Effects of aluminium chloride and aluminium chlorohydrate on DNA repair in MCF10A immortalised non-transformed human breast epithelial cells

Use of underarm aluminium (Al)-based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Longterm (19–21 weeks) exposure to Al chloride or Al chlorohydrate at a 10−4 M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by Western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis.

Future, Fortune, and the graphic design of information

This is a study of graphic information designed for Future Books/Future magazine (UK) and Fortune magazine (USA) in the years immediately after the Second World War. It highlights work made by the Isotype Institute for Future, which is then situated against contributions by Abram Games and F. H. K. Henrion. Similar work in Fortune under the art editorship of Will Burtin is discussed in a parallel account, drawing on examples by him and by others including György Kepes, Matthew Liebowitz, Alex Steinweiss and Ladislav Sutnar. Attention is drawn to links and relationships between to the two periodicals and the graphic information published in both. Further comparisons are made between underlying editorial and design strategies pursued by Otto Neurath (Isotype Institute) and Will Burtin. An argument is made for recognising the little-known innovations of Future alongside the long-acknowledged innovations of Fortune.

Design of associative memories using cellular neural networks

Cellular neural networks (CNNs) have locally connected neurons. This characteristic makes CNNs adequate for hardware implementation and, consequently, for their employment on a variety of applications as real-time image processing and construction of efficient associative memories. Adjustments of CNN parameters is a complex problem involved in the configuration of CNN for associative memories. This paper reviews methods of associative memory design based on CNNs, and provides comparative performance analysis of these approaches.

From Rational Design of Drug Crystals to Understanding of Nucleic Acid Structures: Lamivudine Duplex

A DNA-like duplex of nucleosides is probable to exist even without the 5`-phosphate groups needed to assemble the chain backbone. However, double-stranded helical structures of nucleosides are unknown. Here, we report a duplex of nucleoside analogs that is spontaneously assembled due to stacking of the neutral and protonated molecules of lamivudine, a nucleoside reverse transcriptase inhibitor (NTRI) widely used in anti-HIV drug combinatory medication. The left-handed lamivudine duplex has features similar to those of i-motif DNA, as the face-to-face base stacking and the helix rise per base pair. Furthermore, the protonation pattern on alternate bases expected for it DNA-like duplex stabilized by pairing of neutral and protonated cytosine fragments was observed for the first time in the lamivudine double-stranded helix. This structure demonstrates that hydrogen bonds can substitute for covalent phosphodiester linkage in the stabilization of the duplex backbone. This interesting example of spontaneous molecular self-organization indicates that the 5`-phosphate group could not be a requirement for duplex assembly.

Design of a Modern Liposome and Bee Venom Formulation for the Traditional VIT-Venom Immunotherapy

Traditional venom immunotherapy uses injections of whole bee venom in buffer or adsorbed in Al (OH)(3) in an expensive, time-consuming way. New strategies to improve the safety and efficacy of this treatment with a reduction of injections would, therefore, be of general interest. It would improve patient compliance and provide socio-economic benefits. Liposomes have a long tradition in drug delivery because they increase the therapeutic index and avoid drug degradation and secondary effects. However, bee venom melittin (Mel) and phospholipase (PLA(2)) destroy the phospholipid membranes. Our central idea was to inhibit the PLA(2) and Mel activities through histidine alkylation and or tryptophan oxidation (with pbb, para-bromo-phenacyl bromide, and/or NBSN-bromosuccinimide, respectively) to make their encapsulations possible within stabilized liposomes. We strongly believe that this formulation will be nontoxic but immunogenic. In this paper, we present the whole bee venom conformation characterization during and after chemical modification and after interaction with liposome by ultraviolet, circular dichroism, and fluorescence spectroscopies. The PLA(2) and Mel activities were, measured indirectly by changes in turbidity at 400(nm), rhodamine leak-out, and hemolysis. The native whole bee venom (BV) presented 78.06% of alpha-helical content. The alkylation (A-BV) and succynilation (S-BV) of BV increased 0.44 and 0.20% of its alpha-helical content. The double-modified venom (S-A-BV) had a 0.74% increase of alpha-helical content. The BV chemical modification induced another change on protein conformations observed by Trp that became buried with respect to the native whole BV. It was demonstrated that the liposomal membranes must contain pbb (SPC:Cho:pbb, 26:7:1) as a component to protect them from aggregation and/or fusion. The membranes containing pbb maintained the same turbidity (100%) after incubation with modified venom, in contrast with pbb-free membranes that showed a 15% size decrease. This size decrease was interpreted as membrane degradation and was corroborated by a 50% rhodamine leak-out. Another fact that confirmed our interpretation was the observed 100% inhibition of the hemolytic activity after venom modification with pbb and NBS (S-A-BV). When S-A-BV interacted with liposomes, other protein conformational changes were observed and characterized by the increase of 1.93% on S-A-BV alpha-helical content and the presence of tryptophan residues in a more hydrophobic environment. In other words, the S-A-BV interacted with liposomal membranes, but this interaction was not effective to cause aggregation, leak-out, or fusion. A stable formulation composed by S-A-BV encapsulated within liposomes composed by SPC:Cho:pbb, at a ratio of 26:7:1, was devised. Large unilamellar vesicles of 202.5 nm with a negative surface charge (-24.29 mV) encapsulated 95% of S-A-BV. This formulation can, now, be assayed on VIT.

