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Focused electron beam induced deposition (FEBID) is a direct-write nanofabrication technique able to pattern three-dimensional magnetic nanostructures at resolutions comparable to the characteristic magnetic length scales. FEBID is thus a powerful tool for 3D nanomagnetism which enables unique fundamental studies involving complex 3D geometries, as well as nano-prototyping and specialized applications compatible with low throughputs. In this focused review, we discuss recent developments of this technique for applications in 3D nanomagnetism, namely the substantial progress on FEBID computational methods, and new routes followed to tune the magnetic properties of ferromagnetic FEBID materials. We also review a selection of recent works involving FEBID 3D nanostructures in areas such as scanning probe microscopy sensing, magnetic frustration phenomena, curvilinear magnetism, magnonics and fluxonics, offering a wide perspective of the important role FEBID is likely to have in the coming years in the study of new phenomena involving 3D magnetic nanostructures.
Einleitung
Fantastische Literatur
- Feministische Fantastik
- Schwarze Figuren in der Fantastik
Black Speculative Fiction
- Black Speculative Fiction vs. Afrofuturism
- Die Frauen der Black Speculative Fiction
Schwarzer Feminismus
- Schwarzer Feminismus als Literaturtheorie
Analyse
- Autorinnenschaft
- Intersektionalität: Race, Class und Gender
- Von Unterdrückung zu Widerstand und Befreiung
- Verstummen und Stimme finden
- Stereotype dekonstruiert
Afrikas Einfluss
- Fazit
- Literaturverzeichnis
- Eigenständigkeitserklärung
Background: Patient information materials and decision aids are essential tools for helping patients make informed decisions and share in decision-making. The aim of this study was to investigate the quality of the written patient information materials available at general practices in Styria, Austria.
Methods: We asked general practitioners to send in all patient information materials available in their practices and to answer a short questionnaire. We evaluated the materials using the Ensuring Quality Information for Patients (EQIP-36) instrument.
Results: A total of 387 different patient information materials were available for quality assessment. These materials achieved an average score of 39 out of 100. The score was below 50 for 78% of all materials. There was a significant lack of information on the evidence base of recommendations. Only 9 % of the materials provided full disclosure of their evidence sources. We also found that, despite the poor quality of the materials, 89% of general practitioners regularly make active use of them during consultations with patients.
Conclusion: Based on international standards, the quality of patient information materials available at general practices in Styria is poor. The vast majority of the materials are not suitable as a basis for informed decisions by patients. However, most Styrian general practitioners use written patient information materials on a regular basis in their daily clinical practice. Thus, these materials not only fail to help raise the health literacy of the general population, but may actually undermine efforts to enable patients to make shared informed decisions. To increase health literacy, it is necessary to make high quality, evidence-based and easy-to-understand information material available to patients and the public. For this, it may be necessary to set up a centralized and independent clearinghouse.
Die mediane Sternotomie ist in der Kardio-Chirurgie der wichtigste Zugang zum Herzen. Postoperative Wundheilungsstörungen in diesem Bereich sind seltene, jedoch gefürchtete Komplikationen, die zu schwerwiegenden Konsequenzen führen können. Die zunächst einfache oberflächliche Wundheilungsstörung kann sich verkomplizieren und über eine Osteomyelitis des Sternums zu einer Mediastinitis mit eventuell letalen Konsequenzen führen. Aktuell geben unterschiedliche Autoren eine Inzidenz von 1 % – 8 % an. Die Mortalität der Sternumosteitis wird dabei zwischen 10 % und 30 % angegeben. Wird der Pathomechanismus der Erkrankung zu einem Algorithmus zusammengefasst, so kann sich über einen descendierenden Verlauf eine oberflächliche Wundheilungsstörung zu einer Sternumosteitis und schließlich zu einer Mediastinitis entwickeln. Natürlich kann sich die Infektion auch ascendierend ausbreiten. Über eine Infektion des Mediastinums oder des Sternums kann sich eine Infektion über die Weichteile bis an die Körperoberfläche ausdehnen. Der typische Patient, der eine Wundheilungsstörung erleidet ist in aller Regel polymorbide. Besonders bei diesem Patientenkollektiv sind eine kurze Behandlungsdauer und eine schnelle, postoperative Rehabilitation für das Ergebnis vorrangig. Ist der gewählte Therapieplan nicht aggressiv genug, so kommt es häufig zu chronischen Erkrankungen mit Fistelungen und einem konsekutiven Fortschreiten der Infektion in Weichteilen und Knochen. Neben medizinischen Gesichtspunkten kommen auch der wirtschaftliche Aspekte zu tragen. Wiederholte Operationen, lange Liegezeiten auf der Intensivstation und wiederholte sowie langwierige Rehabilitationsphasen sind nur wenige Beispiele der kostenintensiven Therapiebestandteile. Aufgrund der schwer beherrschbaren Infektsituation ist eine konsequent aggressive, definitive und zuverlässige Versorgung der infizierten Wunden von höchster Priorität. Dabei spielt es keine Rolle, ob es sich dabei um Wundheilungsstörungen im Bereich der Haut- und Unterhautweichteile, des Sternums oder des Mediastinums handelt. Zur Behandlung der Wundheilungsstörung nach medianer Sternotomie existieren verschiedene Behandlungsansätze und Therapieoptionen. Diese reichen von einfachen Debridements mit Sekundärvernähungen über Spül-Saug-Drainagen mit Antibiotika versetzen Lösungen bis hin zu Sternumteilresektionen, Vakuumverbänden und komplexen Lappenplastiken. ...
