Synthesis and screening of potential antimicrobial compounds

Tuberculosis (TB), an infection caused by human pathogen Mycobacterium tuberculosis, continues to kill millions each year and is as prevalent as it was in the pre-antimicrobial era. With the emergence of continuously-evolving multi-drug resistant strains (MDR) and the implications of the HIV epidemic, it is crucial that new drugs with better efficacy and affordable cost are developed to treat TB. With this in mind, the first part of this thesis discusses the synthesis of libraries of derivatives of pyridine carboxamidrazones, along with cyclised (1,2,4-triazole and 1,2,4-oxadiazole) and fluorinated analogues. Microbiological screening against M. tuberculosis was carried out at the TAACF, NIAID and IDRI (USA). This confirmed the earlier findings that 2-pyridyl-substituted carboxamidrazones were more active than the 4-pyridyl-substituted carboxamidrazones. Another important observation was that upon cyclisation of these carboxamidrazones, a small number of the triazoles retained their activity while in most of the remaining compounds the activity was diminished. This might be attributed to the significant increase in logP value caused by cyclisation of these linear carboxamidrazones, resulting in high lipophilicity and decreased permeability. Another reason might be that the rigidity conferred upon the compound due to cyclisation, results in failure of the compound to fit into the active site of the putative target enzyme. In order to investigate the potential change to the compounds’ metabolism in the organism and/or host, the most active compounds were selected and a fluorine atom was introduced in the pyridine ring. The microbiological results shows a drastic improvement in the activity of the fluorinated carboxamidrazone amides as compared to their non fluorinated counterpart. This improvement in the activity could possibly be the result of the increased cell permeability caused by the fluorine. In a subsidiary strand, a selection of long-chain , -unsaturated carboxylic esters, -keto, -hydroxy carboxylic esters and -keto, -hydroxy carboxylic esters, structurally similar to mycolic acids, were synthesised. The microbiological data revealed that one of the open chain compound was active against the Mycobacterium tuberculosis H37Rv strain and some resistant isolates. The possible compound activity could be its potential to disrupt mycobacterial cell wall synthesis by interfering with the FAS-II pathway.

CuII chain compound showing a ferromagnetic coupling through triple N1,N2-1,2,4-triazole bridges

[Cu(hyetrz)3](CF3SO3)2·H2O [hyetrz = 4-(2′-hydroxyethyl)-1,2,4-triazole] represents the first structurally characterised ferromagnetically coupled CuII chain compound containing triple N1,N2-1,2,4-triazole bridges. catena-[μ-Tris{4-(2′-hydroxyethyl)-1,2,4-triazole-N1,N2}copper(II)] bis(trifluoromethanesulfonate) hydrate (C14H23F6S2O10CuN9) crystallises in the triclinic space group Pl, a = 13.54(3), b = 14.37(3), c = 15.61(4) Å, α = 95.9(1), β = 104.9(1), γ = 106.5(1)°, V = 2763(11) Å3, Z = 4 (CuII units). The CuII ions are linked by triple N1,N2-1,2,4-triazole bridges yielding an alternating chain with Cu1−Cu2 = 3.8842(4) Å and Cu2−Cu3 = 3.9354(4) Å. Analysis of the magnetic data according to a high-temperature series expansion gives a J value of +1.45(3) cm−1. The nature and the magnitude of the ferromagnetic exchange have been discussed on the basis of the structural features. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

The implementation of supply chain management theory in practice:an empirical investigation

