An Approach for the Transfer of Real Surfaces in Finite Element Simulations

Virtual simulations are a relevant element in product engineering processes and facilitate engineers to test different concepts during early phases of the development. However, in tribological product engineering, simulations are hardly used because input data such as material behavior are often missing. Besides the material behavior, the surface roughness of the contacting elements is relevant for tribological systems. To expand the capabilities of the virtual engineering of tribological components such as bearings or brakes, the hereby presented approach allows for the depiction of real rough surfaces in finite element simulations. Rough surfaces are scanned by a white-light interferometer (WLI) and further processed by removing the outliers and replacing non-measured samples. Next, a spline generation creates a solid body, which is imported to CAD software and afterwards meshed with triangle and quadrilateral elements in different sizes. The results comprise the evaluation of six differently manufactured (turned, coated, and pressed) real surfaces. The surfaces are compared by the deviations of the roughness values after measuring with the WLI and after meshing them. Furthermore, the elements’ aspect ratios and skewness describe the mesh quality. The results show that the transfer is dependent upon deep cliffs and large Sz values in comparison to the lateral expansion

Abrogation of Experimental Colitis Correlates with Increased Apoptosis in Mice Deficient for Cd44 Variant Exon 7 (Cd44v7)

Experimental colitis in mice is characterized by infiltration of activated T helper (Th) cells and macrophages into the lamina propria. Particularly, these cells expressed CD44 variant exon 7 (CD44v7)-containing isoforms. Upregulation of CD44v7 isoforms was induced by CD40 ligation, an inflammation-driving interaction between activated Th cells and macrophages. To define the role of CD44v7 in colitis, mice bearing a targeted deletion for exon v7 were generated. In trinitrobenzene sulfonic acid–induced colitis, wild-type mice developed severe signs of persistent inflammation. Mice lacking CD44v7 initially showed unspecific inflammation, then recovered completely. The pathogenic origin was shown to reside in bone marrow–derived CD44v7+ cells, because adoptive transfer experiments demonstrated an absolute requirement for CD44v7 on hematopoietic cells for maintenance of colitis. Interleukin (IL)-10–deficient mice, which develop a chronic Th1-driven enterocolitis, were crossbred with CD44v6/v7 null mice. In IL-10 × CD44v6/v7 double deficient mice, intestinal inflammation developed only weakly and at an older age. Analysis of cell death in the inflamed lesions revealed that mononuclear cells in the CD44v7 null infiltrates had higher rates of apoptosis than those from wild-type mice. Thus, the region encoded by CD44v7 appears to be essential for survival of effector lymphocytes, resulting in persistence of inflammation

Cystathionine γ Lyase Sulfhydrates the RNA Binding Protein Human Antigen R to Preserve Endothelial Cell Function and Delay Atherogenesis

Hydrogen sulfide (H2S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and proatherogenic conditions

Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE) vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS)-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC) on complete Freund's adjuvant-induced inflammatory pain in rats.</p> <p>Results</p> <p>POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin.</p> <p>Conclusion</p> <p>Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.</p

Chemical Entities of Biological Interest: an update

Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary of molecular entities focused on ‘small’ chemical compounds. The molecular entities in question are either natural products or synthetic products used to intervene in the processes of living organisms. Genome-encoded macromolecules (nucleic acids, proteins and peptides derived from proteins by cleavage) are not as a rule included in ChEBI. In addition to molecular entities, ChEBI contains groups (parts of molecular entities) and classes of entities. ChEBI includes an ontological classification, whereby the relationships between molecular entities or classes of entities and their parents and/or children are specified. ChEBI is available online at http://www.ebi.ac.uk/chebi/. This article reports on new features in ChEBI since the last NAR report in 2007, including substructure and similarity searching, a submission tool for authoring of ChEBI datasets by the community and a 30-fold increase in the number of chemical structures stored in ChEBI

Serological immune response to cancer testis antigens in patients with pancreatic cancer

Serological screening approaches have allowed for the identification of a large number of potentially relevant tumor antigens in cancer patients. Within this group, cancer testis antigens represent promising targets for cancer immunotherapy, since they are widely expressed in a variety of human cancer entities. In pancreatic cancer, however, there are only few data available about the expression pattern and serological response to cancer testis antigens and other serological-defined tumor antigens. Therefore, we investigated the IgG antibody response against 11 cancer testis antigens (SCP-1, GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5) recombinantly expressed on yeast surface (RAYS) in patients with pancreatic cancer (n = 96), chronic pancreatitis (n = 18) and healthy donors (n = 48). We found in 14% of all patients antibody responses to SCP-1, but not to other cancer testis antigens (GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5). Antibody response correlated with the expression of SCP-1 in the primary tumor of the respective patient as shown by RT-PCR, immunohistochemistry and Western blot. In contrast, no serological response to cancer testis antigens was observed in healthy donors. The humoral immune response against SCP-1 was associated with the size of tumor, but not with other clinico-pathological parameters such as histology, stage, presence of lymph node metastases, grading, age, gender or gemcitabine treatment. In conclusion, antibody response to cancer testis antigen SCP-1 is found in a proportion of pancreatic carcinoma patients. These results indicate that identification of additional tumor antigens by serological screening of tumor cDNA expression libraries by RAYS is a promising goal in pancreatic cancer

Stereotactic or conformal radiotherapy for adrenal metastases: patient characteristics and outcomes in a multicenter analysis

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (&gt; 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (&gt; 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 &lt; 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p&nbsp;=&nbsp;0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p &lt; 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p &lt; 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway

Mitochondrial DNA copy number and function decrease with age in the short-lived fish Nothobranchius furzeri. Aging Cell

Summary Among vertebrates that can be kept in captivity, the annual fish Nothobranchius furzeri possesses the shortest known lifespan. It also shows typical signs of aging and is therefore an ideal model to assess the role of different physiological and environmental parameters on aging and lifespan determination. Here, we used Nothobranchius furzeri to study whether aging is associated with mitochondrial DNA (mtDNA) alterations and changes in mitochondrial function. We sequenced the complete mitochondrial genome of N. furzeri and found an extended control region. Large-scale mtDNA deletions have been frequently described to accumulate in other organisms with age, but there was no evidence for the presence of detectable age-related mtDNA deletions in N. furzeri. However, mtDNA copy number significantly decreased with age in skeletal muscle, brain, liver, skin and dorsal fin. Consistent with this finding, expression of Pgc-1a that encodes a transcriptional coactivator of mitochondrial biogenesis and expression of Tfam and mtSsbp both encoding mtDNA binding factors was downregulated with age. The investigation of possible changes in mitochondrial function revealed that the content of respiratory chain complexes III and IV was reduced in skeletal muscle with age. In addition, ADP-stimulated and succinate-dependent respiration was decreased in mitochondria of old fish. These findings suggest that despite the short lifespan, aging in N. furzeri is associated with a decline in mtDNA copy number, the downregulation of mtDNA-associated genes and an impairment of mitochondrial function