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2022)
The production of the W± bosons measured in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−−√=8.16 TeV and Pb−Pb collisions at sNN−−−−√=5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4<ημlab<−2.5 with transverse momentum pμT>10 GeV/c. While in Pb−Pb collisions the measurements are performed in the forward (2.5<yμcms<4) rapidity region, in p−Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46<yμcms<−2.96) and forward (2.03<yμcms<3.53) rapidity regions. The W− and W+ production cross sections, lepton-charge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p−Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon−nucleon collision ⟨Ncoll⟩. In Pb−Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p−Pb and Pb−Pb collisions is also reported. The results are compared with perturbative QCD (pQCD) calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDF (nPDFs) and in particular of the light-quark distributions.
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2022)
The production of the W± bosons measured in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−−√=8.16 TeV and Pb−Pb collisions at sNN−−−−√=5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4<ημlab<−2.5 with transverse momentum pμT>10 GeV/c. While in Pb−Pb collisions the measurements are performed in the forward (2.5<yμcms<4) rapidity region, in p−Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46<yμcms<−2.96) and forward (2.03<yμcms<3.53) rapidity regions. The W− and W+ production cross sections, lepton-charge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p−Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon−nucleon collision ⟨Ncoll⟩. In Pb−Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p−Pb and Pb−Pb collisions is also reported. The results are compared with perturbative QCD (pQCD) calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDF (nPDFs) and in particular of the light-quark distributions.
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2023)
The production of the W± bosons measured in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−−√=8.16 TeV and Pb−Pb collisions at √sNN=5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4<ημlab<−2.5 with transverse momentum pμT>10 GeV/c. While in Pb−Pb collisions the measurements are performed in the forward (2.5<yμcms<4) rapidity region, in p−Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46<yμcms<−2.96) and forward (2.03<yμcms<3.53) rapidity regions. The W− and W+ production cross sections, lepton-charge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p−Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon−nucleon collision ⟨Ncoll⟩. In Pb−Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p−Pb and Pb−Pb collisions is also reported. The results are compared with perturbative QCD (pQCD) calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDF (nPDFs) and in particular of the light-quark distributions.
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2023)
The production of the W± bosons measured in p–Pb collisions at a centreof-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4 < ηµ lab < −2.5 with transverse momentum p µ T > 10 GeV/c. While in Pb–Pb collisions the measurements are performed in the forward (2.5 < yµ cms < 4) rapidity region, in p–Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46 < yµ cms < −2.96) and forward (2.03 < yµ cms < 3.53) rapidity regions. The W− and W+ production cross sections, leptoncharge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p–Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon–nucleon collision hNcolli. In Pb–Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p–Pb and Pb–Pb collisions is also reported. The results are compared with perturbative QCD calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDFs and in particular of the light-quark distributions.
Rechtswörterbücher beschränken sich für gewöhnlich auf die Erläuterung einer Vielzahl von Begriffen und Instituten des geltenden Rechts. Das gilt jedenfalls für die in Deutschland gängigen Werke. Sie reihen die Erklärung einzelner Rechtsbegriffe nach den herkömmlichen Definitionen aneinander, ohne die Grundlagen unseres Rechtsdenkens zutage treten zu lassen. Nicht so verfährt das hier anzuzeigende, von Denis Alland und Stéphane Rials herausgegebene und im Jahre 2003 in Paris erschienene Dictionnaire de la culture juridique. Es tritt mit dem Anspruch an, das Recht nicht nur als große Ansammlung von rechtsdogmatischen Begriffen zu präsentieren, sondern seine geschichtlichen und vor allem philosophischen Bezüge zu verdeutlichen. Damit sollen Zusammenhänge wiederhergestellt werden, die durch die Reduktion der Jurisprudenz auf eine reine Technik in den letzten Jahren zunehmend verloren gegangen sind. Die innerhalb des Dictionnaire zusammengetragene Stofffülle ist äußerst beeindruckend: Auf mehr als 1600 Seiten vereinigt das Werk insgesamt 409 Artikel aus der Feder von nicht weniger als 213 durchweg angesehenen juristischen Autoren, die ganz überwiegend aus Frankreich stammen. ...
