Hochschule Bonn-Rhein-Sieg
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Dual Agonist/Antagonist Modulation of α9-Containing Nicotinic Acetylcholine Receptors by 2-Ammoniumethyl Ethers of Stilbenol and Stilbenol Analogues
No full text2-(Cyclohexyldimethylammoniumethyl)ether of 4-stilbenol (2), and its styryl-modified analogues 21 and 22, were identified as lead compounds from a series targeting human α9α10, α9, and α7 nicotinic acetylcholine receptors (nAChRs). Compounds 2 and 21 exhibited potent, and subtype-selective modulation of α9-containing receptors, with low nanomolar IC50 values and dual agonist/antagonist activity in a concentration-dependent manner. In contrast, compound 22 acted as a selective, pure antagonist. Molecular dynamics (MD) simulations of compound 21 supported a concentration-dependent allosteric mechanism, with orthosteric binding at low concentrations and vestibular site interaction at higher levels. In a human monocytic cell line, all three compounds inhibited ATP-induced IL-1β release at nanomolar concentrations. These findings identify α9α10-selective ligands as promising scaffolds for the development of nonopioid analgesics and immunomodulators, with favorable selectivity over α7 nAChRs to minimize CNS-related side effects
Isobutyryl-coenzyme a dehydrogenase deficiency: disease, or non-disease?
No full textBACKGROUND
Isobutyryl-coenzyme A dehydrogenase deficiency (IBDD) is a rare inborn error of valine metabolism caused by variants in the ACAD8 gene. Since its initial description in 1998, a wide range of clinical features has been reported, but the disease status and clinical significance of IBDD remain under debate. We systematically studied all published cases of IBDD to provide an overview of the reported phenotype and molecular spectrum.
RESULTS
A comprehensive literature review identified 172 individuals with IBDD reported up to December 2024. Seven children were diagnosed following selective screening due to family history or clinical suspicion, while 165 were identified through expanded newborn screening programs. Elevated blood or plasma C4-acylcarnitine was observed universally, and isobutyrylglycinuria was a common but not invariable urinary marker. Of these 172 individuals, 146 were asymptomatic at follow-up, whereas 26 presented with diverse, non-specific manifestations, including motor delay, failure to thrive, muscular hypotonia, speech delay, developmental delay, and anemia-the latter being the most frequently reported abnormality. Biallelic pathogenic variants in ACAD8 were identified in most cases with available genetic information, with c.286G > A p.(Gly96Ser) emerging as the most prevalent variant, predominantly among individuals of Chinese origin. Notably, altered biochemical markers of liver function were reported in 19 individuals, including 18 with isolated elevations of serum transaminases and γ-glutamyl transferase. One 11-year-old boy exhibited hepatomegaly and ultrasound findings suggestive of hepatic steatosis, along with markedly elevated transaminase levels. Hepatic steatosis has also been observed in an IBDD mouse model, suggesting a potential link between IBDD and liver involvement.
CONCLUSIONS
Most individuals with IBDD remain asymptomatic following detection through newborn screening, yet a minority develop heterogeneous clinical features. Our overview highlights that some liver enzyme abnormalities and hepatic steatosis may occur in some individuals with IBDD. These findings suggest that further research is warranted to clarify possible hepatic implications of IBDD and to determine whether long-term monitoring of affected individuals should be considered, particularly in light of ongoing discussions about the appropriateness of IBDD as a target condition in newborn screening programs
Seasonal Performance Analysis of Monocrystalline and Polycrystalline Photovoltaic Solar Panels Under Dust Deposition in Niamey, Niger
No full textThis paper investigates the impact of dust accumulation and temperature on the performance of monocrystalline and polycrystalline photovoltaic (PV) panels under the climatic conditions of Niamey, Niger, with a focus on seasonal variations. High-resolution performance data were collected across the rainy, Harmattan, and hot seasons to evaluate power output losses. During the rainy season, natural cleaning by rainfall limited power and energy losses to 0.33% and 1.55% for monocrystalline, 5.98% and 6.67% for polycrystalline panels, respectively. In contrast, the Harmattan season showed the most severe reductions, with power and energy losses reaching, respectively, 66.46% and 65.55% for monocrystalline, 57.96% and 57.50% for polycrystalline, due to intense dust accumulation and atmospheric scattering. During the hot season, elevated temperatures and soiling combined to reduce performance by 54.6% and 52.31% for monocrystalline, 43.22% and 42.61% for polycrystalline, respectively. While monocrystalline panels perform better under clean conditions, they are more susceptible to environmental stressors than polycrystalline panels, which demonstrate greater resilience to dust and temperature effects. These findings highlight the importance of regular cleaning, antisoiling technologies, and climate-adaptive PV system design to sustain performance in dusty and high-temperature environments, such as the Sahel
Themenfelder mit Bürokratiebeispielen
No full textIn diesem Kapitel werden die Problemhinweise von den über 70 hinweisgebenden Professorinnen und Professoren (Kap. „Herausgeber, Autoren und Mitglieder der AG Bürokratieabbau“) in 17 Themenfeldern gegliedert. Mit der Anzahl wird kein Anspruch auf Vollständigkeit erhoben. Auch die Reihenfolge der Themenfelder stellt keine Gewichtung dar, sondern entstand chronologisch aus den Beiträgen der Hinweisgebenden. Die Beschreibungen folgen dem Dreiklang „Problem – Verursacher – Lösung“. Jeder eingegangene Hinweis wurde, sofern er namentlich zuzuordnen war, von den herausgebenden Autoren redaktionell bearbeitet und mit einer stichwortartigen Problemnennung als Abschnitts-Überschrift aufgelistet. Diese im Inhaltsverzeichnis aufgelisteten Problemnennungen sollen damit die Kommunikation (Verweis und Zitat) über die erhofften Umsetzungen der Lösungen bei den Verursachern erleichtern
Operations Research and Management
No full textThis textbook introduces quantitative methods in operations management based on operational research. Written for undergraduate and graduate students as well as practitioners, this book serves as a valuable compendium of essential tools for project planning, control and strategic decision making
No evidence of reactivity in accelerometry‐based measurement of physical activity and sleep
No full textObjective: Accelerometry provides more objective estimates of physical activity and sleep parameters than self-report data. However, the use of accelerometry may suffer from reactivity to measurement, that is, changes in behaviour under study due to the awareness of being observed.
Design: In two field-experimental studies, we examined reactivity to measurement in physical activity and sleep parameters estimated with accelerometry. We used within-subjects designs and manipulated if participants were made aware of the measurement intention or if it was concealed.
Methods: During a 2-week study, participants received a red accelerometer for one of the weeks and were informed that their physical activity would be monitored in this week. In the other week, participants received a black accelerometer and were informed that it would monitor sleep. In fact, both the red and the black accelerometers monitored both physical activity and sleep.
Results: We consistently found no evidence for reactivity to measurement for any indicator of physical activity (moderate to vigorous physical activity, steps) or sleep (duration, efficiency).
Conclusion: Accelerometry can provide unbiased measures of indicators of physical activity and sleep and is therefore a valuable addition to the common use of self-report data