Approaches for multicopper oxidases in the design of electrochemical sensors for analytical applications

We report an effective approach for the construction of a biomimetic sensor of multicopper oxidases by immobilizing a cyclic-tetrameric copper(II) species, containing the ligand (4-imidazolyl)ethylene-2-amino-1-ethylpyridine (apyhist), in the Nafion (R) membrane on a vitreous carbon electrode surface. This complex provides a tetranuclear arrangement of copper ions that allows an effective reduction of oxygen to water, in a catalytic cycle involving four electrons. The electrochemical reduction of oxygen was studied at pH 9.0 buffer solution by using cyclic voltammetry, chronoamperometry, rotating disk electrode voltammetry and scanning electrochemical microscopy techniques. The mediator shows good electrocatalytic ability for the reduction of O(2) at pH 9.0, with reduction of overpotential (350 mV) and increased current response in comparison with results obtained with a bare glassy carbon electrode. The heterogeneous rate constant (k(ME)`) for the reduction of O(2) at the modified electrode was determined by using a Koutecky-Levich plot. In addition, the charge transport rate through the coating and the apparent diffusion coefficient of O(2) into the modifier film were also evaluated. The overall process was found to be governed by the charge transport through the coating, occurring at the interface or at a finite layer at the electrode/coating interface. The proposed study opens up the way for the development of bioelectronic devices based on molecular recognition and self-organization. (C) 2010 Elsevier Ltd. All rights reserved.

Design of novel antituberculosis compounds using graph-theoretical and substructural approaches

The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem, two models for the design and prediction of new antituberculosis agents were obtained. The first used a mixed approach, containing descriptors based on fragments and the topological substructural molecular design approach (TOPS-MODE) descriptors. The other model used a combination of two-dimensional (2D) and three-dimensional (3D) descriptors. A data set of 167 compounds with great structural variability, 72 of them antituberculosis agents and 95 compounds belonging to other pharmaceutical categories, was analyzed. The first model showed sensitivity, specificity, and accuracy values above 80% and the second one showed values higher than 75% for these statistical indices. Subsequently, 12 structures of imidazoles not included in this study were designed, taking into account the two models. In both cases accuracy was 100%, showing that the methodology in silico developed by us is promising for the rational design of antituberculosis drugs.

Assessing the Design of the Library's Discovery Interface and Online resources: A Case Study at the University of Maryland

This presentation was offered as part of the CUNY Library Assessment Conference, Reinventing Libraries: Reinventing Assessment, held at the City University of New York in June 2014.

Marknadsundersökning angående design för behållare av ansiktscreme : Marketing reseach concerning the design of beauty cream containers

Detta examensarbete innefattar en teoretisk och en praktisk del om marknadsundersökningar. Inom teoridelen har litteratur inom ämnet studerats för att sedan genomföra en marknadsundersökning. Utöver detta ha resultatet som erhållts ur marknadsundersökningen tillämpats för att ta fram ett designkoncept för en serie ansiktscremer.Marknadsundersökningen utfördes i form av en observationsresearch där ansiktscremer av olika priser och märken jämfördes, samt en webbenkät där målgruppen fick svara på frågor om ansiktscremers behållare och behållarens färg. Målgruppen är satt till män och kvinnor över 15 år som använder ansiktscreme. För att marknadsundersökningen ska vara möjlig att genomföra inom satta tidsramar skickades webbenkäten endast ut till studenter vid Högskolan Dalarna i Borlänge samt till läsare av modebloggen ”Hopplösa Modenördar”.Totalt inkom 469 svar.Resultatet visade att vitt, silver och svart är de färger som tilltalar män mest i fråga om ansiktscremebehållare. För kvinnor var det vitt, guld och rosa som kändes mest tilltalande. Ur resultatet kunde även utläsas att burken var den behållare som tilltalar både män och kvinnor mest.