Purpose: The purpose of the research described in this paper is to disentangle the rhetoric from the reality in relation to supply chain management (SCM) adoption in practice. There is significant evidence of a divergence between theory and practice in the field of SCM. Design/methodology/approach: Based on a review of extant theory, the authors posit a new definitional construct for SCM – the Four Fundamentals – and investigated four research questions (RQs) that emerged from the theoretical review. The empirical work comprised three main phases: focussed interviews, focus groups and a questionnaire survey. Each phase used the authors’ definitional construct as its basis. While the context of the paper’s empirical work is Ireland, the insights and results are generalisable to other geographical contexts. Findings: The data collected during the various stages of the empirical research supported the essence of the definitional construct and allowed it to be further developed and refined. In addition, the findings suggest that, while levels of SCM understanding are generally quite high, there is room for improvement in relation to how this understanding is translated into practice. Research limitations/implications: Expansion of the research design to incorporate case studies, grounded theory and action research has the potential to generate new SCM theory that builds on the Four Fundamentals construct, thus facilitating a deeper and richer understanding of SCM phenomena. The use of longitudinal studies would enable a barometer of progress to be developed over time. Practical implications: The authors’ definitional construct supports improvement in the cohesion of SCM practices, thereby promoting the effective implementation of supply chain strategies. A number of critical success factors and/or barriers to implementation of SCM theory in practice are identified, as are a number of practical measures that could be implemented at policy/supply chain/firm level to improve the level of effective SCM adoption. Originality/value: The authors’ robust definitional construct supports a more cohesive approach to the development of a unified theory of SCM. In addition to a profile of SCM understanding and adoption by firms in Ireland, the related critical success factors and/or inhibitors to success, as well as possible interventions, are identified.

Assessing the value relevance of accounting data after the introduction of IFRS in Europe

Since 2005, European-listed companies have been required to prepare their consolidated financial statements in accordance with the International Financial Reporting Standards (IFRS). We examine whether value relevance increased following the introduction of IFRS, using a sample of 3,721 companies listed on five European stock exchanges: Frankfurt, Madrid, Paris, London, and Milan. We find mixed evidence of an increase in value relevance. However, the influence of earnings on share price increased following the introduction of IFRS in Germany, France, and the United Kingdom, while the influence of book value of equity decreased (except for the United Kingdom). © 2010 Blackwell Publishing Ltd.

A fuzzy expected value approach under generalized data envelopment analysis

Fuzzy data envelopment analysis (DEA) models emerge as another class of DEA models to account for imprecise inputs and outputs for decision making units (DMUs). Although several approaches for solving fuzzy DEA models have been developed, there are some drawbacks, ranging from the inability to provide satisfactory discrimination power to simplistic numerical examples that handles only triangular fuzzy numbers or symmetrical fuzzy numbers. To address these drawbacks, this paper proposes using the concept of expected value in generalized DEA (GDEA) model. This allows the unification of three models - fuzzy expected CCR, fuzzy expected BCC, and fuzzy expected FDH models - and the ability of these models to handle both symmetrical and asymmetrical fuzzy numbers. We also explored the role of fuzzy GDEA model as a ranking method and compared it to existing super-efficiency evaluation models. Our proposed model is always feasible, while infeasibility problems remain in certain cases under existing super-efficiency models. In order to illustrate the performance of the proposed method, it is first tested using two established numerical examples and compared with the results obtained from alternative methods. A third example on energy dependency among 23 European Union (EU) member countries is further used to validate and describe the efficacy of our approach under asymmetric fuzzy numbers.

Fourth National Information Day and Workshop: Open Access to Scientific Information and Data

The paper presents in brief the “2nd Generation Open Access Infrastructure for Research in Europe” project (http://www.openaire.eu/) and what is done in Bulgaria during the last year in the area of open access to scientific information and data.

Progmosis:evaluating risky individual behavior during epidemics using mobile network data

The possibility to analyze, quantify and forecast epidemic outbreaks is fundamental when devising effective disease containment strategies. Policy makers are faced with the intricate task of drafting realistically implementable policies that strike a balance between risk management and cost. Two major techniques policy makers have at their disposal are: epidemic modeling and contact tracing. Models are used to forecast the evolution of the epidemic both globally and regionally, while contact tracing is used to reconstruct the chain of people who have been potentially infected, so that they can be tested, isolated and treated immediately. However, both techniques might provide limited information, especially during an already advanced crisis when the need for action is urgent. In this paper we propose an alternative approach that goes beyond epidemic modeling and contact tracing, and leverages behavioral data generated by mobile carrier networks to evaluate contagion risk on a per-user basis. The individual risk represents the loss incurred by not isolating or treating a specific person, both in terms of how likely it is for this person to spread the disease as well as how many secondary infections it will cause. To this aim, we develop a model, named Progmosis, which quantifies this risk based on movement and regional aggregated statistics about infection rates. We develop and release an open-source tool that calculates this risk based on cellular network events. We simulate a realistic epidemic scenarios, based on an Ebola virus outbreak; we find that gradually restricting the mobility of a subset of individuals reduces the number of infected people after 30 days by 24%.

