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The development of multimodal sensor-based applications designed to support learners with the improvement of their skills is expensive since most of these applications are tailor-made and built from scratch. In this paper, we show how the Presentation Trainer (PT), a multimodal sensor-based application designed to support the development of public speaking skills, can be modularly extended with a Virtual Reality real-time feedback module (VR module), which makes usage of the PT more immersive and comprehensive. The described study consists of a formative evaluation and has two main objectives. Firstly, a technical objective is concerned with the feasibility of extending the PT with an immersive VR Module. Secondly, a user experience objective focuses on the level of satisfaction of interacting with the VR extended PT. To study these objectives, we conducted user tests with 20 participants. Results from our test show the feasibility of modularly extending existing multimodal sensor-based applications, and in terms of learning and user experience, results indicate a positive attitude of the participants towards using the application (PT+VR module).
The quest for new and improved therapies for glioblastoma (GB) has been mostly unsuccessful in more than a decade despite significant efforts. The few exceptions include the optimization of classical alkylating chemotherapy by including lomustine in the first line regimen for GB with a methylated MGMT promoter and tumor treating fields. The GB signaling network has been well-characterized and genetic alterations resulting in activation of receptor tyrosine kinases and especially epidermal growth factor receptor (EGFR) and downstream mammalian target of rapamycin complex 1 (mTORC1) signaling were found in the majority of GBs. ...
Dieses Zitat von Sperone Speroni aus dem "Dialogo d’Amore" (1542) beschreibt eindrücklich die herausragende Stellung des Malers Tizian. Die Hochachtung, die aus diesen Worten hervorgeht, spiegelt sich in der Ausstellung Tizian und die Renaissance in Venedig wieder, die vom 13. Februar bis zum 26. Mai 2019 im Frankfurter Städel Museum zu sehen ist. Die Sonderausstellung mit über 100 Meisterwerken widmet sich nicht nur Tizian, sondern auch anderen wichtigen Vertretern der venezianischen Malerei der Renaissance. So werden unter anderem Gemälde und Zeichnungen von Giovanni Bellini, Jacopo Palma il Vecchio, Sebastiano del Piombo, Lorenzo Lotto, Jacopo Tintoretto, Jacopo Bassano und Paolo Veronese gezeigt. In einer Folge von acht Kapiteln führt die Präsentation dieser Meisterwerke durch ausgewählte Themenfelder, die für die venezianische Malerei im 16. Jahrhundert charakteristisch sind. ...
Background: Obesity impairs a variety of cell types including adipose-derived mesenchymal stem cells (ASCs). ASCs are indispensable for tissue homeostasis/repair, immunomodulation, and cell renewal. It has been demonstrated that obese ASCs are defective in differentiation, motility, immunomodulation, and replication. We have recently reported that some of these defects are linked to impaired primary cilia, which are unable to properly convey and coordinate a variety of signaling pathways. We hypothesized that the rescue of the primary cilium in obese ASCs would restore their functional properties.
Methods: Obese ASCs derived from subcutaneous and visceral adipose tissues were treated with a specific inhibitor against Aurora A or with an inhibitor against extracellular signal-regulated kinase 1/2 (Erk1/2). Multiple molecular and cellular assays were performed to analyze the altered functionalities and their involved pathways.
Results: The treatment with low doses of these inhibitors extended the length of the primary cilium, restored the invasion and migration potential, and improved the differentiation capacity of obese ASCs. Associated with enhanced differentiation ability, the cells displayed an increased expression of self-renewal/stemness-related genes like SOX2, OCT4, and NANOG, mediated by reduced active glycogen synthase kinase 3 β (GSK3β).
Conclusion: This work describes a novel phenomenon whereby the primary cilium of obese ASCs is rescuable by the low-dose inhibition of Aurora A or Erk1/2, restoring functional ASCs with increased stemness. These cells might be able to improve tissue homeostasis in obese patients and thereby ameliorate obesity-associated diseases. Additionally, these functionally restored obese ASCs could be useful for novel autologous mesenchymal stem cell-based therapies.
