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The mixed Si5Ge heterocycle (SiCl2)5(GeMe2) and its Cl− diadduct were synthesized in a highly selective fashion. The assembly mechanism was investigated to explain why precisely one GeMe2 group is incorporated, and reactivity studies were performed.

Two heteroadamantanes with a Si6Sn4 cluster core were prepared in one step synthesis from Me2SnCl2 and Si2Cl6/Cl−. The corresponding Si6Ge4 heteroadamantane was selectively methylated at all four SiCl3 substituents, while both SiCl2 groups remained untouched.

Members of the genus Yersinia cause gastroenteritis in humans but also exhibit toxicity toward invertebrates. A virulence factor required for this environmental life cycle stage is the multisubunit toxin complex (Tc), which is distinct from the insecticidal toxin of Bacillus thuringiensis and has the potential to be used in pest control.

Supplementary Table 1 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Dynamic instability of the microtubule network modulates processes such as cell division and motility, as well as cellular morphology. Overexpression of the microtubule-destabilizing phosphoprotein stathmin is frequent in human malignancies and represents a promising therapeutic target. Although stathmin inhibition gives rise to antineoplastic effects, additional and functionally redundant microtubule-interacting proteins may attenuate the efficiency of this therapeutic approach. We have systematically analyzed the expression and potential protumorigenic effects of stathmin family members in human non–small cell lung cancer (NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues and induced tumor cell proliferation, migration, and matrix invasion in respective cell lines. Accordingly, reduced stathmin and SCLIP levels affected cell morphology and were associated with a less malignant phenotype. Combined inhibition of both factors caused additive effects on tumor cell motility, indicating partial functional redundancy. Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. Our results indicate that the coordinated overexpression of microtubule-destabilizing factors by FBP-1 is a critical step to facilitate microtubule dynamics and subsequently increases proliferation and motility of tumor cells. [Cancer Res 2009;69(6):2234–43]

Supplementary Figure 4 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Supplementary Figure 5 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Supplementary Figure Legends 1-5 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Supplementary Figure 2 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Supplementary Figure 1 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

Supplementary Figure 3 from Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

The Cl

(Cl3Si)4Ge (1; 91%) is accessible from GeCl4, the Si2Cl6/[nBu4N]Cl silylation system, and excess SiCl4. A key intermediate step involves Cl− sequestration with AlCl3 in the course of the reaction between the first-formed germanide [(Cl3Si)3Ge]− and SiCl4. The related adduct Cl2(Me2EtN)SiGe(SiCl3)2 (2; quantitative conversion) was prepared either by amine-induced cleavage of 1 or by a bottom-up synthesis starting from GeCl4 and Si2Cl6.

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The Yersinia genus comprises pathogens that can adapt to an environmental life cycle stage as well as to mammals. Yersinia enterocolitica strain W22703 exhibits both insecticidal and nematocidal activity conferred by the tripartite toxin complex (Tc) that is encoded on the 19-kb pathogenicity island Tc-PAIYe. All tc genes follow a strict temperature regulation in that they are silenced at 37°C but activated at lower temperatures. Four highly conserved phage-related genes, located within the Tc-PAIYe, were recently demonstrated to encode a biologically functional holin-endolysin gene cassette that lyses its own host W22703 at 37°C. Conditions transcriptionally activating the cassette are not yet known. In contrast to Escherichia coli, the overproduction of holin and endolysin did not result in cell lysis of strain W22703 at 15°C. When the holin-endolysin genes were overexpressed at 15°C in four Y. enterocolitica biovars and in four other Yersinia spp., a heterogenous pattern of phenotypes was observed, ranging from lysis resistance of a biovar 1A strain to the complete growth arrest of a Y. kristensenii strain. To decipher the molecular mechanism underlying this temperature-dependent lysis, we constructed a Lon protease-negative mutant of W22703 in which the overexpression of the lysis cassette leads to cell death at 15°C. Overexpressed endolysin exhibited a high proteolytic susceptibility in strain W22703 but remained stable in the W22703 Δlon strain or in Y. pseudotuberculosis. Although artificial overexpression was applied here, the data indicate that Lon protease plays a role in the control of the temperature-dependent lysis in Y. enterocolitica W22703. IMPORTANCE The investigation of the mechanisms that help pathogens survive in the environment is a prerequisite to understanding their evolution and their virulence capacities. In members of the genus Yersinia, many factors involved in virulence, metabolism, motility, or biofilm formation follow a strict temperature-dependent regulation. While the molecular mechanisms underlying the activation of determinants at body temperature have been analyzed in detail, the molecular basis of low-temperature-dependent phenotypes is largely unknown. Here, we demonstrate that a novel phage-related lysis cassette, which is part of the insecticidal and nematocidal pathogenicity island of Y. enterocolitica, does not lyse its own host following overexpression at 15°C and that the Lon protease is involved in this phenotype.

Java ist eine der beliebtesten Entwicklungsplattformen und wird in unterschiedlichen Kontexten eingesetzt. Das Java Runtime Environment (JRE) implementiert eine Sicherheitsarchitektur, die die Ausführung von vertrauenswürdigem und nicht vertrauenswürdigem Code im selben Prozess ermöglicht. In der Vergangenheit gab es jedoch diverse Angriffe, die schwerwiegende Sicherheitslücken aufzeigten. Trotz dieser Angriffe war bisher wenig bekannt über die Gemeinsamkeiten von Exploits, oder in wie fern Designschwächen die Angriffe ermöglichten. Daher haben wir eine Vielzahl von Exploits für unterschiedliche JRE-Versionen gesammelt und analysiert. Wir zeigten, dass eine kleine Menge von Schwachstellen häufig ausgenutzt wird und fanden drei Angriffskategorien. Zudem zeigten wir zwei Designschwächen auf, die viele Angriffe ermöglichten. Hierzu zählt schwaches Information Hiding. Wir zeigten, dass die Sicherheit der Plattform auf der Vertraulichkeit und Integrität von wenigen Variablen ruht. Wir entwickelten eine Lösung, die 84% der Information-Hiding-Angriffe in unserem Datensatz blockiert, jedoch die Rückwärtskompatibilität und Performance erhält. Zusätzlich diskutierten wir einen alternativen Ansatz, der potentiell robuster und performanter ist. Die zweite Designschwäche ist inkonsequente Zugriffskontrolle. Wir zeigten, dass einige Systemklassen Zugriffsprüfungen überspringen, wenn der Aufrufstapel bestimmte Bedingungen erfüllt, wodurch die Wartbarkeit des Codes gemindert und Angriffsfläche erhöht wird. Daher entwickelten wir eine JRE-Variante die weitgehend ohne Abkürzungen funktioniert. Unsere Evaluation zeigte die Rückwärtskompatibilität und hohe Performance unserer Lösung. Abschließend geben wir Hinweise für die Gestaltung und Implementierung sicherer Systeme. Java is one of the most popular development platforms and it is applied in various different application contexts. The Java Runtime Environment (JRE) implements a complex security architecture that supports the execution of trusted and untrusted code within the same process. However, in the past, a large number of attacks revealed many severe vulnerabilities in the JRE that allowed for a full bypass of all security mechanisms. Despite the many examples of attacks, only little was previously known about conceptual commonalities of different exploits and the extent to which design weaknesses in the Java security architecture enabled the attacks. Thus, we collected and analyzed a large body of exploits for different versions of the JRE. We found that there is a small set of commonly abused weaknesses, and we identified three categories of attacks. Finally, we showed that two major design flaws enabled many of the attacks. The first design flaw is weak information hiding. We found that the security of the platform rests on the confidentiality and integrity of individual variables in system classes. We proposed a lightweight solution that blocks 84% of the information-hiding attacks in our sample set, while retaining backward compatibility and high performance. In addition, we presented a heavyweight solution that has the potential to outperform our lightweight solution in terms of robustness and speed. The second design flaw is improper access control. As we show, several system classes skip permission checks if certain hardcoded constraints on the call stack are satisfied, which decreases code maintainability and increases the attack surface. To address this, we created a variant of the JRE that works almost without shortcuts. Our evaluation shows that our solution is backward compatible and has a low performance overhead. ... by Philipp Albert Holzinger ; Advisor: Prof. Dr. Eric Bodden Tag der Verteidigung: 18.10.2019 Universität Paderborn, Dissertation, 2019

The genus Yersinia comprises 19 species of which three are known as human and animal pathogens. Some species display toxicity toward invertebrates using the so-called toxin complex (TC) and/or determinants that are not yet known. Recent studies showed a remarkable variability of insecticidal activities when representatives of different Yersinia species (spp.) were subcutaneously injected into the greater wax moth, Galleria mellonella. Here, we demonstrate that Y. intermedia and Y. frederiksenii are highly toxic to this insect. A member of Y. Enterocolitica phylogroup 1B killed G. mellonella larvae with injection doses of approximately 38 cells only, thus resembling the insecticidal activity of Photorhabdus luminescens. The pathogenicity Yersinia spp. displays toward the larvae was higher at 15°C than at 30°C and independent of the TC. However, upon subtraction of all genes of the low-pathogenic Y. enterocolitica strain W22703 from the genomes of Y. intermedia and Y. frederiksenii, we identified a set of genes that may be responsible for the toxicity of these two species. Indeed, a mutant of Y. frederiksenii lacking yacT, a gene that encodes a protein similar to the heat-stable cytotonic enterotoxin (Ast) of Aeromonas hydrophila, exhibited a reduced pathogenicity toward G. mellonella larvae and altered the morphology of hemocytes. The data suggests that the repertoire of virulence determinants present in environmental Yersinia species remains to be elucidated.

