Tailoring Heme-Thiolate Proteins into Efficient Biocatalysts with High Specificity and Selectivity

Cytochrome P450 monooxygenases, one of the most important classes of heme-thiolate proteins, have attracted considerable interest in the biochemical community because of its catalytic versatility, substrate diversity and great number in the superfamily. Although P450s are capable of catalyzing numerous difficult oxidation reactions, the relatively low stability, low turnover rates and the need of electron-donating cofactors have limited their practical biotechnological and pharmaceutical applications as isolated enzymes. The goal of this study is to tailor such heme-thiolate proteins into efficient biocatalysts with high specificity and selectivity by protein engineering and to better understand the structure-function relationship in cytochromes P450. In the effort to engineer P450cam, the prototype member of the P450 superfamily, into an efficient peroxygenase that utilizes hydrogen peroxide via the “peroxide-shunt” pathway, site-directed mutagenesis has been used to elucidate the critical roles of hydrophobic residues in the active site. Various biophysical, biochemical and spectroscopic techniques have been utilized to investigate the wild-type and mutant proteins. Three important P450cam variants were obtained showing distinct structural and functional features. In P450camV247H mutant, which exhibited almost identical spectral properties with the wild-type, it is demonstrated that a single amino acid switch turned the monooxygenase into an efficient preoxidase by increasing the peroxidase activity nearly one thousand folds. In order to tune the distal pocket of P450cam with polar residues, Leu 246 was replaced with a basic residue, lysine, resulting in a mutant with spectral features identical to P420, the inactive species of P450. But this inactive-species-like mutant showed catalytic activities without the facilitation of any cofactors. By substituting Gly 248 with a histidine, a novel Cys-Fe-His ligation set was obtained in P450cam which represented the very rare case of His ligation in heme-thiolate proteins. In addition to serving as a convenient model for hemoprotein structural studies, the G248H mutant also provided evidence about the nature of the axial ligand in cytochrome P420 and other engineered hemoproteins with thiolate ligations. Furthermore, attempts have been made to replace the proximal ligand in sperm whale myoglobin to construct a heme-thiolate protein model by mimicking the protein environment of cytochrome P450cam and chloroperoxidase.

Biosynthesis of neocarazostatin A reveals the sequential carbazole prenylation and hydroxylation in the tailoring steps

Acknowledgments Y.Y. acknowledges the financial support from “973” Program (2012CB721006) and National Natural Science Foundation of China (31570033). R.E., K.K., H.D., and M.J. acknowledge the financial support of the Leverhulme Trust-Royal Society Africa Award (AA090088).

Resist-substrate interface tailoring for generating high density arrays of Ge and Bi2Se3 nanowires by electron beam lithography

The authors report a chemical process to remove the native oxide on Ge and Bi2Se3 crystals, thus facilitating high-resolution electron beam lithography (EBL) on their surfaces using a hydrogen silsesquioxane (HSQ) resist. HSQ offers the highest resolution of all the commercially available EBL resists. However, aqueous HSQ developers such as NaOH and tetramethylammonium hydroxide have thus far prevented the fabrication of high-resolution structures via the direct application of HSQ to Ge and Bi2Se3, due to the solubility of components of their respective native oxides in these strong aqueous bases. Here we provide a route to the generation of ordered, high-resolution, high-density Ge and Bi2Se3 nanostructures with potential applications in microelectronics, thermoelectric, and photonics devices.                         

Tailoring Magnetic, Mechanical and Dielectric Properties of Magnetorheological Elastomers based on Natural Rubber and Iron by Magnetic Field Assisted Curing for Possible Applications

If magnetism is universal in nature, magnetic materials are ubiquitous. A life without magnetism is unthinkable and a day without the influence of a magnetic material is unimaginable. They find innumerable applications in the form of many passive and active devices namely, compass, electric motor, generator, microphone, loud speaker, maglev train, magnetic resonance imaging, data recording and reading, hadron collider etc. The list is endless. Such is the influence of magnetism and magnetic materials in ones day to day life. With the advent of nanoscience and nanotechnology, along with the emergence of new areas/fields such as spintronics, multiferroics and magnetic refrigeration, the importance of magnetism is ever increasing and attracting the attention of researchers worldwide. The search for a fluid which exhibits magnetism has been on for quite some time. However nature has not bestowed us with a magnetic fluid and hence it has been the dream of many researchers to synthesize a magnetic fluid which is thought to revolutionize many applications based on magnetism. The discovery of a magnetic fluid by Jacob Rabinow in the year 1952 paved the way for a new branch of Physics/Engineering which later became magnetic fluids. This gave birth to a new class of material called magnetorheological materials. Magnetorheological materials are considered superior to electrorheological materials in that magnetorheology is a contactless operation and often inexpensive.Most of the studies in the past on magnetorheological materials were based on magnetic fluids. Recently the focus has been on the solid state analogue of magnetic fluids which are called Magnetorheological Elastomers (MREs). The very word magnetorheological elastomer implies that the rheological properties of these materials can be altered by the influence of an external applied magnetic field and this process is reversible. If the application of an external magnetic field modifies the viscosity of a magnetic fluid, the effect of external magnetic stimuli on a magnetorheological elastomer is in the modification of its stiffness. They are reversible too. Magnetorheological materials exhibit variable stiffness and find applications in adaptive structures of aerospace, automotive civil and electrical engineering applications. The major advantage of MRE is that the particles are not able to settle with time and hence there is no need of a vessel to hold it. The possibility of hazardous waste leakage is no more with a solid MRE. Moreover, the particles in a solid MRE will not affect the performance and durability of the equipment. Usually MR solids work only in the pre yield region while MR fluids, typically work in the post yield state. The application of an external magnetic field modifies the stiffness constant, shear modulus and loss modulus which are complex quantities. In viscoelastic materials a part of the input energy is stored and released during each cycle and a part is dissipated as heat. The storage modulus G′ represents the capacity of the material to store energy of deformation, which contribute to material stiffness. The loss modulusG′′ represents the ability of the material to dissipate the energy of deformation. Such materials can find applications in the form of adaptive vibration absorbers (ATVAs), stiffness tunable mounts and variable impedance surfaces. MREs are an important material for automobile giants and became the focus of this research for eventual automatic vibration control, sound isolation, brakes, clutches and suspension systems

CSR Communication - An Employee Perspective : Tailoring Internal Communication using Employee Preferences for Content, Style and Channel.

Corporate Social Responsibility (CSR) represents a theory and practice that is well-known and communicating its content has shown to play an important role in order to exploit its advantages and engage stakeholders on CSR issues. Even though, CSR communication has shown to be a real challenge, since corporations are encouraged to engage in CSR, but not to communicate too loud about this engagement. This study was inspired by Jenny Dawkins (2005) and her initial idea that tailoring CSR messages by exploring stakeholder preferences for content, style and channel, would solve the communication challenge. One stakeholder group that corporations are highly dependent on is employees and exploring their preferences for CSR communication became the purpose of this thesis: to understand employee preferences for style and channel within the content of CSR. This was of specific interest, since existing research on CSR communication has mainly been centered around financial and external issues on the expense of internal. In addition, the idea of a tailored approach has not gained any interest in research so far, and a possible explanation might be its diffuse meaning, a problem this thesis has addressed. In order to understand employee preferences for internal CSR communication, a qualitative case study research was conducted with in-depth interviews, observations and exercises at site. A total of 20 interviews were arranged in order to collect primary data during a one week prolong engagement at the case. The empirical findings from the respondents’ answers were then transcribed and analyzed using both inductive and theoretical thematic analysis. Based on the findings, the authors of this thesis contribute with two models that help practitioners to understand how to best communicate about various CSR content to employees. The first model developed suggests an implementation of the tailored approach for content, style and channel, and demonstrates a relationship between nature of content and constraint recognition. Also, the model explains how practitioners can provide CSR explanation in order to reduce skepticism and enable endorsement processes where employees communicate CSR to third parties. To show a more dependent relationship between how changes in nature of content and constraint recognition affect employee preferences, the authors created the "CSR Communication Grid". The authors made a theoretical contribution by clarifying and providing a framework for the tailoring approach as initially developed by Dawkins (2005). Additionally, the authors managed to draw a relation between Public Relations (PR) and CSR by referring models of PR to communication styles, which filled this gap in previous research.

Alcohol consumption among university students: a typology of consumption to aid the tailoring of effective public health policy

Objective: Elevated levels of alcohol consumption among university students are well documented. Policymakers have attempted to combat this issue at a university, national and international level. Tailoring public health policy to effectively tackle alcohol use is crucial. Using Q-methodology, the current study aims to develop a typology of alcohol consumption in the Irish university student population. Setting: A large Irish university. Participants Hundreds of possible statements on types of consumption were generated from a systematic review and a set of one-on-one interviews. These were reduced to 36 statements, 6 statements which define each of the 6 previously defined consumption types. Participants were advised to scan through the 36 statements and fill the statements into a ‘forced choice, standardised distribution’. Following this, a 45–90 min interview was conducted with students to illuminate subjectivity surrounding alcohol consumption. Analysis was conducted using PQ Method and NVivo software. Principal component analysis, followed by varimax rotation, was conducted to uncover the final factor information. Results: In total, 43 students completed the Q-study: 19 men and 24 women. A typology describing 4 distinct groupings of alcohol consumer was uncovered: the guarded drinker, the calculated hedonist, the peer-influenced drinker and the inevitable binger. Factor loadings of each of the consumer groupings were noted for type description. Conclusions: This is the first study to propose ideal types of alcohol consumption among a university student population. Further research is required to investigate the degree to which each of these ideal types is subscribed. However, this typology, in addition to informing public policy and strategies, will be a valuable analytic tool in future research.

The potential for a web based intervention to improve young adult passenger safety

Young drivers aged 17-24 are consistently overrepresented in motor vehicle crashes. Research has shown that a young driver’s crash risk increases when carrying similarly aged passengers, with fatal crash risk increasing two to three fold with two or more passengers. Recent growth in access to and use of the internet has led to a corresponding increase in the number of web based behaviour change interventions. An increasing body of literature describes the evaluation of web based programs targeting risk behaviours and health issues. Evaluations have shown promise for such strategies with evidence for positive changes in knowledge, attitudes and behaviour. The growing popularity of web based programs is due in part to their wide accessibility, ability for personalised tailoring of intervention messages, and self-direction and pacing of online content. Young people are also highly receptive to the internet and the interactive elements of online programs are particularly attractive. The current study was designed to assess the feasibility for a web based intervention to increase the use of personal and peer protective strategies among young adult passengers. An extensive review was conducted on the development and evaluation of web based programs. Year 12 students were also surveyed about their use of the internet in general and for health and road safety information. All students reported internet access at home or at school, and 74% had searched for road safety information. Additional findings have shown promise for the development of a web based passenger safety program for young adults. Design and methodological issues will be discussed.

Conceptualisation and facilitation of SOA governance

As organisations strive to improve their capabilities in the areas of Service Management and Service-oriented Architectures (SOA), SOA Governance is becoming an increasingly important success factor. However, the concept of SOA Governance is complex and not well-understood, and the adoption of an adequate SOA Governance approach in an organisation can be difficult. Tools that support SOA Governance mostly have a technical bias and rarely address organisational aspects. In this paper, we contribute to the field by specifying a conceptual meta model for SOA Governance that integrates the structure of major IT and SOA Governance frameworks into one consolidated view. By presenting this conceptualisation and a corresponding prototypical implementation of a tool that supports SOA Governance maturity assessment, reference framework exploration and company-specific tailoring of SOA Governance, we provide insights into the first step of a Design Science research project, i.e. the development of an important IT artefact.

