Aligning operational and corporate goals: a case study in cultivating a whole-of-business approach using a supply chain simulation game

This paper outlines the development and use of an interactive computer-based supply chain game to facilitate the alignment of disconnected operational and corporate goals. A multi-enterprise internal cattle supply chain was simulated targeting the operational property managers and the overall impacts of their decision making on corporate goals A three stage multidisciplinary approach was used. A case study based financial analysis was undertaken across the internal cattle supply chain, a participative action research component (developing the game to simulate the flow of product and associated decisions and financial transactions through the internal supply chain of the company for different operational scenarios using measurable and familiar operational and financial criteria as tracking tools), and a qualitative analysis of organisational learning through player debriefing following playing the game. Evaluation of the managers' learning around the need for a change in general practice to address goal incongruence was positive evidenced by changes in practice and the game regarded by the users as a useful form of organisational training. The game provided property managers with practical insights into the strategic implications of their enterprise level decisions on the internal supply chain and on overall corporate performance. The game is unique and is a tool that can be used to help address an endemic problem across multi-enterprise industries in the agrifood sector in Australia

Eureka and beyond: mining's impact on African urbanisation

This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

Changing women's roles, changing environmental knowledges: evidence from Upper Egypt

The aim of this paper is to investigate the ways in which changing gender roles in a Bedouin community in Upper Egypt, brought about by settlement over the last 20 years on the shores of Lake Nasser, have impacted on the accumulation and development of indigenous environmental knowledges by Bedouin women. The research was carried out among four groups of Ababda Bedouin in the Eastern Desert of Egypt and involved in-depth monthly conversations carried out over a period of 12 months. The main conclusions of the study are that the women of the study area have had to develop new knowledges which, in some cases, are now different from those held by men because of the different economic circumstances in which many find themselves; that these knowledges are fluid, dynamic and ever-changing with their own internal dynamism; and that socially constructed notions of gender are vital in the development process, notions that are sensitive to both men's and women's interests and their interrelationships

Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus

Acute hantavirus infection in humans triggers a rapid expansion and long-term persistence of NK cells

A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria

How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss of transcription factor PLZF and Fc receptor γ-chain. Adaptive NK cells dominated antibody-dependent cellular cytotoxicity responses, and their frequency within total NK cells correlated with lower parasitemia and resistance to malaria. P. falciparum–infected RBCs induced NK cell degranulation after addition of plasma from malaria-resistant individuals. Malaria-susceptible subjects with the largest increase in PLZF-negative NK cells during the transmission season had improved odds of resistance during the subsequent season. Thus, antibody-dependent lysis of P. falciparum–infected RBCs by NK cells may be a mechanism of acquired immunity to malaria. Consideration of antibody-dependent NK cell responses to P. falciparum antigens is therefore warranted in the design of malaria vaccines

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality