Anti-infectives

18.1 Antibiotics 18.1.1 Introduction to bacteria 18.1.2 Introduction to antibiotics 18.1.3 Inhibitors of bacterial cell wall synthesis 18.1.3.1 β-Lactams 18.1.3.2 Glycopeptides 18.1.4 Inhibitors of bacterial protein synthesis 18.1.4.1 Tetracyclines 18.1.4.2 Aminoglycosides 18.1.4.3 Chloramphenicol 18.1.4.4 Macrolides 18.1.4.5 Lincosamides 18.1.4.6 Oxalazidones 18.1.5 Inhibitors of DNA synthesis 18.2. Anti-tuberculotic drugs 18.2.1 Introduction 18.2.2 Isoniazid 18.2.3 Ethambutol 18.2.4 Rifamycin 18.2.5 Pyrazinamide 18.3. Anti-viral drugs 18.3.1 Introduction to viruses 18.3.2 Drugs used to treat herpesviruses 18.3.3 Drugs used to treat the flu 18.3.4 Drugs used to treat HIV/AIDS 18.4. Antifungal drugs 18.4.1 Introduction to Fungi 18.4.2 Antifungal drugs

Plant made anti-HIV microbicides-A field of opportunity

HIV remains a significant global burden and without an effective vaccine, it is crucial to develop microbicides to halt the initial transmission of the virus. Several microbicides have been researched with various levels of success. Amongst these, the broadly neutralising antibodies and peptide lectins are promising in that they can immediately act on the virus and have proven efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate molecules, it appears that current production systems are overburdened and expensive to establish and maintain. With recent developments in vector systems for protein expression coupled with downstream protein purification technologies, plants are rapidly gaining credibility as alternative production systems. Here we evaluate the advances made in host and vector system development for plant expression as well as the progress made in expressing HIV neutralising antibodies and peptide lectins using plant-based platforms. © 2012 Elsevier Inc.

Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production

Background Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system. Results Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs. Conclusion Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.

Ultimate limit states design of concrete railway sleepers

The railway industry has been slow to adopt limit states principles in the structural design of concrete sleepers for its tracks, despite the global take up of this form of design for almost every other type of structural element. Concrete sleeper design is still based on limiting stresses but is widely perceived by track engineers to lead to untapped reserves of strength in the sleepers. Limit design is a more rational philosophy, especially where it is based on the ultimate dynamic capacity of the concrete sleepers. The paper describes the development of equations and factors for a limit design methodology for concrete sleepers in flexure using a probabilistic evaluation of sleeper loading. The new method will also permit a cogent, defensible means of establishing the true capacity of the billions of concrete sleepers that are currently in-track around the world, leading to better utilisation of track infrastructure. The paper demonstrates how significant cost savings may be achieved by track owners.

Briefing: Limit states design of railway concrete sleepers

Recently updated information has raised a concern over not only the existing cost-ineffective design method but also the unrealistic analysis mode of railroad prestressed concrete sleepers. Because of the deficient knowledge in the past, railway civil engineers have been mostly aware of the over-conservative design methods for structural components in any railway track, which rely on allowable stresses and material strength reductions. Based on a number of proven experiments and field data, it is believed that the concrete sleepers which complied with the allowable stress concept possess unduly untapped fracture toughness. A collaborative research project run by the Australian Cooperative Research Centre for Railway Engineering and Technologies (RailCRC) was initiated to ascertain the reserved capacity of Australian railway prestressed concrete sleepers designed using the existing design code. The findings have led to the development of a new limit states design concept. This briefing highlights the conventional and the new limit states design philosophies and their implication to both the railway and the public community.

Social cars : sensing, gathering, sharing and conveying social cues to road users

Intelligent Transport Systems (ITS) resembles the infrastructure for ubiquitous computing in the car. It encompasses a) all kinds of sensing technologies within vehicles as well as road infrastructure, b) wireless communication protocols for the sensed information to be exchanged between vehicles (V2V) and between vehicles and infrastructure (V2I), and c) appropriate intelligent algorithms and computational technologies that process these real-time streams of information. As such, ITS can be considered a game changer. It provides the fundamental basis of new, innovative concepts and applications, similar to the Internet itself. The information sensed or gathered within or around the vehicle has led to a variety of context-aware in-vehicular technologies within the car. A simple example is the Anti-lock Breaking System (ABS), which releases the breaks when sensors detect that the wheels are locked. We refer to this type of context awareness as vehicle/technology awareness. V2V and V2I communication, often summarized as V2X, enables the exchange and sharing of sensed information amongst cars. As a result, the vehicle/technology awareness horizon of each individual car is expanded beyond its observable surrounding, paving the way to technologically enhance such already advanced systems. In this chapter, we draw attention to those application areas of sensing and V2X technologies, where the human (driver), the human’s behavior and hence the psychological perspective plays a more pivotal role. The focal points of our project are illustrated in Figure 1: In all areas, the vehicle first (1) gathers or senses information about the driver. Rather than to limit the use of such information towards vehicle/technology awareness, we see great potential for applications in which this sensed information is then (2) fed back to the driver for an increased self-awareness. In addition, by using V2V technologies, it can also be (3) passed to surrounding drivers for an increased social awareness, or (4), pushed even further, into the cloud, where it is collected and visualized for an increased, collective urban awareness within the urban community at large, which includes all city dwellers.

The extrusion of continuous lengths of YBa2Cu3O7-x wire using hydroxypropyl methylcellulose

Wires of YBa2Cu3O7-x were fabricated by extrusion using a hydroxypropyl methylcellulose (HPMC) binder. As little as 2 wt.% binder was added to an oxide prepared by a novel co-precipitation process, to produce a plastic mass which readily gave continuous extrusion of long lengths of wire in a reproducible fashion. Critical temperatures of 92K were obtained for wires given optimum high-temperature heat treatments. Critical current densities greater than 1000 A cm-1 were measured at 77.3K using heat treatments at around 910°C for 10h. These transport critical current densities, measured on centimeter-long wires, were obtained with microstructures showing a relatively dense and uniform distribution of randomly oriented, small YBa2Cu3O7-x grains. © 1993.

Continuous and non-intrusive identity verification in real-time environments based on free-text keystroke dynamics

Internet services are important part of daily activities for most of us. These services come with sophisticated authentication requirements which may not be handled by average Internet users. The management of secure passwords for example creates an extra overhead which is often neglected due to usability reasons. Furthermore, password-based approaches are applicable only for initial logins and do not protect against unlocked workstation attacks. In this paper, we provide a non-intrusive identity verification scheme based on behavior biometrics where keystroke dynamics based-on free-text is used continuously for verifying the identity of a user in real-time. We improved existing keystroke dynamics based verification schemes in four aspects. First, we improve the scalability where we use a constant number of users instead of whole user space to verify the identity of target user. Second, we provide an adaptive user model which enables our solution to take the change of user behavior into consideration in verification decision. Next, we identify a new distance measure which enables us to verify identity of a user with shorter text. Fourth, we decrease the number of false results. Our solution is evaluated on a data set which we have collected from users while they were interacting with their mail-boxes during their daily activities.

Non-intrusive continuous user behaviour analysis using computerized systems

There are different ways to authenticate humans, which is an essential prerequisite for access control. The authentication process can be subdivided into three categories that rely on something someone i) knows (e.g. password), and/or ii) has (e.g. smart card), and/or iii) is (biometric features). Besides classical attacks on password solutions and the risk that identity-related objects can be stolen, traditional biometric solutions have their own disadvantages such as the requirement of expensive devices, risk of stolen bio-templates etc. Moreover, existing approaches provide the authentication process usually performed only once initially. Non-intrusive and continuous monitoring of user activities emerges as promising solution in hardening authentication process: iii-2) how so. behaves. In recent years various keystroke dynamic behavior-based approaches were published that are able to authenticate humans based on their typing behavior. The majority focuses on so-called static text approaches, where users are requested to type a previously defined text. Relatively few techniques are based on free text approaches that allow a transparent monitoring of user activities and provide continuous verification. Unfortunately only few solutions are deployable in application environments under realistic conditions. Unsolved problems are for instance scalability problems, high response times and error rates. The aim of this work is the development of behavioral-based verification solutions. Our main requirement is to deploy these solutions under realistic conditions within existing environments in order to enable a transparent and free text based continuous verification of active users with low error rates and response times.

Drivers' intention to comply with the speed limit in school zones, in Malaysia

There has been an increasing number of fatal road crashes in Malaysia in the last two decades. Among those who die on Malaysian roads are children aged 0 to 18 years (i.e., 15.5% in 2009) (Mohamed, Wong, Hashim, & Othman, 2011) . The involvement of children in road trauma, and particularly children when they are in and around school zones, generates concern among the general public. The present study utilised an extended Theory of Planned Behaviour (TPB) framework, incorporating the additional predictors of mindfulness and habit, to understand drivers’ intention to comply with the school zone speed limit (SZSL). The study aimed to examine the extent to which TPB constructs, and additional predictors of mindfulness and habit, predicted drivers’ behavioural intention to comply with the SZSL. Malaysian drivers (N = 210) participated in this study via an online survey. Hierarchical regression was conducted, and the results showed that attitude, subjective norm, perceived behavioural control, and habit were significant predictors of intention to comply with the SZSL. Specifically, drivers who expressed more positive attitudes towards compliance, greater belief that significant others would want them to comply, and more confidence in their control of their speed were more likely to report an intention to comply. These drivers appear to have developed a positive habit of compliance, which may simply be a result of the engineering measures in place around school zones in Malaysia. Mindfulness was not a significant predictor in the final model. These findings provide some support for the explanatory value of the extended TPB framework in understanding the factors influencing drivers’ intention to comply with the SZSL. The present study also provides information of potential value in the development of interventions, such as public education and mass media campaigns, aimed at improving drivers’ compliance with the SZSL.

A Process and Outcome Evaluation of the Under the Limit (UTL) Therapeutic Drink Driving Program for Recidivist and High Range Offenders

Drink driving is a major public health issue and this report examines the experiences of convicted offenders who participated in an established drink driving rehabilitation program Under the Limit (UTL). Course completers were surveyed at least three months after they had finished the 11-week UTL course. The aim of this study was to examine whether the UTL program reduced the level of alcohol consumption either directly as a result of participation in the UTL drink driving program or through increased use of community alcohol program by participants. The research involved a self-report outcome evaluation to determine whether the self-reported levels of alcohol use after the course had changed from the initial alcohol use reported by offenders. The findings are based on the responses of 30 drink-driving offenders who had completed the UTL program (response rate: 20%). While a process evaluation was proposed in the initial application, the low response rate meant that this follow up research was not feasible. The response rate was low for two reasons, it was difficult to: recruit participants who consented to follow up, and subsequently locate and survey those who had consented to involvement.

The relationship between anti-mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women : evidence from large population studies

Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause. Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set. Setting: AMH was measured in 27 563 women attending fertility clinics. Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect- EPIC) cohort (n � 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated. Main Outcome: The main outcome was conformity between observed and predicted AMP. Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (�0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report. Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.

Statutory-backed continuous disclosure regime and corporate disclosure behaviour : does corporate governance matter?

Since 1 December 2002, the New Zealand Exchange’s (NZX) continuous disclosure listing rules have operated with statutory backing. To test the effectiveness of the new corporate disclosure regime, we compare the change in quantity of market announcements (overall, non-routine, non-procedural and external) released to the NZX before and after the introduction of statutory backing. We also extend our study in investigating whether the effectiveness of the new corporate disclosure regime is diminished or augmented by corporate governance mechanisms including board size, providing separate roles for CEO and Chairman, board independence, board gender diversity and audit committee independence. Our findings provide a qualified support for the effectiveness of the new corporate disclosure regime regarding the quantity of market disclosures. There is strong evidence that the effectiveness of the new corporate disclosure regime was augmented by providing separate roles for CEO and Chairman, board gender diversity and audit committee independence, and diminished by board size. In addition, there is significant evidence that share price queries do impact corporate disclosure behaviour and this impact is significantly influenced by corporate governance mechanisms. Our findings provide important implications for corporate regulators in their quest for...

Statutory-backed continuous disclosure regime and corporate disclosure behaviour : does corporate governance matter?

Since 1 December 2002, the New Zealand Exchange’s (NZX) continuous disclosure listing rules have operated with statutory backing. To test the effectiveness of the new corporate disclosure regime, we compare the change in quantity of market announcements (overall, non-routine, non-procedural and external) released to the NZX before and after the introduction of statutory backing. We also extend our study in investigating whether the effectiveness of the new corporate disclosure regime is diminished or augmented by corporate governance mechanisms including board size, providing separate roles for CEO and Chairman, board independence, board gender diversity and audit committee independence. Our findings provide a qualified support for the effectiveness of the new corporate disclosure regime regarding the quantity of market disclosures. There is strong evidence that the effectiveness of the new corporate disclosure regime was augmented by providing separate roles for CEO and Chairman, board gender diversity and audit committee independence, and diminished by board size. In addition, there is significant evidence that share price queries do impact corporate disclosure behaviour and this impact is significantly influenced by corporate governance mechanisms. Our findings provide important implications for corporate regulators in their quest for a superior disclosure regime.

Emptiness and fullness : Pinter, anti-architecture and politics

Classical architecture has a long history of representing the idealized proportions of the human body, derived from the Vitruvian man. This association with the idealized human form has also associated architecture as symbiotic with prevailing power structures. Meaning that architecture is always loaded with some signification, it creates a highly inscribed space. In the absence of architecture space is not necessarily without inscription, for within the void there can exist an anti-architecture. Like the black box theatre, it is both empty and full at the same time, in the absence of the architecture, the void of space and how it is occupied becomes much more profound. As Dorita Hannah writes, ‘In denying a purely visual apprehension of built space, and suggesting a profound interiority, the black-box posits a new way of regarding the body in space.’ This paper analyses the work of Harold Pinter and his use of the body to create an anti-architecture to subvert oppressors and power structures. Pinter’s works are an important case study in this research due to their political nature. His works are also heavily tied to territory, which bound the works in a dependent relationship with a simulated ‘place’. In the citation accompanying the playwright’s Nobel Laureate it states, '...in his plays [he] uncovers the precipice under everyday prattle and forces entry into oppression's closed rooms.' In Pinter’s work oppression manifests itself in the representation of a room, the architecture, which is the cause of a power struggle when objectified and defeated when subjectified. The following work examines how Pinter uses the body to subjectify and represent architecture as authority in his earlier works, which relied on detailed mimetic sets of domestic rooms, and then in his later political works, that were freed of representational scenography. This paper will also look at the adaption of Pinter’s work by the Belarus Free Theatre in their 2008 production of ‘Being Harold Pinter.’ The work of Pinter and the Belarus Free Theatre are concerned with authoritarian political structures. That is, political structures that works against ideas of individualism, ascribing to a mass-produced body as an artifact of dictatorship and conservatism. The focus on the body in space on an empty stage draws attention to the individual – the body amongst scenography can become merely another prop, lost in the borders and boundaries the scenery dictates. Through an analysis of selected works by Harold Pinter and their interpretations, this paper examines this paradox of emptiness and fullness through the body as anti-architecture in performance.