Driven by increasing costs for energy and raw material and especially by the European CO
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-emission laws, automotive industry faces the challenge to develop more lightweight and at the same time ...still rigid and crash-stable car bodies, that are affordable for large-scale production. The implementation of weight-reduced constructions depends not only on the availability of lightweight materials and related forming technologies, but also on cost-efficient and reliable joining technologies suitable for multi-material design. This article discusses the challenges and requirements for these technologies, based on the example of joining aluminium with press-hardened boron steels, what is considered as a very important material combination for affordable future lightweight mobility. Besides a presentation of recent developments for extending the process limits of conventional mechanical joining methods, new promising technologies such as resistance element welding are introduced. In addition, the performance, advantages, and disadvantages of the presented technologies are compared and discussed.
Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in ...the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients.
Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received.
The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time.
Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.
The affordable implementation of lightweight constructions in automotive engineering depends not only on the availability of suitable processing technologies for new lightweight materials but also on ...suitable, cost-efficient joining methods for multi-material combinations with high process reliability. Therefore, joining technology plays a key role in realizing energy-efficient vehicles. The systematic development of joining methods is necessary to overcome the metallurgical and thermal incompatibility of steel/aluminium or steel/fibre-reinforced plastic combinations. This paper presents two innovative and highly productive joining technologies and characterizes these processes based on their technological properties for one specific steel/aluminium material combination.
Summary
Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of ...lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti‐tumour response. In addition, lenalidomide‐treated patients showed higher abundance of CD14+ myeloid cells co‐expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid‐derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter‐regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.
Signaling by the stem cell factor receptor Kit in hematopoietic stem and progenitor cells is functionally associated with the regulation of cellular proliferation, differentiation and survival. ...Expression of the receptor is downregulated upon terminal differentiation in most lineages, including red blood cell terminal maturation, suggesting that omission of Kit transduced signals is a prerequisite for the differentiation process to occur. However, the molecular mechanisms by which Kit signaling preserves the undifferentiated state of progenitor cells are not yet characterized in detail. In this study, we generated a mouse model for inducible expression of a Kit receptor carrying an activating mutation and studied its effects on fetal liver hematopoiesis. We found that sustained Kit signaling leads to expansion of erythroid precursors and interferes with terminal maturation beyond the erythroblast stage. Primary KIT(D816V) erythroblasts stimulated to differentiate fail to exit cell cycle and show elevated rates of apoptosis because of insufficient induction of survival factors. They further retain expression of progenitor cell associated factors c-Myc, c-Myb and GATA-2 and inefficiently upregulate erythroid transcription factors GATA-1, Klf1 and Tal1. In KIT(D816V) erythroblasts we found constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, elevated expression of the src kinase family member Lyn and impaired Akt activation in response to erythropoietin. We demonstrate that the block in differentiation is partially rescued by MAPK inhibition, and completely rescued by the multikinase inhibitor Dasatinib. These results show that a crosstalk between Kit and erythropoietin receptor signaling cascades exists and that continuous Kit signaling, partly mediated by the MAPK pathway, interferes with this crosstalk.
Sphenopalatine blocks have been used to treat pain for more than 80 years. Anecdotal support for sphenopalatine ganglion blocks has been very strong in those who believe in the technique, but the ...research results have been inconclusive. Therefore, a double blind, placebo‐controlled study was performed on 61 patients, 42 with fibromyalgia and 19 with myofascial pain syndrome. Pain was measured using visual analogue scales prior to treatment, during treatment, and 28 days after the treatment. Headaches were evaluated in frequency and location prior to and after treatment. Sphenopalatine ganglion blocks were performed under direct vision using 4% lidocaine and sterile water as a placebo. Analysis of the results showed no statistical differences between the lidocaine and the placebo groups.
Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted ...real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.
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