15,468 research outputs found

    An Investigation of the Dynamic Effect of Foreign Direct Investment (FDI) and Interest Rates on GDP in South Africa

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    Economic growth in South Africa has been in the “doldrums†for the past decade. If well managed, foreign direct investment (FDI) and repo rate (interest rate) could have a positive impact and assist in rapid economic growth so urgently needed in South Africa. FDI has been a driving force for growth in many developing economies. Not enough has been done to attract FDI in South Africa. The country has enormous ability and capacity to attract FDI inflows and to have the advantages from it. A quantitative research approach was used to analyse the association amongst the variables which include FDI, GDP and repo rate in the South African economy. The South African Reserve Bank database was used and the period analysed is from 2000 to 2016. Statistical and econometric methods such as correlation analysis, unit root tests, ARDL Bounds test for cointegration, an error correction model (ECM), and the Granger causality tests were used. Subsequently, after the econometric model was estimated, findings indicated the existence of a long-run relationship between the three variables. While, a significant positive relationship exists between FDI and GDP, a negative long-run relationship was found between GDP and repo rate and interestingly a nonsignificant relationship between repo rate and FDI. In the short run, the positive effect of FDI on GDP is minimal whilst a significant and positive relationship exists between GDP and repo rate. The results did also show some limitations in the results, with regards to FDI and repo rate that there is no significant relationship between the variables, meaning that repo rate does not have an impact on FDIs. Although some long-run evidence was found of FDI playing a role in economic growth in South Africa, such impact is limited. Also very interesting is that the repo rate and FDI do not have a statistically significant relationship. This could be due to the rising risks associated with investments in the country. In conclusion, there are many variables which could have a positive impact on the attraction of FDIs and such factors will be explored further in future studies.&nbsp

    Coordinate Activation of Activator Protein 1 and Inflammatory Cytokines in Response to Neisseria gonorrhoeae Epithelial Cell Contact Involves Stress Response Kinases

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    Neisseria gonorrhoeae (Ngo), the etiologic agent of gonorrhea, induce a number of proinflammatory cytokines by contact to epithelial cells. Cytokine genes and a variety of other immune response genes are activated as a result of the regulatory function of immediate early response transcription factors including activator protein 1 (AP-1). Since it is established that phosphorylation of c-Jun, the central component of AP-1, by the stress-activated c-Jun NH2-terminal kinase (JNK) increases the transcriptional activity of AP-1, we studied whether Ngo could induce stress response pathways involving JNK. We found that virulent Ngo strains induce phosphorylation and activation of JNK but not of p38 kinase. Analysis of a nonpathogenic Ngo strain revealed only weak JNK activation. In respect to the molecular components upstream of the JNK signaling cascade, we show that a dominant negative mutant of MAP kinase kinase 4 (MKK4) represses transcription of an AP-1–dependent reporter gene. Regarding upstream stress response factors involved in Ngo-induced MKK4/JNK/AP-1 activation, we identified p21-activated kinase (PAK) but not MAPK/ERK kinase kinase (MEKK1). Inhibition of small GTPases including Rac1 and Cdc42 by Toxin B prevented JNK and AP-1 activation. Our results indicate that Ngo induce the activation of proinflammatory cytokines via a cascade of cellular stress response kinases involving PAK, which directs the signal from the Rho family of small GTPases to JNK/AP-1 activation

    Inflammation, Immunity, and Vaccines for Helicobacter

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    Helicobacter pylori represents the major etiologic agent of gastritis, gastric, and duodenal ulcer disease and can cause gastric cancer and mucosa-associated lymphoid tissue B-cell lymphoma. It is clear that the consequences of infection reflect diverse outcomes of the interaction of bacteria and host immune system. The hope is that by deciphering the deterministic rules – if any – of this interplay, we will eventually be able to predict, treat, and ultimately prevent disease. Over the past year, research on the immunology of this infection started to probe the role of small noncoding RNAs, a novel class of immune response regulators. Furthermore, we learned new details on how infection is detected by innate pattern recognition receptors. Induction of effective cell-mediated immunity will be key for the development of a vaccine, and new work published analyzed the relevance and contribution of CD4 T helper cell subsets to the immune reaction. Th17 cells, which are also induced during natural infection, were shown to be particularly important for vaccination. Cost-efficiency of vaccination was re-assessed and confirmed. Thus, induction and shaping of the effector roles of such protective Th populations will be a target of the newly described vaccine antigens, formulations, and modes of application that we also review here

    A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

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    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents

    An unusual presentation of leishmaniasis in a human immunodeficiency virus-positive individual

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    INTRODUCTION: Leishmaniasis is a neglected tropical disease caused by vector-borne protozoa of the genus Leishmania. Cutaneous and mucocutaneous forms result in disfiguration or mutilation, whilst visceral leishmaniasis (VL) affects multiple organs and is fatal if untreated. Notably, Leishmania are capable of establishing a chronic infection, which may reactivate years after initial infection when the host becomes immune-suppressed. CASE PRESENTATION: A 24-year-old human immunodeficiency virus (HIV)-positive male presented for excision of anal condylomas. At the time of his current condyloma excision, the patient had no additional symptoms or cutaneous findings, but was noted to have been only intermittently compliant with his antiretroviral therapy. Microscopic examination of the haematoxylin and eosin-stained anal condyloma tissue revealed koilocytic change, ulceration and brisk histiocytic inflammation containing numerous small intracellular bodies suggestive of Leishmania amastigotes. A bone marrow biopsy was performed and demonstrated similar intracellular forms. Anal condyloma tissue and bone marrow aspirate were sent to the Centers for Disease Control and Prevention's Parasitic Diseases Branch for confirmation of Leishmania and speciation. Specific immunohistochemical staining for Leishmania in the tissue section was positive and the species was confirmed as Leishmania donovani by PCR. Subsequently, the patient resumed highly active antiretroviral therapy and received anti-Leishmania therapy. CONCLUSION: Whilst the presentation of VL in HIV-positive patients is often similar to those without HIV, here we describe an unusual initial presentation of leishmaniasis in an HIV-positive patient where the parasite was found in an anal condyloma. VL is a critical diagnosis that should be considered and pursued when leishmaniasis is encountered in seemingly illogical clinical settings

    Characterizing Scales of Genetic Recombination and Antibiotic Resistance in Pathogenic Bacteria Using Topological Data Analysis

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    Pathogenic bacteria present a large disease burden on human health. Control of these pathogens is hampered by rampant lateral gene transfer, whereby pathogenic strains may acquire genes conferring resistance to common antibiotics. Here we introduce tools from topological data analysis to characterize the frequency and scale of lateral gene transfer in bacteria, focusing on a set of pathogens of significant public health relevance. As a case study, we examine the spread of antibiotic resistance in Staphylococcus aureus. Finally, we consider the possible role of the human microbiome as a reservoir for antibiotic resistance genes.Comment: 12 pages, 6 figures. To appear in AMT 2014 Special Session on Advanced Methods of Interactive Data Mining for Personalized Medicin

    Spectroscopy of Brown Dwarf Candidates in the rho Ophiuchi Molecular Core

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    We present an analysis of low resolution infrared spectra for 20 brown dwarf candidates in the core of the ρ\rho Ophiuchi molecular cloud. Fifteen of the sources display absorption-line spectra characteristic of late-type stars. By comparing the depths of water vapor absorption bands in our candidate objects with a grid of M dwarf standards, we derive spectral types which are independent of reddening. Optical spectroscopy of one brown dwarf candidate confirms the spectral type derived from the water bands. Combining their spectral types with published near-infrared photometry, effective temperatures and bolometric stellar luminosities are derived enabling us to place our sample on the Hertzsprung-Russell diagram. We compare the positions of the brown dwarf candidates in this diagram with two sets of theoretical models in order to estimate their masses and ages. Considering uncertainties in placing the candidates in the H-R diagram, six objects consistently lie in the brown dwarf regime and another five objects lie in the transition region between stellar and substellar objects. The ages inferred for the sample are consistent with those derived for higher mass association members. Three of the newly identified brown dwarfs display infrared excesses at λ\lambda=2.2 μ\mum suggesting that young brown dwarfs can have active accretion disks. Comparing our mass estimates of the brown dwarf candidates with those derived from photometric data alone suggests that spectroscopy is an essential component of investigations of the mass functions of young clusters.Comment: Astronomical Journal, in press: 25 pages, latex, 5 tables and 6 figures (separate

    To Coalesce or to Repel? An Analysis of MHT, JPDA, and Belief Propagation Multitarget Tracking Methods

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    Joint probabilistic data association (JPDA) filter methods and multiple hypothesis tracking (MHT) methods are widely used for multitarget tracking (MTT). However, they are known to exhibit undesirable behavior in tracking scenarios with targets in close proximity: JPDA filter methods suffer from the track coalescence effect, i.e., the estimated tracks of targets in close proximity tend to merge and can become indistinguishable, and MHT methods suffer from an opposite effect known as track repulsion. In this paper, we review the JPDA filter and MHT methods and discuss the track coalescence and track repulsion effects. We also consider a more recent methodology for MTT that is based on the belief propagation (BP) algorithm, and we argue that BP-based MTT exhibits significantly reduced track coalescence and no track repulsion. Our theoretical arguments are confirmed by numerical results.Comment: 13 page

    Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

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    A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-α and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis
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