Die Welt ist im Wandel, der Globalisierungsprozess weit fortgeschritten. Inwiefern spielen dann Kolonialismus und Unterdrückung noch eine Rolle? Sind diese Zeitgeschehnisse nicht wie man so schön sagt "Geschichte"? Dieser Frage gehen der britisch-ghanaische Künstler John Akomfrah und das Black Audio Film Collective im gemeinsamen Werk "Expeditions 1 – Signs of Empire" (1983) nach. Die zweiteilige Videoarbeit zeigt mithilfe dokumentarischer Fotografien, Textfragmenten und Tonaufzeichnungen des British Empire ein Bild, welches die Potenz heutiger nationalstaatlicher Strukturen des Okzidents in der Unterdrückung und Ausbeutung kolonialisierter Länder verortet – und so den Mythos der moralischen Überlegenheit des Westens dekonstruiert. ...
Der technische Fortschritt ermöglicht die Auswertung großer Datenmengen mittels Algorithmen zur Feststellung bislang unbekannter Korrelationen. Schlagwortartig werden solche Analysen unter dem Begriff Big Data zusammengefasst. Häufig sind personenbezogene Daten Gegenstand von Big-Data-Anwendungen, sei es als Grundlage oder Ergebnis einer Auswertung. In diesen Fällen ist das Datenschutzrecht zu beachten.
Der Zweckbindungsgrundsatz fordert die Angabe eines Verarbeitungszwecks bereits bei Erhebung der Daten und eine Bindung des weiteren Datenumgangs an diesen Zweck. Damit besteht ein Spannungsverhältnis zu Big-Data-Anwendungen, die zu Verarbeitungsbeginn den Zweck allenfalls unspezifisch anzugeben vermögen. Auf Grundlage des alten Bundesdatenschutzgesetzes mit einzelnen Ausblicken auf die Datenschutzgrundverordnung untersucht die Arbeit die datenschutzrechtlichen Anforderungen an die Zweckfestlegung und welche Bindungen aus ihr folgen. Zudem nimmt der Autor mögliche Lösungen des Konflikts zwischen Big-Data-Anwendungen und dem Zweckbindungsgrundsatz in den Blick.
The sphingolipid sphingosine-1-phosphate (S1P) is produced by sphingosine kinases to either signal through intracellular targets or to activate a family of specific G-protein-coupled receptors (S1PR). S1P levels are usually low in peripheral tissues compared to the vasculature, forming a gradient that mediates lymphocyte trafficking. However, S1P levels rise during inflammation in peripheral tissues, thereby affecting resident or recruited immune cells, including macrophages. As macrophages orchestrate initiation and resolution of inflammation, the sphingosine kinase/S1P/S1P-receptor axis emerges as an important determinant of macrophage function in the pathogenesis of inflammatory diseases such as cancer, atherosclerosis, and infection. In this review, we therefore summarize the current knowledge how S1P affects macrophage biology.
Canada’s geographic centre lies in the Territory Nunavut. From here the distance to the geographic North Pole is as far as to the US border. Nunavut takes up about 1/5 of the Canadian land mass but has by far the smallest population with currently about 38,000 residents. 85% of its population are Inuit whose culture dramatically changed within the last 70 years.
As a result, the territory is dealing with several generations of Inuit that are traumatized or at least severely affected by cultural and economic changes that started after World War 2 with the resettlement from the land into permanent communities. No matter if we are talking about the actual elders, mid-age adults or pre-teenagers, each of this generation experienced and still experiences various personal and cultural challenges of identity, financial and housing insecurity, food insecurity, substance abuse education, change of social values ranging from inter-generational and gender relationships to the introduction of a foreign political and legal system.
On the other side, a lot of the traditional societal values are still being practiced in Inuit families. Despite all the tragedies that several generations of Inuit have experienced by now, the society keeps generating the strength and cultural pride that allows many Inuit both, as individuals and as a collective under the umbrella of either Inuit Land Claims or not for profit organizations to advocate on behalf of Inuit culture, to fight for more acknowledgement of Inuit culture and to enhance pride in the historic and present day cultural achievements of Nunavut’s indigenous population.
The social issues, inter- and intra-cultural processes described in my thesis are not exclusive to the situation in Nunavut or to Inuit. Studies from other regions, in Canada or from around the world (LaPrairie 1987; Jensen 1986; Nunatsiaq News 6/30/2010) reveal similar challenges.
Though many structural similarities can be identified by comparing these studies with each other, e.g. marginalization of the indigenous local population, colonization, paternalism and resulting issues like personal and cultural identity loss, it is important to have a more in depth look into the single cases to determine which individual events and developments causes and maybe still cause such a devastating social situation as it is found among many indigenous peoples across the world. From my perspective effective improvements of the situation of a group, a respective community or region can only happen when particularities of socialization, communication and philosophy in the single cultural entities are being considered.
That is why my thesis will exclusively focus on developments in Nunavut and use various case studies of communities. The case studies shall help to identify local differences in historic and recent developments and thus provide starting points for explanations of different developments in different Nunavut communities.
The thesis is looking at both, historic and recent root causes for the many issues in Nunavut.
The data that my my thesis is based on are a combination of literature and about 60 formal and informal interviews that I conducted in three Nunavut communities (Iqaluit, Whale Cove, Kugluktuk) during my 18 months of field work between October 2008 and March 2010. Many more spontaneous unstructured conversations between me and community members added to the pool of first-hand information that I gathered.
Since my field work is limited to those three communities it has a very strong qualitative character. The quantitative side, which allows me to confidently apply my research analyses to entire Nunavut, comes from literature research as well as many informal conversations and a few formal interviews that I conducted with people who had some experience in other communities than Iqaluit, Kugluktuk and Whale Cove.
Furthermore, while I was living at the old residence of the Nunavut Arctic College in Iqaluit, I spend time with college students from across Nunavut. Through them, I obtained „case studies “from following communities: Iqaluit, Qikiqtarjuaq, Kimmirut, Pangnirtung, Clyde River, Pond Inlet, Igloolik, Repulse Bay, Cape Dorset, Chesterfield Inlet, Baker Lake, Rankin Inlet, Whale Cove, Arviat, Taloyoak, Kugluktuk.
My general categorization of “early contact period”, “contact”, “1st generation” and “2nd generation” is very similar to Damas’ terms of “early contact phase”, “contact – traditional”, “resettlement” that he uses to create a timeline that describes the major phases of impact for Inuit society (Damas 2002: 7, 17).
Chapters 2 is meant to provide an inventory of the key aspects of current social issues in Nunavut. In this context I am looking at the four major aspects that in my opinion shape Nunavut’s society:
1) violence and other forms of social dysfunctions
2) the associated services and delivering agencies that try to address those matters
3) Education
4) Inuit cultural particularities in communication and socialization
Those four areas are forming the foundation for the rest of my work. The following chapters will guide the reader through the historic transformation process of Inuit pre-colonial semi-nomadic society to a society that is living in permanent settlements, strongly influenced if not in many ways dominated by Euro-Canadian culture. Each of those chapters will be referring to the social and cultural changes that happened in the different time periods that I labeled with “Pre-settlement, First, Second, and Third Generation”. The relevance of violence and other social dysfunctions, their context and strategies how each generation dealt with those matters will be analyzed while I will be also referring to the impacts that non-Inuit, primarily Euro-Canadians and Euro-Americans had and have on Inuit society.
...
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Die vorliegende Arbeit behandelt einen Rechtsvergleich zwischen dem Neutralitätsgebot in der Bundesrepublik Deutschland und die Laizität in der Türkei aus der Perspektive des Religionsverwaltungsrechts im Referenzgebiet Medienrecht. Der Schwerpunkt liegt in der Darstellung des Türkischen Rechts.
Zu Beginn werden die beiden Begriffe des Neutralitätsgebots und der Laizität als Analyseinstrumente näher erörtert. Insbesondere erfolgt eine historische Begriffsgenese der Laizität im türkischen Rechtssystem in Bezug auf die Verfassungen der Türkei von Kanun-i Esasi 1876 bis hin zur aktuellen Verfassung von 1982. Darüber hinaus wird sowohl in der Rechtsprechung als auch in der Literatur erforscht, welchen Wandel der Laizitätsbegriff seit seiner Aufnahme in die Verfassung erfahren hat.
Es wird festgestellt, dass beide Begriffe einer Begriffskategorie angehören, wobei sie sich überwiegend durch ihre Intensität bei der Trennung vom Sakralem und Säkularem gerade hinsichtlich Kooperationen derselben und der vorherrschenden Koexistenz unterscheiden.
Zusätzlich wird auf die Funktion und die Auswirkungen des Diyanet sowohl auf den Laizitätsbegriff selbst als auch auf das Medienrecht eingegangen.