Open Research Data

Open Research Data - A step by step guide through the research data lifecycle, data set creation, big data vs long-tail, metadata, data centres/data repositories, open access for data, data sharing, data citation and publication.

Open Access to Publications and Research Data in Horizon 2020: What Are the Requirements and How Can Institutional Repositories and OpenAIRE Help to Meet Them?

In the last decade the principle of Open Access to publicly funded research has been getting a growing support from policy makers and funders across Europe, both at national level and within the European Union context. At European level some of the first relevant steps taken by the European Research Council (ERC) with a statement supporting Open Access (2006), shortly followed by guidelines for researchers funded by the ERC (2007) stating that all peer-reviewed publications from ERC funded projects should be made openly accessible shortly after their publication. Those guidelines were revised in October 2013, reinforcing the mandatory character of the requirements and expanding them to monographs.

The Fifth National Information Day: Open Access to Scientific Information and Data

This work was supported in part by the EU „2nd Generation Open Access Infrastructure for Research in Europe" (OpenAIRE+). The autumn training school Development and Promotion of Open Access to Scientific Information and Research is organized in the frame of the Fourth International Conference on Digital Presentation and Preservation of Cultural and Scientific Heritage—DiPP2014 (September 18–21, 2014, Veliko Tarnovo, Bulgaria, http://dipp2014.math.bas.bg/), organized under the UNESCO patronage. The main organiser is the Institute of Mathematics and Informatics, Bulgarian Academy of Sciences with the support of EU project FOSTER (http://www.fosteropenscience.eu/) and the P. R. Slaveykov Regional Public Library in Veliko Tarnovo, Bulgaria.

Representing supply chain events on the Web of data

The Electronic Product Code Information Service (EPCIS) is an EPCglobal standard, that aims to bridge the gap between the physical world of RFID1 tagged artifacts, and information systems that enable their tracking and tracing via the Electronic Product Code (EPC). Central to the EPCIS data model are "events" that describe specific occurrences in the supply chain. EPCIS events, recorded and registered against EPC tagged artifacts, encapsulate the "what", "when", "where" and "why" of these artifacts as they flow through the supply chain. In this paper we propose an ontological model for representing EPCIS events on the Web of data. Our model provides a scalable approach for the representation, integration and sharing of EPCIS events as linked data via RESTful interfaces, thereby facilitating interoperability, collaboration and exchange of EPC related data across enterprises on a Web scale.

A tranzakciós költségek elmélete és a társadalmi csereelmélet hatásai a bizalomra az ellátási láncban (Affects of Transaction cost and Social Exchange Constructs on trust In supply chain relationship)

A szerzők alapvető feltételezése, hogy az ellátási láncban a bizalom ösztönzi a felek közötti elkötelezettséget. Továbbá a bizalom növeli annak a lehetőségét, hogy az ellátási lánc sikeresen működjön. Ugyanakkor, a felek közötti bizalom hiánya gyakran megnöveli a tranzakciós költségeket, és így csökkenti a hatékonyságot. A cikkben bemutatott kutatás adatgyűjtésére több országban – Franciaországban, Magyarországon, Dél-Koreában, Tunéziában és az Egyesült Államokban – került sor. Összesen 729 érvényes kérdőív érkezett vissza, amelyeket a különböző ellátási láncok résztvevői töltöttek ki. A kutatási eredmények szerint az ellátási láncokon belüli üzleti kapcsolatokban a tranzakciós költségek elméletének összetevői (kapcsolatspecifikusság és viselkedési bizonytalanság), valamint a társadalmi csereelmélet tényezői (lecserélhetőség, észlelt megelégedettség, a partner hírneve és észlelt konfliktus) szoros kapcsolatban állnak a bizalom és az elkötelezettség változóival. _____ This article is based on the assumption that trust promotes commitment between partners in the supply chain and improves the chances of return on supply chain success. In contrast, a lack of trust between them often increases transaction costs and results in inefficiency. The results of this research, based on multi-country surveys with 729 returns from France, Hungary, Korea, Tunisia and the United States on supply chain professionals, reveals a strong affect of transaction cost constructs (TCC) (asset specificity and behavioral uncertainty) and social exchange constructs (SEC) (replaceability, perceived satisfaction, partner reputation, and perceived conflict) on trust-commitment variables in partnership based supply chain relationships. This paper employed a structural equation model to extract information from the survey data. Among the findings, the research indicates that a firm’s trustcommitment in dealing with their supply chain partnership is highly associated with not only transaction cost, but more so with social exchange variables. This study may open a new research avenue in that there is another construct, SEC, beside TSC that influences the degree of trust and commitment.

