Centre-right failure in new democracies: the case of the Romanian Democratic Convention

This thesis asks why some centre-right formations have been more successful than others in the new democracies of Central and Eastern Europe. It does so by examining a single centre-right formation – the Romanian Democratic Convention. It adds to an existing body of literature that covers the development of political parties in post-Communist Central and Eastern Europe and to the small number of studies focusing on centre-right parties in the region. Specifically it adds to the literature on party success and failure and to that on Romanian party and electoral politics. The Romanian Democratic Convention is chosen to add new insights: it is unusual because it is a study of organisational failure and because there is a geographical imbalance in the published studies of the politics of the region towards the Visegrad states. The thesis acknowledges existing academic debate about the competing influences of historical legacies, agency and structural factors in relation to post-Communist democratisation. It aims to identify what led the Convention to first establish itself but then fail to consolidate and eventually to collapse. It draws on a range of sources: semi-structured interviews; contemporaneous newspaper reports; published diaries and autobiographies and a number of secondary sources. The thesis is structured thematically, examining the role of legacies and critical events in shaping long term behaviour by politicians (chapters three and four); organisational factors and the influence of operational objectives (chapter five); the search for a broad and integrative ideology (chapter six). The conclusions in chapter seven suggest that successfully crafting a new, broad political formation requires a degree of pragmatism, directive leadership and political entrepreneurship that was missing from the Democratic Convention because it was shaped by Romania’s transition from Communism, by its organisational structure and by differences within its leadership elite so that competing operational objectives could not be reconciled when the formation entered government

On renormalization group flows and the a-theorem in 6d

We study the extension of the approach to the a-theorem of Komargodski and Schwimmer to quantum field theories in d=6 spacetime dimensions. The dilaton effective action is obtained up to 6th order in derivatives. The anomaly flow a_UV - a_IR is the coefficient of the 6-derivative Euler anomaly term in this action. It then appears at order p^6 in the low energy limit of n-point scattering amplitudes of the dilaton for n > 3. The detailed structure with the correct anomaly coefficient is confirmed by direct calculation in two examples: (i) the case of explicitly broken conformal symmetry is illustrated by the free massive scalar field, and (ii) the case of spontaneously broken conformal symmetry is demonstrated by the (2,0) theory on the Coulomb branch. In the latter example, the dilaton is a dynamical field so 4-derivative terms in the action also affect n-point amplitudes at order p^6. The calculation in the (2,0) theory is done by analyzing an M5-brane probe in AdS_7 x S^4. Given the confirmation in two distinct models, we attempt to use dispersion relations to prove that the anomaly flow is positive in general. Unfortunately the 4-point matrix element of the Euler anomaly is proportional to stu and vanishes for forward scattering. Thus the optical theorem cannot be applied to show positivity. Instead the anomaly flow is given by a dispersion sum rule in which the integrand does not have definite sign. It may be possible to base a proof of the a-theorem on the analyticity and unitarity properties of the 6-point function, but our preliminary study reveals some difficulties.Comment: 41 pages, 5 figure

High-Throughput Screening of Australian Marine Organism Extracts for Bioactive Molecules Affecting the Cellular Storage of Neutral Lipids

Mammalian cells store excess fatty acids as neutral lipids in specialised organelles called lipid droplets (LDs). Using a simple cell-based assay and open-source software we established a high throughput screen for LD formation in A431 cells in order to identify small bioactive molecules affecting lipid storage. Screening an n-butanol extract library from Australian marine organisms we identified 114 extracts that produced either an increase or a decrease in LD formation in fatty acid-treated A431 cells with varying degrees of cytotoxicity. We selected for further analysis a non-cytotoxic extract derived from the genus Spongia (Heterofibria). Solvent partitioning, HPLC fractionation and spectroscopic analysis (NMR, MS) identified a family of related molecules within this extract with unique structural features, a subset of which reduced LD formation. We selected one of these molecules, heterofibrin A1, for more detailed cellular analysis. Inhibition of LD biogenesis by heterofibrin A1 was observed in both A431 cells and AML12 hepatocytes. The activity of heterofibrin A1 was dose dependent with 20 µM inhibiting LD formation and triglyceride accumulation by ∼50% in the presence of 50 µM oleic acid. Using a fluorescent fatty acid analogue we found that heterofibrin A1 significantly reduces the intracellular accumulation of fatty acids and results in the formation of distinct fatty acid metabolites in both cultured cells and in embryos of the zebrafish Danio rerio. In summary we have shown using readily accessible software and a relatively simple assay system that we can identify and isolate bioactive molecules from marine extracts, which affect the formation of LDs and the metabolism of fatty acids both in vitro and in vivo

Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases

Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface

A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol trafficking

ORP5 works together with Niemann Pick C-1 to facilitate exit of cholesterol from endosomes and lysosomes

Hrs and SNX3 Functions in Sorting and Membrane Invagination within Multivesicular Bodies

After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs—an adaptor-like protein that binds membrane PtdIns3P via a FYVE motif—and then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis

Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking

Background Pathological accumulation of cholesterol in late endosomes is observed in lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects of cholesterol accumulation in NPC cells, or as phenocopied by the drug U18666A, on late endosomes membrane organization and dynamics. Methodology/Principal Findings Cholesterol accumulation did not lead to an increase in the raft to non-raft membrane ratio as anticipated. Strikingly, we observed a 2–3 fold increase in the size of the compartment. Most importantly, properties and dynamics of late endosomal intralumenal vesicles were altered as revealed by reduced late endosomal vacuolation induced by the mutant pore-forming toxin ASSP, reduced intoxication by the anthrax lethal toxin and inhibition of infection by the Vesicular Stomatitis Virus. Conclusions/Significance These results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation

MoVam7, a Conserved SNARE Involved in Vacuole Assembly, Is Required for Growth, Endocytosis, ROS Accumulation, and Pathogenesis of Magnaporthe oryzae

Soluble NSF attachment protein receptor (SNARE) proteins play a central role in membrane fusion and vesicle transport of eukaryotic organisms including fungi. We previously identified MoSce22 as a homolog of Saccharomyces cerevisiae SNARE protein Sec22 to be involved in growth, stress resistance, and pathogenicity of Magnaporthe oryzae. Here, we provide evidences that MoVam7, an ortholog of S. cerevisiae SNARE protein Vam7, exerts conserved functions in vacuolar morphogenesis and functions in pathogenicity of M. oryzae. Staining with neutral red and FM4-64 revealed the presence of abnormal fragmented vacuoles and an absence of the Spitzenkörper body in the ΔMovam7 mutant. The ΔMovam7 mutant also exhibited reduced vegetative growth, poor conidiation, and failure to produce the infection structure appressorium. Additionally, treatments with cell wall perturbing agents indicated weakened cell walls and altered distributions of the cell wall component chitin. Furthermore, the ΔMovam7 mutant showed a reduced accumulation of reactive oxygen species (ROS) in the hyphal apex and failed to cause diseases on the rice plant. In summary, our studies indicate that MoVam7, like MoSec22, is a component of the SNARE complex whose functions in vacuole assembly also underlies the growth, conidiation, appressorium formation, and pathogenicity of M. oryzae. Further studies of MoVam7, MoSec22, and additional members of the SNARE complex are likely to reveal critical mechanisms in vacuole formation and membrane trafficking that is linked to fungal pathogenicity

Felony Murder and Capital Punishment: an Examination of the Deterrence Question

A proper test of the deterrent effect of the death penalty must consider capital homicides. However, the criterion variable in most investigations has been total homicides—most of which bear no legal or theoretical relationship to capital punishment. To address this fundamental data problem, this investigation used Federal Bureau of Investigation data for 1976–1987 to examine the relationship between capital punishment and felony murder, the most common type of capital homicide. We conducted time series analyses of monthly felony murder rates, the frequency of executions, and the amount and type of television coverage of executions over the period. The analyses revealed occasional departures (for vehicle theft and narcotics killings) from the null hypotheses. However, on balance, and in line with the vast majority of capital punishment studies, this investigation found no consistent evidence that executions and the television coverage they receive are associated significantly with rates for total, index, or different types of felony murder

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements