A robust sheath‐flow CE‐MS interface for hyphenation with Orbitrap MS

The hyphenation of capillary electrophoresis with high‐resolution mass spectrometry, such as Orbitrap MS, is of broad interest for the unambiguous and exceptionally sensitive identification of compounds. However, the coupling of these techniques requires a robust ionization interface that does not influence the stability of the separation voltage while coping with oxidation of the emitter tip at large ionization voltages. Herein, we present the design of a sheath‐flow CE‐ESI‐MS interface which combines a robust and easy to operate set‐up with high‐resolution Orbitrap MS detection. The sheath liquid interface is equipped with a gold coated electrospray emitter which increases the stability and overall lifetime of the system. For the characterization of the interface, the spray stability and durability were investigated in dependence of the sheath‐flow rate, electrospray voltage, and additional gold coating. The optimized conditions were applied to a separation of angiotensin II and neurotensin resulting in LODs of 2.4 and 3.5 ng/mL

Strahlentherapie des Mamma-Karzinoms: Optimierung der oberflächengestützten Patientenpositionierung

Background and purpose Surface guided radiation therapy (SGRT) has established itself as a reliable method for ionizing radiation free, real-time patient positioning and control in recent years. The patient’s surface is scanned and registered to a target surface characterizing the desired position, yielding shift values for correction. It is particularly suited for shallow target volumes like the breast. In spite of widespread use, knowledge about optimal scope of application, conditions and setup, and their influence on accuracy remains vague. These questions were therefore systematically addressed in this thesis. An overview of recent developments in SGRT was given in a review paper. The delineation of a region of interest (ROI), as part of the clinical routine to define the two-dimensional surface area used for the registration, was analyzed in the second study. This was followed by an in-depth evaluation of the dosimetric impact of SGRT-based position deviations in six degrees of freedom (DOF) with a robustness study of treatment plans in order to obtain threshold values for position control. In the fourth study, the conditions for the introduction of a new markerless workflow with SGRT-only fractions and its performance were evaluated. Material and methods All data analyzed in this thesis was obtained in the context of the clinical application of SGRT of breast cancer by means of the AlignRT (VisionRT, London, UK) surface scanner installed on two linear accelerators (linac) at the Department of Radiation Oncology at the Universitätsklinikum Erlangen (UKER). The surface-based correction shifts were compared to the clinically applied shifts originating from the cone beam computed tomography (CBCT based position correction for different ROIs. The dosimetric effect of patient misalignment was evaluated by systematically calculating the original treatment plans with simulated 6DOF position deviations, yielding threshold values based on dose constraints. The newly introduced markerless workflow, which included weekly CBCT scans for patients with small SGRT based position deviations in the first week of treatment, was compared to the old workflow. Results It has been found that the ROI has a significant influence on the surface registration result and must therefore be chosen with care. An optimal ROI comprising the surface of the breast, sternum and the area below both breasts could be identified, reducing particularly deviations from CBCT standard for rotational DOFs from 2.93◦ to 1.96◦ on average. The importance of usually neglected rotations was also highlighted in the robustness study, as well as the necessity of distinguishing between DOFs for the dosimetric evaluation of position deviations. The dose distributions of the treatment plans were particularly sensitive to vertical translations and rotations in roll. An optimal set of threshold values satisfying dose coverage constraints, suitable for clinical surface-based position control, could be identified. Laser and skin markings-based positioning could safely be substituted by SGRT in the newly introduced workflow. Around 40% of the patients could be treated with weekly CBCT and SGRT-only for all other fractions, leading to dose savings and time savings of 97 s, 166 s and 239 s per fraction for patients with the new workflow, without daily CBCT and for SGRT-only fractions, respectively. Conclusion SGRT has proven to be a reliable tool for real time breast cancer patient positioning, capable of substituting laser and skin markings-based pre-positioning and even image guidance under certain conditions. In order to assure a safe dose delivery, however, utmost attention has to be paid to meeting the necessary requirements, particularly with respect to the correct choice of the ROI and threshold values for position control.Hintergrund und Ziele Die oberflächengestützte Strahlentherapie (Surface Guided Radiation Therapy, SGRT) hat sich in den letzten Jahren als zuverlässige Methode zur Echtzeit-Patientenpositionierung und-kontrolle ohne ionisierende Strahlung etabliert. Die Oberfläche der Patienten und Patientinnen wird abgetastet und mit eine Referenzoberfläche registriert, welche die gewünschte Position charakterisiert. Dies liefert Verschiebungswerte zur Positionierungskorrektur. SGRT eignet sich