Inorganic-organic composite particle as a staged delivery platform for plasmid DNA-based biopharmaceuticals

Infectious diseases such as SARS, influenza and bird flu may spread exponentially throughout communities. In fact, most infectious diseases remain major health risks due to the lack of vaccine or the lack of facilities to deliver the vaccines. Conventional vaccinations are based on damaged pathogens, live attenuated viruses and viral vectors. If the damage was not complete, the vaccination itself may cause adverse effects. Therefore, researchers have been prompted to prepare viable replacements for the attenuated vaccines that would be more effective and safer to use. DNA vaccines are generally composed of a double stranded plasmid that includes a gene encoding the target antigen under the transcriptional directory and control of a promoter region which is active in cells. Plasmid DNA (pDNA) vaccines allow the foreign genes to be expressed transiently in cells, mimicking intracellular pathogenic infection and inducing both humoral and cellular immune responses. Currently, because of their highly evolved and specialized components, viral systems are the most effective means for DNA delivery, and they achieve high efficiencies (generally >90%), for both DNA delivery and expression. As yet, viral-mediated deliveries have several limitations, including toxicity, limited DNA carrying capacity, restricted target to specific cell types, production and packing problems, and high cost. Thus, nonviral systems, particularly a synthetic DNA delivery system, are highly desirable in both research and clinical applications.

How to plan and implement an environmental education program for a conservation area : lessons from Australia and Borneo

The Augo Wetland Forest Park, along with other conservation areas around the world, provides an opportunity for a personal connection with the natural world - an opportunity for creating ways to convince people to reverse the degradation of the planet. In this presentation I use the settings approach, as used by the World Health Organisation in health promotion, as a framework. The WHO’s 1986 Ottawa Charter states that "Health is created and lived by people within the settings of their everyday life; where they learn, work, play, and love." I argue that, similarly, a conservation area provides a setting for people to connect with environmental issues and can be the place where positive behaviours and actions for the environment are created and enacted. In a wired and virtual world, such settings may be the only opportunity some people, especially children, get to connect with the environment. An evidence-based, intentionally designed and implemented environmental education program enhances the opportunities for the personal connection and subsequent action. Planning and implementing an Environmental education program for a conservation area requires an understanding of the principles of three domains: • Environmental Communication • Environmental Education • Environmental Interpretation In this presentation I define these domains and demonstrate how they become interdependent within the context of a particular setting such as a conservation area. I outline the principles of each domain and demonstrate how they can be enacted with reference to environmental education program case studies from settings in Australia and Borneo. The first case study is based around a proposal for a planned residential community at Eden’s Crossing, in Brisbane’s high growth Western corridor. The setting featured a number of important natural and heritage conservation characteristics and the developer wanted to be pro-active in informing the market what this development aims to achieve in terms of innovative community and environmental objectives. By designing an education and interpretation program in line with best practice education and interpretation principles the developers would be assisted in their efforts to build community, preserve heritage, and facilitate environmentally sensitive lifestyles for the future residents of Eden’s Crossing. Above all, the strategy focused on advancing sustainability in a way that made the Eden’s Crossing greenfield development significantly greener. It did this by interacting with prospective purchasers, and building knowledge about sustainability with a view to shaping the future community of Eden’s Crossing in terms of attitudes and behaviours. The second case study is based around the development of the Rainforest Interpretation Centre (RIC), now renamed the Rainforest Discovery Centre, an environmental education facility managed by the Sabah Forestry Department (SFD) and located at the edge of the Kabili-Sepilok Forest Reserve in the East Malaysian state of Sabah (Borneo). This setting is of paramount importance for biodiversity conservation and research and a vital habitat for orang utan. As an Environmental Education Consultant I was tasked with developing an environmental education program for this setting as part of the SFD’s long- term strategy towards sustainable forest management. By employing the principles of Environmental Education and Environmental Interpretation I designed and implemented a program with three major components: • an environmental education component for visiting primary and secondary school groups. • an environmental education component for in-service and pre-service teachers and teacher educators. • a public awareness and environmental interpretation component which caters for the general public and tourists. From these modest beginnings the program has expanded and new facilities have been developed to meet the demands of visitors, teachers and students. The effectiveness of the program can be traced back to the grounding in the principles of best practice environmental education, communication and interpretation.