A framework for managing wandering and preventing elopement

Purpose of the Study: A framework aids choice of interventions to manage wandering and prevent elopement in consideration of associated risks and mobility needs of wanderers. ---------- Design and Methods: A literature review, together with research results, published wandering tools, clinical reports, author clinical experience, and consensus-based judgments was used to build a decision-making framework. Results: Referencing a published definition of wandering and originating a clinical description of problematic wandering, authors introduce a framework comprising (1) wandering and related behaviors; (2) goals of wandering-specific care, (3) interpersonally, technologically, and policy-mediated wandering interventions, and (4) estimates of relative frequencies of wandering behaviors, magnitudes of elopement risk, and restrictiveness of strategies. ---------- Implications: Safeguarding wanderers from elopement risk is rendered person-centered and humane when goals of care guide intervention choice. Despite limitations, a reasoned, systematized approach to wandering management provides a basis for tailoring a specialized program of care. The need for framework refinement and related research is emphasized.

The consequences of substance use among gay and bisexual men : a consensual qualitative research analysis

- Background Substance use is common among gay/bisexual men and is associated with significant health risks (e.g. HIV transmission). The consequences of substance use, across the range of substances commonly used, have received little attention. The purpose of this study is to map participant’s beliefs about the effects of substance use to inform prevention, health promotion and clinical interventions. - Methods Participants were interviewed about experiences regarding their substance use and recruited through medical and sexual health clinics. Data were collected though a consumer panel and individual interviews. Responses regarding perceived consequences of substance use were coded using Consensual Qualitative Research (CQR) methodology. - Results Most participants reported lifetime use of alcohol, cannabis, stimulants and amyl nitrite, and recent alcohol and cannabis use. A wide range of themes were identified regarding participant’s thoughts, emotions and behaviours (including sexual behaviours) secondary to substance use, including: cognitive functioning, mood, social interaction, physical effects, sexual activity, sexual risk-taking, perception of sexual experience, arousal, sensation, relaxation, disinhibition, energy/activity level and numbing. Analyses indicated several consequences were consistent across substance types (e.g. cognitive impairment, enhanced mood), whereas others were highly specific to a given substance (e.g. heightened arousal post amyl nitrite use). - Conclusions Prevention and interventions need to consider the variety of effects of substance use in tailoring effective education programs to reduce harms. A diversity of consequences appear to have direct and indirect impacts on decision-making, sexual activity and risk-taking. Findings lend support for the role of specific beliefs (e.g. expectancies) related to substance use on risk-related cognitions, emotions and behaviours.

Healthy children, healthy planet : the case for transformative education in schools and early childhood from an Australian perspective

Climate change is an urgent global public health issue with substantial predicted impacts in the coming decades. Concurrently, global burden of disease studies highlight problems such as obesity, mental health problems and a range of other chronic diseases, many of which have origins in childhood. There is a unique opportunity to engage children in both health promotion and education for sustainability during their school years to help ameliorate both environmental and health issues. Evidence exists for the most effective ways to do this, through education that is empowering, action orientated and relevant to children’s day to day interests and concerns, and by tailoring such education to different educational sectors. The aim of this discussion paper is to argue the case for sustainability education in schools that links with health promotion and that adopts a practical approach to engaging children in these important public health and environmental issues. We describe two internationally implemented whole-school reform movements, Health Promoting Schools (HPS) and Sustainable Schools (SS) which seek to operationalise transformative educational processes. Drawing on international evidence and Australian case examples, we contend that children’s active involvement in such processes is not only educationally engaging and rewarding, it also contributes to human and environmental resilience and health. Further, school settings can play an important ecological public health role, incubating and amplifying the socially transformative changes urgently required to create pathways to healthy, just and sustainable human futures, on a viable planet.

Road safety messages tailored for young adults : Using the Internet and encouraging protective passenger behaviour

Young drivers are at higher risk of crashes than other drivers when carrying passengers. Graduated Driver Licensing has demonstrated effectiveness in reducing fatalities however there is considerable potential for additional strategies to complement the approach. A survey with 276 young adults (aged 17-25 years, 64% females) was conducted to examine the potential and importance of strategies that are delivered via the Internet and potential strategies for passengers. Strategies delivered via the Internet represent opportunity for widespread dissemination and greater reach to young people at times convenient to them. The current study found some significant differences between males and females with regard to ways the Internet is used to obtain road safety information and the components valued in trusted road safety sites. There were also significant differences between males and females on the kinds of strategies used as passengers to promote driver safety and the context in which it occurred, with females tending to take more proactive strategies than males. In sum, young people see value in Internet delivery for passenger safety information (80% agreed/ strongly agreed) and more than 90% thought it was important to intervene while a passenger of a risky driver. Thus tailoring Internet road safety strategies to young people may differ for males and females however there is considerable potential for a passenger focus in strategies aimed at reducing young driver crashes.