Xenocoumacin (Xcn) 1 and 2 are the major antibiotics produced by the insect-pathogenic bacterium Xenorhabdus nematophila. Although the antimicrobial activity of Xcns has been explored, research regarding their action on mammalian cells is lacking. We aimed to investigate the action of Xcns in the context of inflammation and angiogenesis. We found that Xcns do not impair the viability of primary endothelial cells (ECs). Particularly Xcn2, but not Xcn1, inhibited the pro-inflammatory activation of ECs: Xcn2 diminished the interaction between ECs and leukocytes by downregulating cell adhesion molecule expression and blocked critical steps of the NF-κB activation pathway including the nuclear translocation of NF-κB p65 as well as the activation of inhibitor of κBα (IκBα) and IκB kinase β (IKKβ). Furthermore, the synthesis of pro-inflammatory mediators and enzymes, nitric oxide (NO) production and prostaglandin E2 (PGE2), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), was evaluated in leukocytes. The results showed that Xcns reduced viability, NO release, and iNOS expression in activated macrophages. Beyond these anti-inflammatory properties, Xcn2 effectively hindered pro-angiogenic processes in HUVECs, such as proliferation, undirected and chemotactic migration, sprouting, and network formation. Most importantly, we revealed that Xcn2 inhibits de novo protein synthesis in ECs. Consequently, protein levels of receptors that mediate the inflammatory and angiogenic signaling processes and that have a short half-live are reduced by Xcn2 treatment, thus explaining the observed pharmacological activities. Overall, our research highlights that Xcn2 exhibits significant pharmacological in vitro activity regarding inflammation and angiogenesis, which is worth to be further investigated preclinically.
Germany has experienced a rise in xenophobic attacks since it began to welcome refugees from Syria and elsewhere. Sebastian Jäckle and Pascal D. König have mapped these attacks and drawn some striking conclusions about their causes. They were more common in regions with a strong far-right presence and fewer migrants. One attack also tended to spark others – as did condemnation of xenophobia by national leaders, and Islamist terror. Britain saw a similar spike in xenophobic crime after the referendum. The authors ask whether the UK can learn from Germany’s painful experience.
Background and Aim. Spontaneous bacterial peritonitis (SBP) is one of the most common complications of liver cirrhosis. Antibiotics are the main treatment regimen of SBP. Traditional Chinese medicine Xuebijing injection has been used in such patients. Our study aimed to overview the efficacy of Xuebijing injection combined with antibiotics for the treatment of SBP.
Method. We searched the PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang databases. The search items included "Xuebijing", "peritonitis", "liver cirrhosis", and "random" to identify all relevant randomized controlled trials (RCTs). The Cochrane risk of bias tool was used to assess the study quality. The odd ratios (ORs) with 95% confidence intervals (CIs) were calculated by using a random-effect model. Heterogeneity was also calculated.
Results. A total of 9 RCTs were included. The study quality was unsatisfied. The overall (OR = 2.95, 95% CI = 1.97–4.42, p<0.00001) and complete (OR = 2.18, 95% CI = 1.57–3.04, p<0.00001) responses were significantly higher in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. The incidence of cirrhosis related complications, including hepatic encephalopathy and hepatorenal syndrome, was lower in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. No significant heterogeneity was observed among studies.
Conclusion. Additional use of Xuebijing injection may improve the efficacy of antibiotics for the treatment of SBP in liver cirrhosis. However, due to a low level of current evidence, we did not establish any recommendation regarding the use of Xuebijing injection for the treatment of SBP.
Yajnavalkya : seine Philosophie – seine Soteriologie ; Klaus Mylius zum 80. Geburtstag gewidmet
(2010)
Die spezifische Funktion des Sri Cakras in der beschriebenen externen Verehrung besteht in seiner doppelten Funktion zum einen als externes physisches Verehrungsobjekt und zum anderen als mentales Betrachtungsobjekt. Als externes physisches Verehrungsobjekt ermöglicht es dem Sadhaka, sich selbst als Göttin gegenüber zu treten und seine Identität mit der Göttin in der Zusammenführung von sich selbst mit der Göttin im Darbringen von materiellen Gaben, welche symbolisch für die Hingabe seiner selbst stehen, körperlich und sinnlich nachzuvollziehen. Hierbei richtet der Sadhaka seinen Geist und seine Handlung ganz auf die Göttin bzw. ihre Verehrung im Sri Cakra aus, so dass er sich selbst dabei vergisst und zur Göttin wird. Bei seiner externen Verehrung dient das Sri Cakra gleichzeitig auch als mentales Betrachtungsobjekt, dessen konzentrische Form den Verehrer in seine eigene Mitte, und somit zur Identifizierung mit der Göttin führt, und welches dem Sadhaka als Vorlage zur geistigen Durchschreitung des Kosmos und seines eigenen Inneren dient. Während der Sadhaka also seine Identität mit der Göttin in der körperlichen Verehrung nachvollzieht und realisiert, durchschreitet er es geistig und betrachtet hierbei ihre einzelnen Teilkräfte. In mentalen Verehrungsformen funktioniert das Sri Cakra, ebenso wie in der externen Verehrung, als mentales Betrachtungsobjekt, welches den Sadhaka in seine Mitte führt und in dessen Durchschreitung er den Teilkräften der Göttin begegnet, sich ihrer kosmische Bedeutung bewusst wird und sie in sich verwirklicht. Gleichzeitig dient das Sri Cakra als Verehrungsobjekt, während dessen Verehrung der Verehrer die Zusammenführung seiner selbst mit der Göttin jedoch nicht mit Körper und Sinnen nachvollzieht, sondern rein geistig. In der Bhavana-Verehrung wird die Verehrung als Zusammenführung der zwei Ebenen, der Teilgottheit und des Selbst, weder körperlich noch mental nachvollzogen, sondern die Identität der zwei zusammengeführten Ebenen durch Meditation dieselbe direkt verwirklicht. Das Sri Cakra dient hier als Vorlage für die Kräfte und die Reihenfolge, in welcher die Kräfte und ihre Identität mit ihren mikrokosmischen Entsprechungen meditiert werden. Die Identifizierung mit der Gottheit über die schrittweise Verwirklichung ihrer Teilkräfte beinhaltet das Erlangen von psychischen Kräften und Fähigkeiten, Siddhi. Diese Kräfte kann der Sadhaka im Rahmen magischer Rituale im Makrokosmos zum Wohle und zum Schaden anderer einsetzen. Magische Rituale beinhalten eine Verehrung, mittels welcher der Sadhaka sich mit seiner inneren Kraft verbindet und einen Akt, in welchem diese Kraft angewendet wird. In Anwendungen zur Heilung von Krankheiten funktionieren Yantras oft als Amulett, d. h. als Träger in welchen der Sadhaka seine innere Kraft einsetzt und von welchem aus sie auf den Amulett-Träger wirkt. Yantras können wie im Beispiel zum 37. Vers des Saundaryalaharis gezeigt, auch als Verehrungsobjekte funktionieren, durch dessen Verehrung die dem Yantra entsprechende Kraft im Verehrer aktiviert wird. Krankheit hat verschiedene ursächliche Ebenen und verschiedene Ebenen der Manifestation. Sie kann somit auf diesen verschiedenen Ebenen behandelt werden. Das Yantra, welches in einer heilenden Anwendung eingesetzt wird, wird jeweils in Abhängigkeit der Ebene, deren Kräfte mobilisiert werden sollen, ausgewählt. Der nach religiösem Heil strebende Sadhaka verwirklicht im Rahmen seiner schrittweisen Identifikation mit der Göttin nach und nach die Kräfte aller Seinsebenen, und somit auch die Kräfte zur Kontrolle der körperlichen und psychischen Ebenen, sowie Kräfte, die vor negativen Einflüssen schützen und Krankheit und Leiden ausgleichen. Der Weg zu religiösem Heil führt somit über das Erlangen von Gesundheit und die Auflösung von Krankheit und Leiden, sowie zum Schutz vor Gefahren und schädlichen äußeren Einflüssen. Diese auf dem Weg zur Erkenntnis der Göttin erworbenen inneren Kräfte kann der Sadhaka im Makrokosmos einsetzen. Oft dienen hierbei Yantras als Medien, über welche diese Kräfte weitergegeben werden.
Yaratıcı endüstri kavramı, aşırı-teknik-kapitalist toplumların bir zorunluluğu olarak 1990’lı yıllarda gerek gündelik yaşama gerekse bilimsel yazına yerleşmeye başlamıştır. Habermas’ın çift değerlilik yaklaşımı doğrultusunda düşünüldüğünde, yaratıcı endüstrilerin, yaratıcılık ve kültürü kullanarak ürettikleri ürünlerin olumlu yanları kadar olumsuz yanlarının da olacağı açıktır. Bu çalışma yaratıcı endüstrilerin, toplumsal alanda anlaşma yönelimli iletişimsel eylemi koordine eden kültürel-normatif yapılar üzerindeki olası bozucu etkilerine dikkat çekmeye çalışmıştır. Çalışma, bu düşünceyi temellendirmek için, Husserl tarafından geliştirilen “yaşam dünyası” ve Habermas tarafından kuramsallaştırılan “yaşam dünyasının sömürgeleştirilmesi” kavramları doğrultusunda ilerlemiştir. Çalışmamızda kısmen Frankfurt Okulu’nun düşüncelerine başvurulmuştur. Çalışmamız özetle, yaratıcı endüstrilerin, yaşam dünyasının temel bileşenlerinden kültürel yeniden üretim, toplumsal bütünleşme ve toplumsallaşma süreçlerini nasıl etkileyeceğine, iletişimsel eylemi ne şekilde koordine edeceğine ve yaşam dünyasını potansiyel olarak nasıl sömürgeleştireceğine odaklanmıştır.
Background: The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo.
Methods: YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1.
Results: YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment.
Conclusion: The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts.
Im Zentrum dieser Arbeit stehen die Überstrukturphasen des Yb-Cu-Systems. Als Ausgangspunkt für die Kristallzüchtung wird die kongruent schmelzende Verbindung YbCu4:5 gewählt. Um einen genauen Einblick in das Erstarrungsverhalten dieser Phase zu erhalten, werden zunächst im Bereich zwischen 17.3 und 22.4 at-% Yb eine Reihe von DSC-Messungen durchgeführt. Die Ergebnisse lassen sich nur bedingt mit den in der Literatur veröffentlichten Phasendiagrammen (Moffat [Mo92] bzw. Massalski [Ma90] und Giovannini et al. [Gi08]) vereinbaren. Zwar kann eine kongruent schmelzende Phase der Zusammensetzung YbCu4:5 nachgewiesen werden, die Messungen deuten aber die Existenz zusätzlicher Verbindungen an, die allerdings mit Hilfe der EDX-Analyse nicht weiter spezifiziert werden können. Um diese Phasen genauer zu analysieren, werden Einkristallzüchtungsversuche nach der Bridgman-Methode im Bereich zwischen 19 und 19.2 at-% Yb durchgeführt und mittels Einkristallbeugungsmethoden (SC-XRD und SAED) charakterisiert. Auf diese Weise können neben YbCu4:5 die bisher noch unbekannten berstrukturphasen YbCu4:4 und YbCu4:25 nachgewiesen werden, deren Schmelztemperaturen mittels DSC-Untersuchungen zu 934(2)°C und 931(3)°C bestimmt werden. Die Entdeckung der beiden Verbindungen bestätigt die von Cerný et al. [Ce03] bisher nur theoretisch vorhergesagte Existenz der Überstrukturphasen SECux (x=4.4 und 4.25) für das Yb-Cu-System. Mit Hilfe von Polarisations- und Rasterelektronenmikroskopie und unter Anwendung der Laue-Methode wird das Wachstumsverhalten dieser Überstrukturphasen analysiert. Man beobachtet ein Schichtwachstum, wobei sich die Schichten parallel zur a- und b-Richtung ausbilden und in c-Richtung gestapelt vorliegen. Da eine zuverlässige Unterscheidung der YbCux-Verbindungen nur mit Hilfe von Einkristallbeugungsmethoden gelingt, wird im Rahmen dieser Arbeit untersucht, inwiefern eine Charakterisierung mittels Pulverdiffraktometrie möglich ist. Die Messungen mit Synchrotronstrahlung am ESRF in Grenoble erlauben eine eindeutige Unterscheidung der Überstrukturphasen allerdings nicht. Die Analyse des an das Überstrukturgebiet angrenzenden Zusammensetzungsbereichs von 12.5 bis 17.24 at-% Yb bestätigt die Existenz der Verbindung YbCu6:5, eine kupferärmere Phase der Zusammensetzung YbCu5 kann in den DSC-Experimenten nicht nachgewiesen werden. Die Messungen belegen die Existenz einer Phasenbreite von YbCu6:0+x mit 0 <= x <= 0:5 ist, was im Gegensatz zu dem von Giovannini et al. [Gi08] publizierten Phasendiagramm steht. SC-XRD-Aufnahmen an nach der Bridgman-Methode gezüchteten Einkristallen der Zusammensetzung YbCu6:31(9) untermauern das von Hornstra und Buschow [Ho72] gefundene Strukturmodell. Die Verschiebungen der Atompositionen bedingt durch den im Gegensatz zur YbCu5-Verbindung erhöhten Kupferanteil werden mit Hilfe der gemessenen und berechneten Paarverteilungsfunktion nachvollzogen. Phasendiagrammuntersuchungen und Einkristallzüchtungsergebnisse für weitere SE-Cu-Systeme (SE =Ho, Gd) bestätigen die Existenz der Verbindung HoCu4:5 und erhärten den Verdacht sowohl in diesem als auch in den anderen Systemen noch weitere Überstrukturphasen finden zu können.
Mutations in the clk-1 gene result in slower development and increased life span in Caenorhabditis elegans. The Saccharomyces cerevisiae homologue COQ7/CAT5 is essential for several metabolic pathways including ubiquinone biosynthesis, respiration, and gluconeogenic gene activation. We show here that Coq7p/Cat5p is a mitochondrial inner membrane protein directly involved in ubiquinone biosynthesis, and that the defect in gluconeogenic gene activation in coq7/cat5 null mutants is a general consequence of a defect in respiration. These results obtained in the yeast model suggest that the effects on development and life span in C. elegans clk-1 mutants may relate to changes in the amount of ubiquinone, an essential electron transport component and a lipid soluble antioxidant.
Ribosomal RNA undergoes various modifications to optimize ribosomal structure and expand the topological potential of RNA. The most common nucleotide modifications in ribosomal RNA (rRNA) are pseudouridylations and 2'-O methylations (Nm), performed by H/ACA box snoRNAs and C/D box snoRNAs, respectively. Furthermore, rRNAs of both ribosomal subunits also contain various base modifications, which are catalysed by specific enzymes. These modifications cluster in highly conserved areas of the ribosome. Although most enzymes catalysing 18S rRNA base modifications have been identified, little is known about the 25S rRNA base modifications. The m(1)A modification at position 645 in Helix 25.1 is highly conserved in eukaryotes. Helix formation in this region of the 25S rRNA might be a prerequisite for a correct topological framework for 5.8S rRNA to interact with 25S rRNA. Surprisingly, we have identified ribosomal RNA processing protein 8 (Rrp8), a nucleolar Rossman-fold like methyltransferase, to carry out the m(1)A base modification at position 645, although Rrp8 was previously shown to be involved in A2 cleavage and 40S biogenesis. In addition, we were able to identify specific point mutations in Rrp8, which show that a reduced S-adenosyl-methionine binding influences the quality of the 60S subunit. This highlights the dual functionality of Rrp8 in the biogenesis of both subunits.
Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016).
Human GLUTs represent a family of specialized transporters that facilitate the diffusion of hexoses through membranes along a concentration gradient. The 14 isoforms share high sequence identity but differ in substrate specificity and affinity, and tissue distribution. According to their structure similarity, GLUTs are divided into three classes, with class 1 comprising the most intensively studied isoforms GLUTs1 4. An abnormal function of different GLUT members has been related to the pathogenesis of various diseases, including cancer and diabetes. Hence, GLUTs are the subject of intensive research, and efforts concentrate on identifying GLUT-selective ligands for putative medical purposes and their application in studies aiming to further unravel the metabolic roles of these transporters.
The hexose transporter deficient (hxt0) yeast strain EBY.VW4000 is devoid of all its endogenous hexose transporters and unable to grow on glucose or related hexoses. This strain has proven to be a valuable platform to investigate heterologous transporters due to its easy handling, increased robustness, and versatile applications. However, the functional expression of GLUTs in yeast requires certain modifications. Single point mutations of GLUT1 and GLUT5 led to their functional expression in EBY.VW4000, whereas the native GLUT1 was actively expressed in EBY.S7, a hxt0 strain carrying the fgy1 mutation that putatively reduces the phosphatidylinositol-4-phosphate (PI4P) content in the plasma membrane. GLUT4 was only actively expressed in the hxt0 strain SDY.022, which also contains the fgy1 mutation and in which ERG4 is additionally deleted. Erg4 is one of the late enzymes in the ergosterol pathway, and therefore SDY.022 probably has an altered sterol composition in its membrane.
The goal of this thesis was to actively express GLUT2 and GLUT3 in a hxt0 yeast strain, providing a convenient system for their ligand screening. A PCR-derived amino acid exchange in the sequence of GLUT3 enabled its functional expression in EBY.VW4000 and the unmodified GLUT3 protein was active in EBY.S7. Functional expression of GLUT2 was achieved by rational design. The extracellular loop between the transmembrane regions 1 and 2 is significantly larger in GLUT2 than in other class 1 GLUTs. By truncating this loop by 34 amino acids and exchanging an alanine for a serine, a GLUT3-like loop was implemented. The resulting construct GLUT2∆loopS was functional in EBY.S7. With an additional point mutation in the transmembrane region 11, GLUT2∆loopS_Q455R was also actively expressed in EBY.VW4000. Inhibition studies with the known GLUT inhibitors phloretin and quercetin showed a reduced transporter activity for GLUT2 and GLUT3 in uptake assays and growth tests when inhibitors were present, demonstrating that both systems are amenable for ligand screening experiments.
The newly established GLUT2 yeast system was then used to screen a library of compounds pre-selected by in silico screening. Thereby, eleven identified GLUT2 inhibitors exhibited strong potencies with IC50 values ranging from 0.61 to 19.3 µM. By employing the other yeast systems, these compounds were tested for their effects on GLUT1, and GLUTs3-5, revealing that nine of the identified ligands were GLUT2-selective. In contrast, one was a pan-class 1 inhibitor (inhibiting GLUTs1-4), and one affected GLUT2 and GLUT5, the two fructose transporting isoforms. These compounds will serve as useful tools for investigations on the role of GLUT2 in metabolic diseases and might even evolve into pharmaceutical agents targeting GLUT2-associated diseases.
Due to the beneficial effect of the putatively changed sterol composition in SDY.022 (by ERG4 deletion) on the functional expression of GLUT4, it was hypothesized that the presence of the human sterol cholesterol, or cholesterol-like sterols, might have a beneficial effect on GLUT expression, too. Thus, it was attempted to generate hxt0 strains that synthesize these sterols by genetic modifications targeting the ergosterol pathway. In the scope of these experiments, several strains with different sterol compositions were generated. Drop tests on glucose medium with the different strains expressing GLUT1 or GLUT4 revealed that the deletion of ERG6 is clearly advantageous for a functional expression of GLUT1 (but not GLUT4). This indicates that the methyl group at the ergosterol side chain (introduced by Erg6 and reduced by Erg4) negatively influences GLUT1 activity. However, this effect on GLUT1 activity was less pronounced than the putative altered PI4P content in EBY.S7.
Additionally, in this thesis, a new tool to measure glucose transport rates of transporters expressed in the hxt0 yeast system was developed to facilitate their kinetic characterization. For this, the pH-sensitive GFP variant pHluorin was employed as a biosensor for the cytosolic pH (pHcyt) by measuring the ratio (R390/470) of emission intensities at 512 nm from two different excitation wavelengths (390 and 470 nm). Sugar-starved cells exhibit a slightly acidic pHcyt because ATP production is depleted, reducing the activity of ATP-dependent proton pumps.
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Background: A number of scientific papers on yellow fever have been published but no broad scientometric analysis on the published research of yellow fever has been reported. The aim of the article based study was to provide an in-depth evaluation of the yellow fever field using large-scale data analysis and employment of bibliometric indicators of production and quantity.
Methods: Data were retrieved from the Web of Science database (WoS) and analyzed as part of the NewQis platform. Then data were extracted from each file, transferred to databases and visualized as diagrams. Partially by means of density-equalizing mapping makes the findings clear and emphasizes the output of the analysis.
Results: In the study period from 1900 to 2012 a total of 5,053 yellow fever-associated items were published by 79 countries. The United States (USA) having the highest publication rate at 42% (n = 751) followed by far from Brazil (n = 203), France (n = 149) and the United Kingdom (n = 113). The most productive journals are the "Public Health Reports", the "American Journal of Tropical Medicine and Hygiene" and the "Journal of Virology". The gender analysis showed an overall steady increase of female authorship from 1950 to 2011. Brazil is the only country of the five most productive countries with a higher proportion of female scientists.
Conclusions: The present data shows an increase in research productivity over the entire study period, in particular an increase of female scientists. Brazil shows a majority of female authors, a fact that is confirmed by other studies.
Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined including host range, host–virus interactions and correlates of host immunity and pathogenicity. In this article, we review the current state of YFV research, focusing on the viral lifecycle, host responses to infection, species tropism and the success and associated limitations of the YFV-17D vaccine. In addition, we highlight the current lack of available treatments and use publicly available sequence and structural data to assess global patterns of YFV sequence diversity and identify potential drug targets. Finally, we discuss how technological advances, including real-time epidemiological monitoring of outbreaks using next-generation sequencing and CRISPR/Cas9 modification of vector species, could be utilized in future battles against this re-emerging pathogen which continues to cause devastating disease.
Survivin is a drug target and its suppressant YM155 a drug candidate mainly investigated for high-risk neuroblastoma. Findings from one YM155-adapted subline of the neuroblastoma cell line UKF-NB-3 had suggested that increased ABCB1 (mediates YM155 efflux) levels, decreased SLC35F2 (mediates YM155 uptake) levels, decreased survivin levels, and TP53 mutations indicate YM155 resistance. Here, the investigation of 10 additional YM155-adapted UKF-NB-3 sublines only confirmed the roles of ABCB1 and SLC35F2. However, cellular ABCB1 and SLC35F2 levels did not indicate YM155 sensitivity in YM155-naïve cells, as indicated by drug response data derived from the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) databases. Moreover, the resistant sublines were characterized by a remarkable heterogeneity. Only seven sublines developed on-target resistance as indicated by resistance to RNAi-mediated survivin depletion. The sublines also varied in their response to other anti-cancer drugs. In conclusion, cancer cell populations of limited intrinsic heterogeneity can develop various resistance phenotypes in response to treatment. Therefore, individualized therapies will require monitoring of cancer cell evolution in response to treatment. Moreover, biomarkers can indicate resistance formation in the acquired resistance setting, even when they are not predictive in the intrinsic resistance setting.
You are what you eat!
(2019)
Nowadays almost everyone is aware of the link between high blood cholesterol levels and cardiovascular disease. There are effective treatments that target blood cholesterol. his overview highlights some well known and some new mediators implicated in cardiovascular disease with the common theme that all of them can be influenced by the diet.
You reap what you sow! differences in knowledge exchange effectiveness between communication types
(2014)
FOR KNOWLEDGE-INTENSIVE ORGANIZATIONS IN THE FINANCE INDUSTRY, AN EFFECTIVE KNOWLEDGE EXCHANGE AMONG EMPLOYEES IS CRUCIAL FOR THE COMPETITIVE PERFORMANCE. THEREFORE, COMPANIES INCREASINGLY RELY ON SOCIAL MEDIA PLATFORMS TO FACILITATE COMMUNICATION AND COLLABORATION. TO ENHANCE OUR UNDERSTANDING OF SUCCESSFUL COMMUNICATION IN ENTERPRISE SOCIAL MEDIA, WE APPLY HUMAN CODING AND QUANTITATIVE ANALYSIS TO THE CONTENT AND TONE OF 15,505 ENTERPRISE MICROBLOGGING MESSAGES CREATED BY 1,166 EMPLOYEES OF AN INTERNATIONAL FINANCIAL SERVICE PROVIDER. OUR RESULTS SUGGEST THAT A MORE FACTUAL-ORIENTED COMMUNICATION TYPE BENEFITS FROM A HIGHER KNOWLEDGE EXCHANGE EFFECTIVENESS COMPARED TO A PRIMARILY SELF-DISCLOSING COMMUNICATION TYPE.
"… non do una traduzione" (Dieter Nörr). Das ist gut so. Denn das unverständliche punische Geplapper des Hanno: "ythemanethihychirsaelychotsithinaso" im "Poenulus" des Komödiendichters Plautus ist Teil der Komödie. Das zweite Buchstabenungetüm "uocationitantestaminigitur" können Kenner (so auch Gianfranco Lotito) hingegen schnell sezieren und ergänzen: (si in ius) vocat, ito. ni it, antestamino. igitur (em capito): "Wenn er vor Gericht lädt, soll er gehen.Wenn er nicht geht: vorher Zeugen rufen. Sodann ergreifen" – oder so ähnlich. Jedenfalls Tafel I 1 des Zwölftafelgesetzes aus dem 5. Jh. v. Chr., restituiert aus Porphyrios (3. Jh. n.Chr.). ...
Z-boson production in p-Pb collisions at √sNN = 8.16 TeV and Pb-Pb collisions at √sNN = 5.02 TeV
(2020)
Measurement of Z-boson production in p-Pb collisions at sNN−−−√ = 8.16 TeV and Pb-Pb collisions at sNN−−−√ = 5.02 TeV is reported. It is performed in the dimuon decay channel, through the detection of muons with pseudorapidity −4 < ημ < −2.5 and transverse momentum pμT > 20 GeV/c in the laboratory frame. The invariant yield and nuclear modification factor are measured for opposite-sign dimuons with invariant mass 60 < mμμ < 120 GeV/c2 and rapidity 2.5 < yμμcms < 4. They are presented as a function of rapidity and, for the Pb-Pb collisions, of centrality as well. The results are compared with theoretical calculations, both with and without nuclear modifications to the Parton Distribution Functions (PDFs). In p-Pb collisions the center-of-mass frame is boosted with respect to the laboratory frame, and the measurements cover the backward (−4.46 < yμμcms < −2.96) and forward (2.03 < yμμcms < 3.53) rapidity regions. For the p-Pb collisions, the results are consistent within experimental and theoretical uncertainties with calculations that include both free-nucleon and nuclear-modified PDFs. For the Pb-Pb collisions, a 3.4σ deviation is seen in the integrated yield between the data and calculations based on the free-nucleon PDFs, while good agreement is found once nuclear modifications are considered.
Z-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2021)
Measurement of Z-boson production in p-Pb collisions at sNN−−−√=8.16 TeV and Pb-Pb collisions at sNN−−−√=5.02 TeV is reported. It is performed in the dimuon decay channel, through the detection of muons with pseudorapidity −4<ημ<−2.5 and transverse momentum pμT>20 GeV/c in the laboratory frame. The invariant yield and nuclear modification factor are measured for opposite-sign dimuons with invariant mass 60<mμμ<120 GeVc2 and rapidity 2.5<yμμcms<4. They are presented as a function of rapidity and, for the Pb-Pb collisions, of centrality as well. The results are compared with theoretical calculations, both with and without nuclear modifications to the Parton Distribution Functions (PDFs). In p-Pb collisions the center-of-mass frame is boosted with respect to the laboratory frame, and the measurements cover the backward (−4.46<yμμcms<−2.96) and forward (2.03<yμμcms<3.53) rapidity regions. For the p-Pb collisions, the results are consistent within experimental and theoretical uncertainties with calculations that include both free-nucleon and nuclear-modified PDFs. For the Pb-Pb collisions, a 3.4σ deviation is seen in the integrated yield between the data and calculations based on the free-nucleon PDFs, while good agreement is found once nuclear modifications are considered.