Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.

From environmental concerns towards sustainable food provisioning. : Material flow and food consumption scenario studies on sustainability of agri-food systems

Agriculture is an economic activity that heavily relies on the availability of natural resources. Through its role in food production agriculture is a major factor affecting public welfare and health, and its indirect contribution to gross domestic product and employment is significant. Agriculture also contributes to numerous ecosystem services through management of rural areas. However, the environmental impact of agriculture is considerable and reaches far beyond the agroecosystems. The questions related to farming for food production are, thus, manifold and of great public concern. Improving environmental performance of agriculture and sustainability of food production, sustainabilizing food production, calls for application of wide range of expertise knowledge. This study falls within the field of agro-ecology, with interphases to food systems and sustainability research and exploits the methods typical of industrial ecology. The research in these fields extends from multidisciplinary to interdisciplinary and transdisciplinary, a holistic approach being the key tenet. The methods of industrial ecology have been applied extensively to explore the interaction between human economic activity and resource use. Specifically, the material flow approach (MFA) has established its position through application of systematic environmental and economic accounting statistics. However, very few studies have applied MFA specifically to agriculture. The MFA approach was used in this thesis in such a context in Finland. The focus of this study is the ecological sustainability of primary production. The aim was to explore the possibilities of assessing ecological sustainability of agriculture by using two different approaches. In the first approach the MFA-methods from industrial ecology were applied to agriculture, whereas the other is based on the food consumption scenarios. The two approaches were used in order to capture some of the impacts of dietary changes and of changes in production mode on the environment. The methods were applied at levels ranging from national to sector and local levels. Through the supply-demand approach, the viewpoint changed between that of food production to that of food consumption. The main data sources were official statistics complemented with published research results and expertise appraisals. MFA approach was used to define the system boundaries, to quantify the material flows and to construct eco-efficiency indicators for agriculture. The results were further elaborated for an input-output model that was used to analyse the food flux in Finland and to determine its relationship to the economy-wide physical and monetary flows. The methods based on food consumption scenarios were applied at regional and local level for assessing feasibility and environmental impacts of relocalising food production. The approach was also used for quantification and source allocation of greenhouse gas (GHG) emissions of primary production. GHG assessment provided, thus, a means of crosschecking the results obtained by using the two different approaches. MFA data as such or expressed as eco-efficiency indicators, are useful in describing the overall development. However, the data are not sufficiently detailed for identifying the hot spots of environmental sustainability. Eco-efficiency indicators should not be bluntly used in environmental assessment: the carrying capacity of the nature, the potential exhaustion of non-renewable natural resources and the possible rebound effect need also to be accounted for when striving towards improved eco-efficiency. The input-output model is suitable for nationwide economy analyses and it shows the distribution of monetary and material flows among the various sectors. Environmental impact can be captured only at a very general level in terms of total material requirement, gaseous emissions, energy consumption and agricultural land use. Improving environmental performance of food production requires more detailed and more local information. The approach based on food consumption scenarios can be applied at regional or local scales. Based on various diet options the method accounts for the feasibility of re-localising food production and environmental impacts of such re-localisation in terms of nutrient balances, gaseous emissions, agricultural energy consumption, agricultural land use and diversity of crop cultivation. The approach is applicable anywhere, but the calculation parameters need to be adjusted so as to comply with the specific circumstances. The food consumption scenario approach, thus, pays attention to the variability of production circumstances, and may provide some environmental information that is locally relevant. The approaches based on the input-output model and on food consumption scenarios represent small steps towards more holistic systemic thinking. However, neither one alone nor the two together provide sufficient information for sustainabilizing food production. Environmental performance of food production should be assessed together with the other criteria of sustainable food provisioning. This requires evaluation and integration of research results from many different disciplines in the context of a specified geographic area. Foodshed area that comprises both the rural hinterlands of food production and the population centres of food consumption is suggested to represent a suitable areal extent for such research. Finding a balance between the various aspects of sustainability is a matter of optimal trade-off. The balance cannot be universally determined, but the assessment methods and the actual measures depend on what the bottlenecks of sustainability are in the area concerned. These have to be agreed upon among the actors of the area

