The informal economy as a route to market in sub-Saharan Africa – observations amongst Kenyan informal economy entrepreneurs

The objectives of this collection include: To shed new light on the socio-cultural and historical underpinnings of business practice in Africa and their implications for promoting entrepreneurship and business behaviour in the region To ..

Acceptance Criteria for Critical Software Based on Testability Estimates and Test Results

Testability is defined as the probability that a program will fail a test, conditional on the program containing some fault. In this paper, we show that statements about the testability of a program can be more simply described in terms of assumptions on the probability distribution of the failure intensity of the program. We can thus state general acceptance conditions in clear mathematical terms using Bayesian inference. We develop two scenarios, one for software for which the reliability requirements are that the software must be completely fault-free, and another for requirements stated as an upper bound on the acceptable failure probability

Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We found that normal lung tissue was characterized predominantly by saturated phosphatidylcholines and phosphatidylglycerols, which are major lipid components of pulmonary surfactant. In contrast, tumor tissues displayed an increase in phosphatidylinositols and arachidonate-containing phospholipids that can serve as signaling precursors. Deactivating MYC resulted in a rapid and dramatic decrease in arachidonic acid and its eicosanoid metabolites. In tumors with high levels of MYC, we found an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-bound arachidonic acid, stimulating the lipoxygenase (LOX) and COX pathways also amplified by MYC at the level of gene expression. Deactivating MYC lowered cPLA2 activity along with COX2 and 5-LOX mRNA levels. Notably, inhibiting the COX/5-LOX pathways in vivo reduced tumor burden in a manner associated with reduced cell proliferation. Taken together, our results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy.This research was funded by the Medical Research Council (Lipid Profiling and Signaling, MC UP A90 1006 & Lipid Dynamics and Regulation, MC PC 13030) and Cancer Research UK (program grant A12077)

Transformation of spin information into large electrical signals via carbon nanotubes

Spin electronics (spintronics) exploits the magnetic nature of the electron, and is commercially exploited in the spin valves of disc-drive read heads. There is currently widespread interest in using industrially relevant semiconductors in new types of spintronic devices based on the manipulation of spins injected into a semiconducting channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation such that the magnetoresistive signals are below 1%. We overcome this long standing problem in spintronics by demonstrating large magnetoresistance effects of 61% at 5 K in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron gap between epitaxial electrodes of the highly spin polarized manganite La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes is long due the small spin-orbit coupling of carbon, because the high nanotube Fermi velocity permits the carrier dwell time to not significantly exceed this spin lifetime, because the manganite remains highly spin polarized up to the manganite-nanotube interface, and because the interfacial barrier is of an appropriate height. We support these latter statements regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and references. New author include

Topological crystalline insulator states in Pb(1-x)Sn(x)Se

Topological insulators are a novel class of quantum materials in which time-reversal symmetry, relativistic (spin-orbit) effects and an inverted band structure result in electronic metallic states on the surfaces of bulk crystals. These helical states exhibit a Dirac-like energy dispersion across the bulk bandgap, and they are topologically protected. Recent theoretical proposals have suggested the existence of topological crystalline insulators, a novel class of topological insulators in which crystalline symmetry replaces the role of time-reversal symmetry in topological protection [1,2]. In this study, we show that the narrow-gap semiconductor Pb(1-x)Sn(x)Se is a topological crystalline insulator for x=0.23. Temperature-dependent magnetotransport measurements and angle-resolved photoelectron spectroscopy demonstrate that the material undergoes a temperature-driven topological phase transition from a trivial insulator to a topological crystalline insulator. These experimental findings add a new class to the family of topological insulators. We expect these results to be the beginning of both a considerable body of additional research on topological crystalline insulators as well as detailed studies of topological phase transitions.Comment: v2: published revised manuscript (6 pages, 3 figures) and supplementary information (5 pages, 8 figures

Determination of the physiological and pathological roles of E2F3 in adult tissues

While genetically engineered mice have made an enormous contribution towards the elucidation of human disease, it has hitherto not been possible to tune up or down the level of expression of any endogenous gene. Here we describe compound genetically modified mice in which expression of the endogenous E2f3 gene may be either reversibly elevated or repressed in adult animals by oral administration of tetracycline. This technology is, in principle, applicable to any endogenous gene, allowing direct determination of both elevated and reduced gene expression in physiological and pathological processes. Applying this switchable technology to the key cell cycle transcription factor E2F3, we demonstrate that elevated levels of E2F3 drive ectopic proliferation in multiple tissues. By contrast, E2F3 repression has minimal impact on tissue proliferation or homeostasis in the majority of contexts due to redundancy of adult function with E2F1 and E2F2. In the absence of E2F1 and E2F2, however, repression of E2F3 elicits profound reduction of proliferation in the hematopoietic compartments that is rapidly lethal in adult animals.This work was supported by CRUK (Programme Grant A12077), the ERC (Advanced Investigator Award 294851), and the NCI (grants CA98018, CA100193) (all to G.I.E.). D.G. was supported by NIGMS grant #1 R25 GM56847. MB was funded by an EMBO Long-term fellowship and an Australian NHMRC Early Career Fellowship

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Lung cancer diagnosed following an emergency admission: exploring patient and carer perspectives on delay in seeking help

Purpose Compared to others, patients diagnosed with lung cancer following an emergency, unplanned admission to hospital (DFEA) have more advanced disease and poorer prognosis. Little is known about DFEA patients’ beliefs about cancer and its symptoms or about their help-seeking behaviours prior to admission. Methods As part of a larger single-centre, prospective mixed-methods study conducted in one University hospital, we undertook qualitative interviews with patients DFEA and their carers to obtain their understanding of symptoms and experiences of trying to access healthcare services before admission to hospital. Interviews were recorded and transcribed. Framework analysis was employed. Results Thirteen patients and 10 carers plus 3 bereaved carers took part in interviews. Three patient/carer dyads were interviewed together. Participants spoke about their symptoms and why they did not seek help sooner. They described complex and nuanced experiences. Some (n = 12) had what they recalled as the wrong symptoms for lung cancer and attributed them either to a pre-existing condition or to ageing. In other cases (n = 9), patients or carers realised with hindsight that their symptoms were signs of lung cancer, but at the time had made other attributions to account for them. In some cases (n = 3), a sudden onset of symptoms was reported. Some GPs (n = 6) were also reported to have made incorrect attributions about cause. Conclusion Late diagnosis meant that patients DFEA needed palliative support sooner after diagnosis than patients not DFEA. Professionals and lay people interpret health and illness experiences differently

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

The Hubbard model within the equations of motion approach

The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference