The validity of purchasing power parity over the last century

Bibliography: p. 64-73This thesis tests the validity of purchasing power parity (PPP), a theory which summarizes the equilibrium relationship between the exchange rate and relative price levels. In general, previous studies have not found support for PPP in the short run, yet mixed results occurred when PPP was tested over long time periods. This thesis examines the behavior of real exchange rates for a group of 23 OECD countries over 100 years. For the first time, Rescaled Range Analysis, which consists of the Hurst exponent and the modified R/S statistic, is employed to detect the long memory in real exchange rate series. Overall, the results do not provide evidence of stationarity or long memory in real exchange rates, which leads to the rejection of PPP. To ensure the robustness of the results, conventional unit root and stationarity tests were applied, with the same disappointing results

Ukrainian practice of the military radio broadcasting development during the military conflict

The article explored the potential of radio broadcasting in a coverage of the military conflict in Ukraine. It is determined that the most specific for Ukrainian broadcast is an entertaining, social and psychological, arts and cultural, patriotic (ideological and agitational), historical, information and analytics projects, demonstrating that the potentiality of radio broadcasting make such radio programmes closer to the broadcast listener not only at home, but and in the trenches or in the adaptation after the combat area service. The author notes the lack of attention of radio companies to the topics of anti-terrorist operation (ATO), and focuses on the potential of radio broadcasting for the social adaptation of service members and people affected by military conflict in eastern Ukraine and Crimea in the postwar period

Investigating the hepatitis C virus and dengue virus interactions with host lipid pathways : from circulating human microRNAs to lipid modulating agents

Cholesterol and lipid levels are maintained through tightly controlled and complex feedback mechanisms that involve regulation of major metabolic genes. Dysregulation of cellular or plasma lipid levels can lead to a wide range of pathologies, including hyperlipidemia, atherosclerosis and other disorders. A number of viruses, including important human viruses of the Flaviviridae family such as hepatitis C virus (HCV) and dengue virus (DENV), utilize and modulate host lipids to support their lifecycles, and the resulting changes in lipid metabolism may contribute to virus-associated pathologies. The overall aim of this thesis was to determine the role of key regulators of host lipid homeostasis, including microRNAs (miR-122, miR-24 and miR-223) and proprotein convertases (SKI-1/S1P and PCSK9) during viral infection and virus-associated disease. To address this aim, we first examined the molecular interplay between three circulating microRNAs known to act as regulators of lipid homeostasis. The data we present in Chapter 2 shows that specific signatures of the three microRNAs were associated with different treatment outcomes in patients with chronic hepatitis C (CHC), indicating that these microRNAs correlate with HCV infection. We then tested the hypothesis that enzymatic regulators of lipid metabolism could also indicate HCV infection, and in Chapter 3 we show that PCSK9 levels were significantly upregulated in patients who achieved a treatment-based viral cure but not in relapsers. These data indicate that changes in PCSK9 concentrations may have an important role in both HCV infection and in host lipid metabolism. In Chapter 4, we tested whether reducing the abundance of lipid droplets via inhibition of SKI-1/S1P with a small molecule PF-429242 suppresses DENV infection. The inhibitor blocked SKI-1/S1P-mediated accumulation of lipid droplets in hepatoma cells and reduced DENV infection, identifying SKI-1/S1P as a potential target for indirect-acting anti-DENV agents. This study on modulators of lipid metabolism during HCV and DENV infections provides new insights into the complex host-virus interactions that associate with virally-induced disease. We hope that our data lay the foundation for understanding disease pathogenesis and support the development of future strategies for Flaviviridae - associated diseases.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Трансформація та конвергенція в діяльності українських редакцій міжнародних радіостанцій

The purpose of the paper is to study intensive transformational processes and deep convergence in the activities of Ukrainian editorial offices of international radio stations. This analysis will enable to identify the most promising directions for the development of other sectors of Ukrainian-language radio under the competitive conditions in the media environment of the present-day world.Research Methodology. The research is based on the methods of systematization, monitoring, induction, numerical analysis, discourse analysis and forecasting.Results. The work of 8 Ukrainian editorial offices of international radio stations was investigated taking into account the introduction of modern convergent tools into their activities. The paper enlists the perspectives of the use of some atypical means in the Ukrainian-language radio — prolonged playback of audio, audio-databases, music, visualization (text, graphic content, video on demand and studio), social networks, Internet advertising and donations as forms of capitalizing a radio project. These measures are considered the decisive trends of its transformation and the key to increasing the competitiveness of the sector in the global media environment.Novelty. The study is one of the first attempts of the scientific comprehension of the transformation and convergence in the activities of Ukrainian editorial offices of international radio stations and their influence on the development of mainland Ukrainian-language radio space.Practical significance of the paper lies in the formation of a map of the Ukrainian-language radio of the world and the clarification of its competitiveness in the media environment of the world.Key words: convergence, transformation, Ukrainian editorial boards of international radio stations, Ukrainian-language broadcasting.Досліджено діяльність восьми українських редакцій міжнародних радіо-станцій у контексті впровадження сучасних конвергентних інструментів. Осмислено перспективність використання у сфері материкового сектора україномовного радіо нетипових для нього на попередніх етапах відкладеного в часі прослуховування аудіо, банку аудіо, музики, візуалізації (текст, графічний, відео-контент, стрім зі студії), соціальних мереж, інтернет-реклами та пожертв як форми капіталізації діяльності радіопроекту. Ці заходи вважаємо визначальними напрямами трансформації та запорукою підвищення конкурентоспроможності сектора у світовому медіасередовищі.Ключові слова: конвергенція, трансформація, українські редакції міжнародних радіостанцій, україномовне радіомовлення

