Effiziente chemoenzymatische Synthese von dhydroartemisinaldehyd

Artemisinin aus der Pflanze Artemisia annua ist das wirkungsvollste Arzneimittel zur Behandlung von Malaria. Die Sesquiterpen-Cyclase Amorphadien-Synthase, ein Cytochrom-abhängiges CYP450 und eine Aldehyd-Reduktase wandeln in der Pflanze Farnesyl-Diphosphat (FDP) in Dihydroartemisinaldehyd (DHAAl) um, welches ein Schlüsselzwischenprodukt in der Biosynthese von Artemisinin und eine halbsynthetische Vorstufe in der chemischen Synthese des Arzneimittels ist. Hier berichten wir über einen chemoenzymatischen Prozess, der in der Lage ist, DHAAl nur mithilfe der Sesquiterpen-Synthase aus einem gezielt synthetisierten, hydroxylierten FDP-Derivat herzustellen. Dieser Prozess, der die natürliche Sequenz aus Cyclisierung von FDP und Oxidation des Kohlenwasserstoffs umkehrt, stellt eine wesentliche Verbesserung der DHAAl-Synthese dar und zeigt das Potenzial neuer Substrate in der Terpen-Synthase-katalysierten Synthese hochwertiger Naturstoffe auf

Active front-end rectifier modelling using dynamic phasors for more-electric aircraft applications

The More-Electric Aircraft (MEA) has become a dominant trend for next-generation aircraft. The Electrical Power System (EPS) on-board may take many forms: AC, DC, hybrid, frequency-wild, variable voltage, together with the possibility of novel connectivity topologies. To address the stability, availability and capability issues as well as to assess the performance of the power quality and transient behaviour, extensive simulation work is required to develop the EPS architectures. The paper develops a fast-simulation model of active front-end rectifiers based on the dynamic phasor concept. The model is suitable for accelerated simulation studies of EPS under normal, unbalanced and line fault conditions. The performance and effectiveness of the developed model have been demonstrated by comparison against time-domain models in three-phase and synchronous space-vector representations. The experimental verification of the dynamic phasor model is also reported. The prime purpose of the model is for the simulation studies of MEA power architectures at system level; however it can be directly applied for simulation study of any other EPS interfacing with active front-end rectifiers

Intellectual Property and the External Power of the European Community: The New Extension

[T]heory is somewhat lagging behind the facts and developing only in reaction to these facts, argues C.W.A. Timmermans regarding the European Community\u27s (the EC or the Community) legal basis for extending its external power. The Community tends to extend its external competence before having a clear authority for doing so and only later provides a post hoc rationale. This observation suggests that the justification, not the propriety, of a newly acquired external competence is the question. Nowhere is this modus operandi better illustrated, or more sorely tested, than by the Community\u27s growing involvement with and pursuit of international intellectual property issues. Indeed, not only has the EC begun to act before having an obvious or agreed upon legal basis, but it also does so in the face of argument that it cannot

Prevalence of Helicobacter pylori in symptomatic patients and detection of clarithromycin resistance using melting curve analysis

AbstractBackground:Clarithromycin is often a component of combination therapies for Helicobacter pylori eradication; however, increases in resistance rates have decreased the success of the treatment.Objective:This study was designed to determine the prevalence of H pylori infection in symptomatic patients and to detect clarithromycin resistance rates using melting curve analysis.Methods:Patients scheduled for upper endoscopy at the Endoscopy Unit of the Department of Gastroenterology, Duzce University, Medical Faculty Hospital, Konuralp/Duzce, Turkey, were assessed for enrollment in the study. Two pairs of gastric biopsy specimens (antrum and corpus) were obtained from each study patient. Histopathologic examination, rapid urease test, culture, and polymerase chain reaction (PCR) of the specimens were used to identify H pylori infection. Clarithromycin resistance was detected using melting curve analysis.Results:Seventy-five patients (41 women, 34 men; mean [SD]age, 42.6 [14.5] years [range, 17–70 years]) were included in the study. Using histopathology and rapid urease test, H pylori was detected in 40 (53.3%) of the 75 specimens. H pylori was detected using PCR in 40 (53.3%) specimens and by culture in 10 (13.3%) specimens. The specificity and sensitivity of PCR and culture were interpreted by comparing them with the results of histopathologic examination and urease tests. The specificity and sensitivity of PCR were 68.6% and 72.5%, respectively, and the specificity and sensitivity of culture were 97.1% and 22.5%, respectively. Of the 40 isolates, 21 (52.5%) were susceptible to clarithromycin, 12 (30.0%) were resistant, and a mixed susceptibility pattern was detected in 7 (17.5%) specimens. H pylori isolates from 19 (79.2%) of the 24 patients who had formerly used clarithromycin showed clarithromycin resistance.Conclusions:The prevalence of H pylori infection was 53.3% for the symptomatic patients in this study, and 47.5% of the isolates showed clarithromycin resistance using melting curve analysis. The PCR-based system used in this study was accurate for the detection of H pylori infection as well as clarithromycin susceptibility testing directly in biopsy specimens

Chemical composition and mosquitocidal activity of n-hexane and methanolic extracts from Euphorbia anacampseros var. tmolea: An endemic species of Turkey against Aedes aegypti

