Anwendungsorientierte Einführung in die Integralrechnung

Ausarbeitung eines Workshops der T³-Regionaltagung vom 08.11.2003 am Einhard-Gymnasium in Aachen.  Aus der Einleitung: "Die Einführung in die Integralrechnung wird meistens anhand eines Problems aus der Flächenberechnung durchgeführt, und auch in den Übungsaufgaben treten überwiegend Flächenberechnungen auf. Hier soll ein Zugang zur Integralrechnung vorgestellt werden, der von Beginn an auch andere Anwendungen wie Volumina, Mantelflächen und Bogenlängen einbezieht. Der Begriff Integral wird dabei so früh benutzt, dass im Unterricht mehrfach der Übergang von der Summation zur Integration erfolgen kann."</div

Simvastatin and atorvastatin attenuate VCAM-1 and uPAR expression on human endothelial cells and platelet surface expression of CD40 ligand

Background: In addition to their cholesterol lowering ability, statins have proven pleiotropic effects in the cardiovascular system. Chronic inflammation with interactions between platelets and endothelial cells leads to an upregulation of activity markers of atherosclerosis. The purpose of this study was to investigate the effects of simvastatin and atorvastatin on platelets and endothelial cells in an in vitro endothelial cell model. Methods and Results: After a 24 h incubation period with either simvastatin or atorvastatin (1 &#956;mol/L), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide (LPS), and were then incubated in direct contact with activated platelets. Platelet surface expression of CD40L and CD62P and expression of ICAM-1, VCAM-1, uPAR and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MMP-1. The increased expression of VCAM-1 and uPAR on endothelial cells by stimulation with LPS and by direct contact with activated platelets was significantly reduced to a similar extent through pre-incubation with both atorvastatin and simvastatin (p < 0.05). Platelets without endothelial cell contact, but in direct contact with either statin, showed similar significant reductions in surface expression of CD40L (p < 0.005). Conclusions: These effects may explain the ability of statins to reduce the progression of atherosclerosis in addition to their cholesterol-lowering properties. (Cardiol J 2012; 19, 1: 20&#8211;28

Ischemic biomarker heart-type fatty acid binding protein (hFABP) in acute heart failure - diagnostic and prognostic insights compared to NT-proBNP and troponin I

Background: To evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF). Methods: 401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP. Results: Additional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to “rule out” AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1–2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8–8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3–7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml. Conclusions: Combining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM. Trial registration: ClinicalTrials.gov identifier: NCT00143793

Surface Acoustic Wave (SAW) Resonators for Monitoring Conditioning Film Formation

We propose surface acoustic wave (SAW) resonators as a complementary tool for conditioning film monitoring. Conditioning films are formed by adsorption of inorganic and organic substances on a substrate the moment this substrate comes into contact with a liquid phase. In the case of implant insertion, for instance, initial protein adsorption is required to start wound healing, but it will also trigger immune reactions leading to inflammatory responses. The control of the initial protein adsorption would allow to promote the healing process and to suppress adverse immune reactions. Methods to investigate these adsorption processes are available, but it remains difficult to translate measurement results into actual protein binding events. Biosensor transducers allow user-friendly investigation of protein adsorption on different surfaces. The combination of several transduction principles leads to complementary results, allowing a more comprehensive characterization of the adsorbing layer. We introduce SAW resonators as a novel complementary tool for time-resolved conditioning film monitoring. SAW resonators were coated with polymers. The adsorption of the plasma proteins human serum albumin (HSA) and fibrinogen onto the polymer-coated surfaces were monitored. Frequency results were compared with quartz crystal microbalance (QCM) sensor measurements, which confirmed the suitability of the SAW resonators for this application

The proteolytic activation of (H3N2) influenza A virus hemagglutinin is facilitated by different type II transmembrane serine proteases

Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro. Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast, Tmprss2-/- Tmprss4-/- double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo

Risk factor paradox: No prognostic impact of arterial hypertension and smoking in patients with ventricular tachyarrhythmias

Background: Data regarding the outcome of patients with ventricular tachyarrhythmias related to arterial hypertension (AHT) and smoking is limited. The study sought to assess the prognostic impact of AHT and smoking on survival in patients presenting with ventricular tachyarrhythmias. Methods: All consecutive patients surviving ventricular tachycardia (VT) and ventricular fibrillation (VF) upon admission to the University Medical Center Mannheim (UMM), Germany from 2002 to 2016 were included and stratified according to AHT and smoking by propensity score matching. The primary prognostic endpoint was all-cause mortality at 30 months.Results: A total of 988 AHT-matched patients (494 each, with and without AHT) and a total of 872 smoking-matched patients (436 each, with and without smoking) were included. The rates of VT and VF were similar in both groups (VT: AHT 60% vs. no AHT 60%; smokers 61% vs. non-smokers 62%; VF: AHT 35% vs. no AHT 38%; smokers 39% vs. non-smokers 38%). Neither AHT nor smoking were associated with the primary endpoint of long-term all-cause mortality at 30 months (long-term mortality rates: AHT/no AHT, 26% vs. 28%; log-rank p = 0.525; smoking/non-smoking, 22% vs. 25%; log-rank p = 0.683).Conclusions: Paradoxically, neither AHT nor smoking were associated with differences of long-term all-cause mortality in patients presenting with ventricular tachyarrhythmias

Statin therapy is associated with improved survival in patients with ventricular tachyarrhythmias

Objectives: The study sought to assess the impact of statin therapy on survival in patients presenting with ventricular tachyarrhythmias. Background: Data regarding the outcome of patients with statin therapy presenting with ventricular tachyarrhythmias is limited. Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with statin were compared to patients without statin therapy (non-statin). The primary prognostic endpoint was long-term all-cause death at 3 years. Uni- and multivariable Cox regression analyses were applied in propensity-score matched cohorts. Results: A total of 424 matched patients was included. The rates of VT and VF were similar in both groups (VT: statin 71% vs. non-statin 68%; VF: statin 29% vs. 32%; p = 0.460). Statin therapy was associated with lower all-cause mortality at long-term follow-up (mortality rates 16% versus 33%; log rank, p = 0.001; HR = 0.438; 95% CI 0.290–0.663; p = 0.001), irrespective of the underlying type of ventricular tachyarrhythmia (VT/VF), left ventricular ejection fraction (LVEF) &gt; 35%, presence of an activated implantable cardioverter defibrillator (ICD), cardiogenic shock or cardiopulmonary resuscitation (CPR). Conclusion: Statin therapy is independently associated with lower long-term mortality in patients presenting with ventricular tachyarrhythmias on admission. Trial registration: Clinicaltrials.gov, NCT02982473 , 11/29/2016, Retrospectively registered

Die Festigkeitsversuchsarbeiten im Institut für Schiffbau an der Universität Hamburg

Die Festigkeitsversuchsarbeiten im Institut für Schiffbau an der Universität Hambur