Discovering future disaster management capability needs using scenario planning

In recent years disaster risk reduction efforts have focused on disturbances ranging from climate variability, seismic hazards, geo-political instability and public and animal health crises. These factors combined with uncertainty derived from inter-dependencies within and across systems of critical infrastructure create significant problems of governance for the private and public sector alike. The potential for rapid spread of impacts, geographically and virtually, can render a comprehensive understanding of disaster response and recovery needs and risk mitigation issues beyond the grasp of competent authority. Because of such cascading effects communities and governments at local and state-levels are unlikely to face single incidents but rather series of systemic impacts: often appearing concurrently. A further point to note is that both natural and technological hazards can act directly on socio-technical systems as well as being propagated by them: as network events. Such events have been categorised as ‘outside of the box,’ ‘too fast,’ and ‘too strange’ (Lagadec, 2004). Emergent complexities in linked systems can make disaster effects difficult to anticipate and recovery efforts difficult to plan for. Beyond the uncertainties of real world disasters, that might be called familiar or even regular, can we safely assume that the generic capability we use now will suit future disaster contexts? This paper presents initial scoping of research funded by the Bushfire and Natural Hazards Cooperative Research Centre seeking to define future capability needs of disaster management organisations. It explores challenges to anticipating the needs of representative agencies and groups active in before, during and after phases of emergency and disaster situations using capability deficit assessments and scenario assessment.

Lipid-modified azurin of Neisseria meningitidis is a copper protein localized on the outer membrane surface and not regulated by FNR

The laz gene of Neisseria meningitidis is predicted to encode a lipid-modified azurin (Laz). Laz is very similar to azurin, a periplasmic protein, which belongs to the copper-containing proteins in the cupredoxin superfamily. In other bacteria, azurin is an electron donor to nitrite reductase, an important enzyme in the denitrifying process. It is not known whether Laz could function as an electron transfer protein in this important pathogen. Laz protein was heterologously expressed in Escherichia coli and purified. Electrospray mass spectrometry indicated that the Laz protein contains one copper ion. Laz was shown to be redox-active in the presence of its redox center copper ion. When oxidized, Laz exhibits an intense blue colour and absorbs visible light around 626 nm. The absorption is lost when exposed to diethyldithiocarbamate, a copper chelating agent. Polyclonal antibodies were raised against purified Laz for detecting expression of Laz under different growth conditions and to determine the orientation of Laz on the outer membrane. The expression of Laz under microaerobic and microaerobic denitrifying conditions was slightly higher than that under aerobic conditions. However, the expression of Laz was similar between the wild type strain and an fnr mutant, suggesting that Fumarate/Nitrate reduction regulator (FNR) does not regulate the expression of Laz despite the presence of a partial FNR box upstream of the laz gene. We propose that some Laz protein is exposed on the outer membrane surface of N. meningitidis as the αLaz antibodies can increase killing by complement in a capsule deficient N. meningitidis strain, in a dose-dependent fashion.

Engaging a multiple-track approach to building capacity for 21st Century engineering, opportunities and challenges for rapid curriculum renewal

‘Complexity’ is a term that is increasingly prevalent in conversations about building capacity for 21st Century professional engineers. Society is grappling with the urgent and challenging reality of accommodating seven billion people, meeting needs and innovating lifestyle improvements in ways that do not destroy atmospheric, biological and oceanic systems critical to life. Over the last two decades in particular, engineering educators have been active in attempting to build capacity amongst professionals to deliver ‘sustainable development’ in this rapidly changing global context. However curriculum literature clearly points to a lack of significant progress, with efforts best described as ad hoc and highly varied. Given the limited timeframes for action to curb environmental degradation proposed by scientists and intergovernmental agencies, the authors of this paper propose it is imperative that curriculum renewal towards education for sustainable development proceeds rapidly, systemically, and in a transformational manner. Within this context, the paper discusses the need to consider a multiple track approach to building capacity for 21st Century engineering, including priorities and timeframes for undergraduate and postgraduate curriculum renewal. The paper begins with a contextual discussion of the term complexity and how it relates to life in the 21st Century. The authors then present a whole of system approach for planning and implementing rapid curriculum renewal that addresses the critical roles of several generations of engineering professionals over the next three decades. The paper concludes with observations regarding engaging with this approach in the context of emerging accreditation requirements and existing curriculum renewal frameworks.

