1,061 research outputs found

    Coups and Conflict: The Paradox of Coup-Proofing

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    This study develops a leader-centric theory of civil-military relations that expands upon three broad areas of research. Specifically, the study suggests that leaders will evaluate multiple threats to their political survival and will ultimately implement strategy that is most likely to keep them in power. While Downs (1957) has noted such a tendency in democracies, this study expands this rationale to authoritarian regimes by focusing on the primary means of authoritarian removal: the military coup. In contrast to the state-centric nature of traditional international relations theory, this dissertation finds that leaders frequently undermine the power of the state in order to accomplish the self-interested goal of political survival. First, the study carefully describes a number of coup-proofing strategies that leaders can implement. These are broadly defined in terms of influencing either the military’s willingness or its ability to attempt a coup. In addition to testing the effectiveness of these strategies, this study also theoretically explores the implications of coup-proofing for other political development of the state: interstate and intrastate conflict. Second, the study considers the influence of coup-proofing on interstate conflict. This study builds on the diversionary literature by investing coup risk as an incentive to use diversionary tactics as well as coup-proofing as a potential disincentive. The latter can both undermine the necessity of diversion as well as military capabilities, making leaders less capable of utilizing international conflict as a political tool. Third, the dissertation considers the influence of coup-proofing on intrastate conflict. The theory argues that the capability-reducing practice of coup-proofing can have important domestic consequences. Specifically, the practice can increase the mobilizational potential of would-be insurgents, can reduce the mobilizational capacity of the state, and leaders that are particularly fearful of a coup will likely tolerate the rise of an insurgency

    A synthesis of plant invasion effects on biodiversity across spatial scales

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    PREMISE OF THE STUDY: Invasive plant species are typically thought to pose a large threat to native biodiversity, and local-scale studies typically confirm this view. However, plant invaders rarely cause regional extirpations or global extinctions, causing some to suggest that invasive species\u27 influence on native biodiversity may not be so dire. We aim to synthesize the seemingly conflicting literature in plant invasion biology by evaluating the effects of invasive plant species across spatial scales. METHODS: We first conducted a meta-analysis on the effects of invasive plants on the species richness of invaded communities across a range of spatial extents. We then discuss studies that consider the role of invasive plants on regional spatial scales for which such meta-analyses are not possible. Finally, we develop a conceptual framework to synthesize the influence of invasive species across spatial scales by explicitly recognizing how invasive species alter species-occupancy distributions. KEY RESULTS: We found a negative relationship between the spatial extent of the study and the effect size of invasive plants on species richness. Our simulation models suggest that this result can occur if invaders, either proportionately or disproportionately, reduce the occupancy of common species to a greater degree than rare species. CONCLUSIONS: Future studies should consider the influence of invaders on the abundance and occupancy-level changes in native species to inform how invasive plants will influence native species richness relationships across spatial scales. This approach will allow greater predictive ability for forecasting changes in biodiversity in the face of anthropogenic biological invasions and will inform invasive species management and restoration

    Lean Startup as an Entrepreneurial Strategy: Limitations, Outcomes and Learnings for Practitioners

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    Purpose: This paper aims to address threecore questions around (1) what limitations exit with the methodology and/or its use; (2) what is the methodology's impact on performance outcomes; and (3) what learnings can practitioners and educators employ as part of the startup efforts. Methodology: A review of available peer and non-peer review literature relevant to the lean startup methodology, its limitations (pitfalls, fallacies, problems), and outcomes to address the core questions. Findings: This review identifies limitations with the methodology in several areas: business sector fit; issues associated with customer discovery; experimentation; iterating/pivoting; and the minimum viable product. Limitations may be related to the methodology, the incomplete understanding of its fundamental components, inconsistent (and non-rigorous) use of the methodology, and the inability to address risks (e.g., technological) beyond resolving market uncertainty. Also, experience related to outcomes with the lean startup reveals mixed findings due to the diverse methods, populations, and endpoints used. Such facets underly the mix of experiences seen in both the peer and non-peer review literature. This review identifies that rigorous implementation leads to statistically significant (P<0.05) outcome differences (e.g., discarding poor ideas, number of pivots, and revenue realization). Practical Implications: Practitioners and educators should consider educational, implementation, business sector, outside influences, outcomes, and investor preferences to use the methodology. Originality: This paper provides one of the first extensive literature reviews to examine what limits exist, where, and whether these are associated with the methodology or due to user, cultural, or business sector considerations. It also provides several relevant learnings for practitioners and educators to consider when using the methodology. Conclusions: Current evidence indicates that multiple issues do exist. Such limits are related to the methodology's inherent structure and user, sector, and external influence considerations. Further, outcomes vary based on study methods, variables, populations, business verticals, and implementation. Practitioners should consider some of the recommendations offered when utilizing this methodology to optimize their experience and outcomes

    Ferric citrate and ferric EDTA but not ferrous sulfate drive amphiregulin-mediated activation of the MAP kinase ERK in gut epithelial cancer cells.

