Effect of the complex-formation ability of thiosemicarbazones containing (aza)benzene or 3-nitro-1,8-naphthalimide unit towards Cu(II) and Fe(III) ions on their anticancer activity

We recently described a novel class of thiosemicarbazones (TSCs) with a high anticancer activity. Now, we expanded this compound library with a new class of TSCs with a 3-nitro-1,8-naphthalene unit. Thus, a series of novel TSC conjugates was obtained to determine the effect of its chemical structure on spectroscopic properties, metal complexing and biological activity. They were prepared in a microwave reactor, provided compounds with both a high yield and purity. Nuclear magnetic resonance (1H and 13C NMR, COSY, HMQC) and infrared spectroscopy were used to characterize them structurally. Additionally, DFT calculations were performed in order to obtain the optimized ground-state geometry. Physicochemical spectroscopic studies were conducted in different solvents and conditions to assess the effect of the substituent on the optical properties and metal complexing ability. The anticancer activity was tested on three cancer cell lines and then correlated with the spectroscopic results. Here, we show based on in vitro chelating studies, that anticancer activity is closely correlated with the Fe3+ and Cu2+ chelating ability of these compounds

High Log-Scale Expansion of Functional Human Natural Killer Cells from Umbilical Cord Blood CD34-Positive Cells for Adoptive Cancer Immunotherapy

Immunotherapy based on natural killer (NK) cell infusions is a potential adjuvant treatment for many cancers. Such therapeutic application in humans requires large numbers of functional NK cells that have been selected and expanded using clinical grade protocols. We established an extremely efficient cytokine-based culture system for ex vivo expansion of NK cells from hematopoietic stem and progenitor cells from umbilical cord blood (UCB). Systematic refinement of this two-step system using a novel clinical grade medium resulted in a therapeutically applicable cell culture protocol. CD56+CD3− NK cell products could be routinely generated from freshly selected CD34+ UCB cells with a mean expansion of >15,000 fold and a nearly 100% purity. Moreover, our protocol has the capacity to produce more than 3-log NK cell expansion from frozen CD34+ UCB cells. These ex vivo-generated cell products contain NK cell subsets differentially expressing NKG2A and killer immunoglobulin-like receptors. Furthermore, UCB-derived CD56+ NK cells generated by our protocol uniformly express high levels of activating NKG2D and natural cytotoxicity receptors. Functional analysis showed that these ex vivo-generated NK cells efficiently target myeloid leukemia and melanoma tumor cell lines, and mediate cytolysis of primary leukemia cells at low NK-target ratios. Our culture system exemplifies a major breakthrough in producing pure NK cell products from limited numbers of CD34+ cells for cancer immunotherapy

Studium vlivu spin-orbitální interakce v pevných látkách

Jedním z důsledků spin-orbitální interakce v pevných látkách je anomální Hallův jev. V této práci popíšeme procesy vedoucí ke vzniku anomálního Hallova jevu a jeho význam ve fyzice pevných látek. Uvedeme formalismus lineární odezvy a další nástroje nutné pro provádění výpočtů anomální Hallovy vodivosti. Dále uvedeme dva konkrétní modely anomálního Hallova jevu v pevných látkách - je- den založený na Kubově formalismu a druhý založený na výpočtu skrze chemický potenciál. Tyto modely si popíšeme a pak je porovnáme pro jednoduchý případ krystalu Sr2RuO4. Ukážeme, že oba modely dávají v tomto případě velmi podobné výsledky. 1One of the effects the spin orbit interaction leads to is the Anomalous Hall effect. In this thesis we describe the origins of the Anomalous Hall effect and its con- tribution to understanding the solid state physics. We introduce the formalism of linear response theory and other approximations needed to perform calcula- tions of the Anomalous Hall conductivity. We present two different models of the anomalous Hall conductivity - one based on the Kubo formalism and the other based on chemical potential difference. We then compare the models in a simple setting based on Strontium ruthenate. We show that in the case of Strontium ruthenate the models have very similar predictions. 1Katedra fyziky kondenzovaných látekDepartment of Condensed Matter PhysicsMatematicko-fyzikální fakultaFaculty of Mathematics and Physic

