Synthesis, characterisation and magnetic properties of a one-dimensional Iron(II) coordination polymer

A new iron(II) coordination polymer, [FeCl2(NC7H9)2(N2C12H12)], has been synthesized under solvothermal conditions and structurally characterized by single-crystal X-ray diffraction. This material crystallizes in the monoclinic space group C2/c, with a = 11.2850(6), b = 13.8925(7), c = 17.0988(9) Å and β = 94.300(3)º (Z = 4). The crystal structure consists of neutral zig-zag chains, in which the iron(II) ions are octahedrally coordinated. The infinite polymer chains are packed into a three-dimensional structure through C–H···Cl interactions. Magnetic susceptibility measurements reveal the existence of weak antiferromagnetic interactions between the iron(II) ions. The effective magnetic moment, μ eff = 5.33 μ B , is consistent with a high-spin iron(II) configuration.

3-D volume rendering maxillofacial analysis of angular measurements by multislice CT

Objective. This study was designed to determine the precision and accuracy of angular measurements using three-dimensional computed tomography (3D-CT) volume rendering by computer systems. Study design. The study population consisted of 28 dried skulls that were scanned with a 64-row multislice CT, and 3D-CT images were generated. Angular measurements, (n = 6) based upon conventional craniometric anatomical landmarks (n = 9), were identified independently in 3D-CT images by 2 radiologists, twice each, and were then performed by 3D-CT imaging. Subsequently, physical measurements were made by a third examiner using a Beyond Crysta-C9168 series 900 device. Results. The results demonstrated no statistically significant difference between interexaminer and intraexaminer analysis. The mean difference between the physical and 3-D-based angular measurements was -1.18% and -0.89%, respectively, for both examiners, demonstrating high accuracy. Conclusion. Maxillofacial analysis of angular measurements using 3D-CT volume rendering by 64-row multislice CT is established and can be used for orthodontic and dentofacial orthopedic applications.

Selective excitation through tapered silica fibers of fluorescent two-photon polymerized structures

Two-photon polymerization has emerged as a powerful tool to design complex three-dimensional microstructures for applications ranging from biology to nanophotonics. To broaden the application spectrum of such microstructures, different materials have been incorporated to the polymers, aiming at specific applications. In this paper we report the fabrication of microstructures containing rhodamine 610, which display strong fluorescence upon one- and two-photon excitation. The latter increases light-penetration depth and spatial selectivity of luminescence. We also demonstrate that by using silica submicrometric wires we were able to select individual microstructures to be excited, which could be explored for designing microstructure-based optical circuits.

Role of Halogen Bonds in Thyroid Hormone Receptor Selectivity: Pharmacophore-Based 3D-QSSR Studies

Most physiological effects of thyroid hormones are mediated by the two thyroid hormone receptor subtypes, TR alpha and TR beta. Several pharmacological effects mediated by TR beta might be beneficial in important medical conditions such as obesity, hypercholesterolemia and diabetes, and selective TR beta activation may elicit these effects while maintaining an acceptable safety profile, To understand the molecular determinants of affinity and subtype selectivity of TR ligands, we have successfully employed a ligand- and structure-guided pharmacophore-based approach to obtain the molecular alignment of a large series of thyromimetics. Statistically reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models were obtained using the comparative molecular field analysis (CoMFA) method, and the visual analyses of the contour maps drew attention to a number of possible opportunities for the development of analogs with improved affinity and selectivity. Furthermore, the 3D-QSSR analysis allowed the identification of a novel and previously unmentioned halogen bond, bringing new insights to the mechanism of activity and selectivity of thyromimetics.

Quantitative structure-activity relationships for a series of inhibitors of cruzain from Trypanosoma cruzi: Molecular modeling, CoMFA and CoMSIA studies

Human parasitic diseases are the foremost threat to human health and welfare around the world. Trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. Therefore, there is an urgent need for new chemotherapeutic agents. One attractive drug target is the major cysteine protease from Trypanosoma cruzi, cruzain. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted on a series of thiosemicarbazone and semicarbazone derivatives as inhibitors of cruzain. Molecular modeling studies were performed in order to identify the preferred binding mode of the inhibitors into the enzyme active site, and to generate structural alignments for the three-dimensional quantitative structure-activity relationship (3D QSAR) investigations. Statistically significant models were obtained (CoMFA. r(2) = 0.96 and q(2) = 0.78; CoMSIA, r(2) = 0.91 and q(2) = 0.73), indicating their predictive ability for untested compounds. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the information gathered from the 3D CoMFA and CoMSIA contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of cruzain inhibitors, and should be useful for the design of new structurally related analogs with improved potency. (C) 2009 Elsevier Inc. All rights reserved.

Fragment-Based QSAR and Molecular Modeling Studies on a Series of Discodermolide Analogs as Microtubule-Stabilizing Anticancer Agents

Inhibition of microtubule function is an attractive rational approach to anticancer therapy. Although taxanes are the most prominent among the microtubule-stabilizers, their clinical toxicity, poor pharmacokinetic properties, and resistance have stimulated the search for new antitumor agents having the same mechanism of action. Discodermolide is an example of nontaxane natural product that has the same mechanism of action, demonstrating superior antitumor efficacy and therapeutic index. The extraordinary chemical and biological properties have qualified discodermolide as a lead structure for the design of novel anticancer agents with optimized therapeutic properties. In the present work, we have employed a specialized fragment-based method to develop robust quantitative structure - activity relationship models for a series of synthetic discodermolide analogs. The generated molecular recognition patterns were combined with three-dimensional molecular modeling studies as a fundamental step on the path to understanding the molecular basis of drug-receptor interactions within this important series of potent antitumoral agents.

CoMFA and CoMSIA 3D QSAR Models for a Series of Cyclic Imides with Analgesic Activity

Three-dimensional quantitative structure-activity relationships (3D-QSAR) were performed for a series of analgesic cyclic imides using the CoMFA and CoMSIA methods. Significant correlation coefficients ( CoMFA, r(2) = 0.95 and q(2) = 0.72; CoMSIA, r(2) = 0.96 and q(2) = 0.76) were obtained, and the generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel cyclic imides having improved analgesic activity.

Structure-Based Approach for the Study of Estrogen Receptor Binding Affinity and Subtype Selectivity

Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpa (hER alpha) and beta (hER beta). Because the levels and relative proportion of hER alpha and hER beta differ significantly in different target cells, selective hER ligands could target specific tissues or pathways regulated by one receptor subtype without affecting the other. To understand the structural and chemical basis by which small molecule modulators are able to discriminate between the two subtypes, we have applied three-dimensional target-based approaches employing a series of potent hER-ligands. Comparative molecular field analysis (CoMFA) studies were applied to a data set of 81 hER modulators, for which binding affinity values were collected for both hER alpha and hER beta. Significant statistical coefficients were obtained (hER alpha, q(2) = 0.76; hER beta, q(2) = 0.70), indicating the internal consistency of the models. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. Five hER crystal structures were used in GRID/PCA investigations to generate molecular interaction fields (MIF) maps. hER alpha and hER beta were separated using one factor. The resulting 3D information was integrated with the aim of revealing the most relevant structural features involved in hER subtype selectivity. The final QSAR and GRID/PCA models and the information gathered from 3D contour maps should be useful for the design or novel hER modulators with improved selectivity.

