Modelování volatility devizových kurzů

Import 22/07/2015The aim of this Diploma thesis is modelling and in-sample forecasting volatility of selected exchange rates using linear and nonlinear conditional heteroskedasticity models. The main aim of the thesis is supported by two partial aims. The first partial aim is to compare whether linear or nonlinear models are more efficient for modelling conditional heteroskedasticity for exchange rates. The second partial aim is to assess the suitability of estimated models to predict volatility. Tested data are time series of daily exchange rates modified to time series of daily logarithmic returns of Slovenian tolar, Cyprus pound, Slovakian koruna and Latvian lat against Euro. Observed period is divided into three parts in order to model volatility of all exchange rates in different relations of domestic countries to European Union. Thesis is divided into six parts including Introduction and Conclusion. Second and third chapter is theoretical and methodological, while the fourth and fifth chapter is practical and empirical.Cílem Diplomové práce je modelování volatility a ve výběru provedená predikce vybraných měnových kurzů za využití lineárních a nelineárních modelů podmíněné heteroskedasticity. Hlavní cíl práce je dále rozdělen na dva dílčí cíle. První z dílčích cílů se věnuje otázce, zda jsou k modelování měnových kurzů podmíněné heteroskedasticity vhodnější lineární nebo nelineární modely. Druhý dílčí cíl zohledňuje, zda jsou odhadnuté modely vhodné k predikování volatility. Testovaná data jsou časové řady denních měnových kurzů upravené na časové řady denních logaritmovaných výnosů Slovinského tolaru, Kyperské libry, Slovenské koruny a Lotyšského latu vůči Euru. Sledovaná časová perioda je rozdělena na tři části za účelem modelovat volatilitu všech měnových kurzů při různém vztahu domácí země vůči Evropské Unii. Práce je rozdělena na šest částí včetně úvodu a závěru. Druhá a třetí kapitola jsou teoretické a metodologické, zatímco čtvrtá a pátá kapitola jsou praktické a empirické.154 - Katedra financívýborn

Three-hundred-and-fifty-eighth Meeting of the Finance Committee, chaired by Ms Charlotte Jamieson

Three-hundred-and-fifty-eighth Meeting of the Finance Committee, chaired by Ms Charlotte Jamieson, December 201

Multicomponent Synthesis and Binding Mode of Imidazo[1,2‑<i>a</i>]pyridine-Capped Selective HDAC6 Inhibitors

The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo­[1,2-<i>a</i>]­pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode

Multicomponent Synthesis and Binding Mode of Imidazo[1,2‑<i>a</i>]pyridine-Capped Selective HDAC6 Inhibitors

The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo­[1,2-<i>a</i>]­pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode

α-Substituted β-Oxa Isosteres of Fosmidomycin: Synthesis and Biological Evaluation

Specific inhibition of enzymes of the non-mevalonate pathway is a promising strategy for the development of novel antiplasmodial drugs. α-Aryl-substituted β-oxa isosteres of fosmidomycin with a reverse orientation of the hydroxamic acid group were synthesized and evaluated for their inhibitory activity against recombinant 1-deoxy-d-xylulose 5-phosphate reductoisomerase (IspC) of Plasmodium falciparum and for their <i>in vitro</i> antiplasmodial activity against chloroquine-sensitive and resistant strains of P. falciparum. The most active derivative inhibits IspC protein of P. falciparum (<i>Pf</i>IspC) with an IC₅₀ value of 12 nM and shows potent <i>in vitro</i> antiplasmodial activity. In addition, lipophilic ester prodrugs demonstrated improved P. falciparum growth inhibition <i>in vitro</i>

Binding Modes of Reverse Fosmidomycin Analogs toward the Antimalarial Target IspC

1-Deoxy-d-xylulose 5-phosphate reductoisomerase of Plasmodium falciparum (<i>Pf</i>IspC, <i>Pf</i>Dxr), believed to be the rate-limiting enzyme of the nonmevalonate pathway of isoprenoid biosynthesis (MEP pathway), is a clinically validated antimalarial target. The enzyme is efficiently inhibited by the natural product fosmidomycin. To gain new insights into the structure activity relationships of reverse fosmidomycin analogs, several reverse analogs of fosmidomycin were synthesized and biologically evaluated. The 4-methoxyphenyl substituted derivative <b>2c</b> showed potent inhibition of <i>Pf</i>IspC as well as of P. falciparum growth and was more than one order of magnitude more active than fosmidomycin. The binding modes of three new derivatives in complex with <i>Pf</i>IspC, reduced nicotinamide adenine dinucleotide phosphate, and Mg²⁺ were determined by X-ray structure analysis. Notably, <i>Pf</i>IspC selectively binds the <i>S</i>-enantiomers of the study compounds

Modification of <i>var</i> transcription by mosquito transmission.

