Cyclophosphazenes as polymer modifiers

The utilization of Cyclophosphazenes as polymer modifiers is reviewed, with particular concern to their exploitation as versatile chain extenders, possibly for recycle problems, crosslinkers, to enhance mechanical properties of polymeric materials, branchers, to selectively introduce ramifications in linear polymers, and compatibilizers, to favor the formation of blends between originally incompatible organic macromolecules. The great versatility of the synthetic methods put forward for these substrates, together with the ease of controlling their modification, functionalization and reactivity are important parameters for the evaluation of which type of use is more feasible for these trimers. The importance of cyclophosphazenes bearing organic polymeric chains, azide groups, 2-oxazoline derivatives and oxirane rings in connection with organic conventional macromolecules is critically highlighted.     

Synthesis,Kinetics, and Molecular Docking of Novel 9‐(2‐Hydroxypropyl)purine Nucleoside Analogs as Ligands of Herpesviral Thymidine Kinases

In the context of broadening the knowledge on substrate specificity of Herpes simplex virus type 1 thymidine kinase (HSV‐1 TK) and Varicella‐Zoster virus thymidine kinase (VZV TK), new derivatives of 9‐(2‐hydroxypropyl)‐substituted adenine, chloropurine, hypoxanthine, guanine, thiopurine, and (methylsulfanyl)purine were synthesized and subjected to in vitro phosphorylation and binding affinity assays. The interactions between the compounds and the crystallographically determined active site residues of HSV‐1 TK have been studied by molecular modeling with the Lamarckian genetic algorithm of docking program AutoDock 3.0. All compounds mentioned bind to both enzymes in the low mM to sub‐mM range, comparable to binding affinities of existing prodrugs. Findings from the docking procedure indicate multiple binding modes for all of the compounds and are in accordance with the results of phosphorylation and binding‐affinity studies. Furthermore, the studies reveal that hypoxanthine derivatives represent a new class of TK substrates and thiopurine derivatives a new class of TK inhibitors.     

VIP-2 —High-Sensitivity Tests on the Pauli Exclusion Principle for Electrons

The VIP collaboration is performing high sensitivity tests of the Pauli Exclusion Principle for electrons in the extremely low cosmic background environment of the underground Gran Sasso National Laboratory INFN (Italy). In particular, the VIP-2 Open Systems experiment was conceived to put strong constraints on those Pauli Exclusion Principle violation models which respect the so-called Messiah–Greenberg superselection rule. The experimental technique consists of introducing a direct current in a copper conductor, and searching for the X-rays emission coming from a forbidden atomic transition from the L shell to the K shell of copper when the K shell is already occupied by two electrons. The analysis of the first three months of collected data (in 2018) is presented. The obtained result represents the best bound on the Pauli Exclusion Principle violation probability which fulfills the Messiah–Greenberg rule.     

Baseline Methods for the Parameter Estimation of the Generalized Pareto Distribution

In the parameter estimation of limit extreme value distributions, most employed methods only use some of the available data. Using the peaks-over-threshold method for Generalized Pareto Distribution (GPD), only the observations above a certain threshold are considered; therefore, a big amount of information is wasted. The aim of this work is to make the most of the information provided by the observations in order to improve the accuracy of Bayesian parameter estimation. We present two new Bayesian methods to estimate the parameters of the GPD, taking into account the whole data set from the baseline distribution and the existing relations between the baseline and the limit GPD parameters in order to define highly informative priors. We make a comparison between the Bayesian Metropolis–Hastings algorithm with data over the threshold and the new methods when the baseline distribution is a stable distribution, whose properties assure we can reduce the problem to study standard distributions and also allow us to propose new estimators for the parameters of the tail distribution. Specifically, three cases of stable distributions were considered: Normal, Lévy and Cauchy distributions, as main examples of the different behaviors of the tails of a distribution. Nevertheless, the methods would be applicable to many other baseline distributions through finding relations between baseline and GPD parameters via studies of simulations. To illustrate this situation, we study the application of the methods with real data of air pollution in Badajoz (Spain), whose baseline distribution fits a Gamma, and show that the baseline methods improve estimates compared to the Bayesian Metropolis–Hastings algorithm.     