Yersinia enterocolitica is a pathogen that causes gastroenteritis in humans. Because of its low-temperature-dependent insecticidal activity, it can oscillate between invertebrates and mammals as host organisms. The insecticidal activity of strain W22703 is associated with a pathogenicity island of 19 kb (Tc-PAI Ye ), which carries regulators and genes encoding the toxin complex (Tc). The island also harbors four phage-related and highly conserved genes of unknown functions, which are polycistronically transcribed. Two open reading frames showed significant homologies to holins and endolysins and exhibited lytic activity in Escherichia coli cells upon overexpression. When a set of Yersinia strains was tested in an equivalent manner, highly diverse susceptibilities to lysis were observed, and some strains were resistant to lysis. If cell lysis occurred (as demonstrated by membrane staining), it was more pronounced when two accessory elements of the cassette coding for an i-spanin and an o-spanin were included in the overexpression construct. The pore-forming function of the putative holin, HolY, was demonstrated by complementation of the lysis defect of a phage λ S holin mutant. In experiments performed with membrane preparations, ElyY exhibited high specificity for W22703 peptidoglycan, with a cleavage activity resembling that of lysozyme. Although the functionality of the lysis cassette from Tc-PAI Ye was demonstrated in this study, its biological role remains to be elucidated.IMPORTANCE The knowledge of how pathogens survive in the environment is pivotal for our understanding of bacterial virulence. The insecticidal and nematocidal activity of Yersinia spp., by which the bacteria gain access to nutrients and thus improve their environmental fitness, is conferred by the toxin complex (Tc) encoded on a highly conserved pathogenicity island termed Tc-PAI Ye While the regulators and the toxin subunits of the island had been characterized in some detail, the role of phage-related genes within the island remained to be elucidated. Here, we demonstrate that this cassette encodes a holin, an endolysin, and two spanins that, at least upon overexpression, lyse Yersinia strains.

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60-63, 2018. © 2017 Wiley Periodicals, Inc.

Mit sinkender Akzeptanz von Amalgamfullungen stellt sich die Frage nach moglichen Ersatzwerkstoffen.

Angesichts des Heranziehens eines großen osmanischen Heeres im Frühling 1532 waren die Habsburger bemüht, ihre Ostgrenze gegen diese Gefahr zu verteidigen. In den Gesprächen mit den Ständen ihrer eigenen Territorien stieß man bereits auf Hindernisse. Die österreichischen Erbländer hatten unter dem vorangegangenen Osmaneneinfall von 1529 stark gelitten und konnten die geforderte Unterstützung nur schwer aufbringen, die Länder der spanischen Monarchie hätten großteils lieber ihre eigenen Grenzen geschützt gesehen. Auch die Verhandlungen mit den Reichsständen erwiesen sich als schwierig. Zu den reformierten Fürsten war das Verhältnis durch vorangegangene Ereignisse bereits angespannt, andere Oberhäupter befürchteten einen habsburgischen Machtgewinn. Auch über die von den Habsburgern geforderte Erhöhung der zuvor vereinbarten „Reichstürkenhilfe“ wurde heftig debattiert. Während Frankreich und Venedig auf diplomatischem Wege eher gegen Habsburg agierten, kam von jenen europäischen Mächten, die durch das außenpolitische Agieren der letzten Jahre mit Habsburg verbunden waren, wertvolle Unterstützung. So konnte der Kaiser etwa auf Genuas Flotte und auf päpstliche Hilfsgelder bauen. Wenig erfolgreich verhandelte man aber mit den Kriegsgegnern, wo es nicht gelang, Zeit zu gewinnen, geschweige denn, diese zu spalten oder einzubremsen. Der Sultan rückte letztendlich nicht auf Wien vor, doch Ferdinand I. konnte im Gegenzug auch seine Herrschaftsansprüche in Ungarn nicht durchsetzen und die Lage im zerrissenen Königreich nicht stabilisieren., When faced with the approach of a large Ottoman army in spring 1532, the Habsburgs endeavoured to defend their Eastern border against this threat. They quickly ran into obstacles when conducting talks with the estates of their own territories. The Austrian hereditary lands had already greatly suffered from the 1529 Ottoman invasion and struggled to provide the requested support. The Spanish monarchy on the other hand would have preferred to see their own borders protected. Negotiations with the estates of the realm also proved difficult. The relationship to the reformed dukes was already strained due to previous events and other rulers were afraid of a Habsburg gain of power. An increase of the "Reichstürkenhilfe" (an imperial support levied for the defence against the Turks) as requested by the Habsburgs was also subject to heavy debates. While France and Venice used diplomatic channels to covertly act against the Habsburgs, those European forces that were connected to the Habsburg Empire through foreign policies provided valuable assistance. The emperor could, for example, count on Geneva's fleet and financial aid from the pope. Negotiations with wartime enemies were not very successful. It was neither possible to play for time nor to bring about a split or to stall them. The Sultan actually didn’t advance to Vienna, but Ferdinand I. was neither able to secure his claim to power over Hungary nor to stabilise the war-torn kingdom.

Thermal and microwave-activated ring-opening polymerization at 180°C in the presence of titanium tetrabutylate at different e-caprolactone/titanium tetrabutylate molar ratios were compared. A special equipment was developed to control polymerization in the microwave field and to simultaneously monitor viscosity build-up as well as changes in microwave powers corresponding to input, reflection and transmission. Conversion, measured by means of viscosity build-up, and number-average molecular weight of poly(e-caprolactone) were similar for both processes and did not indicate advantages relating to the use of microwave irradiation.