7-Substituted prostaglandin analogues. A new synthetic approach

Starting from methyl 7-oxo-7-(1-cyclopentene)-heptanoate, a simple synthesis of the methyl esters of 7-oxo- and 7-hydroxy-9,11-dideoxy-PGF ₁ as a model for 7-substituted prostaglandin analogues is described.

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7-Substituierte Prostaglandin-Analoge — ein neuer Syntheseweg

Zusammenfassung Ausgehend von Methyl-7-oxo-7-(1-cyclopenten)-heptanoat wird eine einfache Synthese der Methylester von 7-Oxo- und 7-Hydroxy-9,11-dideoxy-PGF ₁ als Modellverbindungen für 7-substituierte Prostaglandinanaloge beschrieben.

     

Antagonistic Effects of Endogenous Nitric Oxide in a Glioblastoma Photodynamic Therapy Model

Gliomas are aggressive brain tumors that are resistant to conventional chemotherapy and radiotherapy. Much of this resistance is attributed to endogenous nitric oxide (NO). Recent studies revealed that 5‐aminolevulinic acid (ALA)‐based photodynamic therapy (PDT) has advantages over conventional treatments for glioblastoma. In this study, we used an in vitro model to assess whether NO from glioblastoma cells can interfere with ALA‐PDT. Human U87 and U251 cells expressed significant basal levels of neuronal NO synthase (nNOS) and its inducible counterpart (iNOS). After an ALA/light challenge, iNOS level increased three‐ to fourfold over 24 h, whereas nNOS remained unchanged. Elevated iNOS resulted in a large increase in intracellular NO. Extent of ALA/light‐induced apoptosis increased substantially when an iNOS inhibitor or NO scavenger was present, implying that iNOS/NO was acting cytoprotectively. Moreover, cells surviving a photochallenge exhibited a striking increase in proliferation, migration and invasion rates, iNOS/NO again playing a dominant role. Also observed was a large iNOS/NO‐dependent increase in matrix metalloproteinase‐9 activity, decrease in tissue inhibitor of metalloproteinase‐1 expression and increase in survivin and S100A4 expression, each effect being consistent with accelerated migration/invasion as a prelude to metastasis. Our findings suggest introduction of iNOS inhibitors as pharmacologic adjuvants for glioblastoma PDT.     

Application of Image Analysis Technique for the Determination of Organophosphorus Pesticides by Thin-Layer Chromatography

JPC – Journal of Planar Chromatography – Modern TLC - A simple and convenient thin-layer chromatography (TLC) method combined with image analysis technique was developed to determine...     

Electrostatic potentials of molecules and prediction of the lewis acid-base properties of solvents,part I. General considerations

Summary Electrostatic potentials in the vicinity of isolated molecules of typical nonaqueous solvents were computed in the MNDO approximation. It was found that the calculated dipole moments are in good agreement with experimental values. However, it turned out that in many cases electrostatic interactions of ions with solvent molecules cannot be described in the frame of ion-dipole interactions. Thus, two computable parameters,UN andUP describing short-range electrostatic interactions of a solvent molecule with a cation or an anion of radiusR were proposed. The dependence ofUN andUP uponR is analyzed in the context of ion-solvent interactions.

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Elektrostatische Potentiale von Molekülen und Voraussage von Lewis-Säure-Base-Eigenschaften von Lösungsmitteln, 1. Mitt.: Allgemeine Grundlagen

Zusammenfassung Es wurden die elektrostatischen Potentiale in der Umgebung von isolierten Molekülen typischer nichtwäßriger Lösungsmittel in der MNDO-Näherung berechnet. Die berechneten Dipolmomente waren in guter Übereinstimmung mit den experimentellen Werten. Es wurde jedoch beobachtet, daß in vielen Fällen die elektrostatischen Wechselwirkungen von Ionen mit Lösungsmittelmolekülen nicht im Rahmen von Ionen-Dipol-Wechselwirkungen beschrieben werden können. Dafür wurden zwei berechenbare ParameterUN undUP zur Beschreibung von elektrostatischen Wechselwirkungen im Nahbereich eines Lösungsmittelmoleküls mit einem Kationen- oder AnionenradiusR vorgeschlagen. Die Abhängigkeit vonUN undUP vonR wurde im Zusammenhang von Ionen-Solvens-Wechselwirkungen untersucht.

