Sulfobutylation of Beta-Cyclodextrin Enhances the Complex Formation with Mitragynine: An NMR and Chiroptical Study

Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ₁₁ = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from ¹H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.     

Crystallography and Morphology of Niobium Carbide in As-Cast HP-Niobium Reformer Tubes

The microstructures of two as-cast heats of niobium-modified HP stainless steels were characterized. Particular attention was paid to the interdendritic niobium-rich carbides formed during solidification of these alloys. At low magnifications, these precipitates are grouped in colonies of similar lamellae. Higher magnifications revealed that the lamellae actually obtain two distinct morphologies. The type I morphology exhibits broad planar interfaces with a smooth platelike shape. Type II lamellae have undulating interfaces and an overall reticulated shape. To provide further insight into the origin of these two different morphologies, the microstructure and crystallography of each have been studied in detail using high resolution scanning electron microscopy, transmission electron microscopy, various electron diffraction methods (electron backscatter diffraction (EBSD), selected area diffraction (SAD), and convergent beam electron diffraction (CBED)), and energy dispersive X-ray spectroscopy.     

Optimized preparation of alumina based fillers for tuning composite properties

Alumina based particles were prepared from aluminium chloride hydroxide as starting material by sol-gel technique. One series of particles was doped with ferrous oxide. Both series of particles were calcinated at three different temperatures: 700?°C, 800?°C and 900?°C. Poly(methyl methacrylate), PMMA, was used as a matrix and two different types of alumina based particles were added into the matrix to form the composites. All composites consisted of 3?wt% of alumina based particles. The aim of this study was to examine whether and how the temperature of particle calcination affects the microhardness and mechanical properties of the composite. The particles were characterized by the X-ray diffraction (XRD) and physical absorption methods. The morphology of the composites was examined using a field emission scanning electron microscope (FESEM). The microhardness of composites was measured using a traditional Vickers hardness (HV) method. The mechanical characteristics of obtained composites were determined using tensile test and impact testing.     

A conundrum in molecular toxicology: molecular and biological changes during neoplastic transformation of human cells

The process of multistage carcinogenesis lends itself to the concept that the effects of carcinogens are mediated through dose-related, multi-hit, linear changes. Multiple in vitro model systems have been developed that are designed to examine the cellular changes associated with the progression of cells through the different stages in the process; however, these systems may have inherent limitations due to the cell lines used for these studies, the manner of assessing the effects of the carcinogens, and the subsequent growth and differentiation of the exposed cells. Each of these variables results in increasing levels of uncertainty relative to the correlation of the events with the actual process of human tumor development. Therefore, the prediction of the ultimate effect of any carcinogen is difficult. Moreover, relationships between individual biological endpoints resulting from carcinogen treatment appear at best to be approximations. The presence of an activated carcinogen inside the cell can give rise to multiple outcomes, only some of which may be critical events. For example, site-specific modification of the 12th and 13th codons of H-ras is different than that in the adjacent 14th and 15th codons. It is interesting to speculate what effect these differences might have on a biological outcome, e.g., transformation to anchorage-independent growth. The use of different model systems to examine the effects of activated carcinogens also creates additional problems. Comparisons of in vitro transformed cells with similar cells isolated from human tumors indicate that the culture environment appears to influence the expression of a particular phenotype, in that human tumor cells in culture express many of the same parameters as those found in cells transformed with carcinogens in vitro. If the process of transformation is linear, then less aggressive phenotypes should progress to a more aggressive transformed stage. However, in carcinogen-transformed human cells, the populations exhibit phenotypic diversity in that many of the transformed cells differentiate and fail to continue to divide in culture. Historically, we have assumed only a limited role for epigenetic modulation of molecular changes that occur during progression; however, our data suggest quite strongly that nonmalignant tumor populations can be converted to a more malignant phenotype without additional mutations taking place and, conversely, malignant populations can be downregulated to a nontumorigenic phenotype. Tumor cell plasticity is not only a fundamental characteristic of diverse types of human tumors, but also appears as an integral characteristic of carcinogen-transformed cells in vitro.     

Number and position of visual stimuli as determinants of reaction time in schizophrenia.

