Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

The recurrence and metastatic spread of cancer are major drawbacks in cancer treatment. Although chemotherapy is one of the most effective methods for the treatment of metastatic cancers, it is nonspecific and causes significant toxic damage. The development of drug resistance to chemotherapeutic agents through various mechanisms also limits their therapeutic potential. However, as we discuss here, the use of nanodelivery systems that are a combination of diagnostics and therapeutics (theranostics) is as relatively novel concept in the treatment of cancer. Such systems are likely to improve the therapeutic benefits of encapsulated drugs and can transit to the desired site, maintaining their pharmaceutical properties. The specific targeting of malignant cells using multifunctional nanoparticles exploits theranostics as an improved agent for delivering anticancer drugs and as a new solution for overriding drug resistance.

Censorship, resistance and transformation in modern Indonesian literature

This paper investigates the way in which Indonesian literature has reflected violations of human rights in Indonesia in the last decade of the New Order (1990-1998). The regime was authoritarian and responded harshly to any challenge which could cause trouble to national stability. Some writers, such as Seno Gumira Ajidarma, used the power of allegory to resist this oppression. The three works examined here – ‘Saksi Mata’, ‘Pelajaran Sejarah’, and ‘Misteri Kota Ninggi’ – can be considered as a form of resistance literature.

Resistance and reconstruction: older women talk about childhood sexual abuse

 This research explores personal stories of 16 Australian women aged 57 years and older who have experienced childhood sexual abuse. It privileges their views and examines how they managed the impact during their lives. The project contributes to professional knowledge by developing anti-ageist practices for social work and human services.

Ecosystems and human well-being

■ Human well-being has several key components: the basic material needs for a good life, freedom and choice, health, good social relations, and personal security. Well-being exists on a continuum with poverty, which has been defined as"pronounced deprivation in well-being."
■ How well-being and ill-being, or poverty, are expressed and experienced is context- and situation-dependent, reflecting local social and personal factors such as geography, ecology, age, gender,and culture.These concepts are complex and value-laden.
■ Ecosystems are essential for human well-being through their provisioning, regulating, cultural, and supporting services. Evidence in recent decades of escalating human impacts. on ecological systems worldwide raises concerns about the consequences of ecosystem changes for human well-being.
■ Human well-being can be enhanced through sustainable human interaction with ecosystems with the support of appropriate instruments, institutions, organizations, and technology. creation of these through participation and transparency may contribute to people's freedoms and choices and to increased economic, social,and ecological security.
■ Some believe that the problems from the depletion and degradation of ecological capital can be largely overcome by the substitution of physical and human capital. Others believe that there are more significant limits to such substitutions.The scope for substitutions varies by socioeconomic status.
■ We identify direct and indirect pathways between ecosystem change and human well-being,whether it be positive or negative.lndirect effects are characterized by more complex webs of causation, involving social, economic, and political threads. Threshold points exist beyond which rapid changes to human well-being can occur.
■ Indigent poorly resourced, and otherwise disadvantaged communities are generally the most vulnerable to adverse ecosystem change. Spirals, both positive and negative, can occur for any population, but the poor are more vulnerable.      
■ Functioning institutions are vital to enable equitable access to ecosystem services. lnstitutions sometimes fail or remain undeveloped because of powerful individuals or groups. Bodies that mediate the distribution of goods and services may also be appropriated for the benefit of powerful minorities.
■ For poor people, the greatest gains in well-being will occur through more equitable and secure access to ecosystem services. In the long run, the rich can contribute greatly to human well-being by reducing their substantial impacts on ecosystems and by facilitating greater access to ecosystem services by the poor.
■ We argue ecological security warrants recognition as a sixth freedom of equal weight with participative freedom, economic   facilities, social opportunities, transparency guarantees, and protective security.

Human carrying capacity and human health

The silence around overpopulation prevents the global health community from making the necessary link between the planner's limited ability to support its people and health and development crises. The author describes how popular thinking on population control has been shaped over the last 200 years and how out failure to address the population explosion may be one cause of recent epidemics and social unrest.

Human carrying capacity and human health

The issue of human overpopulation has fallen out of favor among most contemporary demographers, economists, and epidemiologists. Discussing population control has become a taboo topic. Yet, this taboo has major implications for public health.

The silence around overpopulation prevents the global health community from making the necessary link between the planet's limited ability to support its people (its carrying capacity—see sidebar on following page) and health and development crises. In this article, I describe how popular thinking on population control has been shaped over the last 200 years, and how our failure to address the population explosion may be one cause of recent epidemics and social unrest.

Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci

The promise of cancer immunotherapy is that it will not only eradicate primary tumors but will generate systemic antitumor immunity capable of destroying distant metastases. A major problem that must first be surmounted relates to the immune resistance of large tumors. Here we reveal that immune resistance can be overcome by combining immunotherapy with a concerted attack on the tumor vasculature. The functionally related antitumor drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone acetic acid (FAA), which cause tumor vasculature collapse and tumor necrosis, were used to attack the tumor vasculature, whereas the T-cell costimulator B7.1 (CD80), which costimulates T-cell proliferation via the CD28 pathway, was used to stimulate antitumor immunity. The injection of cDNA (60–180 µg) encoding B7.1 into large EL-4 tumors (0.8 cm in diameter) established in C57BL/6 mice, followed 24 h later by i.p. administration of either DMXAA (25 mg/kg) or FAA (300 mg/kg), resulted in complete tumor eradication within 2–6 weeks. In contrast, monotherapies were ineffective. Both vascular attack and B7.1 immunotherapy led to up-regulation of heat shock protein 70 on stressed and dying tumor cells, potentially augmenting immunotherapy. Remarkably, large tumors took on the appearance of a wound that rapidly ameliorated, leaving perfectly healed skin. Combined therapy was mediated by CD8+ T cells and natural killer cells, accompanied by heightened and prolonged antitumor cytolytic activity (P < 0.001), and by a marked increase in tumor cell apoptosis. Cured animals completely rejected a challenge of 1 x 107 parental EL-4 tumor cells but not a challenge of 1 x 104 Lewis lung carcinoma cells, demonstrating that antitumor immunity was tumor specific. Adoptive transfer of 2 x 108 splenocytes from treated mice into recipients bearing established (0.8 cm in diameter) tumors resulted in rapid and complete tumor rejection within 3 weeks. Although DMXAA and B7.1 monotherapies are complicated by a narrow range of effective doses, combined therapy was less dosage dependent. Thus, a broad range of amounts of B7.1 cDNA were effective in combination with 25 mg/kg DMXAA. In contrast, DMXAA, which has a very narrow range of high active doses, was effective at a low dose (18 mg/kg) when administered with a large amount (180 µg) of B7.1 cDNA. Importantly, combinational therapy generated heightened antitumor immunity, such that gene transfer of B7.1 into one tumor, followed by systemic DMXAA treatment, led to the complete rejection of multiple untreated tumor nodules established in the opposing flank. These findings have important implications for the future direction and utility of cancer immunotherapies aimed at harnessing patients’ immune responses to their own tumors.

Implemetation of electronic commerce and human resource strategies in an Australian retail banking context

As organisations deploy eCommerce and internet technologies for competitive advantage and to satisfy increasingly demanding customers, they will need to develop human resource (HR) strategies that prepare their employees to work with these technologies effectively. Little systematic investigation has been undertaken to discover how companies manage their HR functions to achieve these outcomes. In the retail banking sector these issues have become very important with increased competition, industry changes and heightened competition. This paper examines HR management strategy in one Australian bank as it moves towards online service provision and adopts other eCommerce applications. The paper draws on theoretical insights from Porter’s (2001) views of competitive advantage from the internet and writers discussing the informational society (Castells, 2001) and post-fordist organisations (Clegg, 1990). An analysis of interview data from this case study shows the issues that one bank is dealing with as it seeks competitive advantage from its customer service offerings while it revises its HR strategies.

Linking eCommerce and human resource strategies: a case study in a large Australian retail bank

The implementation of eCommerce technologies has considerably changed how employees in the banking industry interact with customers. For example, some customers use electronic banking applications to such an extent that they find little or no need to go into a branch. This change has had a significant impact on the way that jobs are designed and the way that employees are being managed. The preliminary findings from the case study of a large bank in Australia indicate that moving customers out of the branch to an online environment has created unforeseen issues for the way employees interact with customers and this in turn has changed the way that they do their jobs. The key challenge for banks in the future is how to form effective relationships with customers without some kind of face-to-face interaction. This impacts how organisations recruit and retain their staff as well as the level and type of skills required for jobs redesigned after the implementation of eCommerce applications. It is also an important factor in employee satisfaction.

Understanding what microfinance institutions need to address to aid poverty alleviation, social inclusion and human development

Poverty, in its most basic form can be defined as a deprivation of well-being. It is an issue that has been evident in society for centuries and a concern for government policy makers and more recently for non-government organizations (NGOs). In this paper, we consider how management approaches to resolving the dilemma of poverty can be advanced by drawing on two major areas in the development arena associated with poverty, namely, ‘social exclusion’ and ‘the human development paradigm’. We put forward the argument that for groups of people where social disintegration has already occurred, only structural interventions coupled with a social development mechanism will achieve the desired effect. One method for achieving this is through the use of microfinance programs which provide a broad range of financial services to the poor and low-income households as well as to micro-enterprises. This paper contributes to both management practice and theory by developing a theoretical model that microfinance institutions need to do to aid both ‘human development’ and ‘social inclusion’ processes for the socially excluded and poor.

Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer

We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cisdiaminedichloroplatinum (II) (CDDP).  In this study, we found that ATP7A transfection of Chinese hamster ovary  cells (CHOK1) and fibroblasts isolated from Menkes disease patients  enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10- hydroxy-camptothecin (SN-38),  etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized
doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A   partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that   ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more  resistant to SN-38 than ATP7Anegative cells. Thus, ATP7A confers  resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.

Employment relations : integrating industrial relations and human resource management

Incorporating Human Resource Management policies within the regulatory and institutional framework that governs contemporary industrial relations has always been problematic. This paper details the nature and causes of this problem, noting the different conceptual and practical understandings that underpin each form of labour management when being applied in organisational settings. It then looks at a range of industrial relations realities confronting managers when trying to apply HRM practices, and how these practices might be accommodated within the context of such realities as a means of improving organisational effectiveness. In so doing it delineates four approaches an organisation might take in its relations with trade unions when bargaining and concluding labour contracts, and which of these are consistent and inconsistent with the coexistence of HRM and industrial relations practices. It then looks at the issue of workplace change involving trade unions and collective bargaining in terms of three categorical models—the management-driven model, the trade union gatekeeper model, and the management-union alliance model, the intention again being to show which are consistent and inconsistent with the coexistence of these different forms of labour management. The paper concludes by drawing on these conceptual models to outline the issues and policies that need to be considered when applying HRM practices within an industrial relations setting.