Two-photon absorption spectrum of the photoinitiator Lucirin TPO-L

Two-photon absorption induced polymerization provides a powerful method for the fabrication of intricate three-dimensional microstructures. Recently, Lucirin TPO-L was shown to be a photoinitiator with several advantageous properties for two-photon induced polymerization. Here we measure the two-photon absorption cross-section spectrum of Lucirin TPO-L, which presents a maximum of 1.2 GM at 610 nm. Despite its small two-photon absorption cross-section, it is possible to fabricate excellent microstructures by two-photon polymerization due to the high polymerization quantum yield of Lucirin TPO-L. These results indicate that optimization of the two-photon absorption cross-section is not the only material parameter to be considered when searching for new photoinitiators for microfabrication via two-photon absorption.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers

Objective: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (Sao Paulo, Brazil); Reference formulation (1): ibuprofen (Advil (R); 2 x 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (Alivium (R); 8 ml x 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax) AUC(inf) and C-max. Results: The limit of quantification for ibuprofen was 0.1 mu g x ml(-1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C-max, 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUCinf. The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% Cl = 100.195, 117.25%) for C-max, 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 x 200 mg Reference (1) tablets (p < 0.002). Conclusion: Since the 90% CI for AUC(last), AUC(inf) and C-max ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the Advil (R) and Alivium (R) formulations with regard to both the rate and the extent of absorption.

Crystal and molecular structures of three 2-sulphur-substituted cyclohexanones studied by X-ray crystallography and by ab initio molecular orbital calculations

The conformational features of three 2-sulphur-substituted cyclohexanone derivatives, which differ in the number of sulphur-bound oxygen atoms, i.e. zero (I), one (II) and two (III), were investigated by single crystal X-ray crystallography and geometry optimized structures determined using Hartree-Fock method. In each of (I)-(III) an intramolecular S center dot center dot center dot O(carbonyl) interaction is found with the magnitude correlated with the oxidation state of the sulphur atom, i.e. 2.838(3) angstrom in (I) to 2.924(2) angstrom in (II) to 3.0973(18) angstrom in (III). There is an inverse relationship between the strength of this interaction and the magnitude of the carbonyl bond. The supramolecular aggregation patterns are primarily determined by C-H center dot center dot center dot O contacts and are similarly influenced by the number of oxygen atoms in the molecular structures. Thus, a supramolecular chain is found in the crystal structure of (I). With an additional oxygen atom available to participate in C-H center dot center dot center dot O interactions, as in (II), a two-dimensional array is found. Finally, a three-dimensional network is found for (III). Despite there being differences in conformations between the experimental structures and those calculated in the gas-phase, the S center dot center dot center dot O interactions persist. The presence of intermolecular C-H center dot center dot center dot O interactions involving the cyclohexanone-carbonyl group in the solid-state, disrupts the stabilising intramolecular C-H center dot center dot center dot O interaction in the energetically-favoured conformation. (I): C(12)H(13)NO(3)S, triclinic space group P (1) over bar with a = 5.392(3) angstrom b = 10.731(6) angstrom, c = 11.075(6) angstrom, alpha = 113.424(4)degrees, beta = 94.167(9)degrees, gamma = 98.444(6)degrees, V = 575.5(6) angstrom(3), Z = 2, R(1) = 0.052; (II): C(12)H(13)NO(4)S, monoclinic P2(1)/n, a = 7.3506(15) angstrom, b = 6.7814(14) angstrom, c = 23.479(5) angstrom, beta = 92.94(3)degrees, V = 1168.8(4) angstrom(3), Z = 4, R(1) = 0.046; (III): C(12)H(13)NO(5)S, monoclinic P2(1)/c, a = 5.5491(11) angstrom, b = 24.146(3) angstrom, c = 11.124(3) angstrom, beta = 114.590(10)degrees, V = 1355.3(5) angstrom(3), Z = 4, R(1) = 0.051.

Structural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis

Tuberculosis (TB) is one of the most common infectious diseases known to man and responsible for millions of human deaths in the world. The increasing incidence of TB in developing countries, the proliferation of multidrug resistant strains, and the absence of resources for treatment have highlighted the need of developing new drugs against TB. The shikimate pathway leads to the biosynthesis of chorismate, a precursor of aromatic amino acids. This pathway is absent from mammals and shown to be essential for the survival of Mycobacterium tuberculosis, the causative agent of TB. Accordingly, enzymes of aromatic amino acid biosynthesis pathway represent promising targets for structure-based drug design. The first reaction in phenylalanine biosynthesis involves the conversion of chorismate to prephenate, catalyzed by chorismate mutase. The second reaction is catalyzed by prephenate dehydratase (PDT) and involves decarboxylation and dehydratation of prephenate to form phenylpyruvate, the precursor of phenylalanine. Here, we describe utilization of different techniques to infer the structure of M. tuberculosis PDT (MtbPDT) in solution. Small angle X-ray scattering and ultracentrifugation analysis showed that the protein oligomeric state is a tetramer and MtbPDT is a flat disk protein. Bioinformatics tools were used to infer the structure of MtbPDT A molecular model for MtbPDT is presented and molecular dynamics simulations indicate that MtbPDT i.s stable. Experimental and molecular modeling results were in agreement and provide evidence for a tetrameric state of MtbPDT in solution.

Estrogen receptor: Structural differences and potential implications on selectivity examined by the GRID/CPCA approach

Selective Estrogen Receptor Modulators ( SERMs) have been developed, but the selectivity towards the subtypes ( ER or ER is not well understood. Based on three-dimensional structural properties of ligand binding domains, a model that takes into account this aspect was developed via molecular interaction fields and consensus principal component analysis (GRID/CPCA).

Varumärkning för småföretag

In this degree project a study of the importance of a graphic identity to companies has been done. A questionnaire among small companies in Dalarna has beenmade. From this, three sets of graphic profile-program have been formed andthese are suitable for new companies. Finally a practical application has been made on Greenfield in Mora, a graphic profile has been designed.To cause an identity is to prove that someone or something exists by individualizingand distinguish. Every individual or company has its qualities or charasteristics.The way to a desirable identity is going by a corporate identity-program that containsthe companies strategies, people, products, buildings, trademarks, graphic design. To create an identity a well considered strategy is needed, where all members of the company are involved. This will lead to a positive image and means for an efficient market communication. The identity of the company is that the company wish what the company/product will stand for, but the image is what the market think about the company/product. The surrounding worldwill be convinced that the company is a reliable producer or deliverer. The companyvill also be regarded as useful and responsable, profitable as an object or partner and a good place of work.Today, trademarking is the most important carrier of identity for a company. A trademark, like a word, a picture or a slogan, will distinguish a product from theothers. What is needed to build up a strong trademark? How can a trade markbe developed to an advantage?To get a lot of people in the same direction clear guidlines are needed. Usually you focused on graphic design, especially the symbols and marks of the companies.The results are presented on a graphic profile, documented in a graphic manual.

Coffee table-böcker eller praktverk – begrepp, attityder och arbetssätt : Djupintervjuer med grafiska formgivare och förlagsanställda

Åtta semi-strukturerade djupintervjuer genomfördes i syfte att kartlägga svenska formgivares och förlagsanställdas strategiska och kreativa arbetsprocess samt olika attityder vid arbetet med praktverk och coffee table-böcker. Dessa böckers termer och definitioner diskuterades även, samt boktypens förut-sättningar och utmaningar på marknaden. I denna rapport presenteras funna teman rörande dessa tankemönster och attity-der, samt en generell beskrivning av arbetsprocessen. Produktionen av coffee table-böcker och praktverk fanns vara komplex på grund av att den involverade många personer, tog lång tid i anspråk, var kost-sam och hade relativt små vinstmarginaler vilket därmed kunde förenas med vissa risker. Respondenterna upplevde generellt arbetet som spännande, roligt och givande.Studien belyser även förekomsten av en viss diskrepans vad gäller associationerna till termerna ”coffee table-bok” och ”praktverk”. Coffee table-böcker ansågs främst av de förlagsanställda ha ett innehåll av lägre kvalitet jämfört med det hos ett praktverk.