Two Strands Model of the Soft System Methodology Analysis of Private Sector Investment in Power Generation Sector in Ghana

The paper analyses the causes of low private sector investment (PSI) in power generation (PG) infrastructure in Ghana. Series of interviews and stakeholders’ workshops were employed for data collection and validation of findings. The Two Strands Model of the Soft Systems Methodology (SSM) was adopted to define and resolve the problem situation. However, the SSM approach manifested some inherent weaknesses in the areas of the listing and selecting the relevant sector concerns and designing the human activity systems. Consequently, Systems Thinking tool, Causal Loop Diagram was introduced to scientifically identify the fundamental causes of the limited PSI in PG. The paper, therefore, proposes some methodological improvements in the SSM in this regard. Human activity models as well as guidelines were developed to address the fundamental causes of the sparse private investment in PG in Ghana.     

Oncogenically active MYD88 mutations in human lymphoma

The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.     

Did Einstein prove E=mc2?

Although Einstein's name is closely linked with the celebrated relation E=mc² between mass and energy, a critical examination of the more than half dozen “proofs” of this relation that Einstein produced over a span of forty years reveals that all these proofs suffer from mistakes. Einstein introduced unjustified assumptions, committed fatal errors in logic, or adopted low-speed, restrictive approximations. He never succeeded in producing a valid general proof applicable to a realistic system with arbitrarily large internal speeds. The first such general proof was produced by Max Laue in 1911 (for “closed” systems with a time-independent energy–momentum tensor) and it was generalized by Felix Klein in 1918 (for arbitrary time-dependent “closed” systems).     

HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.     

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration.     

Application of Focus Group Interviews for Quality Management: An Action Research Project

Focus groups have the potential to provide rapid and timely collation, integration and assembly of the views of a variety of different types of stakeholders into a plausible theory. This article reflects on a tertiary education institution's utilisation of focus group interviews (FGIs) as a qualitative evaluation instrument, using action research as the methodology. Our results suggest that employing focus groups is a valuable method of gaining more insight into and adding more depth to quantitative findings during quality management. Results from focus groups enable quality assurance practitioners to provide better remedial action plans. A set of guidelines is provided for the effective conducting of focus group interviews as part of an institutional quality assurance system.     

Stimulation of cyclo-oxygenase by lidocaine, a pro-lipoperoxidant

Lidocaine, which was recently demonstrated to be a good pro-lipoperoxidant, was tested on in vitro PGs biosynthesis, and on arachidonate-induced arterial hypotension, in the rabbit. In the in vitro experiments, lidocaine alone was a poor stimulant of cyclo-oxygenase, but it enhanced significantly the cyclo-oxygenase activation of uric acid. In the rabbit, lidocaine lowered the i.v. arachidonate dose necessary to obtain a significant drop of blood pressure.