HochschulschriftEthanAromatisierungCarbon dioxide capture and utilizationOxidansAntioxidansEmissionsverringerungRecyclingCarbon dioxide capture and storageAlkane
Im Fokus dieser Dissertationsschrift steht die Aromatisierung von Ethan, die durch die Zugabe von Oxidationsmitteln wie Kohlenstoffdioxid und Luftsauerstoff untersucht wurde. Als Katalysatoren wurden kommerzielle Zeolithkatalysatoren durch Festkörper-Ionenaustausch und Imprägnierung erhalten. Die Katalysatoren wurden nach der Modifikation und nach der Katalyse jeweils charakterisiert, um Deaktivierungsprozesse zu beleuchten. Bei der nicht-oxidativen Aromatisierung von Ethan konnte die Wasserstoffbilanz durch experimentelle Daten abgebildet und näher untersucht werden. Bei der Zugabe von Kohlenstoffdioxid konnten Deaktivierungsprozesse in der Aromatisierung beobachtet wird, die auf die Bildung von Wasser zurückgeführt wurde. Die oxidative Aromatisierung mit Luftsauerstoff konnte durch physisches Mischen von H-ZSM-5 und M1-Mischoxidkatalysator realisiert werden. Dabei wurden die Prozessparameter systematisch variiert und der Einfluss von verschiedenen Modifikationen betrachtet.
This dissertation focuses on the aromatization of ethane, which was investigated by the addition of oxidants such as carbon dioxide and atmospheric oxygen. Commercial zeolite catalysts were modified by solid-state ion exchange and impregnation. The catalysts were characterized after modification and after catalysis, respectively, to shed light on deactivation processes. For the non-oxidative aromatization of ethane, the hydrogen balance could be mapped by experimental data and studied in more detail. When carbon dioxide was added, deactivation processes in the aromatization could be observed, which was attributed to the formation of water. Oxidative aromatization with atmospheric oxygen could be realized by physically mixing H-ZSM-5 and M1 mixed oxide catalysts. The process parameters were systematically varied and the influence of different modifications was considered.
VIII, 330 Seiten Illustrationen (überwiegend farbig), Diagramme 24 cm x 17 cm.
Zusatz auf dem Cover: ideale Ergänzung zu Rettungssanitäter Heute ; Titelzusatz auf dem Cover: Fragen - Fallbeispiele - kommentierte Lösungen ; Verlagsangabe auf dem Umschlag: Elsevier, Urban & Fischer
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
von Julia Roeper ; Nikolaj Frost ; Martin Wermke ; Felix Saalfeld ; Daniel Heudobler ; Tobias Pukrop ; Melanie Janning ; Jonas Kuon ; Rieke Kempfer ; Lucia Nogová ; Petros Christopoulos ; Frank Griesinger
von Nikolaj Frost ; Petros Christopoulos ; Diego Kauffmann-Guerrero ; Jan Stratmann ; Richard Riedel ; Monica Schaefer ; Jürgen Alt ; Sylvia Gütz ; Daniel C. Christoph ; Eckart Laack ; Martin Faehling ; Richard Fischer ; Klaus Fenchel ; Sebastian Haen ; Lukas Heukamp ; Christian Schulz ; Frank Griesinger
ALK; brain metastases; early access program; lorlatinib; NSCLC; ROS1; TP53
Introduction:We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.Patients and Methods:Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed.Results:In total, 52 patients were included [median age 57?years (range 32?81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1?4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4?months, 8.0?months, 54% and 13.0?months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6?months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8?month, HR 3.3, p?=?0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p?=?0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS.Conclusions:Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.
Therapeutic advances in medical oncology Thousand Oaks, Calif. : Sage, 2009 13(2021) vom: Jan., Artikel-ID 1758835920980558, Seite 1-15 Online-Ressource
von Petros Christopoulos ; Martina Kirchner ; Farastuk Bozorgmehr ; Nikolaus Magios ; Daniel Kazdal ; Anna-Lena Volckmar ; Lena Marie Brückner ; Tilmann Bochtler ; Mark Kriegsmann ; Volker Endris ; Roland Penzel ; Katharina Kriegsmann ; Martin E. Eichhorn ; Felix Herth ; Claus Peter Heußel ; Rami El-Shafie ; Marc Schneider ; Thomas Muley ; Michael Meister ; Peter Schirmacher ; Helge Bischoff ; Frank Griesinger ; Albrecht Stenzinger ; Michael Thomas
Objective - Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. - Materials and methods - To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). - Results - EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+ NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. - Conclusions - EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.
Lung cancer Amsterdam [u.a.] : Elsevier, 1985 148(2020), Seite 105-112 Online-Ressource
