Decision making improvement by effectively utilising activity-based costing and activity-based management tools

The aim of this study was to suggest ways to effectively utilise Activity-Based Costing and Activity-Based Managment within Eskom Transmission Southern Grid to improve decision making towards improved business and financial performance. The ultimate purpose was to assist managers and staff to implement ABC and ABM effectively for improved business and financial performance. The focus was on the following objective: To suggest ways to effectively utilise ABC & ABM within Eskom Transmission Southern Grid as to improve decision making and business financial performance. Given the selection of management tools available, instruments such as ABC and ABM are usually not implemented alone, but may be supported by one or more approaches. For this reason ABC and ABM are contrasted with several other popular instruments mentioned in the literature. The instruments are: • The value chain; • Continuous improvement; • The theory of constraints; and • Total quality management. Insight will be given to provide managers with more accurate information regarding maintenance for the Grid and tools in identifying critical bottlenecks. By applying the TOC, TQM and continuous improvement strategies, managers will be able to make improved decisions, leading to improved financial performance in the Eskom Transmission Southern Grid. iii The literature study revealed that ABC and ABM prove to be the cornerstone for informed decision making. Since organisations are highly dependent on quality information to make these informed decisions, ABC and ABM reorientate the organisation towards understanding and managing work processes thus impacting financial performance positively. ABC and ABM trace the cost of activities such as engineering and procurement to how maintenance benefits from these activities. The empirical study consisted of a structured questionnaire distributed to a sample population of engineers and managers in Eskom Transmission Southern Grid in Port Elizabeth. It was aimed at gathering information about the use of ABC and ABM within the Grid. Semi-structured interviews were also conducted with financial staff in the Grid and a focus group interview with engineering staff was done. The main findings of the empirical investigation revealed that management and staff lack insight into the use of ABC and ABM and how it can be integrated with existing improvement systems within the organisation. This study is concluded with a number of recommendations. These recommendations address the shortcomings and improvements that can be made to improve the utilisation of ABC and ABM within the organisation. The recommendations address the following: • Ensuring full commitment towards organisational goals and broadening the endorsement of ABC within the organisation; • Highlighting the importance of financial performance throughout the Grid; • Training of Managers, finance staff and engineers is required for proper execution of the ABC system; • Implementers need skills and know-how of the ABC and ABM system ensuring full utilisation; • The main cost drivers are identified, prioritised and efforts channelled into these activities; • Tools such as the Theory Of Constraints and Total Quality Management from the proposed model would assist the Grid in identifying the bottlenecks of a system correctly, thus know explicitly the amount of slack capacity of each activity available during a specific time period