Vyšší kalibrační teorie

V přiložené práci podáváme krátký úvod do vyšších kalibračních teorií. Popisujeme fyzikální pozadí BRST formalizmu a vlastnosti, které nám umožňují tento formalizmus aplikovat na vyšší kalibrační teorie. Dáváme krátký přehled teorie kategorií. Definujeme 2-grupy a ukazujeme, že jsou ekvivalentní s crossed moduly. Dále dáváme krátký úvod do teorie L∞-algeber. Definujeme všechny potřebné pojmy pro zavedení gradovaných variet a Q-variet. Dáváme přehled Homotopy Maurer-Cartanových teorií a ukazujeme, že ve speciálním případě 4-dimenzionálního prostoru a dvoučlenné L∞-algebry je tato teorie shodná s BF teorií. 1This thesis gives a short introduction into the higher gauge algebras. We first in- troduce the BRST formalism in the context of ordinary gauge theories and show the properties that allow us to use it in the context of higher gauge theories. We define the 2-groups and show the correspondence between 2-groups and crossed modules. We then give a brief introduction into the theory of L∞-algebras - we give account of the graded manifolds and Q-manifolds. We give a short account of Homotopy Maurer-Cartan theory and show that it reduces to the BF theory in case of 4-dimensional manifold and 2-term L∞-algebra. 1Matematický ústav UKMathematical Institute of Charles UniversityFaculty of Mathematics and PhysicsMatematicko-fyzikální fakult

Higher gauge theory

This thesis gives a short introduction into the higher gauge algebras. We first in- troduce the BRST formalism in the context of ordinary gauge theories and show the properties that allow us to use it in the context of higher gauge theories. We define the 2-groups and show the correspondence between 2-groups and crossed modules. We then give a brief introduction into the theory of L∞-algebras - we give account of the graded manifolds and Q-manifolds. We give a short account of Homotopy Maurer-Cartan theory and show that it reduces to the BF theory in case of 4-dimensional manifold and 2-term L∞-algebra.

Study of the effect of spin-orbit interaction in solids

One of the effects the spin orbit interaction leads to is the Anomalous Hall effect. In this thesis we describe the origins of the Anomalous Hall effect and its con- tribution to understanding the solid state physics. We introduce the formalism of linear response theory and other approximations needed to perform calcula- tions of the Anomalous Hall conductivity. We present two different models of the anomalous Hall conductivity - one based on the Kubo formalism and the other based on chemical potential difference. We then compare the models in a simple setting based on Strontium ruthenate. We show that in the case of Strontium ruthenate the models have very similar predictions.

Ray of the Rovers: The Working Class Heroine in Popular Football Fiction, 1915 – 25

The First World War became a watershed for the lives of many women in Britain, as they were suddenly thrown into roles that society had previously denied them. Women were expected to enter male spheres in the home and work place as part of the war effort, resulting in a more expendable income for many and profound changes in dress and lifestyle. Trouser suits, shorter hem lines, 'Bobbed' hair and cigarettes were all part of a new androgynous look created to accommodate women's redefined roles. 'Ladies Football', to use their own term, fitted neatly into this new status quo.' However, it was not exclusive to the First World War and nor was it essentially a working class phenomenon, as the football stories would lead us to believe. Firstly, as both Gail Newsham and David Williamson point out in their respective studies, 'Ladies Football' was played during the late nineteenth century. For example, in 1895, Nettie Honeyball was made secretary for the British Ladies and she apparently made a great impression playing before a crowd of 8,000 at Newcastle. In the 1890s a travelling Scottish team, managed by Lady Florence Dixie, was a source of ridicule when it was rumoured that one of the girls played in her brother's underwear However, as football veteran Joan Whalley was quick to point out in an interview for Granada Television, although many came to mock the women, they left the ground impressed by their skill and quality of football. Secondly, a significant number of girls from 'white collar' modes of employment, such as teaching and secretarial work, became involved in 'Ladies Football'. The Atlanta Sports Club, Huddersfield, for instance, was made up of girls from 'white collar' backgrounds." 'Ladies Football' was becoming hugely popular by the end of the war and in the early post-war period. It was commanding huge crowds and raising large sums for charity, while elevating the status of women both in their communities and within their redefined roles, proving that they could function perfectly well within the spheres that convention had denied them for so long. For example, St Helens Ladies AFC played Dick, Kerr's Ladies, raising £3,000 for ex-servicemen at Everton in front of a crowd of 50,00

Exploring the Anti-Cancer Activity of Novel Thiosemicarbazones Generated through the Combination of Retro-Fragments: Dissection of Critical Structure-Activity Relationships

<div><p>Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent <i>in vivo</i> anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds <b>1d</b> and <b>3c</b> demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized “soft” donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the <i>N</i>,<i>N</i>,<i>S</i> donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of <b>1d</b> and <b>3c</b> that warrants further examination.</p></div