Definition of an airworthiness certification framework for civil unmanned aircraft systems

The development of effective safety regulations for unmanned aircraft systems (UAS) is an issue of paramount concern for industry. The development of this framework is a prerequisite for greater UAS access to civil airspace and, subsequently, the continued growth of the UAS industry. The direct use of the existing conventionally piloted aircraft (CPA) airworthiness certification framework for the regulation of UAS has a number of limitations. The objective of this paper is to present one possible approach for the structuring of airworthiness regulations for civilian UAS. The proposed approach facilitates a more systematic, objective and justifiable method for managing the spectrum of risk associated with the diversity of UAS and their potential operations. A risk matrix is used to guide the development of an airworthiness certification matrix (ACM). The ACM provides a structured categorisation that facilitates the future tailoring of regulations proportionate to the levels of risk associated with the operation of the UAS. As a result, an objective and traceable link may be established between mandated regulations and the overarching objective for an equivalent level of safety to CPA. The ACM also facilitates the systematic consideration of a range of technical and operational mitigation strategies. For these reasons, the ACM is proposed as a suitable method for the structuring of an airworthiness certification framework for civil or commercially operated UAS (i.e., the UAS equivalent in function to the Part 21 regulations for civil CPA) and for the further structuring of requirements on the operation of UAS in un-segregated airspace.

Healthy children and a healthy planet : a role for education

Climate change is an urgent global public health issue with substantial predicted impacts in the coming decades. Concurrently, global burden of disease studies highlight problems such as obesity, mental health problems and a range of other chronic diseases, many of which have origins in childhood. There is a unique opportunity to engage children in both health promotion and education for sustainability during their school years to help ameliorate both environmental and health issues. Evidence exists for the most effective ways to do this, through education that is empowering, action orientated and relevant to children’s day to day interests and concerns, and by tailoring such education to different educational sectors. The aim of this chapter is to argue the case for sustainability education in schools that links with health promotion and that adopts a practical approach to engaging children in these important public health and environmental issues. We describe two internationally implemented whole-school reform movements, Health Promoting Schools (HPS) and Sustainable Schools (SS) which seek to operationalise transformative educational processes. Drawing on international evidence and Australian case examples, we contend that children’s active involvement in such processes is not only educationally engaging and rewarding, it also contributes to human and environmental resilience and health. Further, school settings can play an important ecological public health role, incubating and amplifying the socially transformative changes urgently required to create pathways to healthy, just and sustainable human futures, on a viable planet.

Planning for knowledge based urban development in Malaysia : Cyberjaya @ Multimedia Super Corridor

Knowledge based urban development (KBUD) is a new paradigm in urban planning tailoring to the era of knowledge economy. It aims mainly to assist a contemporary city to promote a more sustainable socio-spatial order. The paper reports on the investigation of KBUD initiative in Malaysia which is manifested through the establishment of a project called Multimedia Super Corridor (MSC). MSC Malaysia aims to attract knowledge workers and industries to invest and operate within the area by creating a world class urban corridor with state-of-the-art multimedia infrastructure, efficient transportation system and an attractive living environment. Based on documents analysis and interviews, this paper analyses the strategies, implementations, and achievements of KBUD initiative in Cyberjaya, being the leading intelligent city of the unique Malaysia’s KBUD project-MSC Malaysia. A critical evaluation is made to assess the achievements of MSC, by looking at the physical changes after about ten years since its official launching. The findings recommend some valuable lessons for other cities that strive to develop KBUD strategies, strengthen their sustainable socio-spatial policies, and seek a global recognition.