Business rights and ethnic exclusion in sub-Saharan Africa: Addressing group-based inequality through business rights reform

The business rights pillar of the Legal Empowerment of the Poor agenda is not preoccupied with equality of outcome; it concentrates instead on equality of opportunity. This paper addresses the lacuna in the business rights literature by 'bringing outcomes back in'. Certainly, equal outcomes are difficult to achieve and require understanding of a host of group as well as individual characteristics, and the complex obstacles to distributing benefits more broadly and beneficially, especially to members of groups that have faced historical discrimination in business. In order to understand some of the ways in which the interests of the poor can be advanced in business, and how mere business rights might be complemented, this research extends the analysis to include what I call active business rights reforms

Capitalism and African business cultures

Scholars and practitioners once commonly linked 'African culture' to a distinctive 'African capitalism', at odds with genuine capitalism and the demands of modern business. Yet contemporary African business cultures reveal that a capitalist ethos has taken hold within both state and society. The success and visibility of an emergent, and celebrated, class of African big business reveals that business and profit are culturally acceptable. Existing theories of African capitalism are ill-equipped to explain changes in African business cultures, which increasingly are as diverse as any across the globe. Further, at their core is a growing capacity for reproduction, as capitalists

The action mechanism of daptomycin

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bmc.2016.05.052 © 2016.Daptomycin is a lipopeptide antibiotic produced by the soil bacterium Streptomyces roseosporus that is clinically used to treat severe infections with Gram-positive bacteria. In this review, we discuss the mode of action of this important antibiotic. Although daptomycin is structurally related to amphomycin and similar lipopeptides that inhibit peptidoglycan biosynthesis, experimental studies have not produced clear evidence that daptomycin shares their action mechanism. Instead, the best characterized effect of daptomycin is the permeabilization and depolarization of the bacterial cell membrane. This activity, which can account for daptomycin's bactericidal effect, correlates with the level of phosphatidylglycerol (PG) in the membrane. Accordingly, reduced synthesis of PG or its increased conversion to lysyl-PG promotes bacterial resistance to daptomycin. While other resistance mechanisms suggest that daptomycin may indeed directly interfere with cell wall synthesis or cell division, such effects still await direct experimental confirmation. Daptomycin's complex structure and biosynthesis have hampered the analysis of its structure activity relationships. Novel methods of total synthesis, including a recent one that is carried out entirely on a solid phase, will enable a more thorough and systematic exploration of the sequence space

Measurement and models accounting for cell death capture hidden variation in compound response.

Cancer cell sensitivity or resistance is almost universally quantified through a direct or surrogate measure of cell number. However, compound responses can occur through many distinct phenotypic outcomes, including changes in cell growth, apoptosis, and non-apoptotic cell death. These outcomes have divergent effects on the tumor microenvironment, immune response, and resistance mechanisms. Here, we show that quantifying cell viability alone is insufficient to distinguish between these compound responses. Using an alternative assay and drug-response analysis amenable to high-throughput measurement, we find that compounds with identical viability outcomes can have very different effects on cell growth and death. Moreover, additive compound pairs with distinct growth/death effects can appear synergistic when only assessed by viability. Overall, these results demonstrate an approach to incorporating measurements of cell death when characterizing a pharmacologic response

Impact histories of Vesta and Vestoids inferred from howardites, eucrites and diogenites

The parent body of the howardites, eucrites and diogenites (HEDs) is thought to be asteroid (4) Vesta [1]. However, several eucrites have now been recognized, like NWA 011 and Ibitira, with major element compositions and mineralogy like normal eucrites but with different oxygen isotope compositions and minor element concentrations suggesting they are not from the same body [2, 3]. The discoveries of abnormal eucrites and V-type asteroids that are probably not from Vesta [see 4] raise the question whether the HEDs with normal oxygen isotopes are coming from Vesta [3]. To address this issue and understand more about the evolution of Vesta in preparation for the arrival of the Dawn spacecraft, we integrate fresh insights from Ar-Ar dating and oxygen isotope analyses of HEDs, radiometric dating of differentiated meteorites, as well as dynamical and astronomical studies of Vesta, the Vesta asteroid family (i.e., the Vestoids), and other V-type asteroids

Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes

Membrane binding and oligomer formation by the calcium-dependent lipopeptide antibiotic A54145: a quantitative study with pyrene excimer fluorescence

The final publication is available at Elsevier via http://doi.org/10.1016/j.bpj.2016.07.018 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/A54145 is a lipopeptide antibiotic related to daptomycin that permeabilizes bacterial cell membranes. Its action requires both calcium and phosphatidylglycerol in the target membrane, and it is accompanied by the formation of membrane-associated oligomers. We here probed the interaction of A54145 with model membranes composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol, using the steady-state and time-resolved fluorescence of a pyrene-labeled derivative (Py-A54145). In solution, the labeled peptide was found to exist as a monomer. Its membrane interaction occurred in two stages that could be clearly distinguished by varying the calcium concentration. In the first stage, which was observed between 0.15 and 1 mM calcium, Py-A54145 bound to the membrane, as indicated by a strong increase in pyrene monomer emission. At the same calcium concentration, excimer emission increased also, suggesting that Py-A54145 had oligomerized. A global analysis of the time-resolved pyrene monomer and excimer fluorescence confirmed that Py-A54145 forms oligomers quantitatively and concomitantly with membrane binding. When calcium was raised beyond 1 mM, a distinct second transition was observed that may correspond to a doubling of the number of oligomer subunits. The collective findings confirm and extend our understanding of the action mode of A54145 and daptomycin.This work was supported by the Natural Sciences and Engineering Research Council of Canada operating grants to J.D. (201603-2013), M.P. (250265-2013), and S.T. (155283-2012)

Two successive calcium-dependent transitions mediate membrane binding and oligomerization of daptomycin and the related antibiotic A54145

The final publication is available at Elsevier via http://doi.org/10.1016/j.bbamem.2016.05.020 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Daptomycin and A54145 are homologous lipopeptide antibiotics that permeabilize the cell membranes of Gram-positive bacteria. Membrane permeabilization depends on the presence of both phosphatidylglycerol (PG) and calcium, and it involves the formation of oligomeric transmembrane pores that consist of approximately 6-8 subunits. We here show that each lipopeptide molecule binds two calcium ions in separable, successive steps. The first calcium ion causes the lipopeptide molecule to bind to the target membrane, and likely to form a loosely associated oligomer. Higher calcium concentrations induce binding of a second ion, which produces the more tightly associated and more deeply membrane-inserted final, functional form of the oligomer. Both calcium dependent steps are accompanied by fluorescence signals that indicate transition of specific amino acid residues into less polar environments, suggestive of insertion into the target membrane. Our findings agree with the earlier observation that two of the four acidic amino acid residues in the daptomycin molecule are essential for antibacterial activity. (C) 2016 Elsevier B.V. All rights reserved.This study was supported by operating grants by NSERC to Scott Taylor (155283-2012) and Michael Palmer (250265-2013)

Pattern of Reaction Diffusion Front in Laminar Flows

Autocatalytic reaction between reacted and unreacted species may propagate as solitary waves, namely at a constant front velocity and with a stationary concentration profile, resulting from a balance between molecular diffusion and chemical reaction. The effect of advective flow on the autocatalytic reaction between iodate and arsenous acid in cylindrical tubes and Hele-Shaw cells is analyzed experimentally and numerically using lattice BGK simulations. We do observe the existence of solitary waves with concentration profiles exhibiting a cusp and we delineate the eikonal and mixing regimes recently predicted.Comment: 4 pages, 3 figures. This paper report on experiments and simulations in different geometries which test the theory of Boyd Edwards on flow advection of chemical reaction front which just appears in PRL (PRL Vol 89,104501, sept2002