Combining Structural with Functional Model Properties in Iron Synthetic Analogue Complexes for the Active Site in Rabbit Lipoxygenase

Iron complexes that model the structural and functional properties of the active iron site in rabbit lipoxygenase are described. The ligand sphere of the mononuclear pseudo-octahedral cis-(carboxylato)­(hydroxo)­iron­(III) complex, which is completed by a tetraazamacrocyclic ligand, reproduces the first coordination shell of the active site in the enzyme. In addition, two corresponding iron­(II) complexes are presented that differ in the coordination of a water molecule. In their structural and electronic properties, both the (hydroxo)­iron­(III) and the (aqua)­iron­(II) complex reflect well the only two essential states found in the enzymatic mechanism of peroxidation of polyunsaturated fatty acids. Furthermore, the ferric complex is shown to undergo hydrogen atom abstraction reactions with O–H and C–H bonds of suitable substrates, and the bond dissociation free energy of the coordinated water ligand of the ferrous complex is determined to be 72.4 kcal·mol–1. Theoretical investigations of the reactivity support a concerted proton-coupled electron transfer mechanism in close analogy to the initial step in the enzymatic mechanism. The propensity of the (hydroxo)­iron­(III) complex to undergo H atom abstraction reactions is the basis for its catalytic function in the aerobic peroxidation of 2,4,6-tri­(tert-butyl)­phenol and its role as a radical initiator in the reaction of dihydroanthracene with oxygen

Charge collection and efficiency measurements of the TJ-Monopix2 DMAPS in 180 \,nm CMOS technology

Monolithic CMOS pixel detectors have emerged as competitive contenders in the field of high-energy particle physics detectors. By utilizing commercial processes they offer high-volume production of such detectors. A series of prototypes has been designed in a 180$\,$nm Tower process with depletion of the sensor material and a column-drain readout architecture. The latest iteration, TJ-Monopix2, features a large 2$\,$cm x 2$\,$cm matrix consisting of 512 x 512 pixels with 33.04$\,$um pitch. A small collection electrode design aims at low power consumption and low noise while the radiation tolerance for high-energy particle detector applications needs extra attention. With a goal to reach radiation tolerance to levels of $10^{15}\,1\,$MeV n$_\text{eq}\,$cm$^{-2}$ of NIEL damage a modification of the standard process has been implemented by adding a low-dosed n-type silicon implant across the pixel in order to allow for homogeneous depletion of the sensor volume. Recent lab measurements and beam tests were conducted for unirradiated modules to study electrical characteristics and hit detection efficiency.Comment: Conference proceedings for PIXEL2022 conference, submitted to Po

Modeling flexibility in energy systems : comparison of power sector models based on simplified test cases

Model-based scenario analyses of future energy systems often come to deviating results and conclusions when different models are used. This may be caused by heterogeneous input data and by inherent differences in model formulations. The representation of technologies for the conversion, storage, use, and transport of energy is usually stylized in comprehensive system models in order to limit the size of the mathematical problem, and may substantially differ between models. This paper presents a systematic comparison of nine power sector models with sector coupling. We analyze the impact of differences in the representation of technologies, optimization approaches, and further model features on model outcomes. The comparison uses fully harmonized input data and highly simplified system configurations to isolate and quantify model-specific effects. We identify structural differences in terms of the optimization approach between the models. Furthermore, we find substantial differences in technology modeling primarily for battery electric vehicles, reservoir hydro power, power transmission, and demand response. These depend largely on the specific focus of the models. In model analyses where these technologies are a relevant factor, it is therefore important to be aware of potential effects of the chosen modeling approach. For the detailed analysis of the effect of individual differences in technology modeling and model features, the chosen approach of highly simplified test cases is suitable, as it allows to isolate the effects of model-specific differences on results. However, it strongly limits the model's degrees of freedom, which reduces its suitability for the evaluation of fundamentally different modeling approaches

Verbundvorhaben FlexMex: Modellexperiment zur zeitlich und räumlich hoch aufgelösten Untersuchung des zukünftigen Lastausgleichs im Stromsystem

