This study presents investigations on the additive manufacturing of hot work steel with the energy-reduced gas metal arc welding (GMAW) process, which is a cold metal transfer (CMT) process. The ...paper analyses the influence of arc energy and the thermal field on the resulting mechanical properties and microstructure of the material. The investigations were carried out with hot work tool steel X37CrMoV 5-1, which is used for the manufacturing of plastic moulds, hot extrusion dies, and forging dies. The results show that this steel can be used to generate 3D metal components or structures with high reproducibility, near-net-shaped geometry, absence of cracks, and a deposition rate of up to 3.6 kg/h. The variation of the wire feed speed and the welding speed enables the production of weld beads of width up to 9.4 mm. The mechanical properties of the generated structures can be adapted by the dominant thermal field, which in turn is influenced by the bypass temperature and the electric arc energy. A determining factor to describe the main variables of the welding process is represented by energy per unit length EL. If the bypass temperature is above the martensite start temperature (Ms), there is a homogeneous hardness level along the height of the additively manufactured structure height as long as the energy produced by the welding arc is enough to keep the temperature of all layers above Ms.
Circulating NAMPT (PBEF/visfatin) has pleiotropic functions and is secreted from adipocytes. Since it is doubtful whether serum levels can be explained by secretion from adipocytes alone, we asked ...whether hepatocytes are also able to liberate NAMPT. Using HepG2 cells and primary rat and human hepatocytes, release of NAMPT into the cell culture supernatant was found to occur constitutively in a time-dependent manner. In primary human hepatocytes, secretion within 24h was far higher than the cellular content, but was neither influenced by inhibitors of secretion nor by glucose, insulin or TNFα. As determined by size exclusion chromatography, HepG2 lysates and supernatants primarily contained the dimeric form of NAMPT which exhibited similar in vitro specific enzymatic activity. In primary human hepatocytes, secreted NAMPT was less active. Our results demonstrate that human hepatocytes are a potential source of circulating NAMPT.
Since the beginning of the outbreak, the COVID-19 pandemic has caused an increased demand for psychosocial support for patients, their family members, and healthcare workers. Concurrently, ...possibilities to provide this support have been hindered. Quarantine, social isolation, and SARS-CoV‑2 infections represent new and severe stressors that have to be addressed with innovative psychosocial care.
This article describes the COVID-19 psychosocial first aid concept at the University Hospital Munich (LMU Klinikum) developed by an interdisciplinary team of psychiatric, psychological, spiritual care, psycho-oncological, and palliative care specialists.
A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements.
The concept integrates innovative and sustainable ideas, e.g. telemedicine-based approaches and highlights the importance of multidisciplinary collaboration to cope with challenges in the healthcare system.
The SH2/SH3 adapter proteins of the Crk family are potent signal transducers after receptor tyrosine kinase stimulation with insulin or IGF-1. We have employed a yeast two-hybrid approach and ...mutational analysis to dissect the capabilities of the insulin receptor and the IGF-I receptor to directly associate with Crk isoforms. Insulin receptor stably recruits full length Crk by association with its SH2 domain in an auto-phosphorylation dependent manner. In contrast, interaction of the IGF-I receptor with the Crk-IISH2 domain was only detectable when Crk-II was truncated in its C-terminal part, indicating the transient nature of this interaction. From these data it can be concluded that members of the insulin receptor family activate Crk proteins in a differential manner.
The insulin-like growth factor (IGF) receptor (IGF1R) is essential for normal development and growth. IGF1R mutations cause IGF-1 resistance resulting in intrauterine and postnatal growth failure. ...The phenotypic spectrum related to IGF1R mutations remains to be fully understood.
Auxological and endocrinological data of a patient identified previously were assessed. The patient's fibroblasts were studied to characterize the IGF1R deletion, mRNA fate, protein expression and signalling capabilities.
The boy, who carries a heterozygous IGF1R exon 6 deletion caused by Alu element-mediated recombination and a heterozygous SHOX variant (p.Met240Ile), was born appropriate for gestational age but developed proportionate short stature postnatally. IGF-1 levels were low-normal. None of the stigmata associated with SHOX deficiency or sporadically observed in IGF1R mutation carriers were present. Nonsense-mediated mRNA decay led to a substantial decline of IGF1R dosage and IGF-1-dependent receptor autophosphorylation but not impaired downstream signalling.
We present the first detailed report of an intragenic IGF1R deletion identified in a patient who, apart from short stature, deviates from all established markers that qualify a growth-retarded child for IGF1R analysis. Although such children will usually escape routine clinical mutation screenings, they can contribute to the understanding of factors and mechanisms that cooperate with the IGF1R.
Although insulin receptor (InsR) and type I insulin-like growth factor receptor (IGF-IR) elicit different physiological effects in their target tissues, their signaling capabilities are similar to a ...large extent. In the present work, we investigated the potential of the third member of the family, insulin receptor-related receptor (IRR), to associate with known interaction partners of the InsR and the IGF-I receptor in a yeast two-hybrid assay. Using the intracellular part of the IRR we found no association with any of the tested signaling molecules. Phosphotyrosine detection revealed a lack in the constitutive activation of the IRR described for analogous constructs of the two other members of the family. Replacement of the kinase domain of the IGF-IR or its C-terminal lobe alone into the IRR caused a complete restoration of the tyrosine phosphorylation of the IRR. The reestablishment of autophosphorylation was paralleled by restoration of interaction with a specific range of signaling molecules.
Context: The insulin receptor-related receptor (IRR) is an orphan receptor belonging to the insulin receptor (IR) family. Despite its unknown function, the specific tissue expression and the high ...sequence homology with the IR and the insulin-like growth factor 1 receptor (IGF1R) suggest a biological role in β-cells.
Objectives: In this study we investigated the influence of a stimulatable IRR-tyrosine kinase on major IR/IGF1R signaling pathways and on proliferation and apoptosis of INS-1E β-cells.
Methods: INS-1E cells were stably transfected with a colony stimulating factor 1 receptor (CSF1R)/IRR construct activated by a macrophage colony stimulating factor.
Results and conclusion: After stimulation the construct showed time and dose dependent autophosphorylation and transient extracellular signal regulated kinase 1/2 activation. Protein kinase b was not phosphorylated and also an effect on proliferation and apoptosis of INS-1E could not be demonstrated. Thus, no obvious biologic function of the IRR is present in INS-1E β-cells.
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