Envelope C2-V3-C3-specific antibodies from HIV-1 infected patients from Angola correlate with neutralization activity in plasma

Poster presented at the 2015 Keystone Symposia Conference X5: HIV Vaccines. Banff, Alberta, Canada, 22-27 March 2015

Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses

Influenza viruses are promising mucosal vaccine vectors for HIV but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. We developed recombinant influenza viruses incorporating the HIV-1 p24 gag capsid into the NS-segment of PR8 (H1N1) and X31 (H3N2) influenza viruses with the use of multiple 2A ribosomal skip sequences. Despite the insertion of a sizable HIV-1 gene into the influenza genome, recombinant viruses were readily rescued to high titers. Intracellular expression of p24 capsid was confirmed by in vitro infection assays. The recombinant influenza viruses were subsequently tested as mucosal vaccines in BALB/c mice. Recombinant viruses were attenuated and safe in immunized mice. Systemic and mucosal HIV-specific CD8 T-cell responses were elicited in mice that were immunized via intranasal route with a prime-boost regimen. Isolated HIV-specific CD8 T-cells displayed polyfunctional cytokine and degranulation profiles. Mice boosted via intravaginal route induced recall responses from the distal lung mucosa and developed heightened HIV-specific CD8 T-cell responses in the vaginal mucosa. These findings demonstrate the potential utility of recombinant influenza viruses as vaccines for mucosal immunity against HIV-1 infection.

Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy. (C) 2015 Elsevier Ltd. All rights reserved.

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.

UNLABELLED: In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8(+)and CD4(+)T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE: Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols.

Engineering a financial bloodbath: how sub-prime securitization destroyed the legitimacy of financial capitalism

"This book investigates the origins and implications of the securitization crisis, described by the chief executive of ANZ as a "financial services bloodbath". Based on extensive interviews it offers an integrated series of case studies drawn from the United States, the United Kingdom and Australia. A central purpose is to not only chart what went wrong with the investment houses and why the regulatory systems failed, but also provide policy guidance. The book therefore combines the empirical with the normative. In so doing, it provides a route map to navigate one of the most significant financial and regulatory failures in modern times."

Application of Dynamic Hysteresis Band Height Control to Improve Output Voltage Transient in Boost and Positive Buck-Boost Converters

This paper presents dynamic hysteresis band height control to reduce the overshoot and undershoot issue on output voltage caused by load change. The converters in this study are Boost and Positive Buck-Boost (PBB) converters. PBB has been controlled to work in a step up conversion and avoid overshoot when load is changed. Simulation and experimental results have been presented to verify the proposed method.

Utilizing robustness of positive buck-boost converter against input voltage and load current disturbances

A Positive Buck- Boost (PBB) converter is a known DC-DC converter that can operate in step up and step down modes. Unlike Buck, Boost, and Inverting Buck Boost converters, the inductor current of a PBB can be controlled independently of its voltage conversion ratio. In other words, the inductor of PBB can be utilised as an energy storage unit in addition to its main function of energy transfer. In this paper, the capability of PBB to store energy has been utilised to achieve robustness against input voltage fluctuations and output current changes. The control strategy has been developed to keep accuracy, affordability, and simplicity acceptable. To improve the efficiency of the system a Smart Load Controller (SLC) has been suggested. Applying SLC extra current storage occurs when there is sudden loads change otherwise little extra current is stored.

Can Risk Management boost the supply of Affordable Housing Development and Management?

A shortage of affordable housing is a major problem in Australia today. This is mainly due to the limited supply of affordable housing that is provided by the non-government housing sector. Some private housing developers see the provision of affordable housing for lower income people as a high risk investment which offers a lower return than broader market-based housing. The scarcity of suitable land, a limited government ‘subsidy’, and increasing housing costs have not provided sufficient development incentives to encourage their investment despite the existing high demand for affordable housing. This study analyses the risk management process conducted by some private and not-for-profit housing providers in South East Queensland, and draws conclusions about the relationship between risk assessments/responses and past experiences. In-depth interviews of selected non-government housing providers have been conducted to facilitate an understanding of their approach to risk assessment/response in developing and in managing affordable housing projects. These developers use an informal risk management process as part of their normal business process in accordance with industry standards. A simple qualitative matrix has been used to analyse probability and impacts using a qualitative scale - low, medium and high. For housing providers who have considered investing in affordable housing but have not yet implemented any such projects, affordable housing development is seen as an opportunity that needs to be approached with caution. The risks associated with such projects and the levels of acceptance of these are not consistently identified by current housing providers. Many interviewees agree that the recognition of financial risk and the fear of community rejection of such housing projects have restrained them from committing to such investment projects. This study suggests that implementing improvements to the risk mitigation and management framework may assist in promoting the supply of affordable housing by non-government providers.

Can risk management boost the supply of affordable housing development and management?

Purpose: The purpose of this paper is to analyse the risk management process conducted by some private and not-for-profit affordable housing providers in South East Queensland, and draw conclusions about the relationship between risk assessments/responses and past experiences.----- Design/methodology/approach: In-depth interviews of selected non-government housing providers have been conducted to facilitate an understanding of their approach to risk assessment in developing and in managing affordable housing projects. Qualitative data are analysed using thematic analysis to find emerging themes suggested by interview participants.----- Findings: The paper finds that informal risk management process is used as part of normal business process in accordance with industry standards. Many interviewees agree that the recognition of financial risk and the fear of community rejection of such housing projects have restrained them from committing to such investment projects. The levels of acceptance of risk are not always consistent across housing providers which create opportunities to conduct multi-stakeholder partnership to reduce overall risk.----- Research limitations/implications: The paper has implications for developers or investors who seek to include affordable housing as part of their portfolio. However, data collected in the study are a cross-section of interviews that will not include the impact on recent tax incentives offers by the Australian Commonwealth Government.----- Practical implications: The study suggests that implementing improvements to the risk mitigation and management framework may assist in promoting the supply of affordable housing by non-government providers.----- Originality/value: The focus of the study is the interaction between partnerships and risk management in development and management of affordable rental housing.

Cross voltage control with inner hysteresis current control for multi-output boost converter

Multi-output boost (MOB) converter is a novel DC-DC converter unlike the regular boost converter, has the ability to share its total output voltage and to have different series output voltage from a given duty cycle for low and high power applications. In this paper, discrete voltage control with inner hysteresis current control loop has been proposed to keep the simplicity of the control law for the double-output MOB converter, which can be implemented by a combination of analogue and logical ICs or simple microcontroller to constrain the output voltages of MOB converter at their reference voltages against variation in load or input voltage. The salient features of the proposed control strategy are simplicity of implementation and ease to extend to multiple outputs in the MOB converter. Simulation and experimental results are presented to show the validity of control strategy.

A general approach to control a positive buck-boost converter to achieve robustness against input voltage fluctuations and load changes

A Positive Buck-Boost converter is a known DC-DC converter which may be controlled to act as Buck or Boost converter with same polarity of the input voltage. This converter has four switching states which include all the switching states of the above mentioned DC-DC converters. In addition there is one switching state which provides a degree of freedom for the positive Buck-Boost converter in comparison to the Buck, Boost, and inverting Buck-Boost converters. In other words the Positive Buck-Boost Converter shows a higher level of flexibility for its inductor current control compared to the other DC-DC converters. In this paper this extra degree of freedom is utilised to increase the robustness against input voltage fluctuations and load changes. To address this capacity of the positive Buck-Boost converter, two different control strategies are proposed which control the inductor current and output voltage against any fluctuations in input voltage and load changes. Mathematical analysis for dynamic and steady state conditions are presented in this paper and simulation results verify the proposed method.

Multi-output buck-boost converter with enhanced dynamic response to load and input voltage changes

This paper presents a new multi-output DC/DC converter topology that has step-up and step-down conversion capabilities. In this topology, several output voltages can be generated which can be used in different applications such as multilevel converters with diode-clamped topology or power supplies with several voltage levels. Steady state and dynamic equations of the proposed multi-output converter have been developed, that can be used for steady state and transient analysis. Two control techniques have been proposed for this topology based on constant and dynamic hysteresis band height control to address different applications. Simulations have been performed for different operating modes and load conditions to verify the proposed topology and its control technique. Additionally, a laboratory prototype is designed and implemented to verify the simulation results.

Poverty in perception : a study of the twentieth-century prime ministers of Australia and New Zealand

Australia and New Zealand, as English-speaking nations with dominant white populations, present an ethnic anomaly not only in South East Asia, but also in the Southern Hemisphere. Colonised by predominantly workingclass British immigrants from the late eighteenth century, an ethnic and cultural connection grew between these two countries even though their indigenous populations and ecological environments were otherwise very different. Building a new life in Australia and New Zealand, the colonists shared similar historic perceptions of poverty – perceptions from their homelands that they did not want to see replicated in their new adopted countries. Dreams of a better life shaped their aspirations, self-identity and nationalistic outlook. By the twentieth century, national independence and self-government had replaced British colonial rule. The inveterate occurrence of poverty in Australia and New Zealand had created new local perspectives and different perceptions of, and about, poverty. This study analyses what relationship existed between the political directions adopted by the twentieth-century prime ministers of Australia and New Zealand and their perceptions of poverty. Using the existential phenomenological theory and methodology of Maurice Merleau-Ponty, the study adds to the body of knowledge about poverty in Australia and New Zealand by revealing the structure and origin of the poverty perceptions of the twentieth-century prime ministers.

A new pulsed power supply topology based on positive buck-boost converters concept

Improving efficiency and flexibility in pulsed power supply technologies is the most substantial concern of pulsed power systems specifically with regard to plasma generation. Recently, the improvement of pulsed power supply has become of greater concern due to the extension of pulsed power applications to environmental and industrial areas. With this respect, a current source based topology is proposed in this paper as a pulsed power supply which gives the possibility of power flow control during load supplying mode. The main contribution in this configuration is utilization of low-medium voltage semiconductor switches for high voltage generation. A number of switch-diode-capacitor units are designated at the output of topology to exchange the current source energy into voltage form and generate a pulsed power with sufficient voltage magnitude and stress. Simulations carried out in Matlab/SIMULINK platform as well as experimental tests on a prototype setup have verified the capability of this topology in performing desired duties. Being efficient and flexible are the main advantages of this topology.