Public Health Psychology: A Conceptual and Practical Framework

Introduction For many years concern for public health has transcended the boundaries of the medical sciences and epidemiology. For the last 50 years or so psychologists have been increasingly active in this field. Recently, psychologists have not only begun to see the need to take action to mould health promoting behaviours in individuals, but have also pointed out the need to join in an effort to develop appropriate social, political, economic and institutional conditions which would help to improve the state of public health. Psychologists have postulated the need to distinguish a new subdiscipline of psychology called public health psychology which, together with other disciplines, would further the realization of this goal. In the following article the historical and international context of health psychology and the changing nature of public health are put forward as having important implications for the establishment of a ‘public health psychology’. These implications are addressed in later sections of the article through the description of conceptual and practical framework of public health psychology in which theory, methods and practice are considered. Many aspects of the conceptual and practical framework of public health psychology have relevance to the health social sciences more generally and forming a basis for interdisciplinary work. The framework of public health psychology, together with the obstacles that need to be overcome, are critically examined within an overall approach that contends it is necessary to increase and improve the contribution of health psychology to public health.

Au-Pd alloy nanoparticle catalyzed selective oxidation of benzyl alcohol and tandem synthesis of imines at ambient conditions

Alloy nanoparticles (NPs) of gold and palladium on ZrO2 support (Au–Pd@ZrO2) were found to be highly active in oxidation of benzyl alcohols and can be used for the tandem synthesis of imines from benzyl alcohols and amines via a one-pot, two-step process at mild reaction conditions. The first step of the process is oxidation of benzyl alcohol to benzaldehyde, excellent yields were achieved after 7 h reaction at 40 °C without addition of any base. In the second step, aniline was introduced into the reaction system to produced N-benzylideneaniline. The benzaldehyde obtained in the first step was completely consumed within 1 h. A range of benzyl alcohols and amines were investigated for the general applicability of the Au–Pd alloy catalysts. It is found that the performance of the catalysts depends on the Au–Pd metal contents and composition. The optimal catalyst is 3.0 wt% Au–Pd@ZrO2 with a Au:Pd molar ratio 1:1. The alloy NP catalyst exhibited superior catalytic properties to pure AuNP or PdNP because the surface of alloy NPs has higher charge heterogeneity than that of pure metal NPs according to simulation of density function theory (DFT)

Exploring collaborative modeling of business processes on large interactive touch display walls - video

Analyzing and redesigning business processes is a complex task, which requires the collaboration of multiple actors. Current approaches focus on collaborative modeling workshops where process stakeholders verbally contribute their perspective on a process while modeling experts translate their contributions and integrate them into a model using traditional input devices. Limiting participants to verbal contributions not only affects the outcome of collaboration but also collaboration itself. We created CubeBPM – a system that allows groups of actors to interact with process models through a touch based interface on a large interactive touch display wall. We are currently in the process of conducting a study that aims at assessing the impact of CubeBPM on collaboration and modeling performance. Initial results presented in this paper indicate that the setting helped participants to become more active in collaboration.

Exploring collaborative modeling of business processes on large interactive touch display walls

Analyzing and redesigning business processes is a complex task, which requires the collaboration of multiple actors. Current approaches focus on collaborative modeling workshops where process stakeholders verbally contribute their perspective on a process while modeling experts translate their contributions and integrate them into a model using traditional input devices. Limiting participants to verbal contributions not only affects the outcome of collaboration but also collaboration itself. We created CubeBPM – a system that allows groups of actors to interact with process models through a touch based interface on a large interactive touch display wall. We are currently in the process of conducting a study that aims at assessing the impact of CubeBPM on collaboration and modeling performance. Initial results presented in this paper indicate that the setting helped participants to become more active in collaboration.