Im Folgenden wird das Medienrecht in beiden Ländern aus der Perspektive der öffentlichen Medien, insbesondere der Rundfunkanstalten untersucht. Hierbei werden in der Bundesrepublik Deutschland alle öffentlich-rechtlichen Rundfunkanstalten, ihre Organisationsstruktur und Regelungen zur Vertretung der Religionsgemeinschaften behandelt, die gängigen Regelungen diesbezüglich ausführlich erörtert und aktuelle Unterschiede derselben bei der Vertretung der Religionsgemeinschaften im jeweiligen Rundfunkrat mitunter auch tabellarisch aufgezeigt. Durch die Behandlung der Vertretungsregelungen werden Mängel aufgewiesen. Diese ergeben sich beispielsweise in Hessen bei der Auswahl der vertretungsberechtigten Organisationen, da bei den parlamentarischen Überlegungen hierzu möglicherweise nicht hinreichend sachdienliche Gutachten herangezogen wurden. Eine andere Quelle für Fehler wird in der Anwendung von bestimmten Rechtsbegriffen als Parameter für die Eignung der Religionsgemeinschaften zur Vertretung gesehen, die ihrerseits auf christliche Religionsgemeinschaften zugeschnitten sind, jedoch gerade die innerhalb der Bevölkerung am stärksten vertretene Minderheitengruppe, nämlich die Muslime, mangels Körperschaftsstatus, außen vor lässt. Letztendlich werden auch gerade für die Bundesrepublik Deutschland Lösungsansätze herausgearbeitet.
Im türkischen Recht erfolgt eine ebensolche Darstellung, wobei als Besonderheit auch der TMSF als Einlagensicherungsfonds, sowie die These behandelt werden, dass durch die Eingriffe des TMSF öffentlich-rechtliche Printmedien vorhanden seien. Speziell werden die Entstehung und Entwicklung des Medienrechts, der Aufbau und die Kompetenzen der öffentlich-rechtlichen Medien und die Eingriffe auf diese dargestellt.
In der Türkei werden bereits in der verwaltungsrechtlichen Normierung der Kompetenzen einzelner Institutionen und erst Recht in der verwaltungsrechtlichen Praxis gravierende Mängel festgestellt.
Over the last years, many microRNAs (miRNAs) have been identified that regulate the formation of bioactive lipid mediators such as prostanoids and leukotrienes. Many of these miRNAs are involved in complex regulatory circuits necessary for the fine-tuning of biological functions including inflammatory processes or cell growth. A better understanding of these networks will contribute to the development of novel therapeutic strategies for the treatment of inflammatory diseases and cancer. In this review, we provide an overview of the current knowledge of miRNA regulation in eicosanoid pathways with special focus on novel miRNA functions and regulatory circuits of leukotriene and prostaglandin biosynthesis.
The lateralization of neuronal processing underpinning hearing, speech, language, and music is widely studied, vigorously debated, and still not understood in a satisfactory manner. One set of hypotheses focuses on the temporal structure of perceptual experience and links auditory cortex asymmetries to underlying differences in neural populations with differential temporal sensitivity (e.g., ideas advanced by Zatorre et al. (2002) and Poeppel (2003). The Asymmetric Sampling in Time theory (AST) (Poeppel, 2003), builds on cytoarchitectonic differences between auditory cortices and predicts that modulation frequencies within the range of, roughly, the syllable rate, are more accurately tracked by the right hemisphere. To date, this conjecture is reasonably well supported, since – while there is some heterogeneity in the reported findings – the predicted asymmetrical entrainment has been observed in various experimental protocols. Here, we show that under specific processing demands, the rightward dominance disappears. We propose an enriched and modified version of the asymmetric sampling hypothesis in the context of speech. Recent work (Rimmele et al., 2018b) proposes two different mechanisms to underlie the auditory tracking of the speech envelope: one derived from the intrinsic oscillatory properties of auditory regions; the other induced by top-down signals coming from other non-auditory regions of the brain. We propose that under non-speech listening conditions, the intrinsic auditory mechanism dominates and thus, in line with AST, entrainment is rightward lateralized, as is widely observed. However, (i) depending on individual brain structural/functional differences, and/or (ii) in the context of specific speech listening conditions, the relative weight of the top-down mechanism can increase. In this scenario, the typically observed auditory sampling asymmetry (and its rightward dominance) diminishes or vanishes.
The three major autoimmune diseases (ADs) of the liver are primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH). All of those diseases show an aggressive immune reaction resulting in the destruction of liver tissue and finally to the development of hepatic fibrosis.
PSC is an autoimmune mediated disease of unknown etiology. It is characterized by inflammation of intra- and extrahepatic bile ducts. The progressive destruction of the bile ducts can lead to liver cirrhosis and finally to liver failure. Clinical signs for PSC are increased alkaline phosphatase (AP) and gamma glutamyltransferase (GGT) levels, presence of perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and bile ducts with characteristic strictures and dilations of the biliary tree as well as onion skin fibrosis surrounding the damaged bile ducts. Currently, there is no established treatment for PSC patients. The administration of ursodeoxycholic acid (UDCA) is being use as a therapy. However, it merely serves a symptomatic treatment to reduce serum AP and GGT as well as the formation of gallstones. In the advanced stage of PSC, liver transplantation is the last therapeutic option. Mdr2-/- mice are an excepted mouse model for human PSC. Such mice show lymphocytes infiltration into the liver, bile duct lesions, as well as the presence of the typical onion skin-like pericholangitis and periductal fibrosis.
AIH is a rare chronic autoimmune disease of the liver that results from the loss of self-tolerance to hepatocytes and leads to destruction of the hepatic parenchyma with the onset of cirrhosis. Clinical signs for AIH are elevated alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, hypergammaglobulinemia and different types of autoantibodies. In addition, interphase hepatitis with lymphocytic and plasmacellular infiltrates in the periportal field are characteristic for AIH. Two different subtypes of AIH exist and depending on their autoantibody profile they can be distinguished into AIH type 1 which is characterized by the presence of anti-nuclear (ANA) and/or anti-smooth muscular (SMA) autoantibodies, and AIH type 2 showing liver/kidney microsomal autoantibodies (LKM-1). LKM-1 recognizes the major autoantigen, the 2D6 isoform of the cytochrome P450 enzyme family (CYP2D6). One mouse model for AIH is the CYP2D6 model in which the injection of Ad-2D6 leads to a breakdown of the immune tolerance by the destruction of hepatocytes.
There are some patients with autoimmune diseases of the liver who have both cholestatic and hepatic liver enzymes and histological features suggestive of two different liver diseases. These patients are diagnosed with an overlap syndrome (OS).
In my thesis I generated an animal model with characteristics of both diseases, which would mimic features of human PSC-AIH OS. Mdr2-/- mice which spontaneously develop PSC were infected with Ad-2D6 to trigger the autoimmune-driven hepatic injury. Pathogenesis of PSC-AIH OS mice was compared to mice with solitary PSC or AIH. Naïve FVB wild type mice have been used as healthy controls. The characterization of the PSC-AIH OS model was done by analyzing serological parameters like ALT, AP, different antibodies like pANCA, LKM-1 like CYP2D6 and total IgG. Additionally, fibrosis and cholangitis were analyzed by immunohistochemistry and Western blotting. Moreover, cellular infiltrations of CD4+ and CD8+ T cells, dendritic cells (DCs), monocytes/macrophages and neutrophils were determined with immunohistochemistry. Finally, the overall immune balance in the liver and the frequency of CYP specific T cells were analyzed via flow cytometry. Our new mouse model indeed represents the characteristics of both PSC and AIH and mimics features of the human PSC-AIH OS. It allows studying the development of a PSC-AIH OS and how the two overlapping diseases are influencing one another. In a second approach I wanted to induce CYP2D6-specific tolerance in AIH mice. Therefore, I tried four different approaches, namely intranasal peptide administration, injection of tolerogenic DCs, antigen-coupled splenocytes, and Ag-coupled nanoparticles (NP) and evaluated their potential to induce CYP2D6 specific Treg with the capacity to prevent AIH in mice. Unfortunately, the intranasal peptide administration and also the injection of tolerogenic DCs did not increase the amount of CYP2D6 specific Treg which would lead to a reduction of the frequency of inflammatory T cells. Surprisingly, the injection of antigen-coupled splenocytes showed the opposite effect characterized by a very strong cytokine secretion in the tolerized mice. The use of NPs led to an increase in CYP2D6 specific Treg as well as in decrease in the frequency of inflammatory T cells and finally has the potential for a therapeutic approach.
In summary, the generated PSC-AIH OS model represents many clinical signs which can also be observed in PSC-AIH OS patients. This model can be used to study the etiology of this overlap syndrome and further to test potential therapeutic approaches. The different immune tolerance induction pathways which I tried in the AIH model show that NPs have to potential to induce immune tolerance but this approach has to be refined and the outcome has to be characterized in more detail.