The latitude dependent irradiation distribution in Europe and its implication for the design of stationary concentrators

When a stationary solar concentrator is designed, the spatial distribution of the available irradiation is of vital interest. An irradiation distribution based only on solar geometry will look similar at different sites. The only difference is that the distribution of the incident irradiation is shifted to lower solar altitudes when latitude is increased. However, real irradiation distribution will show strong asymmetry at high latitude sites, since the winter irradiation is reduced by absorption and scattering in the atmosphere, and by seasonal changes in the climate. The reduced winter irradiation at high latitudes implies that the available annual radiation is concentrated to a narrower angular interval. This means that the degree of concentration that is possible increases with latitude.In the paper examples of irradiation distribution from different sites in Europe from latitude 38°N to 65°N are shown. The origin of the reduced winter irradiation with increased latitude is discussed, and numerical examples on the performance of different types of stationary concentrators for different latitudes are given.

The impact of high latitudes on the optical design of solar systems

Irradiation distribution functions based on the yearly collectible energy have been derived for two locations; Sydney, Australia which represents a mid-latitude site and Stockholm, Sweden, which represents a high latitude site. The strong skewing of collectible energy toward summer solstice at high latitudes dictates optimal collector tilt angles considerably below the polar mount. The lack of winter radiation at high latitudes indicates that the optimal acceptance angle for a stationary EW-aligned concentrator decreases as latitude increases. Furthermore concentrator design should be highly asymmetric at high latitudes.

Design of gas filled solar collectors

With a suitable gas filling used between cover glass and absorber in a flat plate solar collector, it is possible achieving better thermal performance at the same time as the distance betweenabsorber and glass can be reduced. Though, even if there is no vacuum inside the box, there will be potential risks for exhaustion due to stresses depending on the gas volume varies as the temperature varies. This study found out that it is possible build such a collector with less material in the absorber and the tubes and still getting better performance, without risks for exhaustion.

Supervision as control system : the design of supervision as a regulatory instrument in the social services sector in Sweden

In this article, the prevailing official view of supervision as a regulatory instrument is examined as it applies to the social services sector in Sweden. The study is based on a comparison of the views expressed on the design of supervision as a regulatory instrument by two government commissions, the Supervision Commission and the Commission on Supervision within the Social Services (UTIS), and on the positions taken by the Government regarding the definitions of the concept of supervision proposed by these commissions. The view of supervision as a regulatory instrument expressed in these policy documents is analysed with the help of a theoretical framework describing the components, their functions and the governance characteristics of control systems. In the framework separate interrelated characteristics of the components are identified and summarized into two models of control systems. The analysis shows that supervision in the Swedish social services sector can be described in terms of both a disciplinary and non-disciplinary system. By its system theoretical basis and the identification of interrelated characteristics the study contributes to a broadened understanding of the construction and functions of supervision as a regulatory instrument and of how supervision within the Swedish social sector is meant to be designed.

Manual and electroacupuncture for labour pain : study design of a longitudinal randomized controlled trial

Introduction. Results from previous studies on acupuncture for labour pain are contradictory and lack important information on methodology. However, studies indicate that acupuncture has a positive effect on women's experiences of labour pain. The aim of the present study was to evaluate the efficacy of two different acupuncture stimulations, manual or electrical stimulation, compared with standard care in the relief of labour pain as the primary outcome. This paper will present in-depth information on the design of the study, following the CONSORT and STRICTA recommendations. Methods. The study was designed as a randomized controlled trial based on western medical theories. Nulliparous women with normal pregnancies admitted to the delivery ward after a spontaneous onset of labour were randomly allocated into one of three groups: manual acupuncture, electroacupuncture, or standard care. Sample size calculation gave 101 women in each group, including a total of 303 women. A Visual Analogue Scale was used for assessing pain every 30 minutes for five hours and thereafter every hour until birth. Questionnaires were distributed before treatment, directly after the birth, and at one day and two months postpartum. Blood samples were collected before and after the first treatment. This trial is registered at ClinicalTrials.gov: NCT01197950.