1,384 research outputs found
Knowledge-Based Support in Quantitative Consumer Behavior Analysis
No full textGaul W, Decker R, Plötz M. Knowledge-Based Support in Quantitative Consumer Behavior Analysis. In: Gaul W, Rademacher FJ, Schader M, Solte D, eds. 3rd International Workshop on „Data, Expert Knowledge and Decisions“. FAW Ulm: Ulm; 1991: 37-40
Corneal morphology in vitro after superficial keractomy with Q-switched Er: YSSG and free-tunning ER: YAG lasers
No full textPURPOSE: Examination of morphology in corneal ablation induced by a q-switched Er:YSGG (2.79 mu m) laser and a free-running Er:YAG laser (2.94 mu m).LOBKampmeier J (reprint author), Univ Ulm, Augenklin & Poliklin, Prittwitzstr 43, Ulm, D-89075 Germany Univ Ulm, Hosp Eye, Dept Ophthalmol, Ulm, Germany Univ Ulm, Inst Lasertechnol Med & Messtech, Ulm, Germany Cited References: 1
Datensatz Notaufnahme Version 2010
No full textDie vorliegenden Dokumente beschreiben die Version 2010 des Datensatz Notaufnahme. Die genannten Autoren stehen stellvertretend für die Mitglieder der Sektion Notaufnahmeprotokoll der DIVI. Weiterführende Informationen zu dem Datensatz erhalten Sie über den korrespondierenden Autor:
Martin Kulla
2. Sprecher der Sektion Notaufnahmeprotokoll der DIVI
Bundeswehrkrankenhaus Ulm
Klinik für Anästhesiologie und Intensivmedizin
Oberer Eselsberg 40
89081 Ulm
E-Mail: [email protected]
Der Datensatz Notaufnahme wird in:
Kulla M, Röhrig R, Helm M, Bernhard M, Gries A, Lefering R, Walcher F, Sektion Notaufnahmeprotokoll der DIVI: [National data set “emergency department”. Development, structure and approval by the Deutsche Interdisziplinäre Vereinigung für Intensivmedizin und Notfallmedizin]. Anaesthesist 63: 243-255 (2014)
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Kulla M, Baacke M, Schöpke T, Walcher F, Ballaschk A, Röhrig R, Ahlbrandt J, Helm M, Lampl L, Bernhard M, Brammen D: [Core Dataset “Emergency Department” of the German Interdisciplinary Association of Critical Care and Emergency Medicin (DIVI). Basis for healthcare research and quality control in emergency departments]. Notfall Rettungsmed 17: 671-681 (2014)
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Southern Minnesota Initiative Foundation: Early Childhood Initiative Grant
No full textIncludes bibliographical references
Two Survival Tree Models for Myocardial Infarction Patients
No full textIn the search of a better prognostic survival model for post-acute myocardial infarction patients, the scientists at the Technical University of Munich's "Klinikum rechts der Isar" and the German Heart Center in Munich have developed some new parameters using 24-hour ECG (Schmidt et al 1999). A series of investigations were done using these parameters on different data sets and the Cox-PH model (Schmidt et al 1999, Ulm et al 2000). This paper is a response to the discussion paper by Ulm et al (2000), which suggests a Cox model for calculating the risk stratification of the MPIP data set patients including the predictors ejection fraction and heart rate turbulence. The current paper suggests the use of the classification and regression trees technique for survival data in order to deduct a survival stratification model for the NIRVPIP data set. Two models are compared: one contains the variables suggested by Ulm et al (2000) the other model has two additional variables, namely presence of couplets and number of extra systolic beats in the longest salvo of the patient's 24-hour ECG. The second model is shown to be an improvement on the first one
Vertebrobasilar junction giant aneurysm: Lessons learned from a neurosurgical audit and anatomical investigation
No full textThe treatment of vascular lesions of the vertebrobasilar junction (VBJ) remains a challenging task in the neurosurgical practice and the gold standard therapy is still under debate. In this article, the authors report a detailed postmortem study of a VBJ giant aneurysm (GA) previously endovascularly treated.Although the decision-making process for the vast majority of neurosurgical treatment can nowadays be accurately carried out during the preoperative planning (i.e., with the aid of neuroimaging fusion protocols, neuronavigation platforms, etc.) meant to maximize the anatomical understanding of the lesions and minimize possible intraprocedural challenges, this postmortem study represents the ultimate essence of neurosurgical audit as the laboratory investigations allowed to reevaluate the clinical history of VBJ GA, and reassess the multiple strategies available for its treatment with a straightforward anatomical perspective. Specifically, the lessons learned through this clinical and laboratory work uphold a great educational value regarding the complex management of those lesions, including the possible role of combined skull base surgical approaches
Countable random 𝑝-groups with prescribed Ulm-invariants
No full textIn this paper we present a probabilistic construction of countable abelian
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-groups with prescribed Ulm-sequence. This result provides a different proof for the existence theorem of abelian
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-groups with any given countable Ulm-sequence due to Ulm, which is sometimes called Zippin’s theorem. The basic idea, applying probabilistic arguments, comes from a result by Erdős and Rényi. They gave an amazing probabilistic construction of countable graphs which, with probability
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, produces the universal homogeneous graph, therefore also called the random graph. P. J. Cameron says about this in his book Oligomorphic Permutation Groups [Cambridge University Press, 1990]: In 1963, Erdős and Rényi proved the following paradoxical result. … It is my contention that mathematics is unique among academic pursuits in that such an apparently outrageous claim can be made completely convincing by a short argument. The algebraic tool in the present paper needs methods developed in the 1970s, the theory of valuated abelian
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-groups. Valuated abelian
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-groups are natural generalizations of abelian
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-groups with the height valuation, investigated in detail by F. Richman and E. Walker, and others. We have to establish extensions of finite valuated abelian
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-groups dominated by a given Ulm-sequence. Probabilistic results of a similar nature have been established by A. Blass and G. Braun, and by M. Droste and D. Kuske.</p
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
No full textApproaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
High throughput analysis of antibody glycosylation and the related metabolome in consequence of microRNA transfection in CHO cells
No full textThe N-linked glycosylation profile of (monoclonal) antibodies (mAb) is a critical product quality attribute due to its effect on antibody-dependent cellular cytotoxicity. As a consequence, a rapid characterization of changes in the glycosylation pattern of mAbs in a high throughput manner is required in various fields such as cell line development or clone selection. The majority of currently available analytical workflows require a sample preparation that is time and cost consuming. This lack of appropriate analytical workflows is addressed in this thesis by developing, validating, and applying two suitable workflows to characterize intact mAb glycosylation directly out of cell supernatants. The here developed workflows were applied during a miRNA library screening within the PROmiGlykAN research project for the identification of miRNA sequences that can modify the mAb glycosylation.
The developed workflows were based on capillary electrophoresis (CE) and liquid chromatography (LC) coupled with a Quadrupole-Time-Of-Flight (QTOF) mass spectrometer (MS) or an Orbitrap MS. Critical parameters for the workflow development were MS spectra quality, sensitivity, duration per measurement, and usability for the high throughput glycosylation analysis. Both separation methods had a high MS spectra quality since they offered an intensive, sharp, and narrow peak of the mAb. Whereas CE had an advantage with regard to the peak width since longitudinal diffusion is the only cause of peak broadening. A new definition of the “LOD” was introduced as the lowest concentration of a mAb sample where a glycosylation pattern can be confidentially obtained. This was defined by (i) the completeness of a pattern of major glycoforms, (ii) the repeatability, and (iii) the concentration independency of the respective pattern. The Orbitrap MS offered better concentration sensitivity as a consequence of the lower noise within the MS spectra compared to the QTOF. The LOD of the CE-Orbitrap MS workflow (nanoCEasy CE-MS interface) was 25 µg/mL and for the LC-Orbitrap MS workflow 5 µg/mL. The duration per measurement was 10 and 15 minutes for the LC-MS and CE-MS workflows, respectively. Due to the lower detection limit and a higher level of automatization, the LC-MS workflow was validated as the primary analytical tool for the high throughput miRNA library screening.
The performed miRNA library screening requires an efficient data processing and evaluation platform because of the large number of measurements. Here, two processing strategies were developed owing to the high homogeneity of the measured glycosylation pattern within the reference data set and the higher variation within the transiently transfected triplicates of the miRNA sample set. During the entire screening, no systematic tendency in the glycosylation pattern of the analytical QCs and biological reference was observed. The evaluation of the variability of the mAb glycosylation pattern showed, that the biological variability for the least intensive glycoform of the pattern accounted for 66 % of the total variance of this glycoform. Consequently, the LC-MS method is suitable to provide evidence of miRNA-induced changes in the glycosylation pattern. Out of the 1939 miRNAs of the miRNA library, 140 miRNA candidates were identified and validated in a second screen. These candidate miRNAs were identified by their induced changes on the mAb glycosylation pattern compared to the reference glycosylation pattern. The validation resulted in 82 miRNA hits that induce the same significant change to mAb glycosylation as determined during the initial screening.