Photoinduced DNA and Protein Cleavage Activity of Ferrocene-Conjugated Ternary Copper(II) Complexes

Ferrocene-conjugated ternary copper(II) complexes [Cu(L)(B)](ClO4)(2), where L is FcCH(2)N(CH2Py)(2) (Fc = (eta(5)-C5H4)Fe-II(eta(5)-C5H5)) and B is a phenanthroline base, viz., 2,2'-bipyridine (bpy, 1), 1, 10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4), have been synthesized and characterized by various spectroscopic and analytical techniques. The bpy complex 1, as its hexafluorophosphate salt, has been structurally characterized by X-ray crystallography. The molecular structure shows the copper(II) center having an essentially square-pyramidal coordination geometry in which L with a pendant ferrocenyl (Fc) moiety and bpy show respective tridentate and bidentate modes of binding to the metal center. The complexes are redox active, showing a reversible cyclic voltammetric response of the Fc(+)-Fc couple near 0.5 V vs SCE and a quasi-reversible Cu(II)-Cu(I) couple near 0.0 V. Complexes 2-4 show binding affinity to calf thymus (CT) DNA, giving binding constant (K-b) values in the range of 4.2 x 10(4) to 2.5 x 10(5) M-1. Thermal denaturation and viscometric titration data suggest groove binding and/or a partial intercalative mode of binding of the complexes to CT DNA. The complexes show good binding propensity to the bovine serum albumin (BSA) protein, giving K-BSA values of similar to 10(4) M-1 for the bpy and phen complexes and similar to 10(5) M-1 for the dpq and dppz complexes. Complexes 2-4 exhibit efficient chemical nuclease activity in the presence of 3-mercapto-propionic acid (MPA) as a reducing agent or hydrogen peroxide (H2O2) as an oxidizing agent. Mechanistic studies reveal formation of hydroxyl radicals as the reactive species. The dpq and dppz complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to visible light of different wavelengths including red light using an argon-krypton mixed gas ion laser. Mechanistic investigations using various inhibitors reveal the fort-nation of hydroxyl radicals in the DNA photocleavage reactions. The dppz complex 4, which shows efficient photoioduced BSA cleavage activity, is a potent multifunctional model nuclease and protease in the chemistry of photodynamic therapy (PDT) of cancer.

Simultaneous Electrodeposition of MnO2 and Mn(OH)(2) for Supercapacitor Studies

Among the various Mn compounds, both MnO2 and Mn(OH)2 are electrochemically active in supercapacitor studies. MnO2 and Mn(OH)2 are simultaneously deposited, through a one-pot method, on the anode and cathode, respectively, of a galvanostatic electrolysis cell consisting of aqueous Mn(NO3)2 electrolyte. MnO2 and Mn(OH)2 coated stainless steel (SS) electrodes are found to exhibit a capacitive behavior with a high specific capacitance. MnO2/SS and Mn(OH)2/SS electrodes are used as the negative and positive electrodes, respectively, in assembling nonsymmetrical capacitors and testing. The results indicate that both Mn-based electrodes prepared simultaneously in a single electrolysis possess interesting electrochemical properties for supercapacitor application.

Rikollisia sattumalta? : Naisten keskinäistä haureutta koskevat oikeudenkäynnit 1950-luvun Itä-Suomessa

The main focus of the research is on the genealogy of women's same-sex fornication in Finnish criminal law from 1889/1894 to 1971. Why were women included in the concept of same-sex fornication in Finland and why, where, and when was the law put into effect? Which women were tried, how did the trial proceedings evolve, and what kind of effects did the trials have afterwards? Which concepts were used? These questions have been approached through the analysis of the Finnish Penal Code, the criminal law science and four trial proceedings in Eastern Finland during the 1950s. The research draws on the epistemology of the closet and the concept of heteronormativity adapted from queer theories. It is method critical in utilising ethnography, micro history and feminist ethical self-reflection. The research consists of six scientific refereed articles (see appendix) and of a theoretical introduction. The main results of the research are: 1) The genealogy of Finnish decency [Sittlichkeit] can not be researched without oral histories, due to the late modernisation of Finnish society and the legal system, which does not follow the pattern of English, French and German societies. 2) The inclusion of women's same-sex fornication in the Finnish Penal Code is not incomprehensible when compared to the early modern European legislations and court practices. Women have been punished for the sins of Sodom, though not directly under the 1734 Swedish law. 3) Fornication and decency were ambivalent concepts in the 1889/1894 law, and juridical authorities offered controversial interpretations of them during the late 19th and early 20th centuries. 4) A peak in women's convictions occurred in the 1950s, and most of the trial proceedings took place in rural Eastern Finland. Neither the state nor the police were active in prosecuting; instead, the trial proceedings began "by accident". 5) From 1940 to 1960 police training lacked instructions concerning the interrogation of women suspected of same-sex fornication. 6) The figure of the penitent woman was produced in the chiasmic encounter of confession and police interrogation which moulded and was moulded by the epistemological matrix of shame, honour, and decency. Women's speech acts were judicialised as confessions which enabled the disciplinary tampering with the women's bodies. 7) Gender and personality, more than sexuality, or "criminality" defined the status of the convicted women in their village communities after the trials. 8) Relations between police training, sexuality, and decency have not been well researched in Finland. 9) Decriminalisation in 1971 did not mark the end of homophobic legal discourse, even though the 1999 reform of sexual crimes took the form of gender neutral conceptualisation