A bizalmat befolyásoló tényezők vizsgálata az üzleti kapcsolatokban (Affects of Transaction cost and Social Exchange Constructs on trust In supply chain relationship)

Az üzleti célú kapcsolatok vizsgálatakor legtöbbször felmerül a bizalom fogalma is, amellyel először a szociálpszichológia és a szociológia foglalkozott. A szerző cikkében azzal foglalkozik, hogy milyen tényezők befolyásolják a bizalmat az üzleti kapcsolatokban. Ezért magyarországi szervezeteket (elsősorban üzleti vállalkozásokat) kérdezett meg kvantitatív módszer alkalmazásával. Ez az empirikus kutatás igyekszik a bizalom lehető legtöbb tényezőit összegyűjteni, ahol a kérdőívben a válaszolók egyik létező – vevői vagy beszállítói – kapcsolatukra gondolva válaszoltak a bizalmon túl a partner hírnevére, az észlelt elégedettségre és konfliktusra, az információcserére, a lecserélhetőségre, valamint a kapcsolatspecifikus beruházásokra vonatkozóan. Az eredmények azt mutatják, hogy egyik változó sem jelent kizárólagos befolyásoló erőt, hanem közösen alakítják ki a bizalom adott szintjét. _______ This article is based on the assumption that trust promotes commitment between partners in the supply chain and improves the chances of return on supply chain success. In contrast, a lack of trust between them often increases transaction costs and results in inefficiency. The results of this research, based on multi-country surveys with 729 returns from France, Hungary, Korea, Tunisia and the United States on supply chain professionals, reveals a strong affect of transaction cost constructs (TCC) (asset specificity and behavioral uncertainty) and social exchange constructs (SEC) (replaceability, perceived satisfaction, partner reputation, and perceived conflict) on trust-commitment variables in partnership based supply chain relationships. This paper employed a structural equation model to extract information from the survey data. Among the findings, the research indicates that a firm’s trustcommitment in dealing with their supply chain partnership is highly associated with not only transaction cost, but more so with social exchange variables. This study may open a new research avenue in that there is another construct, SEC, beside TSC that influences the degree of trust and commitment.

Elemental, biomarker, palynology and maceral data from Seam 1, Schöningen and associated interbeds

Sphagnum moss is the dominant plant type in modern boreal and (sub)arctic ombrotrophic bogs and is of particular interest due to its sensitivity to climate and its important role in wetland biogeochemistry. Here we reconstruct the occurrence of Sphagnum moss - and associated biogeochemical change - within a thermally immature, early Paleogene (~55 Ma) lignite from Schöningen, NW Germany using a high-resolution, multi-proxy approach. Changes in the abundance of Sphagnum-type spores and the C23/C31n-alkane ratio indicate the expansion of Sphagnum moss within the top of the lignite seam. This Sphagnum moss expansion is associated with the development of waterlogged conditions, analogous to what has been observed within modern ombrotrophic bogs. The similarity between biomarkers and palynology also indicates that the C23/C31n-alkane ratio may be a reliable chemotaxonomic indicator for Sphagnum during the early Paleogene. The d13C value of bacterial hopanes and mid-chain n-alkanes indicates that a rise in water table is not associated with a substantial increase in aerobic methanotrophy. The absence of very low d13C values within the top of the seam could reflect either less methanogenesis or less efficient methane oxidation under waterlogged sulphate-rich conditions.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.