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    Ferric chelates may be used as oral iron supplements or phosphate binders but both ferric citrate and ferric EDTA have been shown to promote tumor burden in murine models of colon cancer. Here we studied their effects on cancer cell growth, at typical supplemental iron levels encountered in the gastrointestinal tract (0.01-0.2 mM). Caco-2 and/or Hutu-80 cells were exposed to these forms of chelated iron or to ferrous sulfate and outcomes were assessed using cell proliferation assays, proteome profiler arrays, western blot, and ELISA. Ferric EDTA and ferric citrate increased cellular levels of the onco-protein amphiregulin and its receptor (EGFr) which in turn stimulated the activation of the MAP kinase ERK. Simultaneously, the expression of the negative Wnt regulator, DKK-1, increased suggesting that cell proliferation through the Wnt pathway may be less pronounced in the presence of ferric EDTA and ferric citrate, unlike for ferrous sulfate. Moreover, ferrous sulfate did not increase levels of cellular amphiregulin or EGFr. We conclude that specific iron compounds affect cell signaling differently and some may increase the risk of colon cancer advancement in an amphiregulin-dependent fashion. Further scrutiny of safe oral iron use is merited

    Oded Haklai, Palestinian Ethnonationalism in Israel (Philadelphia: University of Pennsylvania Press)

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    Plants respond to pathogens either by investing more resources into immunity which is costly to development, or by accelerating reproductive processes such as flowering time to ensure reproduction occurs before the plant succumbs to disease. In this study we explored the link between flowering time and pathogen defense using the interaction between Arabidopsis thaliana and the root infecting fungal pathogen Fusarium oxysporum. We report that F. oxysporum infection accelerates flowering time and regulates transcription of a number of floral integrator genes, including FLOWERING LOCUS C (FLC), FLOWERING LOCUS T (FT) and GIGANTEA (GI). Furthermore, we observed a positive correlation between late flowering and resistance to F. oxysporum in A. thaliana natural ecotypes. Late-flowering gi and autonomous pathway mutants also exhibited enhanced resistance to F. oxysporum, supporting the association between flowering time and defense. However, epistasis analysis showed that accelerating flowering time by deletion of FLC in fve-3 or fpa-7 mutants did not alter disease resistance, suggesting that the effect of autonomous pathway on disease resistance occurs independently from flowering time. Indeed, RNA-seq analyses suggest that fve-3 mediated resistance to F. oxysporum is most likely a result of altered defense-associated gene transcription. Together, our results indicate that the association between flowering time and pathogen defense is complex and can involve both pleiotropic and direct effects

    Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening

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    Since newborn screening (NBS) began in the 1960s, technological advances have enabled its expansion to include an increasing number of disorders. Recent developments now make it possible to sequence an infant’s genome relatively quickly and economically. Clinical application of whole-exome and whole-genome sequencing is expanding at a rapid pace but presents many challenges. Its utility in NBS has yet to be demonstrated and its application in the pediatric population requires examination, not only for potential clinical benefits, but also for the unique ethical challenges it presents

    Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials.

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    Bacterial resistance to antimicrobial therapies is an increasing clinical problem. This is as true for topical applications as it is for systemic therapy. Topically, copper ions may be effective and cheap antimicrobials that act through multiple pathways thereby limiting opportunities to bacteria for resistance. However, the chemistry of copper does not lend itself to facile formulations that will readily release copper ions at biologically compatible pHs. Here we have developed nanoparticulate copper hydroxide adipate tartrate (CHAT) as a cheap, safe and readily synthesised material that should enable antimicrobial copper ion release in an infected wound environment. First, we synthesised CHAT and showed that this had disperse aquated particle sizes of 2-5 nm, and mean zeta potential of -40 mV. Next, when diluted into bacterial medium, CHAT demonstrated similar efficacy to copper chloride against Escherichia coli and Staphylococcus aureus, with dose-dependent activity occurring mostly around 12.5-50 mg/L of copper. Indeed, at these levels, CHAT very rapidly dissolved and, as confirmed by a bacterial copper biosensor, showed identical intracellular loading to copper ions derived from copper chloride. However, when formulated at 250 mg/L in a topically-applied matrix, namely hydroxyethyl cellulose, the benefit of CHAT over copper chloride was apparent. The former yielded rapid sustained release of copper within the bactericidal range but the copper chloride, which formed insoluble precipitates at such concentration and pH, achieved a maximum release of 10 ± 7 mg/L copper by 24 hours. We provide a practical formulation for topical copper - based antimicrobial therapy. Further studies, especially in vivo, are merited

    Differential patterns of histone acetylation in inflammatory bowel diseases

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    Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation

    2D Cine DENSE with Low Encoding Frequencies Accurately Quantifies Cardiac Mechanics with Improved Image Characteristics

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    BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (ke) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a ke of 0.10 cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high ke. Additionally, the high sensitivity comes with the costs of increased phase wrapping and intra-voxel dephasing. We hypothesized that ke below 0.10 cycles/mm can be used to improve image characteristics and provide accurate measures of cardiac mechanics. METHODS: Spiral cine DENSE images were obtained for 10 healthy subjects and 10 patients with a history of heart disease on a 3 T Siemens Trio. A mid-ventricular short-axis image was acquired with different ke: 0.02, 0.04, 0.06, 0.08, and 0.10 cycles/mm. Peak twist, circumferential strain, and radial strain were compared between acquisitions employing different ke using Bland-Altman analyses and coefficients of variation. The percentage of wrapped pixels in the phase images at end-systole was calculated for each ke. The dephasing of the blood signal and signal to noise ratio (SNR) were also calculated and compared. RESULTS: Negligible differences were seen in strains and twist for all ke between 0.04 and 0.10 cycles/mm. These differences were of the same magnitude as inter-test differences. Specifically, the acquisitions with 0.04 cycles/mm accurately quantified cardiac mechanics and had zero phase wrapping. Compared to 0.10 cycles/mm, the acquisitions with 0.04 cycles/mm had 9 % greater SNR and negligible differences in blood pool dephasing. CONCLUSIONS: For 2D cine DENSE with through-plane dephasing, the encoding frequency can be lowered to 0.04 cycles/mm without compromising the quantification of twist or strain. The amount of wrapping can be reduced with this lower value to greatly simplify the input to unwrapping algorithms. The strain and twist results from studies using different encoding frequencies can be directly compared
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