Kansallista vai modernia : Taidegrafiikka osana 1930-luvun taidejärjestelmää

The theme of this doctoral thesis is the Finnish printmaking in the years 1930-1939. During this decade, there were approximately 100 artists making prints in Finland. Indeed, the period was an especially important one for printmaking. Associations for printmakers were founded in Helsinki and Turku, training in the field was launched, and the number of printmaking exhibitions increased considerably. Through their national organisations, Finnish printmakers participated in many exhibitions abroad, interaction with Nordic printmakers being especially intense. Thus, a firm basis for post-war developments was created. However, printmakers' activity- which had continued throughout the 1930s - declined notably after the Winter War broke out in the autumn of 1939. As a result, the period 1930-1939 forms a coherent and distinct unity in Finnish printmaking history. The study consists of two parts: the main text and an appendix in which the production of each printmaking artist active in the 1930s is examined separately. The study also includes a comprehensive list of the prints made in the course of the decade. One of the central themes is the printmakers' relationship to "Finnish nationalist" art and concepts of art in the 1930s. I analyse the various manifestations of this way of thinking in the visual arts of the period. Finnish fine art in the period between the world wars has usually been characterised as conservative, introverted and spiritually isolated from the modern European trends of the time. On the basis of this study, such a view is too simple. Many artists and printmakers adopted a modernistic notion of art that approached the newest in European modernism, including such trends as avant-garde classicism and general European new Objective Realism (Die neue Sachlichkeit). On the other hand, choosing Finnish nationalist motifs did not necessarily mean that the artist was opposed to modernism: modernist artists could still be interested in national themes. The relationship of 1930s printmaking to the world of nationalist ideas is examined in this doctoral thesis from several perspectives. Towards the end of the main text, I examine the issue from the point of view of selected artists. Another feature that emerged during the study and turned out to be surprisingly widespread was the close relationship of many artists to religious, theosophical and pantheistic views. I deal with this issue in greater detail through a few representative printmakers.

Kalleuksia isänmaalle : Eliel Aspelin-Haapkylä taiteen keräilijänä ja taidehistorioitsijana

