Terminal Ligand and Packing Effects on Slow Relaxation in an Isostructural Set of [Dy(H2_{2}dapp)X2_{2}]+ Single Molecule Magnets**

Three new dysprosium complexes with a pentadentate ligand occupying five equatorial sites differ only in the nature of the axial ligands. These help tune the relaxation properties as judged by an analysis of the AC susceptibility data. More in depth analysis by using two recently suggested fitting equations lead to similar outcomes for all three systems. As a further contribution to the relaxation pathway involving the phonon bath it is concluded that a short nitrate-nitrate interaction between molecules helps dampen the spin phonon coupling. We report three structurally related single ion Dy compounds using the pentadentate ligand 2,6-bis((E)-1-(2-(pyridin-2-yl)-hydrazineylidene)ethyl)pyridine (H$_{2}$dapp) [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]NO$_{3}$ (1), [Dy(H$_{2}$dapp)(OAc)$_{2}$]Cl (2) and [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]Cl$_{0.92}$(NO$_{3}$)$_{0.08}$ (3). The (H$_{2}$dapp) occupies a helical twisted pentagonal equatorial arrangement with two anionic ligands in the axial positions. Further influence on the electronic and magnetic structure is provided by a closely associated counterion interacting with the central N−H group of the (H$_{2}$dapp). The slow relaxation of the magnetisation shows that the anionic acetates give the greatest slowing down of the magnetisation reversal. Further influence on the relaxation properties of compounds1 and 2 is the presence of short nitrate-nitrate intermolecular ligand contact opening further lattice relaxation pathways

GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

<p>Abstract</p> <p>Background</p> <p>Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH).</p> <p>Methods</p> <p>GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein.</p> <p>Results</p> <p>GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein.</p> <p>Conclusions</p> <p>GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients.</p

Regulation of GDF-15, a distant TGF-β superfamily member, in a mouse model of cerebral ischemia

GDF-15 is a novel distant member of the TGF-β superfamily and is widely distributed in the brain and peripheral nervous system. We have previously reported that GDF-15 is a potent neurotrophic factor for lesioned dopaminergic neurons in the substantia nigra, and that GDF-15-deficient mice show progressive postnatal losses of motor and sensory neurons. We have now investigated the regulation of GDF-15 mRNA and immunoreactivity in the murine hippocampal formation and selected cortical areas following an ischemic lesion by occlusion of the middle cerebral artery (MCAO). MCAO prominently upregulates GDF-15 mRNA in the hippocampus and parietal cortex at 3 h and 24 h after lesion. GDF-15 immunoreactivity, which is hardly detectable in the unlesioned brain, is drastically upregulated in neurons identified by double-staining with NeuN. NeuN staining reveals that most, if not all, neurons in the granular layer of the dentate gyrus and pyramidal layers of the cornu ammonis become GDF-15-immunoreactive. Moderate induction of GDF-15 immunoreactivity has been observed in a small number of microglial cells identified by labeling with tomato lectin, whereas astroglial cells remain GDF-15-negative after MCAO. Comparative analysis of the size of the infarcted area after MCAO in GDF-15 wild-type and knockout mice has failed to reveal significant differences. Together, our data substantiate the notion that GDF-15 is prominently upregulated in the lesioned brain and might be involved in orchestrating post-lesional responses other than the trophic support of neurons

1) Colour of Case2 Waters in Remote Sensing of Ocean Colour in Coastal and Other Optically-Complex Waters. 2) Case2 Ocean-Colour Applications.

Abstract not availableJRC.(SAI)-Space Application Institut

Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer

Purpose!#!Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis.!##!Methods!#!Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients.!##!Results!#!Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients.!##!Conclusion!#!FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability