Design, synthesis and evaluation of cyclothialidine analogues as DNA gyrase inhibitors

Cyclothialidine, a natural product isolated from Streptomyces .filipinensis NR0484, has been proven to be a potent and selective inhibitor of the bacterial enzyme DNA gyrase. Gyrase inhibition results in cell death, the enzyme being the target of several currently used antibiotics. Cyclothialidine showed poor activity against whole bacterial cells, highlighting scope for improvement regarding cell membrane pemeability in order for the full potential of this new class of antibiotics to be realised, Structurally, cyclothialidine contains a 12-membered lactone ring which is partly integrated into a pentapeptide chain, with a substituted aromatic moiety bordering the lactone, Retrosynthetically it can be traced back to cis-3-hydroxyproline, 3,5-dihydroxy-2,6-dimethylbenzoic acid and four commercially available amino acids; two serine, one cysteine and one alanine. In this work, a model of cyclothialidine was synthesised in order to establish the methodology for more complex compounds. Analogues with hydroxy, dihydroxy and dihydroxymethyl substituted aromatic moieties were then prepared to ensure successful protection methods could be performed and the pharmacophore synthesised. The key aromatic moiety, 2,6-dimethyl-3,5-dihydroxybenzoic acid was produced via two successive Mannich reaction/reduction steps. Acid protection using 4-nitrobenzyl bromide and TBDMS hydroxyl protection followed by bromination of one methyl afforded the desired intermediate. Reaction with a serine/cysteine dipeptide, followed by deprotection and cyclisation under Mitsunobu conditions lead to the 12-membered lactone. An amine substituted aromatic analogue and also replacement of the cysteine sulphur by oxygen were attempted but without success. In an effort to improve cell permeability, a conjugate was synthesised between the pharmacophore and a cholesterol moiety. It was hoped the steroid fragment would serve to increase potency by escorting the molecule through the lipid environment of the cell membrane. The pharmacophore and conjugate were tested against a variety of bacterial strains but the conjugate failed to improve activity.

Synthesis and evaluation of antibacterial activity of the dual-action agents: beta-lactamase inhibitors with cytotoxic agents or beta-lactam antibiotics

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Design, implementation and control of a small industrial manufacturing system

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Implementation and characterization of liquid-level sensor based on a long-period fiber grating Mach-Zehnder interferometer

An optical liquid-level sensor (LLS) based on a long-period fiber grating (LPG) interferometer is proposed and experimentally demonstrated. Two identical 3-dB LPGs are fabricated to form an in-fiber Mach-Zehnder interferometer, and the fiber portion between two LPGs is exposed to the liquid as the sensing element. The sensitivity and measurement range of the sensors employing different orders of cladding modes are investigated both theoretically and experimentally. The experimental results show good linearity and large measurement range. One of the significant advantages of such a sensing structure is that the measurement level is not limited to the length of the LPG itself. Also, the measurement range and sensitivity of the proposed LLS can be readily tailored for a particular applications.

Design and evaluation for the future of m-interaction

Mobile technology has been one of the major growth areas in computing over recent years (Urbaczewski, Valacich, & Jessup, 2003). Mobile devices are becoming increasingly diverse and are continuing to shrink in size and weight. Although this increases the portability of such devices, their usability tends to suffer. Fuelled almost entirely by lack of usability, users report high levels of frustration regarding interaction with mobile technologies (Venkatesh, Ramesh, & Massey, 2003). This will only worsen if interaction design for mobile technologies does not continue to receive increasing research attention. For the commercial benefit of mobility and mobile commerce (m-commerce) to be fully realized, users’ interaction experiences with mobile technology cannot be negative. To ensure this, it is imperative that we design the right types of mobile interaction (m-interaction); an important prerequisite for this is ensuring that users’ experience meets both their sensory and functional needs (Venkatesh, Ramesh, & Massey, 2003). Given the resource disparity between mobile and desktop technologies, successful electronic commerce (e-commerce) interface design and evaluation does not necessarily equate to successful m-commerce design and evaluation. It is, therefore, imperative that the specific needs of m-commerce are addressed–both in terms of design and evaluation. This chapter begins by exploring the complexities of designing interaction for mobile technology, highlighting the effect of context on the use of such technology. It then goes on to discuss how interaction design for mobile devices might evolve, introducing alternative interaction modalities that are likely to affect that future evolution. It is impossible, within a single chapter, to consider each and every potential mechanism for interacting with mobile technologies; to provide a forward-looking flavor of what might be possible, this chapter focuses on some more novel methods of interaction and does not, therefore, look at the typical keyboard and visual display-based interaction which, in essence, stem from the desktop interaction design paradigm. Finally, this chapter touches on issues associated with effective evaluation of m-interaction and mobile application designs. By highlighting some of the issues and possibilities for novel m-interaction design and evaluation, we hope that future designers will be encouraged to “think out of the box” in terms of their designs and evaluation strategies.