Transformations of N-heteroarylformamidines and N-heteroarylformamidine oximes new syntheses and transformations of oxazolo[5,4—c]pyridazines

New approaches to the synthesis of oxazolo[5,4—c]pyridazine derivatives7 and15 starting from the substituted N-pyridazin-5-ylformamide oximes5 and13 are described. Under mild conditions the transformations of the amino or substituted amino group at position 2 of the oxazolo[5,4—c]pyridazine system were observed to give the compounds16 and17, while under more drastic reaction conditions the nucleophilic attack at position 2 followed by the ring opening of the oxazole part of the molecule was taking place to give the compounds18, 20, and21.

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Transformationen von N-Heteroarylformamidinen und N-Heteroarylformamidinoximen. Neue Synthesen und Transformationen von Oxazolo[5,4—c]pyridazinen

Zusammenfassung Neue Synthesemöglichkeiten von Oxazolo[5,4—c]pyridazinen7 und15, ausgehend von substitutierten N-Pyridazin-5-ylformamid-oximen5 und13 werden beschrieben. Unter milden Reaktionsbedingungen trat Transformation der Amino- oder substituierten Aminogruppe an der Position 2 des Oxazolo[5,4—c]pyridazin-Systems unter Bildung der Verbindungen16 und17 ein, währenddessen unter drastischeren Reaktionsbedingungen ein nucleophiler Angriff am Kohlenstoff der Position 2, gefolgt von einer Ringöffnung des Oxazol-Teils des Moleküls zu Verbindungen18, 20 und21 führte.

     

Computation of local radius of information in SM-IBC identification of nonlinear systems

System identification consists in finding a model of an unknown system starting from a finite set of noise-corrupted data. A fundamental problem in this context is to asses the accuracy of the identified model. In this paper, the problem is investigated for the case of nonlinear systems within the Set Membership—Information Based Complexity framework of [M. Milanese, C. Novara, Set membership identification of nonlinear systems, Automatica 40(6) (2004) 957–975]. In that paper, a (locally) optimal algorithm has been derived, giving (locally) optimal models in nonlinear regression form. The corresponding (local) radius of information, providing the worst-case identification error, can be consequently used to measure the quality of the identified model. In the present paper, two algorithms are proposed for the computation of the local radius of information: The first provides the exact value but requires a computational complexity exponential in the dimension of the regressor space. The second is approximate but involves a polynomial (quadratic) complexity.     

Development and Validation of a Densitometric HPTLC Method for Quantitative Analysis of Levofloxacin in Human Plasma

JPC – Journal of Planar Chromatography – Modern TLC -     

Electron ionization mass spectrometry of the ryanodine receptor‐based Ca2+‐channel stabilizer S‐107 and its implementation into routine doping control

New insights into the biochemistry of cardiac arrhythmia and skeletal muscle fatigue have yielded new drug candidates to counteract these phenomena. Major biological targets have become ryanodine receptor (RyR)‐based Ca²⁺‐release channels, which tend to ‘leak’ under various circumstances including strenuous exercise and, thus, cause aberrant calcium sparks that entail impaired muscle function. Therapeutics, which are referred to as rycals, are currently being developed to treat cardiac arrhythmia via enhancement of calstabin‐ryanodine affinities that causes a stabilization of the RyR. These therapeutics possess potential for misuse in sports, and an early implementation of target analytes such as the benzothiazepine derivatives S‐107 and JTV‐519 or putative metabolites into doping control screening procedures is recommended. Reference compounds, deuterated analogues, and a putative metabolic product were synthesized, and electron ionization mass spectra of these products were studied and dissociation pathways elucidated by means of tandem mass spectrometry (MS/MS) and accurate mass measurements. The characterized analytes were incorporated into existing sports drug testing assays based on liquid‐liquid extraction and subsequent gas chromatography/mass spectrometry (GC/MS) analysis, and specificity, lower limit of detection (4–6 ng/mL), intraday and interday precision (1.5–17.2%), as well as recovery (63–66%) were determined. The established procedure proved suitable for routine doping control analysis to detect a potential misuse of the drug candidate S‐107 in elite sport. Copyright © 2009 John Wiley & Sons, Ltd.