Immersive Analytics of Large Dynamic Networks via Overview and Detail Navigation

Analysis of large dynamic networks is a thriving research field, typically relying on 2D graph representations. The advent of affordable head mounted displays however, sparked new interest in the potential of 3D visualization for immersive network analytics. Nevertheless, most solutions do not scale well with the number of nodes and edges and rely on conventional fly- or walk-through navigation. In this paper, we present a novel approach for the exploration of large dynamic graphs in virtual reality that interweaves two navigation metaphors: overview exploration and immersive detail analysis. We thereby use the potential of state-of-the-art VR headsets, coupled with a web-based 3D rendering engine that supports heterogeneous input modalities to enable ad-hoc immersive network analytics. We validate our approach through a performance evaluation and a case study with experts analyzing a co-morbidity network

Qualitätsmanagement nach DIN EN ISO 9001: 2000 an der HNO-Universitätsklinik Frankfurt/Main

Im Jahr 2003 begann die HNO-Universitätsklinik Frankfurt / Main mit der Einführung eines Qualitätsmanagement-Systems, die im August 2005 zur erfolgreichen Zertifizierung nach der vom Klinikumsvorstand geforderten DIN EN ISO 9001:2000 führte. Ziele unseres Qualitätsmanagements waren die Optimierung der internen Betriebsabläufe und die Standardisierung von Arbeitsvorgängen unter Einbeziehung von logistischen Schnittstellen mit externen Strukturen unter Berücksichtigung der besonderen Anforderungen einer Universitätsklinik. Neben einer grundsätzlichen Prüfung und Optimierung sämtlicher Organisationsabläufe wurden für die Kernprozesse unserer Klinik Zielvorgaben festgelegt. Diese Ziele betrafen die Qualität der Arbeitsabläufe für alle Bereiche der HNO-ärztlichen ambulanten und stationären Versorgung ebenso, wie Aufgaben in Forschung und Lehre, die durch ein Ausbildungscurriculum für Mitarbeiter und Sudenten abgebildet wurde. Es wurden aber auch Serviceaspekte, wie Terminvergabe und Befundübermittlung, sowie ökonomische und wirtschaftliche Aspekte unserer Arbeit optimiert. Durch Umstrukturierung und Neuorganisation konnte die Effizienz der Arbeitsabläufe deutlich gesteigert werden, wovon vor allem Patienten und Mitarbeiter erheblich profitieren. Die Einführung eines Qualitätsmanagementsystems in der Frankfurter HNO-Universitätsklinik war zunächst mit einem entsprechenden Arbeitsaufwand verbunden und erforderte ein Umdenken in den einzelnen Funktionsbereichen. Insgesamt überwiegt der positive Einfluss auf die Struktur und Arbeitsabläufe, sodass die Umsetzung eines Qualitätsmanagementsystems in der Universitätsklinik empfehlenswert ist

Human Subtilase SKI-1/S1P Is a Master Regulator of the HCV Lifecycle and a Potential Host Cell Target for Developing Indirect-Acting Antiviral Agents

HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs). One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1) – or site-1 protease (S1P). SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of novel broad-spectrum biopharmaceuticals that could lead to novel indirect-acting antiviral options with the current standard of care

"Die eigene Lehre untersuchen" - ein Erfolgsfaktor?

Strukturierte Phasen von Untersuchung-Erprobung-Reflexion-Input, kombiniert mit konkreten Lehrsituationen („volle Situiertheit“), versprechen verbesserte Lernresultate und Praxistransfers. In zwei Modulen einer hochschuldidaktischen Weiterbildung fokussieren die Dozierenden individuelle Lehrsituationen. Dabei soll der ‚Shift from Teaching to Learning‘ und eine datenbasierte Selbstreflexion befördert werden. Im ersten Szenario reflektieren die Teilnehmenden eine eigene Lehr-Lernsituation aus der Perspektive der Expertiseforschung. Im zweiten bearbeiten sie eine eigene didaktische Herausforderung mit dem formativen „Luuise“-Verfahren. Es erweist sich in Begleitstudien als vielversprechend. 29.03.2017 | Monika Wyss, Wolfgang Beywl, Kathrin Pirani & Donat Knech

Oligomeric State of β-Coronavirus Non-Structural Protein 10 Stimulators Studied by Small Angle X-ray Scattering

The β-coronavirus family, encompassing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory Syndrome Coronavirus (SARS), and Middle East Respiratory Syndrome Coronavirus (MERS), has triggered pandemics within the last two decades. With the possibility of future pandemics, studying the coronavirus family members is necessary to improve knowledge and treatment. These viruses possess 16 non-structural proteins, many of which play crucial roles in viral replication and in other vital functions. One such vital protein is non-structural protein 10 (nsp10), acting as a pivotal stimulator of nsp14 and nsp16, thereby influencing RNA proofreading and viral RNA cap formation. Studying nsp10 of pathogenic coronaviruses is central to unraveling its multifunctional roles. Our study involves the biochemical and biophysical characterisation of full-length nsp10 from MERS, SARS and SARS-CoV-2. To elucidate their oligomeric state, we employed a combination of Multi-detection Size exclusion chromatography (Multi-detection SEC) with multi-angle static light scattering (MALS) and small angle X-ray scattering (SAXS) techniques. Our findings reveal that full-length nsp10s primarily exist as monomers in solution, while truncated versions tend to oligomerise. SAXS experiments reveal a globular shape for nsp10, a trait conserved in all three coronaviruses, although MERS nsp10, diverges most from SARS and SARS-CoV-2 nsp10s. In summary, unbound nsp10 proteins from SARS, MERS, and SARS-CoV-2 exhibit a globular and predominantly monomeric state in solution

わが国の臨床看護技術に関するランダム化比較試験のシステマティックレビュー

目的:わが国の臨床看護技術に関する過去5年間のランダム化比較試験(RCT)のシステマティックレビューを行い,品質が保証された研究成果を明らかにする.方法:医学中央雑誌Web版を含む8つの文献検索サイトを用いて検索し,キーワードは「看護」,論文種類は原著論文とし,その中でわが国の臨床看護技術を研究し,日本語表記の論文を対象とした.そして,RCTの妥当性,再現性の評価と,研究成果を抽出した.結果:58件の論文を得た.3件の論文は妥当性が評価されたが,対照群の介入の再現性に差がみられた.得られた研究成果は,心臓カテーテル検査初回患者に対する検査説明リラクセーションプログラムの睡眠時間延長効果と,手術予定幼児に対するビデオを用いた家庭でのプレパレーションの体温,心拍数,心理面への安定効果,の2件(3.4%)であった.結論:品質が保証された研究成果は僅か2件であり,妥当性の向上に努める必要がある.Objectives : This study was conducted to produce a systematic review of randomized controlled trials (RCTs) over the past five years of clinical nursing skills in Japan and identify studies based on RCTs with proven quality. Methods : Eight websites for literature searches, including the web version of Japana Centra Revuo Medicina, were used. Using the keyword "Nursing Care", we searched for original papers written in Japanese on clinical nursing skills. We then assessed the validity and reproducibility of RCTs and identified the results of related studies with proven quality. Results : We retrieved 58 papers. In three studies, the validity of which had been verified, there were differences in the reproducibility of data in the intervention and control groups. Research results with proven quality were generated by two studies (3.4%), "The effects of a relaxation program, including sleep extension, designed to explain the examination procedures for patients undergoing the first cardiac catheterization test" and "Preparation at home using videos for infants undergoing surgery - Its effects to maintain their body temperature, heart rate, and psychological stability". Conclusions : We identified only two studies yielding results with proven quality, which indicated that efforts should be made to increase the validity of RCTs.報

Application of Optical Biosensors in Small-Molecule Screening Activities

The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value-adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR) and optical waveguide grating (OWG), in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA) format in contrast to traditional direct binding assays (DBA). Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms

First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model

Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg-1 body weight to study acute effects or using daily doses of 10 μg cereulide kg-1 body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations

Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML.

Hypomethylating agents decitabine and azacytidine are regarded as interchangeable in the treatment of acute myeloid leukemia (AML). However, their mechanisms of action remain incompletely understood, and predictive biomarkers for HMA efficacy are lacking. Here, we show that the bioactive metabolite decitabine triphosphate, but not azacytidine triphosphate, functions as activator and substrate of the triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation. Retrospective immunohistochemical analysis of bone marrow specimens from AML patients at diagnosis revealed that SAMHD1 expression in leukemic cells inversely correlates with clinical response to decitabine, but not to azacytidine. SAMHD1 ablation increases the antileukemic activity of decitabine in AML cell lines, primary leukemic blasts, and xenograft models. AML cells acquire resistance to decitabine partly by SAMHD1 up-regulation. Together, our data suggest that SAMHD1 is a biomarker for the stratified use of hypomethylating agents in AML patients and a potential target for the treatment of decitabine-resistant leukemia

Sensory Communication

Contains table of contents for Section 2, an introduction, reports on ten research projects and a list of publications.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Grant 5 R01 DC00270National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant 2 R01 DC00100National Institutes of Health Grant 7 R29 DC00428National Institutes of Health Grant 2 R01 DC00126U.S. Air Force - Office of Scientific Research Grant AFOSR 90-0200U.S. Navy - Office of Naval Research Grant N00014-90-J-1935National Institutes of Health Grant 5 R29 DC00625U.S. Navy - Office of Naval Research Grant N00014-91-J-145