Eignung von Fernerkundungsdaten zur Ableitung des flächendeckenden Wärmebedarfs von Wohngebäuden in Baden - Württemberg

Die vorliegende Arbeit befasst sich mit der Einbettung von Datenprodukten, sowie Methoden der Fernerkundung in den Kontext kommunaler Wärmeplanung. Um die Zielsetzung der Arbeit ableiten zu können, sollen in diesem Kapitel zunächst die Möglichkeiten beschrieben werden, die der Fernerkundung als wissenschaftliche Disziplin im Bereich des Wärmesektors zugesprochen werden. Im Folgenden werden die Grundlagen der kommunalen Wärmeplanung erläutert. Anschließend erfolgt eine Gegen- überstellung zwischen den Anforderungen der Planung einerseits und den Möglichkeiten, bzw. dem Potenzial von Fernerkundung als unterstützende Komponente andererseits

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 Å crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix α10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site, thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation

Theorie und Praxis wissenschaftlich-technischer Neuerungsprozesse Beitraege der Konferenz des Instituts fuer Theorie, Geschichte und Organisation der Wissenschaft der AdW der DDR und des Internationalen Instituts fuer Probleme der Leitung (Moskau) in Berlin vom 16.-17. April 1984

UuStB Koeln=38*-910106090 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Theorie und Praxis wissenschaftlich-technischer Neuerungsprozesse Beitraege der Konferenz des Instituts fuer Theorie, Geschichte und Organisation der Wissenschaft der AdW der DDR und des Internationalen Instituts fuer Probleme der Leitung (Moskau) in Berlin vom 16.-17. April 1984

UuStB Koeln=38*-910106090 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Method for creating nuclear receptor activity modulating pharmaceuticals

Methods for screening, identifying and/or designing agents that modulate nuclear receptors are provided. These agents contact a site on a nuclear receptor involved in dimer/heterodimer formation, cofactor molecule interactions, and/or folding, which is termed the nuclear receptor dimer/heterodimer regulatory site (DHRS). Methods employing the DHRS are included, along with nuclear receptor:agent complexes and libraries of agents

Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor

Selective therapeutics for nuclear receptors would revolutionize treatment for endocrine disease. Specific control of nuclear receptor activity is challenging because the internal cavities that bind hormones can be virtually identical. Only one highly selective hormone analog is known for the thyroid receptor, GC-24, an agonist for human thyroid hormone receptor beta. The compound differs from natural hormone in benzyl, substituting for an iodine atom in the 3' position. The benzyl is too large to fit into the enclosed pocket of the receptor. The crystal structure of human thyroid hormone receptor beta at 2.8-A resolution with GC-24 bound explains its agonist activity and unique isoform specificity. The benzyl of GC-24 is accommodated through shifts of 3-4 A in two helices. These helices are required for binding hormone and positioning the critical helix 12 at the C terminus. Despite these changes, the complex associates with coactivator as tightly as human thyroid hormone receptor bound to thyroid hormone and is fully active. Our data suggest that increased specificity of ligand recognition derives from creating a new hydrophobic cluster with ligand and protein components