     

Application of the TLC image analysis technique for the simultaneous quantitative determination of L-proline and L-lysine in dietary supplement

A simple and sensitive thin-layer chromatography (TLC) method coupled with an image analysis technique was developed for the simultaneous quantitative determination of L-proline and L-lysine in dietary supplement with good precision and accuracy. Separation was performed on silica gel plates using ethanol‒toluene (2:3, V/V) as the mobile phase. The visualization of chromatograms was based on iodine–azide reaction; therefore, pre-chromatographic derivatization reaction of amino acids with phenyl isothiocyanate was performed. Digital images of TLC plate chromatograms were converted into peak chromatograms, and quantitative analysis was conducted using TLSee software.

     

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.     

A genetic design of linguistic terms for fuzzy rule based classifiers

The determination of fuzzy information granules including the estimation of their membership functions play a significant role in fuzzy system design as well as in the design of fuzzy rule based classifiers (FRBCSs). However, although linguistic terms are fundamental elements in the process of elucidating expert’s knowledge, the problem of linguistic term design along with their fuzzy-set-based semantics has not been fully addressed, since term-sets of attributes have not been interpreted as a formalized structure. Thus, the essential relationship between linguistic terms, as syntax, and the constructed fuzzy sets, as their quantitative semantics, or in other words, the problem of the natural semantics of terms behind the linguistic literal has not been addressed. In this paper, we introduce the problem of the design of optimal linguistic terms and propose a method of the design of FRBCSs which may incorporate with the design of linguistic terms to ensure that the presence of linguistic literals are supported not only by data but also by their natural semantics. It is shown that this problem plays a primordial role in enhancing the performance and the interpretability of the designed FRBCSs and helps striking a better balance between the generality and the specificity of the desired fuzzy rule bases for fuzzy classification problems. A series of experiments concerning 17 Machine Learning datasets is reported.     

Rule-based models of multivariable functions

This study is devoted to fuzzy rule based modelling of multiple-input single-output nonlinear numerical relationships. The model under investigation is viewed as a collection of conditional statements “if state Ω_i then y = g_i(x, a_i)”, i = 1, 2,…, N with Ω_i being a fuzzy relation defined in the space of the input variables. In contrast to the commonly encountered identification approach that is dwelled upon discrete experimental data, the one proposed in this study is concerned with explicitly articulated nonlinear input-output relationship. The main thrust is in the development of a fuzzy partition of the input variables completed through a sequence of fuzzy relations rather than Cartesian products of fuzzy sets. This approach allows us to maintain the number of necessary rules under control and avoid a combinatorial explosion otherwise inevitable in situations of highly multivariable functions. Introduced are criteria of separability and function variability whose objective is to guide a distribution and granularity of the linguistic labels forming the condition part of the rules.     

Mining axiomatic fuzzy set association rules for classification problems

In this paper, we propose a novel method to mine association rules for classification problems namely AFSRC (AFS association rules for classification) realized in the framework of the axiomatic fuzzy set (AFS) theory. This model provides a simple and efficient rule generation mechanism. It can also retain meaningful rules for imbalanced classes by fuzzifying the concept of the class support of a rule. In addition, AFSRC can handle different data types occurring simultaneously. Furthermore, the new model can produce membership functions automatically by processing available data. An extensive suite of experiments are reported which offer a comprehensive comparison of the performance of the method with the performance of some other methods available in the literature. The experimental result shows that AFSRC outperforms most of other methods when being quantified in terms of accuracy and interpretability. AFSRC forms a classifier with high accuracy and more interpretable rule base of smaller size while retaining a sound balance between these two characteristics.     

On Mincʼs sheltered middle path

This paper shows that a construction, which was introduced by Piotr Minc in connection with a problem that came from Helly type theorems and that allows to replace three PL-arcs with a “sheltered middle path”, can in the case of general (non-PL) paths result in the topologist?s sine curve.