Purchasing power parity over a century

Purpose – The purpose of this paper is to revisit the evidence for purchasing power parity (PPP) using long, low-frequency data (over 100 years) for 23 organization for economic co-operation and development (OECD) countries against each of four different base currencies – the Deutsch mark, the Japanese yen, the British pound, and the US dollar. Design/methodology/approach – The paper uses standard unit root tests and level and trend stationarity tests, and also investigates the robustness of the results to alternative testing methodologies from statistical physics, such as Lo's modified rescaled range statistic and the Hurst exponent. Findings – The results indicate that the theory of PPP does not hold. Originality/value – Motivated by the mixed results from previous research on the validity of the theory of PPP, the robustness of standard unit root and stationarity tests to alternative testing methodologies are investigated. In particular, the paper uses two tests from statistical physics – Lo's modified R/S statistic and the Hurst exponent.Currencies, Exchange rates, Purchasing power

ZCCHC14 is a novel host factor that is required for Hepatitis B virus RNA polyadenylation

The hallmark of chronic hepatitis B virus (CHB) infection is the presence of high levels of circulating non-infectious small lipid vesicles containing HBV surface antigen (HBsAg). Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy and is considered a functional cure. A novel, potent and orally bioavailable small molecule RG7834 has been previously reported to inhibit HBsAg expression putatively targeting host non-canonical poly(A) RNA polymerases, PAP-associated domain-containing protein 5 and 7 (PAPD5 and PAPD7). In this study, we describe a forward genetic screen exploiting CRISPR-mediated genome-wide editing to identify novel host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. Several genes were enriched in a cell population resisting to RG7834-mediating HBsAg inhibition, including PAPD5 and a novel host factor zinc finger CCHC-type containing 14 (ZCCHC14). The role of ZCCHC14, PAPD5 as well as its homolog PAPD7 were further confirmed by the siRNA knockdown studies which phenotypically similarly to RG7834 were associated with the strong reduction in polyA tails of HBV-specific RNAs. In addition, as seen previously with RG7834, inhibition of HBsAg expression by ZCCHC14 and PAPD5/7 complex requires intact SL? in the HBV post-transcriptional regulatory elements. In conclusion, we identify ZCCHC14 as a novel cellular factor, which acts together with the PAPD5 and PAPD7 complex to polyadenylate HBV transcripts and as a new therapeutic target for the HBV cure

First crystal structure of a nonstructural hepatitis E viral protein identifies a putative novel zinc-binding protein

Hepatitis E virus (HEV) is a 7.2-kb positive-sense, single-stranded RNA virus containing three partially overlapping reading frames, ORF1 to ORF3. All nonstructural proteins required for viral replication are encoded by ORF1 and are transcribed as a single transcript. Computational analysis of the complete ORF1 polyprotein identified a previously uncharacterized region of predicted secondary structure bordered by two disordered regions coinciding partially with a region predicted as a putative cysteine protease. Following successful cloning, expression, and purification of this region, the crystal structure of the identified protein was determined and identified to have considerable structural homology to a fatty acid binding domain. Further analysis of the structure revealed a metal binding site, shown unambiguously to specifically bind zinc via a nonclassical, potentially catalytic zinc-binding motif. Based on the structural homology of the HEV protein with known structures, along with the presence of a catalytic zinc-binding motif, it is possible that the identified protein corresponds to the HEV protease, which could require activation or repression through the binding of a fatty acid. This represents a significant step forward in the characterization and the understanding of the molecular mechanisms of the HEV genome. We present analysis for the first time of this identified nonstructural protein, expanding the knowledge and understanding of the complex mechanisms of HEV biology

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n = 72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis — circulating miR-24, miR-223 and PCSK9 — whose regulation is affected by HCV infection and treatment-based viral cure

eLive revised manuscript: A POLYOMAVIRUS PEPTIDE BINDS TO THE CAPSID VP1 PORE AND HAS POTENT ANTIVIRAL ACTIVITY AGAINST BK AND JC POLYOMAVIRUSES

In pursuit of therapeutics for human polyomaviruses, we identified a peptide derived from the BK polyomavirus (BKV) minor structural proteins VP2/3 that is a potent inhibitor of BKV infection with no observable cellular toxicity. The thirteen-residue peptide binds to major structural protein VP1 with single-digit nanomolar affinity. Alanine scanning of the peptide identified three key residues, substitution of each of which results in ~1000-fold loss of binding affinity with a concomitant reduction in antiviral activity. Structural studies demonstrate specific binding of the peptide to the five-fold pore of pentameric VP1. Cell-based assays demonstrate nanomolar inhibition (EC50) of BKV infection and suggest that the peptide acts early in the viral entry pathway. Homologous peptide exhibits similar binding to JC polyomavirus VP1 and inhibits infection with similar potency to BKV in a model cell line. Lastly, these studies validate targeting the VP1 pore as a novel strategy for the development of anti-polyomavirus agents