Functional role of the Mso1p-Sec1p complex in membrane fusion regulation

Sec1/Munc18 (SM) protein family members are evolutionary conserved proteins. They perform an essential, albeit poorly understood function in SNARE complex formation in membrane fusion. In addition to the SNARE complex components, only a few SM protein binding proteins are known. Typically, their binding modes to SM proteins and their contribution to the membrane fusion regulation is poorly characterised. We identified Mso1p as a novel Sec1p interacting partner. It was shown that Mso1p and Sec1p interact at sites of polarised secretion and that this localisation is dependent on the Rab GTPase Sec4p and its GEF Sec2p. Using targeted mutagenesis and N- and C-terminal deletants, it was discovered that the interaction between an N-terminal peptide of Mso1p and the putative Syntaxin N-peptide binding area in Sec1p domain 1 is important for membrane fusion regulation. The yeast Syntaxin homologues Sso1p and Sso2p lack the N-terminal peptide. Our results show that in addition to binding to the putative N-peptide binding area in Sec1p, Mso1p can interact with Sso1p and Sso2p. This result suggests that Mso1p can mimic the N-peptide binding to facilitate membrane fusion. In addition to Mso1p, a novel role in membrane fusion regulation was revealed for the Sec1p C-terminal tail, which is missing in its mammalian homologues. Deletion of the Sec1p-tail results in temperature sensitive growth and reduced sporulation. Using in vivo and in vitro experiments, it was shown that the Sec1p-tail mediates SNARE complex binding and assembly. These results propose a regulatory role for the Sec1p-tail in SNARE complex formation. Furthermore, two novel interaction partners for Mso1p, the Rab GTPase Sec4p and plasma membrane phospholipids, were identified. The Sec4p link was identified using Bimolecular Fluorescence Complementation assays with Mso1p and the non-SNARE binding Sec1p(1-657). The assay revealed that Mso1p can target Sec1p(1-657) to sites of secretion. This effect is mediated via the Mso1p C-terminus, which previously has been genetically linked to Sec4p. These results and in vitro binding experiments suggest that Mso1p acts in cooperation with the GTP-bound form of Sec4p on vesicle-like structures prior to membrane fusion. Mso1p shares homology with the PIP2 binding domain of the mammalian Munc18 binding Mint proteins. It was shown both in vivo and in vitro that Mso1p is a phospholipid inserting protein and that this insertion is mediated by the conserved Mso1p amino terminus. In vivo, the Mso1p phospholipid binding is needed for sporulation and Mso1p-Sec1p localisation at the sites of secretion at the plasma membrane. The results reveal a novel layer of membrane fusion regulation in exocytosis and propose a coordinating role for Mso1p in connection with membrane lipids, Sec1p, Sec4p and SNARE complexes in this process.

Lattice density-functional theory on graphene

A density-functional approach on the hexagonal graphene lattice is developed using an exact numerical solution to the Hubbard model as the reference system. Both nearest-neighbour and up to third nearest-neighbour hoppings are considered and exchange-correlation potentials within the local density approximation are parameterized for both variants. The method is used to calculate the ground-state energy and density of graphene flakes and infinite graphene sheet. The results are found to agree with exact diagonalization for small systems, also if local impurities are present. In addition, correct ground-state spin is found in the case of large triangular and bowtie flakes out of the scope of exact diagonalization methods.

Relationships in food chains: an empirical examination of trust, commitment and communication

This report derives from the EU funded research project “Key Factors Influencing Economic Relationships and Communication in European Food Chains” (FOODCOMM). The research consortium consisted of the following organisations: University of Bonn (UNI BONN), Department of Agricultural and Food Marketing Research (overall project co-ordination); Institute of Agricultural Development in Central and Eastern Europe (IAMO), Department for Agricultural Markets, Marketing and World Agricultural Trade, Halle (Saale), Germany; University of Helsinki, Ruralia Institute Seinäjoki Unit, Finland; Scottish Agricultural College (SAC), Food Marketing Research Team - Land Economy Research Group, Edinburgh and Aberdeen; Ashtown Food Research Centre (AFRC), Teagasc, Food Marketing Unit, Dublin; Institute of Agricultural & Food Economics (IAFE), Department of Market Analysis and Food Processing, Warsaw and Government of Aragon, Center for Agro-Food Research and Technology (CITA), Zaragoza, Spain. The aim of the FOODCOMM project was to examine the role (prevalence, necessity and significance) of economic relationships in selected European food chains and to identify the economic, social and cultural factors which influence co-ordination within these chains. The research project considered meat and cereal commodities in six different European countries (Finland, Germany, Ireland, Poland, Spain, UK/Scotland) and was commissioned against a background of changing European food markets. The research project as a whole consisted of seven different work packages. This report presents the results of qualitative research conducted for work package 5 (WP5) in the pig meat and rye bread chains in Finland. Ruralia Institute would like to give special thanks for all the individuals and companies that kindly gave up their time to take part in the study. Their input has been invaluable to the project. The contribution of research assistant Sanna-Helena Rantala was significant in the data gathering. FOODCOMM project was coordinated by the University of Bonn, Department of Agricultural and Food Market Research. Special thanks especially to Professor Monika Hartmann for acting as the project leader of FOODCOMM.