Treasures of a Patriot Eliel Aspelin-Haapkylä as an art collector and art historian Treasures of a Patriot is a study of Eliel Aspelin-Haapkylä (1847 - 1917), professor of aesthetics and modern literature, as an art collector and art historian. The study combines the biographical perspective, art history as a discipline in the 19th-century Finland, and Aspelin-Haapkylä s art historical scholarship. My intention was to answer to questions such as what kind of an art collector an academic art historian was, why he collected art and cultural-historical objects and what the purpose of his collecting was. Aspelin-Haapkylä was an ideal choice for the main character because the ideologies of the era, culture, art and European ideas, especially German ideas about museums, are intertwined in his life. In addition, the ideas of the Fennomen can be found in his ideological background. Together with his wife, Ida Aspelin-Haapkylä, he bequeathed a rich donation to the National Museum of Finland, and a wideranging archive concerning the collection, his writings, and letters to the Finnish Literature Society. I have highlighted the materials from the archives related both to the collection and art history, especially the letters between Aspelin-Haapkylä and artists, fellow members of academia, his spouse and relatives. The content and the structure of the research are divided into seven main chapters. First, I discuss Susan M. Pearce s theory of collecting and the history of collecting. I also introduce some other art historians who were private collectors. The late 19th-century Fennomen and other nationalists who were active in cultural life and the arts, are introduced in the second chapter. In the third I deal with Aspelin-Haapkylä s collection of European art combined with his writings, his early published works, studies and many trips to Europe. The fourth and the fifth chapters are dedicated to those Finnish artists who he wrote biographies of, and the artists of his own era whom he supported. The sixth chapter discusses institutions and channels of influence and power through which the initiative to found the National Museum of Finland, his action in the Antell Delegation and co-operation with the art merchant Henryk Bukowski, rise up to the fore. Finally, I process the last will and the fate of the collection from 1917 until 1932. As an appendix, I have included a report and reconstruction of the art collection. The catalogue is based on the words in Aspelin-Haapkylä s the so-called blue notebooks, which I have completed with additions from other sources.

Oncolytic Adenoviruses for Gynecologic Cancer

Gene therapy is a promising novel approach for treating cancers resistant to or escaping currently available modalities. Treatment approaches are based on taking advantage of molecular differences between normal and tumor cells. Various strategies are currently in clinical development with adenoviruses as the most popular vehicle. Recent developments include improving targeting strategies for gene delivery to tumor cells with tumor specific promoters or infectivity enhancement. A rapidly developing field is as well replication competent agents, which allow improved tumor penetration and local amplification of the anti-tumor effect. Adenoviral cancer gene therapy approaches lack cross-resistance with other treatment options and therefore synergistic effects are possible. This study focused on development of adenoviral vectors suitable for treatment of various gynecologic cancer types, describing the development of the field from non-replicating adenoviral vectors to multiple-modified conditional replicating viruses. Transcriptional targeting of gynecologic cancer cells by the use of the promoter of vascular endothelial growth factor receptor type 1 (flt-1) was evaluated. Flt-1 is not expressed in the liver and thus an ideal promoter for transcriptional targeting of adenoviruses. Our studies implied that the flt-1 promoter is active in teratocarcinomas.and therefore a good candidate for development of oncolytic adenoviruses for treatment of this often problematic disease with then poor outcome. A tropism modified conditionally replicating adenovirus (CRAd), Ad5-Δ24RGD, was studied in gynecologic cancers. Ad5-Δ24RGD is an adenovirus selectively replication competent in cells defective in the p16/Rb pathway, including many or most tumor cells. The fiber of Ad5-Δ24RGD contains an integrin binding arginine-glycine-aspartic acid motif (RGD-4C), allowing coxackie-adenovirus receptor independent infection of cancer cells. This approach is attractive because expression levels of CAR are highly variable and often low on primary gynecological cancer cells. Oncolysis could be shown for a wide variety of ovarian and cervical cancer cell lines as well as primary ovarian cancer cell spheroids, a novel system developed for in vitro analysis of CRAds on primary tumor substrates. Biodistribution was evaluated and preclinical safety data was obtained by demonstrating lack of replication in human peripheral blood mononuclear cells. The efficicacy of Ad5-Δ24RGD was shown in different orthotopic murine models including a highly aggressive intraperitoneal model of disseminated ovarian cancer cells, where Ad5-Δ24RGD resulted in complete eradication of intraperitoneal disease in half of the mice. To further improve the selectivity and specificity of CRAds, triple-targeted oncolytic adenoviruses were cloned, featuring the cyclo-oxygenase-2 (cox-2) promoter, E1A transcomplementation and serotype chimerism. Those viruses were evaluated on ovarian cancer cells for specificity and oncolytic potency with regard to two different cox2 versions and three different variants of E1A (wild type, delta24 and delta2delta24). Ad5/3cox2Ld24 emerged as the best combination due to enhanced selectivity without potency lost in vitro or in an aggressive intraperitoneal orthotopic ovarian tumor model. In summary, the preclinical therapeutic efficacy of the CRAds tested in this study, taken together with promising biodistribution and safety data, suggest that these CRAds are interesting candidates for translation into clinical trials for gynecologic cancer.