Afterward, stable overexpressing miRNA CHO cell pools were created using single or multiple (miRNA) copy plasmids, followed by a clone selection process. The fold change of the mAb glycosylation was permanently monitored by the LC-MS glycosylation analysis. The creation of stable cell pools turns out that after the 11th day, the fold change of the fucosylation was decreased as a result of the antibiotic treatment and reached its stable optimum on the 23rd day. Furthermore, a suitable metabolomics workflow based on HILIC-MS (hydrophilic interaction liquid chromatography) was developed, validated, and applied to characterize the miRNA-induced changes in the CHO cell metabolome of the stable cell pools. The evaluation of selected target metabolites related to the mAb fucosylation within a principal component analysis (PCA) showed clusters of cell pools according to the effect on the mAb glycosylation and the type of the used plasmids.
Due to the chemical complexity of the cell metabolome, a single analytical method could cover just a part of the entire metabolome. A combination of different analytical methods increases the gained information from the metabolome analysis. Owing to that, a software toolbox was here developed for untargeted evaluation of multiplatform-based metabolomics data based on an augmented region of interest algorithm, introduced as AriumMS (Augmented region of interest for untargeted metabolomics mass spectrometry). AriumMS provides a novel mid-level data fusion approach for multiplatform data analysis to simplify and speed up data processing and evaluation. For the evaluation of AriumMS, five analytical methods were utilized according to their different selectivities and peak characteristics. As a case study, two Saccharomyces cerevisiae (yeast) cell pools were treated with a growth inhibitor. AriumMS successfully differentiated these two cell pools based on a multiplatform metabolome analysis. As a result, AriumMS is proposed as a powerful tool to improve the accuracy and selectivity of metabolome analysis by the integration of several HILIC-MS/CE-MS techniques.Die N-Glykosylierung von (monoklonalen) Antikörpern (mAb) ist ein kritisches Produktmerkmal aufgrund ihres Einfluss auf die antikörperabhängige zelluläre Zytotoxizität. Aufgrund dessen wird in vielen Bereichen der biopharmazeutischen Produktentwicklung z.B. Zelllinienentwicklung oder Klonselektionierung eine schnelle Hochdurchsatz-charakterisierung von Veränderungen im mAb Glykosylierungsmuster benötigt. Die meisten der derzeitig dafür verfügbaren analytischen Workflows erfordern allerdings eine zeit- und kostenintensive Probenvorbereitung. Um den Mangel an geeigneten analytischen Workflows zu überwinden, wurden im Rahmen dieser Forschungsarbeit zwei Methoden für die Charakterisierung der intakten mAb Glykosylierung direkt aus Zellüberständen entwickelt, validiert und angewendet. Die Anwendung der hier entwickelten Workflows fand während des Screenings einer miRNA-Sequenzbibliothek im Rahmen des PROmiGlykAN-Forschungsprojekts statt. Das Ziel war die Identifizierung von miRNA-Sequenzen, die in der Lage sind, die mAb-Glykosylierung zu verändern.