Handbook of research on user interface design and evaluation for mobile technology

In recent years, mobile technology has been one of the major growth areas in computing. Designing the user interface for mobile applications, however, is a very complex undertaking which is made even more challenging by the rapid technological developments in mobile hardware. Mobile human-computer interaction, unlike desktop-based interaction, must be cognizant of a variety of complex contextual factors affecting both users and technology. The Handbook of Research on User Interface Design and Evaluation provides students, researchers, educators, and practitioners with a compendium of research on the key issues surrounding the design and evaluation of mobile user interfaces, such as the physical environment and social context in which a mobile device is being used and the impact of multitasking behavior typically exhibited by mobile-device users. Compiling the expertise of over 150 leading experts from 26 countries, this exemplary reference tool will make an indispensable addition to every library collection.

Making policy in theory and practice:by Hugh Bochel and Sue Duncan (eds)

Book review: Hugh Bochel and Sue Duncan (eds), Policy Press, 2007, 251 pp. (including references and index), £23 (pb), ISBN: 1861349033

Policy, economic federalism, and product market entry:the Indian experience

Productivity growth has long been associated with, among other things, contestability of markets which, in turn, is dependent on the ease with which potential competitors to the incumbent firms can enter the product market. There is a growing consensus that in emerging markets regulatory and institutional factors may have a greater influence on a firm's ability to enter a product market than strategic positions adopted by the incumbent firms. We examine this proposition in the context of India where the industrial policies of the 1980s and the 1990s are widely believed to be pro-incumbent and pro-competition, respectively, thereby providing the setting for a natural experiment with 1991 as the watershed year. In our analysis, we also take into consideration the possibility that the greater economic federalism associated with the reforms of the 1990s may have affected the distribution of industrial units across states after 1991. Our paper, which uses the experiences of the textiles and electrical machinery sectors during the two decades as the basis for the analysis, finds broad support for both these hypotheses.

Browsing for information by highlighting automatically generated annotations:a user study and evaluation

The realization of the Semantic Web is constrained by a knowledge acquisition bottleneck, i.e. the problem of how to add RDF mark-up to the millions of ordinary web pages that already exist. Information Extraction (IE) has been proposed as a solution to the annotation bottleneck. In the task based evaluation reported here, we compared the performance of users without access to annotation, users working with annotations which had been produced from manually constructed knowledge bases, and users working with annotations augmented using IE. We looked at retrieval performance, overlap between retrieved items and the two sets of annotations, and usage of annotation options. Automatically generated annotations were found to add value to the browsing experience in the scenario investigated. Copyright 2005 ACM.

A strategic activity model of Enterprise System implementation and use:scaffolding fluidity

This paper builds on a Strategic Activity Framework (Jarzabkowski, 2005) and activity based theories of development (Vygotsky, 1978) to model how Enterprise Systems are used to support emerging strategy. It makes three contributions. Firstly, it links fluidity and extensiveness of system use to patterns of strategising. Fluidity - the ability to change system use as needs change - is supported by interactive strategising, where top managers communicate directly with the organisation. Extensiveness requires procedural strategising, embedding system use in structures and routines. Secondly, it relates interactive and procedural strategising to the importance of the system - procedural strategising is more likely to occur if the system is strategically important. Thirdly, using a scaffolding metaphor it identifies patterns in the activities of top managers and Enterprise System custodians, who identify process champions within the organisational community, orient them towards system goals, provide guided support, and encourage fluidity through pacing implementation with learning.© 2013 Published by Elsevier B.V. All rights reserved.

The design and evaluation of an automated drug partitioning system for thermodynamic studies

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