Overview on different sterilization techniques for baby food

The nutritional quality of the product as well as other quality attributes like microbiological and sensory quality are essential factors in baby food industry, and therefore different alternative sterilizing methods for conventional heating processes are of great interest in this food sector. This report gives an overview on different sterilization techniques for baby food. The report is a part of the work done in work package 3 ”QACCP Analysis Processing: Quality – driven distribution and processing chain analysis“ in the Core Organic ERANET project called Quality analysis of critical control points within the whole food chain and their impact on food quality, safety and health (QACCP). The overall objective of the project is to optimise organic production and processing in order to improve food safety as well as nutritional quality and increase health promoting aspects in consumer products. The approach will be a chain analysis approach which addresses the link between farm and fork and backwards from fork to farm. The objective is to improve product related quality management in farming (towards testing food authenticity) and processing (towards food authenticity and sustainable processes. The articles in this volume do not necessarily reflect the Core Organic ERANET’s views and in no way anticipate the Core Organic ERANET’s future policy in this area. The contents of the articles in this volume are the sole responsibility of the authors. The information contained here in, including any expression of opinion and any projection or forecast, has been obtained from sources believed by the authors to be reliable but is not guaranteed as to accuracy or completeness. The information is supplied without obligation and on the understanding that any person who acts upon it or otherwise changes his/her position in reliance thereon does so entirely at his/her own risk. The writers gratefully acknowledge the financial support from the Core Organic Funding Body: Ministry of Agriculture and Forestry, Finland, Swiss Federal Office for Agriculture, Switzerland and Federal Ministry of Consumer Protection, Food and Agriculture, Germany.

Key Factors Influencing Economic Relationships and Communication in Finnish Food Chains

The aim of this report is to discuss the role of the relationship type and communication in two Finnish food chains, namely the pig meat-to-sausage (pig meat chain) and the cereal-to-rye bread (rye chain) chains. Furthermore, the objective is to examine those factors influencing the choice of a relationship type and the sustainability of a business relationship. Altogether 1808 questionnaires were sent to producers, processors and retailers operating in these two chains of which 224 usable questionnaires were returned (the response rate being 12.4%). The great majority of the respondents (98.7%) were small businesses employing less than 50 people. Almost 70 per cent of the respondents were farmers. In both chains, formal contracts were stated to be the most important relationship type used with business partners. Although for many businesses written contracts are a common business practice, the essential role of the contracts was the security they provide regarding the demand/supply and quality issues. Relative to the choice of the relationship types, the main difference between the two chains emerged especially with the prevalence of spot markets and financial participation arrangements. The usage of spot markets was significantly more common in the rye chain when compared to the pig meat chain, while, on the other hand, financial participation arrangements were much more common among the businesses in the pig meat chain than in the rye chain. Furthermore, the analysis showed that most of the businesses in the pig meat chain claimed not to be free to choose the relationship type they use. Especially membership in a co-operative and practices of a business partner were mentioned as the reasons limiting this freedom of choice. The main business relations in both chains were described as having a long-term orientation and being based on formal written contracts. Typical for the main business relationships was also that they are not based on the existence of the key persons only; the relationship would remain even if the key people left the business. The quality of these relationships was satisfactory in both chains and across all the stakeholder groups, though the downstream processors and the retailers had a slightly more positive view on their main business partners than the farmers and the upstream processors. The businesses operating in the pig meat chain seemed also to be more dependent on their main business relations when compared to the businesses in the rye chain. Although the communication means were rather similar in both chains (the phone being the most important), there was some variation between the chains concerning the communication frequency necessary to maintain the relationship with the main business partner. In short, the businesses in the pig meat chain seemed to appreciate more frequent communication with their main business partners when compared to the businesses in the rye chain. Personal meetings with the main business partners were quite rare in both chains. All the respondent groups were, however, fairly satisfied with the communication frequency and information quality between them and the main business partner. The business cultures could be argued to be rather hegemonic among the businesses both in the pig meat and rye chains. Avoidance of uncertainty, appreciation of long-term orientation and independence were considered important factors in the business cultures. Furthermore, trust, commitment and satisfaction in business partners were thought to be essential elements of business operations in all the respondent groups. In order to investigate which factors have an effect on the choice of a relationship type, several hypotheses were tested by using binary and multinomial logit analyses. According to these analyses it could be argued that avoidance of uncertainty and risk has a certain effect on the relationship type chosen, i.e. the willingness to avoid uncertainty increases the probability to choose stable relationships, like repeated market transactions and formal written contracts, but not necessary those, which require high financial commitment (like financial participation arrangements). The probability of engaging in financial participation arrangements seemed to increase with long-term orientation. The hypotheses concerning the sustainability of the economic relations were tested by using structural equation model (SEM). In the model, five variables were found to have a positive and statistically significant impact on the sustainable economic relationship construct. Ordered relative to their importance, those factors are: (i) communication quality, (ii) personal bonds, (iii) equal power distribution, (iv) local embeddedness and (v) competition.