An enabling environment for independent power producers in renewable electricity

The increasing demand for electricity, the rising price of energy from conventional sources and limited electricity supply are a global concern. The demand on electricity generation could be alleviated by diversifying the sources from which electricity is obtained to achieve the goals of long-term electricity supply. Diversification implies finding alternative sources of energy such as renewable energy for the production of electricity. The South African electricity system is under increased pressure to provide and maintain electricity supply to its users. Electricity production may be regarded as a key contributor to the social and economic development of South Africa. The challenges are so serious that it will gradually become increasingly difficult to extract sufficient resources to satisfy increasing electricity demand. Growth in the electricity and industrial sectors signifies profound changes in the entire energy industry. The South African power utility Eskom, supplies 94% of South Africa’s electricity but the risk of inadequate supply because of increasing electricity demand is mitigated through the employment of Independent Power Producers (IPPs) which supply to the grid. However, although a limited number of IPP entrepreneurs sell electricity to the Eskom grid, there is no enabling entrepreneurial environment in which they can thrive. There is no positive movement to inaugurate policies and processes. This has created an opportunity for Smart Grid access as a viable option to accommodate IPP entrepreneurs into the grid. Investing in renewable electricity sources may provide feasible alternatives for the electricity industry, it would alleviate pressure on current supply whilst creating an enabling entrepreneurial environment for IPP entrepreneurs and increase entrepreneurial activity. This study investigates a proposed model for an enabling entrepreneurial environment for IPPs in the RE sector that can be utilised to ensure increased entrepreneurial activity within the electricity industry. Establishing such an enabling environment would contribute positively to the alleviation of the electricity demand crisis, result in lower carbon emissions and create a sustainable, more diverse electricity generation mix. This proposed IPP industry model for an enabling entrepreneurial environment is presented to address the problems experienced at the different levels of the electricity industry. The model can be utilised to increase entrepreneurial activity while eradicating major electricity challenges at different levels in the South African electricity industry. The results indicate that that RE, in the form of solar and wind, has the potential to expand the South African electricity industry significantly. Therefore, in order to reform the South African electricity industry, stakeholders need to embrace entrepreneurship as IPP entrepreneurs. This can be done effectively by the incorporation of IPP entrepreneurs into the electricity network. However, an enabling entrepreneurial environment in which to operate must be ensured. In this study, five important variables support the establishment of an enabling entrepreneurial environment for IPP entrepreneurs. These have been identified as; Smart Grids, Entrepreneurship, Renewable electricity environment, SA policy and Stakeholder theory. An important contribution has been made towards Stakeholder Theory. This has proven to be instrumental within the RE sector of the electricity industry in South Africa, as the mentioned role players have a reciprocal role to play. Three surveys were conducted at three levels of the electricity industry, namely, at organisational, legislative and entrepreneurial levels and included Eskom Management, National Energy Regulator (NERSA) Management and Approved and Non-approved IPPs. Both qualitative and quantitative research methods were utilised in this research study. The results indicate that SA Policy is instrumental in assisting stakeholders to facilitate the IPP process and feed the power from RE generation into the network. Most respondents were positive about the role of Smart Grids in future electricity generation and their contribution towards creating an enabling entrepreneurial environment for IPP entrepreneurs. Respondents indicated that by policy decisions, greater emphasis can be placed on the results of climate change and environmental challenges. Emphasis on the incorporation of stakeholders proved imperative to this group (IPPs). The results indicated that stakeholder management is a key factor contributing to the establishment of an enabling entrepreneurial environment. The major contribution of this study is a proposed entrepreneurial model that can improve future sustainability of the electricity supply

The chronology of reindeer hunting on Norway's highest ice patches.

The melting of perennial ice patches globally is uncovering a fragile record of alpine activity, especially hunting and the use of mountain passes. When rescued by systematic fieldwork (glacial archaeology), this evidence opens an unprecedented window on the chronology of high-elevation activity. Recent research in Jotunheimen and surrounding mountain areas of Norway has recovered over 2000 finds-many associated with reindeer hunting (e.g. arrows). We report the radiocarbon dates of 153 objects and use a kernel density estimation (KDE) method to determine the distribution of dated events from ca 4000 BCE to the present. Interpreted in light of shifting environmental, preservation and socio-economic factors, these new data show counterintuitive trends in the intensity of reindeer hunting and other high-elevation activity. Cold temperatures may sometimes have kept humans from Norway's highest elevations, as expected based on accessibility, exposure and reindeer distributions. In times of increasing demand for mountain resources, however, activity probably continued in the face of adverse or variable climatic conditions. The use of KDE modelling makes it possible to observe this patterning without the spurious effects of noise introduced by the discrete nature of the finds and the radiocarbon calibration process

A hot spot on interferon α/β receptor subunit 1 (IFNAR1) underpins its interaction with interferon-β and dictates signaling

The interaction of IFN-β with its receptor IFNAR1 (interferon α/β receptor subunit 1) is vital for host-protective anti-viral and anti-proliferative responses, but signaling via this interaction can be detrimental if dysregulated. Whereas it is established that IFNAR1 is an essential component of the IFNAR signaling complex, the key residues underpinning the IFN-β-IFNAR1 interaction are unknown. Guided by the crystal structure of the IFN-β-IFNAR1 complex, we used truncation variants and site-directed mutagenesis to investigate domains and residues enabling complexation of IFN-β to IFNAR1. We have identified an interface on IFNAR1-subdomain-3 that is differentially utilized by IFN-β and IFN-α for signal transduction. We used surface plasmon resonance and cell-based assays to investigate this important IFN-β binding interface that is centered on IFNAR1 residues Tyr240 and Tyr274 binding the C and N termini of the B and C helices of IFN-β, respectively. Using IFNAR1 and IFN-β variants, we show that this interface contributes significantly to the affinity of IFN-β for IFNAR1, its ability to activate STAT1, the expression of interferon stimulated genes, and ultimately to the anti-viral and anti-proliferative properties of IFN-β. These results identify a key interface created by IFNAR1 residues Tyr240 and Tyr274 interacting with IFN-β residues Phe63, Leu64, Glu77, Thr78, Val81, and Arg82 that underlie IFN-β-IFNAR1-mediated signaling and biological processes

Structure of the murine CD94 – NKG2A receptor in complex with Qa‐1b presenting an MHC‐I leader peptide

The heterodimeric natural killer cells antigen CD94 (CD94)–NKG2‐A/NKG2‐B type II integral membrane protein (NKG2A) receptor family expressed on human and mouse natural killer (NK) cells monitors global major histocompatibility complex (MHC) class I cell surface expression levels through binding to MHC class Ia‐derived leader sequence peptides presented by HLA class I histocompatibility antigen, alpha chain E (HLA‐E; in humans) or H‐2 class I histocompatibility antigen, D‐37 (Qa‐1b; in mice). Although the molecular basis underpinning human CD94–NKG2A recognition of HLA‐E is known, the equivalent interaction in the murine setting is not. By determining the high‐resolution crystal structure of murine CD94–NKG2A in complex with Qa‐1b presenting the Qa‐1 determinant modifier peptide (QDM), we resolved the mode of binding. Compared to the human homologue, the murine CD94–NKG2A–Qa‐1b–QDM displayed alterations in the distribution of interactions across CD94 and NKG2A subunits that coincide with differences in electrostatic complementarity of the ternary complex and the lack of cross‐species reactivity. Nevertheless, we show that Qa‐1b could be modified through W65R + N73I mutations to mimic HLA‐E, facilitating binding with both human and murine CD94–NKG2A. These data underscore human and murine CD94–NKG2A cross‐species heterogeneity and provide a foundation for humanising Qa‐1b in immune system models

Complete Genome Sequences of Two Temperate Bacillus subtilis Phages Isolated at Tumamoc Hill Desert Laboratory

Bacteriophages are important in structuring bacterial communities, including desert soils dominated by Bacillus species. Here, we describe two genetically similar temperate phages isolated on a Bacillus subtilis strain from soil in Tucson, Arizona. Their double-stranded DNA (dsDNA) genomes contain 98 and 102 genes, with a set of 4 genes being found in only one phage

Mutational and Structural Analysis of KIR3DL1 Reveals a Lineage-Defining Allotypic Dimorphism That Impacts Both HLA and Peptide Sensitivity

Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation

Degenerate recognition of MHC class I molecules with Bw4 and Bw6 motifs by a killer cell Ig-like receptor 3DL expressed by macaque NK cells

The killer cell immunoglobulin-like receptors (KIRs) expressed on the surface of natural killer (NK) cells recognize specific major histocompatibility complex class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In human immunodeficiency virus (HIV) infection, survival is linked to host KIR and MHC-I genotypes. In the simian immunodeficiency virus (SIV) macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. Here, we describe the first characterization of a KIR-MHC interaction in pig-tailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs

A subset of HLA-I peptides are not genomically templated: evidence for cis- and trans-spliced peptide ligands

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy

Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR–HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C