Volatile composition of the n-hexane and methanol extracts from E. anacampseros var. tmolea was analyzed by head space-solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Chemical characterization of the methanolic extract was determined by LC-ESI-MS/MS. Both extracts were bioassayed against 1st instar larvae and adult female Ae. aegypti. The main components identified from the E. anacampseros var. tmolea n-hexane fraction were 1,8-cineole (27.5 %), p-cymene (25 %), ?-terpinene (12.8 %), limonene (9.9 %). Methyl hexanoate (18.8 %), methyl nonanoate (13.3 %), dimethyl succinate (6.5 %), methyl octanoate (6 %) and methyl phenylacetate (5.3 %) were identified from the methanolic fraction. The n-hexane extract showed 100 % mortality at 0.1 µg/ µL against 1st instar larvae of Ae. aegypti and the methanolic extract exhibited 83.3 % mortality at 5 µg/mosquito against adult female Ae. aegypti. The bioassay-guided study demonstrates that n-hexane and methanol extracts of E. anacampseros var. tmolea contain compounds with natural mosquito larvicidal and adulticidal activity.U.S. Department of DefenseThis study was partly funded by the Deployed War-Fighter Protection Research Program via grants from the U.S. Department of Defense through the Armed Forces Pest Management Board. The authors thank Miss Jessica Louton (USDA-ARS, CMAVE, Gainesville, FL) for the mosquito bioassays

A two-layered mechanical model of the rat esophagus. Experiment and theory

BACKGROUND: The function of esophagus is to move food by peristaltic motion which is the result of the interaction of the tissue forces in the esophageal wall and the hydrodynamic forces in the food bolus. The structure of the esophagus is layered. In this paper, the esophagus is treated as a two-layered structure consisting of an inner collagen-rich submucosa layer and an outer muscle layer. We developed a model and experimental setup for determination of elastic moduli in the two layers in circumferential direction and related the measured elastic modulus of the intact esophagus to the elastic modulus computed from the elastic moduli of the two layers. METHODS: Inflation experiments were done at in vivo length and pressure-diameters relations were recorded for the rat esophagus. Furthermore, the zero-stress state was taken into consideration. RESULTS: The radius and the strain increased as function of pressure in the intact as well as in the individual layers of the esophagus. At pressures higher than 1.5 cmH(2)O the muscle layer had a larger radius and strain than the mucosa-submucosa layer. The strain for the intact esophagus and for the muscle layer was negative at low pressures indicating the presence of residual strains in the tissue. The stress-strain curve for the submucosa-mucosa layer was shifted to the left of the curves for the muscle layer and for the intact esophagus at strains higher than 0.3. The tangent modulus was highest in the submucosa-mucosa layer, indicating that the submucosa-mucosa has the highest stiffness. A good agreement was found between the measured elastic modulus of the intact esophagus and the elastic modulus computed from the elastic moduli of the two separated layers

Türkiye’de bulunan yoğun bakımlarda sabun, kağıt havlu ve alkol bazlı el dezenfektanı yeterli mi?: Phokai çalışması sonuçları

Introduction: Hand hygiene is one of the most effective infection control measures to prevent the spread of healthcare-associated infections (HCAI). Water, soap, paper towel and hand disinfectant must be available and adequate in terms of effective hand hygiene. The adequacy of hand hygiene products or keeping water-soap and paper towel is still a problem for many developing countries like Turkey. In this multicenter study, we analyzed the adequacy in number and availability of hand hygiene products.Materials and Methods: This study was performed in all intensive care units (ICUs) of 41 hospitals (27 tertiary-care educational, 10 state and four private hospitals) from 22 cities located in seven geographical regions of Turkey. We analyzed water, soap, paper towel and alcohol-based hand disinfectant adequacy on four different days, two of which were in summer during the vacation time (August, 27th and 31st 2016) and two in autumn (October, 12th and 15th 2016).Results: The total number of ICUs and intensive care beds in 41 participating centers were 214 and 2357, respectively. Overall, there was no soap in 3-11% of sinks and no paper towel in 10-18% of sinks while there was no alcohol-based hand disinfectant in 1-4.7% of hand disinfectant units on the observation days. When we compared the number of sinks with soap and/or paper towel on weekdays vs. weekends, there was no significant difference in summer. However, on autumn weekdays, the number of sinks with soap and paper towel was significantly lower on weekend days (p<0.0001, p<0.0001) while the number of hand disinfectant units with alcohol-based disinfectant was significantly higher (p<0.0001).Conclusion: There should be adequate and accessible hand hygiene materials for effective hand hygiene. In this study, we found that soap and paper towels were inadequate on the observation days in 3-11% and 10-18% of units, respectively. Attention should be paid on soap and paper towel supply at weekends as well

Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern

<p>Abstract</p> <p>Background</p> <p>Initial assessment of dyspepsia often includes noninvasive testing for <it>Helicobacter pylori </it>infection. Commercially available tests vary widely in cost and accuracy. Although there is extensive literature on the cost-effectiveness of <it>H. pylori </it>treatment, there is little information comparing the cost-effectiveness of various currently used, noninvasive testing strategies.</p> <p>Methods</p> <p>A Markov simulation was used to calculate cost per symptom-free year and cost per correct diagnosis. Uncertainty in outcomes was estimated using probabilistic sensitivity analysis.</p> <p>Results</p> <p>Under the baseline assumptions, cost per symptom-free year was $122 for empiric proton pump inhibitor (PPI) trial, and costs for the noninvasive test strategies ranged from$123 (stool antigen) to $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.</p> <p>Conclusions</p> <p>Under our assumptions for how testing for <it>H. pylori </it>infection is employed in United States medical practice, the available noninvasive tests all have similar cost-effectiveness between one another as well as with empiric PPI trial.</p