Voittoa tavoittelemattoman organisaation brandin rakentaminen. Case Slow Food

Tämän pro gradu-tutkielman tavoitteena oli kartoittaa voittoa tavoittelemattoman Slow Food-organisaation brandiin liitettyjä mielikuvia ja niitä tekijöitä, joilla brandin tavoitekuvaa tulisi jatkossa rakentaa. Koska nykyisin brandi ei ole enää pelkkien liikeyritysten yksityisomaisuutta, tutkimuksen teoreettinen asemointi perustui yhtäältä organisaation tunnettuuden kasvattamiseen brandin rakentamisen avulla ja toisaalta voittoa tavoittelemattoman toimintaympäristön erityispiirteiden näkökulmaan. Case-osion avulla haluttiin tarkastella globalisaation ja elintarviketalouden keskittymiselle vaihtoehtoisen, paikallisuuteen perustuvan ruokajärjestelmän vaikutuksia, mahdollisuuksia ja haasteita. Tutkimuksen empiirinen osuus muodostui laadullisesta tapaustutkimuksesta, jonka kohteena oli Slow Food-organisaatio. Tutkimus suoritettiin haastattelemalla kahtatoista Slow Food-organisaation sidosryhmien edustajaa Italian Piemontessa henkilökohtaisin haastatteluin, joiden pohjana oli brandi identiteetin elementeistä luodut kaksi teemaa: mielleyhtymiin ja arvoväittämään liittyvät tekijät. Aineiston analysoinnissa käytettiin teemoittelua ja sisällönanalyysia. Tutkimuksen lähestymistapa oli abduktiivinen. Tulosten mukaan Slow Food-brandi identifioituu sidosryhmilleen ensisijaisesti luotettavan ruoan kautta, johon katsottiin kuuluvan aidot, puhtaat raaka-aineet ja paikallisesti tuotetun ja jalostamattoman ruoan hyvä jäljitettävyys. Myös tiettyyn paikkaan ja arvoihin sidottujen kokemusten ja odostusten täyttymisen kautta saatu sosiaalinen ja kulttuurinen jatkuvuus nimettiin brandin vahvuudeksi. Lisäksi vastuullisen tuottamisen ja kuluttamisen sekä aitojen makujen ja laadukkaan ruokavalion edistäminen korostuivat jonkin verran vastauksissa. Näillä perusvahvuuksilla toivottiin brandin identiteettiä rakennettavan myös tulevaisuudessa. Haastateltavien mielestä Slow Food-organisaatio erilaistaa itsensä muista ensisijaisesti lupaamalla yksilölle korkealuokkaisia, aitoja tuotteita ja palveluja, joilla on henkilökohtaisten hyötyjen lisäksi positiivisia seuraamuksia myös oman alueen työllisyyden ja talouden kehitykseen. Organisaation tulisi myös jatkossa luoda uskottavuutta toimintaansa eritoten sen kautta, että brandi lunastaa lupauksensa laadusta ja aitoudesta. Toisaalta erottautuakseen muista lähi- ja luomuruokabrandeista Slow Food-brandin arvoväittämässä tulisi tulevaisuudessa selkeämmin korostua myös toiminnan voittoa tavoittelemattomuus ja brandiin liittyvä elämyksellisyys. Sidosryhmien kiinnostusta ja brandin lupauksen tehoa alentaviksi tekijöiksi nimettiin yleinen ruoan arvostuksen väheneminen sekä Slow Food-tuotteiden ja -palvelujen korkea hinta, huono saatavuus ja näkyvyys. Keskeisimpinä ratkaisuina pidettiin kuluttajien informatiivisen tiedon lisäämisen ohella pientuottajien verkostoitumista ja uusia yhteistyön muotoja kuten tuottajien yhteisiä jakeluketjuja ja paikallismyymälöitä. Näiden lisäksi brandin tunnistettavuuden parantaminen ja aktiivisempi tarjonta kyltityksin, tuotteiden pysyvän läsnäolon ja vähittäiskaupan mukaantulon kautta sekä eräät muut markkinoinnin osa-alueet kuten sosiaalinen media, Internet ja kansainväliset ruoka-alan tapahtumat nimettiin brandin lupausta kirkastaviksi elementeiksi. Pientuotannon lisääminen verotuksen kohdentumisen muutoksilla nähtiin keinoksi pudottaa paikallisen ruoan hintaa.Toisaalta korkeaa hintaa perusteltiin laadukkaaseen imagoon liittyvien argumenttien lisäksi luonnollisen kysynnän kasvulla, jota arveltiin saatavan tulevaisuudessa suurista ikäluokista, yhä kasvavasta koulutus- ja tulotasosta sekä valveutuneemmista kuluttajista.

