfect transmission conditions between dissimilar materials into commercial FEM software MSC.Marc using Fortran user subroutine: Plane strain case

Thin soft elasto-plastic interphase adhesively bonded materials are replaced by nonlinear imperfect transmission conditions in commercial FEM software MSC.Marc using Fortran user subroutine. The idea of replacement is based upon iteratively finding artificial stiffness of springs which maps elasto-plastic behaviour of interphase. Plane strain case is considered.     

Triangle-Free Geometric Intersection Graphs with Large Chromatic Number

Several classical constructions illustrate the fact that the chromatic number of a graph may be arbitrarily large compared to its clique number. However, until very recently no such construction was known for intersection graphs of geometric objects in the plane. We provide a general construction that for any arc-connected compact set $X$ X in $\mathbb{R }^2$ R 2 that is not an axis-aligned rectangle and for any positive integer $k$ k produces a family $\mathcal{F }$ F of sets, each obtained by an independent horizontal and vertical scaling and translation of $X$ X , such that no three sets in $\mathcal{F }$ F pairwise intersect and $\chi (\mathcal{F })>k$ χ ( F ) > k . This provides a negative answer to a question of Gyárfás and Lehel for L-shapes. With extra conditions we also show how to construct a triangle-free family of homothetic (uniformly scaled) copies of a set with arbitrarily large chromatic number. This applies to many common shapes, like circles, square boundaries or equilateral L-shapes. Additionally, we reveal a surprising connection between coloring geometric objects in the plane and on-line coloring of intervals on the line.     

On-Line Dimension of Semi-Orders

We analyze the on-line dimension of partially ordered sets as a value of a two-person game between Algorithm and Spoiler. The game is played in rounds. Spoiler presents an on-line order of width at most w, one point at a time. Algorithm maintains its realizer, i.e., the set of d linear extensions which intersect to the presented order. Algorithm may not change the ordering of the previously introduced elements in the existing linear extensions. The value of the game val(w) is the least d such that Algorithm has a strategy against Spoiler presenting any order of width at most w. For interval orders Hopkins showed that val $(w) \leqslant 4w-4$ . We analyze the on-line dimension of semi-orders i.e., interval orders admitting a unit-length representation. For up-growing semi-orders of width w we prove a matching lower and upper bound of w. In the general (not necessarily up-growing) case we provide an upper bound of 2w.     

Relative uniform convergence of a sequence of functions at a point and Korovkin-type approximation theorems

Positivity - We prove a Korovkin-type approximation theorem using the relative uniform convergence of a sequence of functions at a point, which is a method stronger than the classical ones. We give...