Das Projekt FlexMex konzentrierte sich auf einen Modellvergleich zur Untersuchung der Nutzung von Flexibilitätsoptionen zum Ausgleich der Stromerzeugung aus variablen erneuerbaren Energien. Die zentrale Frage war, wie unterschiedliche Optimierungs- und Technologiemodellie-rungsansätze den Anlageneinsatz in stündlich aufgelösten Stromsektormodellen beeinflussen. Darüber hinaus wurde der Einfluss unterschied-licher Modellumfänge auf den Einsatz von Flexibilitätsoptionen untersucht. Um datenbedingte von modellbedingten Unterschieden in den Ergebnissen konsequent zu trennen, wurden die Eingangsdaten der neun beteiligten Modelle vollständig harmonisiert. Die Anwendung der Modelle wurde dann in zwei Hauptexperimente unterteilt. Im ersten Experiment wurden auf der Grundlage einer umfassenden qualitativen Analyse der Modelle und ihrer Unterschiede einzelne Flexibilitätsoptionen untersucht. Anhand stark reduzierter Testfälle konnten modellspe-zifische Effekte isoliert und quantifiziert werden. Ergänzende Analysen befassten sich mit dem modellendogenen Ausbau von Stromspeichern, Stromnetzen und regelbaren Kraftwerken. Aufbauend auf den technologiespezifischen Analysen wurden im zweiten Modellexperiment komplexere Szenarien betrachtet. Dort wurden sechzehn stilisierte Szenarien betrachtet, die sich in Versorgungsanteil erneuerbarer Ener-gien, Technologieumfang und Optimierungsumfang unterscheiden. Trotz der hohen Anzahl der Modelle und der interagierenden Modellun-terschiede können die Ergebnisabweichungen auf die Modelleigenschaften zurückgeführt werden. Das Experiment zeigt, dass Unterschiede im Modellierungsansatz und der Technologieabbildung zu vergleichsweise geringen Abweichungen führen, während ein heterogener Modell-umfang einen deutlich größeren Einfluss haben kann. Zusammenfassend können die Ergebnisse des FlexMex-Projekts ein besseres Verständ-nis für die Wirkung unterschiedlicher Modellierungsansätze liefern und damit zur Interpretation von Modellergebnissen beitragen

Reflections

The American Society of International Law Committee recommended that the Manley 0. Hudson Medal be awarded to Professor Eric Stein for his lifetime of significant contributions to international and comparative law. Stein, the Hessel E. Yntema Professor of Law, Emeritus, at the University of Michigan Law School, had been an active supporter of ASIL as Honorary Vice President, Counsellor, and Honorary Editor of, and frequent contributor to, the American Journal of International Law. His many books and articles established him as a leading thinker and writer on European Community law and on what he described in a famous article as the Uses, Misuses, and Nonuses of Comparative Law

Zum Zusammenhang von Geschlechterungleichheiten in Bildung, Beruf und Karriere : ein Ausblick

Ziel der folgenden Ausführungen im abschliessenden Teil dieses Sammelbands zur Entwicklung und Genese von geschlechtsspezifischen Bildungsungleichheiten ist es, den Blick zu öffnen in Richtung Berufsleben. Wie sind die verbesserten Bildungsmöglichkeiten von Frauen zu interpretieren? Ist es in den letzten Jahrzehnten gelungen, eines der grundlegendsten gesellschaftlichen Ungleichheitsverhältnisse zu beseitigen? Oder beginnt sich dieses sogar zu verkehren in eine gesellschaftliche Benachteiligung der Männer? Wir gehen bei unseren Überlegungen von der These aus, dass ein Abbau von Benachteiligungen der Frauen im Bildungssystem für sich genommen noch wenig aussagekräftig ist, wenn wir uns mit der klassischen soziologischen Frage der Persistenz bzw. des Wandels von gesellschaftlichen Ungleichheiten befassen wollen. Erst wenn die ganze Verknüpfung von Bildung und gesellschaftlicher Ungleichheit in den Blick genommen wird und sich dabei zeigt, dass Frauen ihre Bildungsgewinne auch in entsprechende Chancen im Beschäftigungssystem umsetzen können, sind ihre verbesserten Bildungschancen ein Gewinn für die Individuen und ein Fortschritt für die Gesellschaft – und erst dann könnten mögliche Bildungsvorteile von Frauen, wie sie in den vorliegenden Aufsätzen z.T. diagnostiziert werden, gar als neue gesellschaftliche Benachteiligungen von Männern skandalisiert werden

New insights into the prevalence of depressive symptoms and depression in rheumatoid arthritis – Implications from the prospective multicenter VADERA II study

Objectives To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease. Methods In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation. Results In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age 2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy. Conclusions Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms. Clinical trial registration number This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483)

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment