Surviving in the BRICS: the struggle of South African business in coping with new partners and investors

The purpose of this paper is to improve our understanding of how South African economic actors react to the gradual entry of non-South African BRICS firms in their established business areas. Throughout the twentieth century, South Africa’s trade and investment activities were conducted overwhelmingly with Western countries. However, the end of apartheid coincided with significant shifts as new players had a wider and growing presence. South Africa entering the BRICS alliance is symbolic of the change. Ease of entry into the South African economy has increased greatly. South African businesses in key subsectors in the mining and capital equipment industry have had to adapt to new players, and find space in new structures, value chains and initiatives. This paper presents the results of this research activity from the perspective of the South African political economy. Practice-oriented research investigated how six local companies forge new partnerships and how well South African firms adapt and cope with an altered and often unstable environment. It assumed that entrepreneurial activity is not autonomous but takes place within a larger organisational framework. Entrepreneurial activity facilitates the effective exploitation of particular niches and relationships with service providers

North Atlantic right whale foraging ecology and its role in human-caused mortality

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Ecology Progress Series 581 (2017): 165-181, doi:10.3354/meps12315.Endangered North Atlantic right whales Eubalaena glacialis suffer from unacceptably high rates of ship strikes and fishing gear entanglements, but little is known of the role that diving and foraging behavior plays in mediating human-caused mortality. We conducted a study of right whale foraging ecology by attaching tags to whales for short periods of time (hours), tracking their movements during daytime, and repeatedly sampling oceanographic conditions and prey distribution along the whales’ tracks. Right whales were tagged from late winter to late fall in 6 regions of the Gulf of Maine and southwestern Scotian Shelf from 2000 to 2010. The diving behavior of the tagged whales was governed by the vertical distribution of their primary prey, the copepod Calanus finmarchicus. On average, right whales tagged during spring spent 72% of their time in the upper 10 m (within the draft of most large commercial vessels), indicating the need for expanded ship speed restrictions in western Gulf of Maine springtime habitats. One out of every 4 whales dove to within 5 m of the sea floor during the short time they were tagged, spending as much as 45% of their total tagged time in this depth stratum. Right whales dove to the sea floor in each habitat studied except for one (where only 1 whale was tagged). This relatively high incidence of near-bottom diving raises serious concerns about the continued use of floating ground lines in pot and trap gear in coastal Maine and Canadian waters.Support for this research was provided by the NOAA Right Whale Grants Program, Northeast Consortium, Woods Hole Oceanographic Institution, NOAA Northeast Fisheries Science Center, and the Office of Naval Research

Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion

Organ gene therapy represents a promising tool to correct diseases or improve graft survival after transplantation. Polymorphic variation of the major histocompatibility complex (MHC) antigens remains a major obstacle to long-term graft survival after transplantation. Previously, we demonstrated that MHC-silenced cells are protected against allogeneic immune responses. We also showed the feasibility to silence MHC in the lung. Here, we aimed at the genetic engineering of the kidney toward permanent silencing of MHC antigens in a rat model. We constructed a sub-normothermic ex vivo perfusion system to deliver lentiviral vectors encoding shRNAs targeting β2-microglobulin and the class II transactivator to the kidney. In addition, the vector contained the sequence for a secreted nanoluciferase. After kidney transplantation (ktx), we detected bioluminescence in the plasma and urine of recipients of an engineered kidney during the 6 weeks of post-transplant monitoring, indicating a stable transgene expression. Remarkably, transcript levels of β2-microglobulin and the class II transactivator were decreased by 70% in kidneys expressing specific shRNAs. Kidney genetic modification did not cause additional cell death compared to control kidneys after machine perfusion. Nevertheless, cytokine secretion signatures were altered during perfusion with lentiviral vectors as revealed by an increase in the secretion of IL-10, MIP-1α, MIP-2, IP-10, and EGF and a decrease in the levels of IL-12, IL-17, MCP-1, and IFN-γ. Biodistribution assays indicate that the localization of the vector was restricted to the graft. This study shows the potential to generate immunologically invisible kidneys showing great promise to support graft survival after transplantation and may contribute to reduce the burden of immunosuppression

Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links

BACKGROUND: Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. METHODS: During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs RESULTS: Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995–2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995–2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615629 €) a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995–2000. CONCLUSION: Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with the introduction of new antifungal drugs

The Natural Product Domain Seeker NaPDoS: A Phylogeny Based Bioinformatic Tool to Classify Secondary Metabolite Gene Diversity

New bioinformatic tools are needed to analyze the growing volume of DNA sequence data. This is especially true in the case of secondary metabolite biosynthesis, where the highly repetitive nature of the associated genes creates major challenges for accurate sequence assembly and analysis. Here we introduce the web tool Natural Product Domain Seeker (NaPDoS), which provides an automated method to assess the secondary metabolite biosynthetic gene diversity and novelty of strains or environments. NaPDoS analyses are based on the phylogenetic relationships of sequence tags derived from polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, respectively. The sequence tags correspond to PKS-derived ketosynthase domains and NRPS-derived condensation domains and are compared to an internal database of experimentally characterized biosynthetic genes. NaPDoS provides a rapid mechanism to extract and classify ketosynthase and condensation domains from PCR products, genomes, and metagenomic datasets. Close database matches provide a mechanism to infer the generalized structures of secondary metabolites while new phylogenetic lineages provide targets for the discovery of new enzyme architectures or mechanisms of secondary metabolite assembly. Here we outline the main features of NaPDoS and test it on four draft genome sequences and two metagenomic datasets. The results provide a rapid method to assess secondary metabolite biosynthetic gene diversity and richness in organisms or environments and a mechanism to identify genes that may be associated with uncharacterized biochemistry

Animal Models in Allogenic Solid Organ Transplantation

Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research

Animal Models in Allogenic Solid Organ Transplantation

Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research

723-3 Endothelin in the Skin Microcirculation of Patients with Coronary Heart Disease: Effect of Endothelin Antagonist and Calcium Antagonist

Endothelin, a potent vasoconstrictor peptide released from endothelial cells, is elevated in different cardiovascular diseases, i.e. atherosclerosis, acute myocardial infarction, diabetes mellitus and pulmonary hypertension. The effects of the ETA-endothelin receptor antagonist PD 147953 (PD; 10-8mol) and the calcium-antagonist diltiazem (D; 10-7mol) on endothelin-1 (ET; 10-12mol) induced changes in blood flow of skin microcirculation were studied in 10 patients (7 male, 3 female) with angiographically documented coronary heart disease (CHD) and in 10 healthy controls with a newly developed double injection model. Changes in blood flow were assessed with laserDoppler-flowmetry. Data are shown as mean difference from saline±SEM.ConclusionsIn patients with CHD, the vasoconstriction to endothelin-1 is reduced compared to healthy young controls.The calcium-antagonist diltiazem inhibits endothelin induced vasoconstriction in healthy volunteers and in patients with CHD. The endothelinantagonist PD 147953 fully prevents endothelin-induced vasoconstriction in the skin microcirculation of patients with CH D in a 10 times lower concentration than the calcium antagonist