Benefits and Drawbacks of Model-based Design

The Model-based Design approach, as propagated by The MathWorks, is a state-of-the-art method in the fields of aerospace, defense and automotive developments. The obvious advantages of Model-based Design of a convenient, understandable graphical description of systems, continuous verification and validation at all stages of development as well as its inherent robustness against coding errors have made it a state-of-the-art method in fields such as automotive systems and aerospace and defense. Despite the vast number of success stories associated with this approach, Model-based Design is not a standard method throughout the entire industry, especially not for small and medium sized enterprises. Hence, consulting on the introduction of Model-based Design into development teams is a recurring task for the author. Presenting an industrial project, the development of a velocimeter (spatial frequency sensor system), benefits as well as obstacles corresponding to Model-based Design are introduced. The paper’s object is giving detailed insight into the method based on first-hand experience. It will be concluded that Model-based Design is a favorable approach even for small and medium sized enterprises

correlating structural motifs and catalytic activity

Manganese based precious metal-free electrocatalysts for the oxygen evolution reaction (OER) are promising materials for energy storage systems based on dark or photo-coupled water electrolysis, because they are active, inexpensive and of low toxicity. In this work, atomic scale structure–activity relationships of two different nano-structured manganese oxides, MnOx, are established using a combination of X-ray absorption, diffraction and electrochemistry. Prepared by chemical symproportionation (s-MnOx) and impregnation (i-MnOx), the s-MnOx catalyst consisted of a layered structure similar to δ-MnO2 while the i-MnOx catalyst displayed a mixture of tunnelled, 3D cross-linked β- and defective γ-MnO2 structures. During electrocatalytic oxygen evolution the structural motifs of both MnOx remain largely unchanged, but the oxidation state of Mn increases from 3.5 to 3.9–4. Kinetic parameters of the electrocatalytic oxygen evolution reaction were extracted using Tafel slope analysis and pH titration experiment, and the role of the protons abstracted was analyzed. The study reveals fundamental differences of general importance in the catalytic activity between layered and cross-linked structures. The exclusive presence of di-μ-oxo-bridged Mn ions in the layered structure is coupled to a pronounced redox and charge capacity behaviour. This ensured efficient use of surface and bulk active sites, and resulted in a relatively large Tafel slope. Consequently, the intrinsic OER activity is especially high in s-MnOx. In contrast, 3D cross-linked structures with both mono- and di-μ-oxo-bridged Mn ions resulted in lower intrinsic activity but smaller Tafel slope, and thus favourable activity at technological water- splitting rates. The insights from this comparative study will provide guidance in the structural design and optimization of other non precious metal oxide OER catalysts

Electrochemical water splitting by layered and 3D cross-linked manganese oxides: correlating structural motifs and catalytic activity

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Manganese based precious metal-free electrocatalysts for the oxygen evolution reaction (OER) are promising materials for energy storage systems based on dark or photo-coupled water electrolysis, because they are active, inexpensive and of low toxicity. In this work, atomic scale structure–activity relationships of two different nano-structured manganese oxides, MnOx, are established using a combination of X-ray absorption, diffraction and electrochemistry. Prepared by chemical symproportionation (s-MnOx) and impregnation (i-MnOx), the s-MnOx catalyst consisted of a layered structure similar to δ-MnO2 while the i-MnOx catalyst displayed a mixture of tunnelled, 3D cross-linked β- and defective γ-MnO2 structures. During electrocatalytic oxygen evolution the structural motifs of both MnOx remain largely unchanged, but the oxidation state of Mn increases from 3.5 to 3.9–4. Kinetic parameters of the electrocatalytic oxygen evolution reaction were extracted using Tafel slope analysis and pH titration experiment, and the role of the protons abstracted was analyzed. The study reveals fundamental differences of general importance in the catalytic activity between layered and cross-linked structures. The exclusive presence of di-μ-oxo-bridged Mn ions in the layered structure is coupled to a pronounced redox and charge capacity behaviour. This ensured efficient use of surface and bulk active sites, and resulted in a relatively large Tafel slope. Consequently, the intrinsic OER activity is especially high in s-MnOx. In contrast, 3D cross-linked structures with both mono- and di-μ-oxo-bridged Mn ions resulted in lower intrinsic activity but smaller Tafel slope, and thus favourable activity at technological water-splitting rates. The insights from this comparative study will provide guidance in the structural design and optimization of other non precious metal oxide OER catalysts.DFG, EXC 314, Unifying Concepts in Catalysi

Potential of process information transfer along the process chain of hybrid components for process monitoring of the cutting process

The production of hybrid components involves a long process chain, which leads to high investment costs even before machining. To increase process safety and process quality during finishing, it is necessary to provide information about the semi-finished parts geometry for the machining process and to identify defect components at an early stage. This paper presents an investigation to predict variations in dimension and cavities inside the material during cross-wedge rolling of shafts based on measured tool pressure. First, the process is investigated with respect to the variation in diameter for three roll gaps and two materials. Subsequently, features are generated from the hydraulic pressures of the tools and multi-linear regression models are developed in order to determine the resulting diameters of the shaft shoulder. These models show better prediction accuracy than models based on meta-data about set roll gap and formed material. The features are additionally used to successfully monitor the process with regard to the Mannesmann effect. Finally, a sensor concept for a new cross-wedge rolling machine to improve the prediction of the workpiece geometry and a new approach for monitoring machining processes of workpieces with dimensional variations are presented for upcoming studies

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age

CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD

Age-related macular degeneration (AMD) is a prevalent cause of blindness in Western societies. Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age-related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown. Here, we analyzed association between variants in CFH, C3 and ARMS2 and disease progression of geographic atrophy (GA) due to AMD. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P = 1.6x10(-9), 3.2x10(-3), and P = 2.6x10(-12), respectively) when compared to 612 unrelated healthy control individuals. In cases, median progression rate of GA over a mean follow-up period of 3.0 years was 1.61 mm(2)/year with high concordance between fellow eyes. No association between the progression rate and any of the genetic risk variants at the three loci was observed (P>0.13). This study confirms that variants at CFH, C3, and ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Über den katalytisch aktiven Zustand und Struktur-Aktivitäts-Korrelationen von 3d Übergangsmetalloxiden für die elektrochemische Wasserspaltung

Die Entwicklung von aktiven, stabilen und kostengünstigen Elektrokatalysatoren für die Sauerstoffevolutionsreaktion (OER) ist der Schlüssel, um elektrische Energie mittels Wasserelektrolyse effizient in die chemische Energie von molekularem Wasser- und Sauerstoff umzuwandeln. Dieser Wasserstoff kann in großem Maßstab als Energiespeicher für die unstetig verfügbaren erneuerbaren Energieträger dienen. Die Entwicklung von verbesserten Elektrokatalysatoren aber benötigt ein besseres Verständnis über deren aktivitätsbestimmenden Eigenschaften und deren Struktur im katalytisch-aktiven Zustand. In dieser Arbeit wurden Katalysatoren basierend auf den Übergangsmetallen Mn und Co hergestellt und auf ihre OER Aktivität und Redoxchemie im neutralen und alkalischen Elektrolyten untersucht. Die Katalysatoren wurden vor und nach der OER umfangreich im Hinblick auf ihre Morphologie, Kristall- und lokale atomare Struktur sowie auf ihre elektronische Struktur und Komposition in den oberflächennahen Bereichen untersucht. Des Weiteren wurde die Struktur im katalytisch-aktiven Zustand mittels röntgenbasierten in situ Methoden bestimmt. Das Ziel dieser Arbeit ist es Struktur-Aktivitäts-Beziehungen zu identifizieren und die Ergebnisse in den wissenschaftlichen Kontext zu setzen. Die Untersuchungen von zwei nanostrukturierten, geträgerten Mn Oxiden deckten dabei einen positiven Einfluss einer 3D statt einer 2D Verknüpfung von Mn-O Oktaedern auf die OER-Aktivität auf. Der katalytisch-aktive Zustand von beiden Mn-Oxiden besteht aus Mn4+ Ionen. Die Untersuchung von Co-basierten Elektrokatalysatoren enthüllte ein gemeinsames Strukturmotiv von di-µ-oxo verknüpften Co3+/4+ Oh Ionen im katalytisch-aktiven Zustand. Dabei verwandeln sich die oberflächennahen Bereiche der Co3O4 Kristallite während der OER reversibel in eine röntgenamorphe CoOx(OH)y Schale mit 3D verknüpften Co Oktaedern, welche unter nichtkatalytischen Bedingungen wieder kristallisiert. Im Gegensatz dazu verändern Co2+ Oxide ihre Struktur durch die OER partiell aber irreversibel in ein CoOx(OH)y mit hauptsächlich Co3+ Oh Ionen. Es wurde entdeckt, dass die Anwesenheit von reduzierbaren Co3+ Ionen sehr vorteilhaft für die OER Aktivität ist und diese Ionen konnten mit einer speziellen oktaedrischen Bindungsumgebung in den oberflächennahen Regionen des CoOx(OH)y erklärt werden. Außerdem wurden deren elektrochemischen und spektroskopischen Fingerabdrücke identifiziert. Diese Arbeit zeigt die Wichtigkeit einer speziellen Koordination der Metallionen mit terminierenden O Atomen sowie einer Verknüpfung über di-µ2-oxo Brücken für eine hohe OER-Aktivität. Diese Zentren können in ein mechanistisches Konzept integriert werden und entstehen durch strukturelle Unordnung wie eine kleine Domänengröße oder sind wegen einer speziellen Kristallstruktur vorhanden. Die Ergebnisse dieser Arbeit können zu einem vereinheitlichten Verständnis der elektrochemischen Wasserspaltung sowie der Identifizierung von bisher unentdeckten aktivitätsbestimmenden Eigenschaften führen und wird dabei helfen weiter verbesserte Katalysatoren für die Wasserelektrolyse zu entwickeln.The development of active, stable and inexpensive electrocatalysts for oxygen evolution reaction (OER) is a key step to efficiently transform electrical energy into the energy of chemical bonds of molecular hydrogen and oxygen using water electrolysis. This hydrogen can serve as storage medium for renewable energy sources with intermittent availability on large grid-scale. But the design of improved electrocatalysts requires better understanding of their activity-determining properties and their structure in the catalytically active state. In this work 3d transition metal oxides based on Mn and Co were synthesized and tested for their OER activity and redox electrochemistry in neutral and alkaline electrolyte. These electrocatalysts were extensively investigated before and after OER with respect to their morphology, their crystal and local atomic structure as well as their electronic structure and near-surface composition. Furthermore, the structure of their catalytically active state was identified using in situ X-ray techniques. This work aims at identifying structure-activity correlations and at relating the findings to state-of-art OER catalyst materials. The investigation of two nanostructured, supported Mn oxides uncovered a beneficial influence of a 3D compared to a 2D layered cross-linking of Mn-O octahedra on the resulting OER activity. The catalytically active state of both Mn oxides exhibits mainly Mn4+ ions. The investigation of structurally-different Co-based electrocatalysts revealed a common structural motif of di-µ-oxo bridged Co3+/4+ Oh ions in the catalytically active state. Therein, the near-surface region of the Co3O4 crystallites transforms reversibly during OER characterized by an amorphous CoOx(OH)y shell with 3D octahedral cross-linking. This shell recrystallizes under non-catalytic rest conditions. In contrast, the structure of initially Co2+ oxides transforms partially but irreversibly after OER to a CoOx(OH)y with mainly Co3+ Oh. The presence of reducible Co3+ sites was found to be highly beneficial for OER activity and could be explained by a special octahedral Co bonding environment in the near-surface structure of the CoOx(OH)y. The electrochemical and spectroscopic fingerprints of this activity-determining property were identified. This work reveals the importance of special metal coordination with di-µ2-oxo bridging as well as terminating O sites for high OER activity. These sites can be integrated into a mechanistic framework and originate from structural disorder as in case of low domain size or are prevalent due to the specific crystal structure. The results of this work can lead to a unified understanding of heterogeneous electrochemical water oxidation as well as to the identification of activity-determining properties and will help to develop improved electrocatalysts for water electrolysis