<p>(A) The rate difference of the median expression for each individual <i>var</i> variant and the housekeeping controls shows the overexpression of the entire <i>var</i> gene family <i>in vivo</i> with exception of the <i>var2csa</i> gene PFL0030c in comparison to the parental Master Cell Bank (MCB) parasite line. Each point reflects the median for the volunteer samples at the day of patent infection (n = 18) divided by the median observed for the parasite generations 6, 8 and 21 from two vials of the MCB cell line (n = 6). Housekeeping genes used as controls, <i>var</i> gene names and groups are indicated. (B) Differences in gene expression on group level between the pre-mosquito MCB parasite lines and parasites recovered from the infected volunteers (VOL) at the day of patent infection determined by thick blood smear are displayed as group median with interquartile range (IQR). Significant differences in distributions between MCB and VOL series were tested via a Wilcoxon rank-sum test using a Bonferroni corrected significance level. The graph contains a scale brake at the y-axis to account for the huge variability in the gene expressions. Group affiliations are indicated above the graph. Red (A), orange (A, subfamily <i>var3</i>), dark red (A, subfamily <i>var1</i>), purple (B/A), blue (B), turquoise (B/C), green (C) and yellow (E).</p

<i>Var</i> transcription profiles of parental parasite lines used for volunteer infection.

<p>(A) The gene expression of each <i>var</i> gene and control genes relative to <i>sbp1</i> expression is shown in dot plots for the pre-mosquito Master Cell Bank (MCB) parasite line. Each point represents values observed per test generation for the MCB samples taken from two independently thawed parasite stocks after 6, 8 and 21 parasite generations, respectively (n = 6). The median expression per <i>var</i> gene is shown, housekeeping genes used as controls, <i>var</i> gene names and groups are indicated. (B) The MCB cell line exclusively expresses the group E <i>var2csa</i> gene as shown by the proportion of <i>var</i> transcripts according to <i>var</i> group affiliation. The genomic proportion of each <i>var</i> gene group is indicated after the color code.</p

IspC as Target for Antiinfective Drug Discovery: Synthesis, Enantiomeric Separation, and Structural Biology of Fosmidomycin Thia Isosters

The emergence and spread of multidrug-resistant pathogens are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of “reverse” thia analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an α-substituted fosmidomycin derivative

Blood Schizontocidal and Gametocytocidal Activity of 3‑Hydroxy‑<i>N</i>′‑arylidenepropane­hydrazonamides: A New Class of Antiplasmodial Compounds

3-Hydroxy-<i>N</i>′-arylidenepropanehydrazonamides represent a new class of antiplasmodial compounds. The two most active phenanthrene-based derivatives showed potent in vitro antiplasmodial activity against the 3D7 (sensitive) and Dd2 (multidrug-resistant) strains of <i>Plasmodium falciparum</i> with nanomolar IC₅₀ values in the range of 8–28 nM. Further studies revealed that the most promising derivative, bearing a 4-fluorobenzylidene moiety, demonstrated in vivo antiplasmodial activity after oral administration in a <i>P. berghei</i> malaria model, although no complete parasite elimination was achieved with a four-dose regimen. The in vivo efficacy correlated well with the plasma concentration levels, and no acute toxicity symptoms (e.g., death or changes in general behavior or physiological activities) were observed, which is in agreement with a >1000-fold lower activity against L6 cells, a primary cell line derived from mammalian (rat) skeletal myoblasts. This indicates that lead compound <b>29</b> displays selective activity against <i>P. falciparum</i>. Moreover, both phenanthrene-based derivatives were active against stage IV/V gametocytes of <i>P. falciparum</i> in vitro