Notes that RT in normal Ss has been shown to be linearly related to stimulus complexity, defined as the log of the number of equally probable stimuli to which a response may be made. Data from an earlier study of 40 short- and long-term paranoid and nonparanoid male schizophrenics and 10 male hospital employees were reanalyzed and compared with P. Venable's (see record 1959-10789-001) study of schizophrenic deficit. Although experimental procedures were dissimilar, both studies found that increased complexity did not result in schizophrenics having steeper regression slopes than normal Ss. Consideration of the position of the critical stimulus, however, clearly indicated that long-term, nonparanoid schizophrenics narrow attention to central cues when confronted by an increase in complexity. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Computation of steady and time-dependent temperature distribution for building elements: A general three-dimensional solution

A computational method of temperature distribution calculation for building elements in two- and three-dimensional time-dependent heat flow problems is developed with a general approximate solution using, as a numerical approach, the finite difference method. An analytical evaluation method of the accuracy of calculations is developed. The method described was compared with experimental values and good correspondence was obtained. The time-dependent study which is presented includes thermal resistance and inertia (heat capacity) of the components' materials and different geometric compositions.     

Symbolic target detection in SAR imagery via rotationally invariant-weighted feature extraction

This article introduces the application of a physics-based symbolic image partitioning method to detect targets in synthetic aperture radar (SAR) imagery. ‘Targets’ in this case refer to vehicular objects which produce a distinct radar return pattern, and have spatial characteristics that are known a priori. The proposed Rotationally Invariant Symbolic Histogram (RISH) detection method co-analyses both target and speckle statistics, and significantly reduces computational requirements by partitioning the data into a discrete number of state representations. RISH requires only one pass for robust detection, unlike other SAR detection methods which rely on difference metrics calculated using multiple passes. To improve performance in high-resolution data, RISH uses a weighted feature extraction algorithm to avoid the common requirement of processing each pixel of the image equally. The weighted structure extracts geometrically undefined and rotationally invariant target features. This article details the analysis of 24 experimentally obtained very high-frequency (VHF)-band SAR magnitude images using this novel approach to SAR target detection. In localizing small (~8.4 m²) foliage-concealed targets, without the aid of pre-processing, this method results in high performance characteristics (90% true positive) with a low Type-II error rate of 6.4 false alarms per 1 × 10⁶ m². With the addition of change detection, RISH lowers the error rate by 85%.     

Corrosion study of copper in the presence of benzotriazole and its hydroxy derivative

The inhibitory properties of benzotriazole (BTAH) and its hydroxy derivative, 1‐hydroxy‐benzotriazole (BTAOH) on copper corrosion, were compared in 3% NaCl solution using cyclic voltammetry (CV), immersion tests, profilometry and scanning electron microscopy (SEM) combined with energy dispersive spectroscopy (EDX). CV experiments showed rapid interaction of both inhibitors with a Cu surface, but only at high concentrations. Immersion tests under stationary conditions showed that BTAOH offered corrosion protection only at concentration of 10 mM. Moreover, it was not effective under stirring conditions at any of the concentrations investigated. In contrast, BTAH exhibited good corrosion inhibition ability in all immersion tests. BTAOH, at up to 1 mM, increased the surface roughness of Cu more than 3% NaCl solution alone, but a significant reduction of surface roughening was observed when BTAH was present. Porous cross‐linked acicular structures and star‐like structures were observed using SEM/EDX in the case of BTAOH treatment. When Cu was treated with BTAH, roundish surface structures composed of bent plates with toothed‐like edges, acicular structures and non‐porous few hundred nm thick plates were observed.     

High-Performance Membrane Chromatography of Small Molecules

High-performance membrane chromatography (HPMC) proved to be a very efficient method for fast protein separations. Recently, it was shown to be applicable also for the isocratic chromatography of plasmid DNA conformations. However, no study about the separation of small molecules has been performed until now. In this work, we investigated the possibility of gradient and isocratic HPMC of small molecules with Convective Interaction Media disks of different chemistries and tried to explain the mechanism that enables their separation. We demonstrated that it is possible to achieve efficient separations of oligonucleotides and peptides in the ion-exchange mode as well as the separation of small hydrophobic molecules in the reversed-phase mode. It was shown that similar peak resolution can be provided in both gradient and isocratic modes.     

An Algebra for Pomsets

We study languages for manipulatingpartially orderedstructures withduplicates(e.g., trees, lists). As a general framework, we consider thepomset(partially ordered multiset) data type. We introduce an algebra forpomsets, which generalizes traditional algebras for (nested) sets, bags, and lists. This paper is motivated by the study of the impact of different language primitives on the expressive power. We show that the use of partially ordered types increases the expressive power significantly. Surprisingly, it turns out that the algebra when restricted to both unordered (bags) and totally ordered (lists) intermediate types, yields the same expressive power as fixpoint logic with counting on relational databases. It therefore constitutes a rather robust class of relational queries. On the other hand, we obtain a characterization of PTIME queries on lists by considering only totally ordered types.