Adhesion,Presence and Antifouling of Deinococcus geothermalis in Paper Machine Environment

This thesis has two items: biofouling and antifouling in paper industry. Biofouling means unwanted microbial accumulation on surfaces causing e.g. disturbances in industrial processes, contamination of medical devices or of water distribution networks. Antifouling focuses on preventing accumulation of the biofilms in undesired places. Deinococcus geothermalis is a pink-pigmented, thermophilic bacterium, and extremely resistant towards radiation, UV-light and desiccation and known as a biofouler of paper machines forming firm and biocide resistant biofilms on the stainless steel surfaces. The compact structure of biofilm microcolonies of D. geothermalis E50051 and the adhesion into abiotic surfaces were investigated by confocal laser scanning microscope combined with carbohydrate specific fluorescently labelled lectins. The extracellular polymeric substance in D. geothermalis microcolonies was found to be a composite of at least five different glycoconjugates contributing to adhesion, functioning as structural elements, putative storages for water, gliding motility and likely also to protection. The adhesion threads that D. geothermalis seems to use to adhere on an abiotic surface and to anchor itself to the neighbouring cells were shown to be protein. Four protein components of type IV pilin were identified. In addition, the lectin staining showed that the adhesion threads were covered with galactose containing glycoconjugates. The threads were not exposed on planktic cells indicating their primary role in adhesion and in biofilm formation. I investigated by quantitative real-time PCR the presence of D. geothermalis in biofilms, deposits, process waters and paper end products from 24 paper and board mills. The primers designed for doing this were targeted to the 16S rRNA gene of D. geothermalis. We found D. geothermalis DNA from 9 machines, in total 16 samples of the 120 mill samples searched for. The total bacterial content varied in those samples between 107 to 3 ×1010 16S rRNA gene copies g-1. The proportion of D. geothermalis in those same samples was minor, 0.03 1.3 % of the total bacterial content. Nevertheless D. geothermalis may endanger paper quality as its DNA was shown in an end product. As an antifouling method towards biofilms we studied the electrochemical polarization. Two novel instruments were designed for this work. The double biofilm analyzer was designed for search for a polarization program that would eradicate D. geothermalis biofilm or from stainless steel under conditions simulating paper mill environment. The Radbox instrument was designed to study the generation of reactive oxygen species during the polarization that was effective in antifouling of D. geothermalis. We found that cathodic character and a pulsed mode of polarization were required to achieve detaching D. geothermalis biofilm from stainless steel. We also found that the efficiency of polarization was good on submerged, and poor on splash area biofilms. By adding oxidative biocides, bromochloro-5,5-dimethylhydantoin, 2,2-dibromo-2-cyanodiacetamide or peracetic acid gave additive value with polarization, being active on splash area biofilms. We showed that the cathodically weighted pulsed polarization that was active in removing D. geothermalis was also effective in generation of reactive oxygen species. It is possible that the antifouling effect relied on the generation of ROS on the polarized steel surfaces. Antifouling method successful towards D. geothermalis that is a tenacious biofouler and possesses a high tolerance to oxidative stressors could be functional also towards other biofoulers and applicable in wet industrial processes elsewhere.