Die hier entwickelten Workflows basieren auf Kapillarelektrophorese (CE) und Flüssigchromatographie (LC) gekoppelt mit einem Quadrupol-Flugzeitmassenspektrometer (QTOF-MS) oder einem Orbitrap MS. Die wichtigsten Parameter für die Entwicklung der Workflows waren die Qualität der MS-Spektren, die Empfindlichkeit, die Dauer pro Messung und deren Eignung für die Hochdurchsatz Glykosylierungsanalyse. Beide Trennmethoden wiesen eine hohe MS-Spektrenqualität auf, da sie einen intensiven, scharfen und schmalen Peak des mAb lieferten. Die CE-Methode hatte hier einen Vorteil, da bei ihr Längsdiffusion der einzige Grund für eine Peakverbreiterung ist. Außerdem wurde eine neue Definition des „LOD“ eingeführt als die niedrigste Probenkonzentration bei der das Glykosylierungsmuster genau bestimmt werden kann. Definiert wurde dieses durch (i) die Vollständigkeit eines Glykosylierungsmuster (Hauptformen), (ii) die Wiederholbarkeit und (iii) die Konzentrationsunabhängigkeit des Musters. Im Vergleich zum QTOF bot das Orbitrap-MS in Folge des geringeren Rauschens in den MS-Spektren eine bessere Konzentrationsempfindlichkeit. Der LOD des CE-Orbitrap MS-Workflows (nanoCEasy CE-MS-Interface) betrug 25 µg/mL und für den LC-Orbitrap MS-Workflow 5 µg/mL, bei einer Dauer von 15 (CE-MS) bzw. 10 min (LC-MS) pro Messung. Der LC-MS Workflow wurde aufgrund der niedrigeren Nachweisgrenze und des höheren Automatisierungsgrads als primäre Methode für das Hochdurchsatzscreening der miRNA-Sequenzbibliothek validiert.
Das durchgeführte Screening der miRNA-Sequenzbibliothek erfordert aufgrund der großen Anzahl von Messungen eine effiziente Datenverarbeitungs- und Auswertungsplattform. Aufgrund der Homogenität der gemessenen Glykosylierungsmuster innerhalb des Referenzdatensatzes und der höheren Variation innerhalb des miRNA-Sequenzscreening Probensatzes (transient transfizierte Triplikate) wurden hier zwei Datenprozessierungs-strategien entwickelt. Während des gesamten Screenings wurde keine systematische Tendenz im Glykosylierungsmuster der analytischen QCs und der biologischen Referenz beobachtet. Die Auswertung der Varianz des mAb-Glykosylierungsmusters zeigte, dass die biologische Variabilität für die am wenigsten intensive Glykoform des Musters 66 % der Gesamtvarianz dieser Glykoform ausmachte. Folglich ist die LC-MS-Methode geeignet, um die miRNA-induzierten Veränderungen im Glykosylierungsmuster zu identifizieren. Von den 1939 miRNAs der miRNA-Sequenzbibliothek wurden 140 miRNA-Kandidaten identifiziert und in einem zweiten Screening validiert. Die miRNA-Kandidaten wurden anhand ihrer induzierten Änderungen im Glykosylierungsmuster des mAbs relativ zum Referenz-Glykosylierungsmuster bestimmt. Die anschließende Validierung ergab 82 miRNA Sequenzen die dieselbe signifikante Veränderung der mAb-Glykosylierung hervorrufen, wie sie im ersten Screening ermittelt wurde.
Im Anschluss an das Screening der miRNA-Sequenzbibliothek wurden stabil miRNA überexprimierende CHO-Zellpools unter Verwendung von Plasmiden mit einer oder mehreren (miRNA-)Kopien hergestellt, gefolgt von einem Klonselektionsverfahren. Dabei wurde der Fold-Change der mAb-Glykosylierung permanent durch die LC-MS-Glykosylierungsanalytik überwacht. Bei der Herstellung der stabilen Zellpools zeigte sich, dass nach dem 11. Tag der Fold-Change der Fucosylierung infolge der Antibiotikabehandlung abnahm und am 23. Tag sein stabiles Optimum erreichte. Darüber hinaus wurde ein geeigneter Metabolomicsworkflow auf der Basis von HILIC-MS (Hydrophilic Interaction Liquid Chromatography) entwickelt, validiert und angewendet, um die miRNA-induzierten Veränderungen im CHO-Zellmetabolom der stabilen Zellpools zu charakterisieren. Eine Hauptkomponentenanalyse (PCA) mit ausgewählten Targetmetaboliten die im Zusammenhang mit der mAb-Fucosylierung stehen, zeigte Cluster von Zellpools entsprechend der Auswirkung auf die mAb-Glykosylierung und der Art der verwendeten Plasmide.
