Refine
Has Fulltext
- yes (7)
Is part of the Bibliography
- no (7)
Keywords
- Hofmannsthal, Hugo von (2)
- Biomarker (1)
- Bipolar disorder (1)
- CVID (1)
- Der Turm (1)
- Deutsch (1)
- Diagnostic test (1)
- Differential diagnosis (1)
- European Society for Immunodeficiencies (ESID) (1)
- Forschungsbericht (1)
Institute
Spherical harmonics coeffcients for ligand-based virtual screening of cyclooxygenase inhibitors
(2011)
Background: Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings: We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance: 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.
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.
Ein Gegenstand des vorliegenden Jahrbuchs ist mit den "Turm"-Dramen ein Werkkomplex, der den Lesenden und Forschenden die Rezeption nicht leichtmacht. Zweifellos ist der späte Hofmannsthal mit seinen Schrifttumsbelehrungen und taumelnden Führerschaften, seinen mitteleuropäischen Größenphantasien und dem aggressiven Kulturkonservativismus nicht eben populär - weder unter den Hofmannsthal-Leserinnen und -Lesern, noch in der Forschung. Das Unternehmen der 18. internationalen Tagung der Hugo von Hofmannsthal-Gesellschaft, sich im September 2014 in Basel ausschließlich diesem formal zerklüfteten und schwer zugänglichen Werkkomplex zu widmen, stellte daher ein Wagnis dar. Ein Wagnis auch deshalb, weil die einzig angemessene analytische Zugangsweise zu den drei im Zeitraum zwischen 1925 und 1927 entstandenen Dramen die ideologiekritische zu sein scheint. Doch hat die Forschung zu den politischen Ideologien des späten Hofmannsthal diese ideologiekritische Arbeit bekanntlich bereits geleistet. So wurde im weiteren Kontext der politischen Schriften der 1920er Jahre die erste Fassung des Dramas als für den Totalitarismus ideengebender Denkraum gedeutet. Die Frage nach den Herrschafts- und Souveränitätskonzeptionen, die im Zentrum der "Turm"-Dramen steht, wurde von einer fatalen historischen Finalität her gelesen, nämlich der Annahme einer Zwangsläufigkeit des Wegs von der Avantgarde in den Nationalsozialismus.
Der als Sprachkrise inszeniertea "mystische Weg", den Hofmannsthal rückblickend als Weg des Lord Chandos beschworen hat, bezeichnet weniger den "Anstand des Schweigens", als vielmehr eine literarisch äußerst produktive und semiotisch folgenreiche Poetologie des inneren Sehens, der endogenen Bilder des Bewußtseins.
Mitteleuropa. Kontakte und Kontroversen. II. Kongress des Mitteleuropäischen Germanistenverbandes (MGV) in Olomouc, 13.-16.09.2007 (Jürgen Joachimsthaler)
Otakar Veselý zu Ehren: die Aussiger Tagung Uferdasein in Ústí nad Labem, 19.09.2007 (Jana Hrdličková)
Kanon – Kontakte – Kultur. Zum österreichisch-tschechischen Germanist/innen-Treffen in Olomouc, 20.-23.09.2007 (Sabine Eschgfäller)
Komparatistik und die Weltliteratur in der Epoche der Globalisierung. Bericht aus dem Kongress KCTOS in Wien, 06.-09.12.2007 (Mária Bieliková)
„Ein oft kopiertes Format“. 12. Münchner Bohemisten-Treffen des Collegium Carolinum, 07.03.2008 (Vera Schneider)
Hauptwerke der österreichischen Literatur aus der Sicht der internationalen Literaturwissenschaft. Tagung der Franz Werfel-Stipendiat/innen in Wien, 28.-29.03.2008 (Renata Cornejo)
Ein weiblicher „Prager Kreis“? Symposion des Instituts für Wissenschaft und Kunst in Wien, 24.-25.04.2008 (Vera Schneider)
Germanistik und die neuen Herausforderungen in Forschung und Lehre. Germanistentreffen in Telč, 22.-23.05.2008 (Věra Janíková, Jaroslav Kovář)
„Franz Kafka und Robert Walser“. Internationales Symposium der Germanistik in Maribor, 19.-20. 06. 2008 (Vesna Kondrič Horvat)
Treue oder Veränderung: Ein Literaturpreis im Wandel? Bericht über die 32. Tage der deutschsprachigen Literatur in Klagenfurt, 27.-28.06.2008 (Anne Guhlich)
Forschungsprojekt: Die Identitätssuche der böhmisch-deutsch-jüdischen Autorin Irma Singer aus Prag (Rahel Rosa Neubauer)
Introduction: Affective disorders are a major global burden, with approximately 15% of people worldwide suffering from some form of affective disorder. In patients experiencing their first depressive episode, in most cases it cannot be distinguished whether this is due to bipolar disorder (BD) or major depressive disorder (MDD). Valid fluid biomarkers able to discriminate between the two disorders in a clinical setting are not yet available.
Material and Methods: Seventy depressed patients suffering from BD (bipolar I and II subtypes) and 42 patients with major MDD were recruited and blood samples were taken for proteomic analyses after 8 h fasting. Proteomic profiles were analyzed using the Multiplex Immunoassay platform from Myriad Rules Based Medicine (Myriad RBM; Austin, Texas, USA). Human DiscoveryMAPTM was used to measure the concentration of various proteins, peptides, and small molecules. A multivariate predictive model was consequently constructed to differentiate between BD and MDD.
Results: Based on the various proteomic profiles, the algorithm could discriminate depressed BD patients from MDD patients with an accuracy of 67%.
Discussion: The results of this preliminary study suggest that future discrimination between bipolar and unipolar depression in a single case could be possible, using predictive biomarker models based on blood proteomic profiling.
Highlights
• A panel of 20 biomarkers was identified capable of differentiating BD patients from controls.
• Excellent discrimination between established BD patients and controls.
• Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients.
• Fair to good discrimination between pre-diagnostic BD patients and controls.
• Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD.
Abstract
Background: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
Methods and findings: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.
We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
Conclusions: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.