Sortase A : an ideal target for anti-virulence drug development

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.

On the need for an international effort to capture, share and use crystallization screening data

When crystallization screening is conducted many outcomes are observed but typically the only trial recorded in the literature is the condition that yielded the crystal(s) used for subsequent diffraction studies. The initial hit that was optimized and the results of all the other trials are lost. These missing results contain information that would be useful for an improved general understanding of crystallization. This paper provides a report of a crystallization data exchange (XDX) workshop organized by several international large-scale crystallization screening laboratories to discuss how this information may be captured and utilized. A group that administers a significant fraction of the worlds crystallization screening results was convened, together with chemical and structural data informaticians and computational scientists who specialize in creating and analysing large disparate data sets. The development of a crystallization ontology for the crystallization community was proposed. This paper (by the attendees of the workshop) provides the thoughts and rationale leading to this conclusion. This is brought to the attention of the wider audience of crystallographers so that they are aware of these early efforts and can contribute to the process going forward. © 2012 International Union of Crystallography All rights reserved.

Tools, building blocks, and rewards : traditional media organizations learn to engage with productive audiences

This paper explores how traditional media organizations (such as magazines, music, film, books, and newspapers) develop routines for coping with an increasingly productive audience. While previous studies have reported on how such organizations have been affected by digital technologies, this study makes a contribution to this literature by being one of the first to show how organizational routines for engaging with an increasingly productive audience actually emerge and diffuse between industries. The paper explores to what extent routines employed by two traditional media organizations have been brought in from other organizational settings, specifically from so-called ‘software platform operators’. Data on routines for engaging with productive audiences have been collected from two information-rich cases in the music and the magazine industries, and from eight high-profile software platform operators. The paper concludes that the routines employed by the two traditional media organizations and by the software platform operators are based on the same set of principles: Provide the audience with (a) tools that allow them to easily generate cultural content; (b) building blocks which facilitate their creative activities; and (c) recognition and rewards based on both rationality and emotion.

Landform characterization using geophysics—Recent advances, applications, and emerging tools

This paper presents an overview of the strengths and limitations of existing and emerging geophysical tools for landform studies. The objectives are to discuss recent technical developments and to provide a review of relevant recent literature, with a focus on propagating field methods with terrestrial applications. For various methods in this category, including ground-penetrating radar (GPR), electrical resistivity (ER), seismics, and electromagnetic (EM) induction, the technical backgrounds are introduced, followed by section on novel developments relevant to landform characterization. For several decades, GPR has been popular for characterization of the shallow subsurface and in particular sedimentary systems. Novel developments in GPR include the use of multi-offset systems to improve signal-to-noise ratios and data collection efficiency, amongst others, and the increased use of 3D data. Multi-electrode ER systems have become popular in recent years as they allow for relatively fast and detailed mapping. Novel developments include time-lapse monitoring of dynamic processes as well as the use of capacitively-coupled systems for fast, non-invasive surveys. EM induction methods are especially popular for fast mapping of spatial variation, but can also be used to obtain information on the vertical variation in subsurface electrical conductivity. In recent years several examples of the use of plane wave EM for characterization of landforms have been published. Seismic methods for landform characterization include seismic reflection and refraction techniques and the use of surface waves. A recent development is the use of passive sensing approaches. The use of multiple geophysical methods, which can benefit from the sensitivity to different subsurface parameters, is becoming more common. Strategies for coupled and joint inversion of complementary datasets will, once more widely available, benefit the geophysical study of landforms.Three cases studies are presented on the use of electrical and GPR methods for characterization of landforms in the range of meters to 100. s of meters in dimension. In a study of polygonal patterned ground in the Saginaw Lowlands, Michigan, USA, electrical resistivity tomography was used to characterize differences in subsurface texture and water content associated with polygon-swale topography. Also, a sand-filled thermokarst feature was identified using electrical resistivity data. The second example is on the use of constant spread traversing (CST) for characterization of large-scale glaciotectonic deformation in the Ludington Ridge, Michigan. Multiple CST surveys parallel to an ~. 60. m high cliff, where broad (~. 100. m) synclines and narrow clay-rich anticlines are visible, illustrated that at least one of the narrow structures extended inland. A third case study discusses internal structures of an eolian dune on a coastal spit in New Zealand. Both 35 and 200. MHz GPR data, which clearly identified a paleosol and internal sedimentary structures of the dune, were used to improve understanding of the development of the dune, which may shed light on paleo-wind directions.

