Das Zusammenspiel zwischen Elektronendefizit und Elektronenreichtum in guanidinatstabilisierten Boran-Kationen

Boron(III) cations are widely used as highly Lewis acidic reagents in synthetic chemistry. By contrast, boron(II) cations are extraordinarily rare and their number is limited to only some few examples with an almost completely unknown reactivity. The compounds are both Lewis acids and electron donors, properties that ensure a rich and diverse chemistry. The use of bridging bicyclic guanidinate substituents in the diborane(4) compound allows the stabilization and investigation of these exceptional boron(II) species. This doctoral thesis deals with the synthesis, characterization and reactivity of base stabilized di-, tri- and tetraborane cations. Starting with the already known diborane(4) compound [HB(hpp)]2 some new potential precursors [XB(hpp)]2 (X = Cl, Me, n-Bu) were obtained. Proceeding from the dichloro-diborane, the chloride abstraction with AlCl3 and GaCl3 was studied. Irrespectively of the salt chosen, the reaction led to formation of a radical tricationic tetraborane [{B(hpp)}4]3+· and permitted some new insights into the reaction mechanism. In the further course of this work a highly electron-deficient sigma-aromatic tetraborane(4) intermediate [{B(hpp)}4]4+ was isolated and fully characterized. This unprecedented compound represents the first cationic structural derivative of [B4H4]4+ and is stabilized by the lattice energy. In addition, the repertoire of electron-deficient cyclic boranes was expanded by a new cationic triborane [{B(hpp)}2(BH2)]+. The second part of this thesis focuses on the double reactivity pattern of boron(II) cations. Starting with the diborane(4) [(TfO)B(hpp)]2 with two easily exchangeable triflate substituents, a facile synthesis of several new boron(II) cations is reported. By systematically increasing the pi-acceptor properties of the sigma-Lewis basic reaction partners, first examples are presented in which the combined Lewis acidity and electron donor properties were used for the reduction of organic substrates. Expanding the organic sigma-donors by redox-active N-heterocyclic linkers resulted in the first members of an unprecedented family of highly charged cationic cyclophanes with integrated diboranyl units. The findings of this thesis provide deeper insight into the structural variety and potential application of borane(II) cations in organic synthesis as well as supramolecular materials

Impact of the -174G/C interleukin-6 (IL-6) gene polymorphism on the risk of paediatric ischemic stroke, its symptoms and outcome

Ischemic stroke remains one of the top ten causes of death in children. There is evidence for the role of pro-inflammatory cytokines, such as IL-6 and the -174G>C promoter polymorphism of the IL-6 gene, in the occurrence and outcome of stroke in adults. The aim of the present study was to determine a possible association between the -174G>C IL-6 polymorphism and occurrence of paediatric stroke, its symptoms and outcome. The study group consisted of 340 individuals: 80 stroke children, 122 parents of patients and 138 controls. The -174G/C polymorphism was genotyped using the RFLP method. For the analysis of the relationship between genotypes and stroke we used two alternative methods: the case-control model and the transmission test for linkage disequilibrium using data from families. We observed no differences in the transmission of alleles from parents to children. We also did not find any statistical differences in distribution of genotypes and alleles between patients and controls. However, the analysis showed that post-stroke epilepsy was genotype-dependent. All children with epilepsy were G allele carriers and none of them was a CC homozygote whereas about 25% of children without epilepsy had the CC genotype. Our study did not show any associations between the IL-6 -174 G>C polymorphism and the occurrence of stroke but we observed a relation between post-stroke epilepsy and the G allele carrier-state

Visualizing Entanglement in multi-Qubit Systems

In the field of quantum information science and technology, the representation and visualization of quantum states and related processes are essential for both research and education. In this context, a focus especially lies on ensembles of few qubits. There exist many powerful representations for single-qubit and multi-qubit systems, such as the famous Bloch sphere and generalizations. Here, we utilize the dimensional circle notation as a representation of such ensembles, adapting the so-called circle notation of qubits and the idea of representing the n-particle system in an n-dimensional space. We show that the mathematical conditions for separability lead to symmetry conditions of the quantum state visualized, offering a new perspective on entanglement in few-qubit systems and therefore on various quantum algorithms. In this way, dimensional notations promise significant potential for conveying nontrivial quantum entanglement properties and processes in few-qubit systems to a broader audience, and could enhance understanding of these concepts as a bridge between intuitive quantum insight and formal mathematical descriptions.Comment: 22 pages, 20 figure

Polimorfizm C242T genu kodującego cytochrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci : analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

Background and purpose: Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. Material and methods: The study group consisted of 238 in - dividuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction – restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. Results: The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC – 50.0%, CT – 38.6%, TT – 11.4% vs. controls: CC – 52.0%, CT – 36.0%, TT – 12.0%). Conclusions: The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in childre

Polimorfizm C242T genu kodującego cytohrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci: analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

Background and purpose Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. Material and methods The study group consisted of 238 individuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction – restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. Results The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC – 50.0%, CT – 38.6%, TT – 11.4% vs. controls: CC – 52.0%, CT – 36.0%, TT – 12.0%). Conclusions The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in children.Wstęp i cel pracy Reaktywne formy tlenu pełnią istotną funkcję zarówno w fizjologii, jak i patologii tętnic mózgowych, także w patogenezie udaru niedokrwiennego mózgu. Gen cytochromu b-245 alfa (gen CYBA) koduje lekki łańcuch cytochromu b-245 (białko p22phox), kluczowy składnik oksydaz NAD(P)H, najważniejszego źródła anionorodnika ponadtlenkowego w obrębie tętnic mózgowych. W niniejszej pracy, poszukując genetycznych czynników ryzyka predysponujących do udaru mózgu u dzieci, oceniano możliwe związki pomiędzy polimorfizmem C242T genu CYBA i chorobą. Materiał i metody W badaniu wzięło udział 238 osób: 70 dzieci z udarem niedokrwiennym mózgu, 118 ich biologicznych rodziców oraz 50 dzieci bez żadnych objawów udaru. Polimorfizm C242T genu CYBA genotypowano metodą polimorfizmu długości fragmentów restrykcyjnych w reakcji łańcuchowej polimerazy. Do oceny możliwych związków pomiędzy polimorfizmem i udarem zastosowano dwie niezależne metody: wewnątrzrodzinny test transmisji i badanie kliniczno-kontrolne. Wyniki Allel C242 był częściej przekazywany chorym dzieciom przez heterozygotycznych rodziców niż allel 242T (62,2% w porównaniu z 37,8%), jednak obserwowane częstości nie odbiegały znamiennie od oczekiwanych (p = 0,10). Nie wykazano także znaczących różnic w rozkładzie alleli i genotypów pomiędzy pacjentami i dziećmi z grupy kontrolnej (pacjenci: CC – 50,0%, CT – 38,6%, TT – 11,4%; grupa kontrolna: CC – 52,0%, CT – 36,0%, TT – 12,0%). Wnioski Wyniki badań nie wykazały, aby polimorfizm C242T genu CYBA był czynnikiem ryzyka udaru niedokrwiennego u dzieci

Protein and molecular characterization of a clinically compliant amniotic fluid stem cell derived extracellular vesicle fraction capable of accelerating muscle regeneration through the enhancement of angiogenesis

The secretome of human amniotic fluid stem cells (AFSC) has great potential as a therapeutic agent in regenerative medicine. However it must be produced in a clinically compliant manner before it can be used in humans. Here we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EV) that harbour much but not all the biological activity of the whole secretome. Proteomic characterisation of the EV and free secretome fraction show the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly we show that the EVs only contain miRNA and not mRNA. This suggests tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than the imposition of new, signalling pathways. The EVs harbour significant anti-inflammatory activity as well as promoting angiogenesis; the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury

Skin Electroporation: Effects on Transgene Expression, DNA Persistence and Local Tissue Environment

BACKGROUND: Electrical pulses have been used to enhance uptake of molecules into living cells for decades. This technique, often referred to as electroporation, has become an increasingly popular method to enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination (gene delivery followed by electroporation) is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers. However, the mode of action at molecular level is not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates intradermal DNA electrovaccination in detail and describes the effects on expression of the vaccine antigen, plasmid persistence and the local tissue environment. Gene profiling of the vaccination site showed that the combination of DNA and electroporation induced a significant up-regulation of pro-inflammatory genes. In vivo imaging of luciferase activity after electrovaccination demonstrated a rapid onset (minutes) and a long duration (months) of transgene expression. However, when the more immunogenic prostate specific antigen (PSA) was co-administered, PSA-specific T cells were induced and concurrently the luciferase expression became undetectable. Electroporation did not affect the long-term persistence of the PSA-expressing plasmid. CONCLUSIONS/SIGNIFICANCE: This study provides important insights to how DNA delivery by intradermal electrovaccination affects the local immunological responses of the skin, transgene expression and clearance of the plasmid. As the described vaccination approach is currently being evaluated in clinical trials, the data provided will be of high significance