besonders für oberflächennahe Zielvolumina wie die Brust. Trotz der weit verbreiteten Anwendung ist Wissen über Anwendungsvoraussetzungen, den optimalen Anwendungsbereich und das optimale klinische Setup sowie deren Einfluss auf die Genauigkeit nach wie vor lückenhaft. Diese Fragen wurden daher in dieser Arbeit systematisch behandelt. Ein Überblick über die jüngsten Entwicklungen in der SGRT wurde in einem Übersichtsartikel gegeben. Die Abgrenzung einer Region of Interest (ROI) als Teil der klinischen Routine zur Definition der zweidimensionalen Fläche, die für die Registrierung verwendet wird, wurde in der zweiten Studie analysiert. Es folgte eine eingehende Auswertung der dosimetrischen Auswirkungen von SGRT-basierten Positionsabweichungen in sechs Freiheitsgraden (DOF) im Rahmen einer Robustheitsstudie von Behandlungsplänen, um Schwellenwerte für die Positionskontrolle zu erhalten. In der vierten Studie wurden die Vorraussetztungen zur Einführung eines neuen markerlosen Arbeitsablaufs mit reinen SGRT-Fraktionen und dessen Leistungsfähigkeit bewertet. Material und Methoden Alle in dieser Arbeit analysierten Daten wurden im Rahmen der klinischen Anwendung der SGRT bei Brustkrebs mit dem Oberflächenscanner AlignRT (VisionRT, London, UK) gewonnen, der an zwei Linearbeschleunigern in der Strahlenklinik des Universitätsklinikums Erlangen (UKER) installiert sind. Die oberflächenbasierten Korrekturverschiebungen wurden für verschiedene ROIs mit den klinisch angewandten Verschiebungen verglichen, die sich aus der Conebeam-CT-basierten Positionskorrektur ergeben. Die dosimetrischen Auswirkungen der Positionsabweichungen wurden durch systematische Berechnung der ursprünglichen Behandlungspläne mit simulierten 6DOFAbweichungen evaluiert, wobei Schwellenwerte auf der Grundlage von Dosisbeschränkungen ermittelt wurden. Der neu eingeführte markerlose Arbeitsablauf, der wöchentliche CBCT-Scans für Patientinnen mit geringen SGRT-basierten Positionsabweichungen in der ersten Behand lungswoche umfasste, wurde mit dem alten Arbeitsablauf verglichen. Ergebnisse und Beobachtungen Es hat sich herausgestellt, dass die ROI einen erheblichen Einfluss auf das Ergebnis der Oberflächenregistrierung hat und daher mit Sorgfalt ausgewählt werden muss. Es konnte eine optimale ROI identifiziert werden, welche die Oberfläche der Brust, das Brustbein und den Bereich unterhalb beider Brüste umfasst und insbesondere die Abweichungen von der CBCT-Norm für Rotations-Freiheitsgrade von durchschnittlich 2.93◦ auf 1.96◦ reduziert. Die Bedeutung der üblicherweise vernachlässigten Rotationen wurde auch in der Robustheitsstudie hervorgehoben, ebenso wie die Notwendigkeit der Unterscheidung zwischen den Freiheitsgeraden für die dosimetrische Bewertung von Positionierungsabweichungen. Die Dosisverteilungen der Behandlungspläne waren besonders empfindlich gegenüber vertikalen Translationen und Rotationen in roll. Es konnte ein optimaler Satz von Schwellenwerten identifiziert werden, der die Anforderungen an die Dosisabdeckung erfüllt und für die klinische oberflächenbasierte Positionskontrolle geeignet ist. Die auf Laser- und Hautmarkierungen basierende Positionierung konnte in dem neu eingeführten Arbeitsablauf sicher durch SGRT ersetzt werden. Etwa 40% der Patientinnen konnten mit wöchentlichem CBCT und mit SGRT für alle anderen Fraktionen behandelt werden. Dies führte zu Dosiseinsparungen und zu Zeiteinsparungen von 97s, 166s bzw. 239s pro Fraktion für Patientinnen, die mit dem neuen Arbeitsablauf bzw. ohne tägliches CBCT behandelt wurden bzw. für reine SGRT-Fraktionen. Schlussfolgerungen SGRT hat sich als zuverlässiges Instrument für die Echtzeit-Positionierung von Brustkrebspatientinnen erwiesen und kann unter bestimmten Bedingungen die auf Laser- und Hautmarkierungen basierende Vorpositionierung und sogar die bildgestützte Strahlentherapie ersetzen. Um eine sichere Dosisapplikation zu gewährleisten, ist jedoch größte Aufmerksamkeit auf die Erfüllung der notwendigen Anforderungen zu richten, insbesondere im Hinblick auf die richtige Wahl der ROI und der Schwellenwerte für die Positionskontrolle

Iron-Mediated Peptide Formation in Water and Liquid Sulfur Dioxide under Prebiotically Plausible Conditions

Peptides have essential structural and catalytic functions in living organisms. The formation of peptides requires the overcoming of thermodynamic and kinetic barriers. In recent years, various formation scenarios that may have occurred during the origin of life have been investigated, including iron(III)-catalyzed condensations. However, iron(III)-catalysts require elevated temperatures and the catalytic activity in peptide bond forming reactions is often low. It is likely that in an anoxic environment such as that of the early Earth, reduced iron compounds were abundant, both on the Earth's surface itself and as a major component of iron meteorites. In this work, we show that reduced iron activated by acetic acid mediates efficiently peptide formation. We recently demonstrated that, compared to water, liquid sulfur dioxide (SO2) is a superior reaction medium for peptide formations. We thus investigated both and observed up to four amino acid/peptide coupling steps in each solvent. Reaction with diglycine (G(2)) formed 2.0 % triglycine (G(3)) and 7.6 % tetraglycine (G(4)) in 21 d. Addition of G(3) and dialanine (A(2)) yielded 8.7 % G(4). Therefore, this is an efficient and plausible route for the formation of the first peptides as simple catalysts for further transformations in such environments

Application Of The Dynamic Tolerancing Approach To The Assembly Of Fuel Cell Stacks

The proton exchange membrane fuel cell (PEM-FC) makes it possible to provide electrical energy for a wide range of applications without polluting emissions as a by-product. However, various challenges need to be overcome before widespread use of this technology is possible. In addition to optimizing its performance and lifetime, a key challenge is to reduce production costs. Production processes significantly affect these three objectives. Tighter manufacturing tolerances on the main components, membrane exchange assembly and bipolar plate, for example, can improve the functions above. However, manufacturing to tighter tolerances usually leads to higher production costs. To resolve the contradiction between 'tight tolerances' and 'low costs', the principle of dynamic tolerancing was developed. So far, this principle has only been implemented for a shaft-hub connection. The approach presented here applies the principle to the assembly process of a stack for a PEM-FC and shows how the channel offset within a stack can be reduced without increasing the requirements for individual part tolerances

Thermal Transients to Accelerate Cyclic Aging of Lithium‐Ion Batteries

Cyclic aging tests of lithium-ion batteries are very time-consuming. Therefore, it is necessary to reduce the testing time by tightening the testing conditions. However, the acceleration with this approach is limited without altering the aging mechanisms. In this paper, we investigate whether and how thermal transients accelerate the aging. The tests are performed on NMC/graphite pouch cells by applying temperatures in a range of 5 °C to 45 °C to the cell surface. The results show, that an accelerated capacity loss can be achieved in comparison to the reference cell at a steady-state temperature of 25 °C. However, capacity difference analysis (CDA) prognoses a covering layer for the transient cells, which is confirmed upon post-mortem analysis. We suspect the origin to lie in the dynamics of temperature fields and current distribution during temperature changes when charging. More specifically, areas of higher temperature in the cell lead to high local current densities and plating. Subsequently, high temperatures promote the reaction of the plated lithium with electrolyte. The results show that thermal transients are a critical condition for lifetime and safety and should be treated with caution as they can occur during real life operation

Влияние пластификации на тепловое расширение полимеров

В статье рассмотрено влияние пластификации и модификации некоторых полимеров на температуру стеклования и параметры теплового расширения. В термопластичных полимерах, с достаточно гибкими макромолекулярными цепями, введение пластификатора или модификатора не влияет на величину свободного объема при Т=ТС и поведение таких систем подчиняется эмпирическому правилу Симха и Бойера. Отклонения от него наблюдаются лишь при больших концентрациях пластификатора, ограниченно совмещающегося с полимером

From amino acid mixtures to peptides in liquid sulphur dioxide on early Earth

The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution. Liquid sulphur dioxide proves to be a superior alternative for copper-catalyzed peptide condensations. Compared to water, amino acids are activated in sulphur dioxide, leading to the incorporation of all 20 proteinogenic amino acids into proteins. Strikingly, even extremely low initial reactant concentrations of only 50 mM are sufficient for extensive peptide formation, yielding up to 2.9% of dialanine in 7 days. The reactions carried out at room temperature and the successful use of the Hadean mineral covellite (CuS) as a catalyst, suggest a volcanic environment for the formation of the peptide world on early Earth

Region of interest optimization for surface guided radiation therapy of breast cancer

Abstract Purpose The goal of this study was to investigate how the choice of the region of interest (ROI) affects the registration results of surface imaging for daily positioning of breast cancer patients. Methods The AlignRT system (VisionRT, London) and the XVI Cone beam CT (CBCT; Elekta, Stockholm) installed on two Versa HD linacs (Elekta) were used in this study, which included 28 patients (160 fractions). In the clinical workflow, patients were prepositioned with AlignRT and then shifted in 6 degrees of freedom (DOF) according to the CBCT. A new reference capture was taken immediately afterward. Retrospectively, the surface capture resulting from prepositioning was registered to the latest reference capture. By varying the ROI used for registration, the surface‐based results were optimized in terms of minimizing the deviation to the clinically applied CBCT shifts. Two sets of ROIs were used: one obtained by applying a variable margin to the breast surface, another by combining ROIs of anatomical structures, including the sternum and contralateral breast. Results Registration results showed significant differences from one ROI to another. Generally, the results improved with increasing ROI size, especially for rotational DOFs. ROIs, including the axilla or supraclavicular lymph drainage region, did not yield an improved registration result. On the other hand, an ROI comprising the breast surface, sternum, and a belt caudal to the breasts decreased the average magnitude of the translational and rotational deviations by 6.6% and 30.8% (p < 0.01), respectively, compared to the breast surface only results. Conclusion The influence of the ROI choice on surface imaging registration results was analyzed and the surface‐based shifts were compared to clinically applied CBCT shifts. An optimal ROI for the treatment of breast cancer patients, consisting of the breast surface, sternum, and a belt, was identified