Ethical screening and financial performance : the case of Islamic equity funds

Whether ethical screening affects portfolio performance is an important question that is yet to be settled in the literature. This paper aims to shed further light on this question by examining the performance of a large global sample of Islamic equity funds (IEFs) from 1984 to 2010. We find that IEFs underperform conventional funds by an average of 40 basis points per month, consistent with the underperformance hypothesis. In line with popular media claims that Islamic funds are a safer investment, IEFs outperformed conventional funds during the recent banking crisis. However, we find no such outperformance for other crises or high volatility periods. Based on fund holdings-based data, we provide evidence of a negative curvilinear relation between fund performance and ethical screening intensity, consistent with a return trade-off to being more ethical.

Tourism advertisement management and effective tools in tourism industry

The definition of tourism “is the travel for recreational, leisure, family or business purposes, usually of a limited duration. Tourism is commonly associated with trans-national travel, but may also refer to travel to another location within the same country”. Tourism as an industry, in today’s modern language is a means of global communication between nations and travelers of all countries, introducing them to the various cultures and societies abroad, as well there history, ancient, historical sites, and languages. Hence, advertising overall has become a tool of necessity in this ever-growing global industry. Given that, tourism is a part of the infrastructure of any country’s economy the growth and development of tourism is of great importance. Advertising plays a vital and is a crucial tool in developing the countries tourism by attractively presenting the nations points-of-interests, historical and cultural. Advertising has a central role in expanding this industry, generating economic growth in this area, as well as creating direct and indirect employment, but most importantly a creative innovating competition in the national and international travel industry. Importantly, to achieve a successful tourist industry, the Travel Agencies and governmental offices of the Ministry’s of Tourism and Business must work hand-in-hand to attain these goals. This article shows the impact of the various media and advertising methods used in tourism, which assisted in identifying the correct tool for expanding the country’s industry of tourism. The results of this study illustrated that the appropriate tools for promotional strategies to attract domestic and foreign traveler’s, found to be the most effective were, handbook, internet advertising, TV, brochures, newspapers

Understanding, utilizing and valuing design tools in business

This chapter examines the tools and activities (referred to as approaches) used by a catalyst while facilitating a design-led transformation within an Australian manufacturing small to medium enterprise (SME). Design-led innovation (DLI) aids the use of design at a higher strategic level; however few existing studies investigate the relative influence of approaches used by a catalyst while helping a firm to make a transition in the utilisation of design, specifically from a styling tool to a strategic process. This paper identifies the triggers to encouraging a shift toward understanding, utilising and valuing the business level outcomes of design through a range of design tools and activities within the participating company. Through a 12 month action research program, staff interviews and a reflective journal were utilised as data collection techniques to assess the successfulness of the approaches used during this project. It was found that, through the use of both successful and unsuccessful approaches, the catalyst achieved two key outcomes within the firm: 1) Improvements in the firm’s ability to challenge internal assumptions and standard practices; and 2) the creation of an informed and accurate awareness of company and industry issues. Approaches that made a higher impact of the firm were deemed successful, and were generally relatable to the task at hand, as perceived by employees. Additionally, the sequence in which the approaches were utilised was found to have a direct influence on their successfulness. Learnings from this research will assist future catalysts to facilitate a design-led transformation within a manufacturing SME through the use of design tools and activities with greater effectiveness.