Spatial ecology of food webs : herbivore-parasitoid communities on the pedunculate oak

Herbivorous insects, their host plants and natural enemies form the largest and most species-rich communities on earth. But what forces structure such communities? Do they represent random collections of species, or are they assembled by given rules? To address these questions, food webs offer excellent tools. As a result of their versatile information content, such webs have become the focus of intensive research over the last few decades. In this thesis, I study herbivore-parasitoid food webs from a new perspective: I construct multiple, quantitative food webs in a spatially explicit setting, at two different scales. Focusing on food webs consisting of specialist herbivores and their natural enemies on the pedunculate oak, Quercus robur, I examine consistency in food web structure across space and time, and how landscape context affects this structure. As an important methodological development, I use DNA barcoding to resolve potential cryptic species in the food webs, and to examine their effect on food web structure. I find that DNA barcoding changes our perception of species identity for as many as a third of the individuals, by reducing misidentifications and by resolving several cryptic species. In terms of the variation detected in food web structure, I find surprising consistency in both space and time. From a spatial perspective, landscape context leaves no detectable imprint on food web structure, while species richness declines significantly with decreasing connectivity. From a temporal perspective, food web structure remains predictable from year to year, despite considerable species turnover in local communities. The rate of such turnover varies between guilds and species within guilds. The factors best explaining these observations are abundant and common species, which have a quantitatively dominant imprint on overall structure, and suffer the lowest turnover. By contrast, rare species with little impact on food web structure exhibit the highest turnover rates. These patterns reveal important limitations of modern metrics of quantitative food web structure. While they accurately describe the overall topology of the web and its most significant interactions, they are disproportionately affected by species with given traits, and insensitive to the specific identity of species. As rare species have been shown to be important for food web stability, metrics depicting quantitative food web structure should then not be used as the sole descriptors of communities in a changing world. To detect and resolve the versatile imprint of global environmental change, one should rather use these metrics as one tool among several.

X-ray Crystallographic Analysis of the Complexes of Enoyl Acyl Carrier Protein Reductase of Plasmodium falciparum with Triclosan Variants to Elucidate the Importance of Different Functional Groups in Enzyme Inhibition

Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors. (C) 2010 IUBMB IUBMB Life, 62(6): 467-476.

Hexagonally ordered arrays of metallic nanodots from thin films of functional block copolymers

We demonstrate a new and simple route to fabricate highly dense arrays of hexagonally close packed inorganic nanodots using functional diblock copolymer (PS-b-P4VP) thin films. The deposition of pre-synthesized inorganic nanoparticles selectively into the P4VP domains of PS-b-P4VP thin films, followed by removal of the polymer, led to highly ordered metallic patterns identical to the order of the starting thin film. Examples of Au, Pt and Pd nanodot arrays are presented. The affinity of the different metal nanoparticles towards P4VP chains is also understood by extending this approach to PS-b-P4VP micellar thin films. The procedure used here is simple, eco-friendly, and compatible with the existing silicon-based technology. Also the method could be applied to various other block copolymer morphologies for generating 1-dimensional (1D) and 2-dimensional (2D) structures. (c) 2010 Elsevier Ltd. All rights reserved.

PROMIDS: A PROtotype multi-rIng data flow system for functional programming languages

This paper presents a detailed description of the hardware design and implementation of PROMIDS: a PROtotype Multi-rIng Data flow System for functional programming languages. The hardware constraints and the design trade-offs are discussed. The design of the functional units is described in detail. Finally, we report our experience with PROMIDS.