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Poland and Germany in the German and Polish press

Stosunki polsko-niemieckie różniły się na przestrzeni lat z uwagi na dość burzliwą przeszłość historyczną tych dwóch krajów. Dziś kontakty polsko-niemieckie wydają się lepsze. Wielu Polaków wyjeżdża do Niemiec w poszukiwaniu pracy, również młodzi ludzie decydują się na przeprowadzkę. Także Niemcy coraz częściej opuszczają swój kraj i przenoszą się do Polski, gdzie zakładają rodzinę.Pomimo tego, że stosunki polsko-niemieckie wydają się polepszać, wzajemne postrzeganie tych dwóch krajów jest często zniekształcane przez stereotypy. Chociaż z jednej strony Polska i Polacy często kojarzą się Niemcom z rozkwitem gospodarczym, dobrze wykształconymi pracownikami lub gościnnością, to z drugiej strony pojawia się też wizerunek Polaka złodzieja i taniej siły roboczej.Z kolei Polacy często postrzegają Niemców jako zdyscyplinowanych, dobrze zorganizowanych czy też oszczędnych. Drugi, negatywny wizerunek Niemiec, który pojawia się wśród Polaków, to wojna, wróg i obozy koncentracyjne. Niniejsza praca zajmuje się wspomnianą tematyką. Przedstawia stereotypy i uprzedzenia, które pojawiają się wśród Niemców na temat Polaków, a także wśród Polaków na temat Niemców. Ponadto główna część pracy poświęcona jest analizie tekstów prasowych znanych gazet niemieckich i polskich. Przedstawia tematy poruszane w mediach niemieckich i polskich oraz to w jaki sposób są opisywane, pozytywny czy negatywny.Polish-German relations were different over the years, in view of the rather turbulent historical past of these two countries. Today, Polish-German contacts seem to be better. Many Poles go to Germany to look for a job, also young people decide to move. However, Germans are leaving their country and moving to Poland as well, where they get married.Despite the fact that Polish-German relations seem to be better, the mutual perception of these two countries is often distorted by stereotypes. Although on the one hand Poland and Poles are often associated with economic prosperity, well-educated employees or hospitality, on the other hand, there is also the image of a Polish thief and cheap labour.In turn, Poles often perceive Germans as disciplined, well-organized or thrifty. The second, negative image of Germany that appears among Poles is war, enemy or concentration camps.This master's thesis deals with this topic. It presents stereotypes and prejudices that appear among Germans about Poles, as well as among Poles about Germans. In addition, the main part of the work is devoted to the analysis of press texts of well-known newspapers, both German and Polish. It presents what topics are discussed in the German and Polish media and how they are described, positive or negative.Die deutsch-polnischen Beziehungen waren im Laufe der Zeit aufgrund der stürmischen historischen Vergangenheit dieser beiden Länder unterschiedlich. Heute scheinen die polnisch-deutschen Kontakte besser zu werden. Viele Polen wohnen in Deutschland, erbeiten mit den Deutschen zusammen, ohne auf die Vergangenheit zu achten. Auch immer mehr Deutsche verlassen ihre Heimat und ziehen nach Polen. Obwohl sich die polnisch-deutschen Beziehungen verbessert haben, wird die gegenseitige Wahrnehmung dieser beiden Länder oft durch Stereotype verzerrt. Polen wird einerseits mit gut prosperierter Wirtschaft oder Gastfreundschaft assoziiert. Andererseits existiert ein anderes, negatives Bild von Polen unter den Deutschen, nämlich Polen als Diebe oder billige Arbeitskraft.Polen wiederum empfinden oft die Deutschen als diszipliniert, gut organisiert oder ordentlich. Das zweite, negative Bild von Deutschland, das unter den Polen erscheint, ist Krieg, Feind oder Konzentrationslager.Die vorliegende Arbeit beschäftigt sich mit diesem Thema. Sie zeigt Stereotype und Vorurteile auf, die bei Deutschen über Polen und bei Polen über Deutsche auftreten. Der Hauptteil der Arbeit wird der Analyse von Pressetexten der bekannten deutschen und polnischen Zeitungen. Sie stellt dar, welche Themen in den deutschen und polnischen Medien diskutiert werden und wie sie beschrieben werden, positiv oder negativ