Aufgrund der chemischen Komplexität des Zellmetaboloms kann eine einzige Analysemethode nur einen Teil des gesamten Metaboloms abdecken. Daher erhöht eine Kombination verschiedener Analysemethoden den Informationsgewinn aus der Metabolomanalyse. Aus diesem Grund wurde hier eine Software-Toolbox für die Non-Target Auswertung von multiplatform Metabolomdaten entwickelt. Diese basiert auf einem Augmented Region of Interest-Algorithmus und trägt den Namen AriumMS (Augmented region of interest for untargeted metabolomics mass spectrometry). AriumMS verfolgt einen neuartigen Ansatz der die Datenverarbeitung und -auswertung vereinfacht und beschleunigt indem er die Datensätze der Verschiedenen Methoden auf der Ebene der Features (mittleres Datenprozessierungslevel) fusioniert. Für die Evaluierung von AriumMS wurden fünf Analysemethoden mit unterschiedlichen Selektivitäten und Peak-Charakteristika verwendet. AriumMS konnte die im Rahmen einer Fallstudie gewonnen Daten von einer multiplattform Metabolomanalyse von zwei Saccharomyces cerevisiae (Hefe)-Zellpools die mit einem Wachstumsinhibitor behandelt wurden erfolgreich differenzieren. Die Studie zeigt, dass AriumMS ein leistungsfähiges Werkzeug für die multiplattform Metabolomanalyse ist, da es die Genauigkeit und Selektivität der Metabolomanalyse durch die Integration mehrerer HILIC-MS/CE-MS-Techniken verbessert
Cardiovascular risk assessment and biopsychological effects of acute and repeated social stress in German soldiers
No full textAbstract
Soldiers face a work environment which can provide challenging tasks, especially during foreign deployment. Away from their known social network and life the challenges result in a higher risk for perceived social stress during their job performance but work-related stressors can also be found at domestic deployment like exhaustion due to workload or long hours. It has been found that acute and chronic psychosocial stress can adversely affect cardiovascular risk and is significantly related to myocardial infarction. Military personnel are facing high rates of coronary artery disease (CAD) and health-threatening behavior and soldiers with combat experiences are more likely to suffer from hypertension. Furthermore, CAD risk is directly linked to increased short-term DNA damage, mainly visible as single or double strand breaks. The adaptation to social stress over time also provides insights into functioning biopsychological coping mechanisms. Exposure to social stress can cause physiological changes like altered hormone rates or blood pressure and influence mental health including negative emotions like anxiety and tension.
This synopsis aimed to provide an overview about risk assessment and biopsychological effects of social stress in healthy German soldiers. Different questionnaires about social stress led to a stress index for cardiovascular risk investigation. Experimentally induced acute and repeated social stress enabled the measurement of physiological and psychological reactions and changes. Especially the comparisons to the baseline and between three points of measurement for soldiers with and without a mission abroad were of interest. Associations with cardiovascular risk were also assessed in this cohort. The investigations were conducted as part of the BEST (German Armed Forces Deployment and Stress)-study, which used the Trier Social Stress Test for groups (TSST-G) to experimentally induce stress response. Two hundred thirty-four soldiers were recruited from the German Armed Forces hospital in Ulm and from military barracks in Dornstadt, Laupheim and Ulm. Participants underwent the TSST-G three times, with data collected before (t0), 4-6 weeks after (t1), and one year after (t2) a mission abroad. Therefore, soldiers with (experimental group) and without (control group) a mission abroad during study time were compared and all participants underwent the same procedure. During the TSST-G, 3-6 participants simultaneously prepared and were interviewed for a mock job interview and a mental arithmetic task in front of study personnel in lab coats and in the presence of the other participants.
Data analyses led to a Global Stress Index as a fair fitting model which was generated with structural equation modeling using the questionnaires HADS, TICS, CTQ, PSS4, DRRI-2 (section prior stressors) and PDS for acute and chronic social stress. It could also be found that the psychological responses (MDBF, STAI-S, PASA) to social stress significantly habituated over the three points of measurement whereas the bio-physiological stress response (HRV, heart rate, blood pressure, sAA, cortisol) did not. No significant differences in soldier’s habituation patterns between the groups with/without foreign deployment during study time could be found. Furthermore, results showed that induced social stress significantly increased oxidative DNA damage, especially for soldiers with a higher 10-year cardiovascular risk, with no effects for non-risk individuals. The degree of DNA damage was dependent on the increase in sympathetic tone. The examinations showed that bio-physiological and psychological reactions are not linked or show similar adaptation patterns for repeated social stress. Nevertheless, emphasizing the role of social stress alongside biological factors in cardiovascular risk calculation is crucial, and the Global Stress Index highlights its importance and practicality as a simple and statistically well-founded tool. It becomes clear that it is important to frequently consider social stress as a key factor affecting mental and physical health in the military
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