A novel approach for simulating a sawing process with reduced simulation time

The numerical simulation of machining processes enables the analysis of thermo-mechanical effects and can be used to predict process-specific quantities such as cutting force and chip shape. This involves, however, a great amount of computational effort and time depending on the model design. Basically, a simulation can be carried out two- or three-dimensionally. Due to the lower computational effort, 2D simulations were often used in the past to analyse the machining properties. In orthogonal cutting, this leads to a good approximation to the real processes if a suitable ratio between cutting width and depth of cut is applied. Nevertheless, most industrially relevant machining processes cannot be completely simulated with a 2D simulation. For these purposes, 3D simulations must be created. This requires a much greater computational effort, which increases the simulation time. This paper shows an approach to determine the cutting force and the information about the chip shape during sawing (bound orthogonal cutting) with a shortened calculation time. This was achieved by dividing the entire cut into 2D and 3D areas. The ratio between the cutting width and the depth of cut defines the criterion for the division. When it was greater than 10, the cutting process between the corner radii was assumed to be a plane two-dimensional strain state. The results showed a good agreement of the cutting force calculated from the 2D–3D simulation approach with experimental investigations and a 3D simulation. The computing time could be reduced by more than 50%

Potential Neutrino Signals from Galactic Gamma-Ray Sources

The recent progress made in Galactic gamma-ray astronomy using the High Energy Stereoskopic System (H.E.S.S.) instrument provides for the first time a population of Galactic TeV gamma-rays, and hence potential neutrino sources, for which the neutrino flux can be estimated. Using the energy spectra and source morphologies measured by H.E.S.S., together with new parameterisations of pion production and decay in hadronic interactions, we estimate the signal and background rates expected for these sources in a first-generation water Cherenkov detector (ANTARES) and a next-generation neutrino telescope in the Mediterranean Sea, KM3NeT, with an instrumented volume of 1 km^3. We find that the brightest gamma-ray sources produce neutrino rates above 1 TeV, comparable to the background from atmospheric neutrinos. The expected event rates of the brightest sources in the ANTARES detector make a detection unlikely. However, for a 1 km^3 KM3NeT detector, event rates of a few neutrinos per year from these sources are expected, and the detection of individual sources seems possible. Although generally these estimates should be taken as flux upper limits, we discuss the conditions and type of gamma-ray sources for which the neutrino flux predictions can be considered robust.Comment: 20 pages, 4 figures; v2: ERROR in energy scale of KM3NeT effective neutrino area corrected which resulted in event rates being about a factor 3 too low; v3: grammatical changes and update of references after receiving proof

Simulation-based evaluation of the 3D fluid dynamics of a coolant lubricant in the narrow-closed cutting gap during circular sawing

A method for simulation-based analysis of the 3D fluid dynamics of a coolant lubricant in the saw tooth space is presented. The examination serves on the one hand to characterize the flow around the bounding surfaces of the narrow-closed cutting gap regarding the local flow conditions. On the other hand, the outflow behaviour of the coolant lubricant out of the narrow-closed cutting gap is analysed to get a deeper understanding of the cooling mechanism. Therefore, the model design is described considering the computational domain and the boundary conditions. Finally, an evaluation method for the local flow behaviour at different surfaces and the coolant lubricant outflow of the tooth space in the narrow-closed cutting gap is illustrated

The contribution of pUL74 to growth of human cytomegalovirus is masked in the presence of RL13 and UL128 expression

The glycoproteins gH and gL of human cytomegalovirus (HCMV) form a complex either with pUL74 (trimeric complex) or with proteins of the UL128 locus (pentameric complex). While the pentameric complex is dispensable for viral growth in fibroblasts, deletion of pUL74 causes a small plaque phenotype in HCMV lab strains, accompanied by greatly reduced cell-free infectivity. As HCMV isolates shortly after cultivation from clinical specimens do not release cell-free infectious virus, we wondered whether deletion of pUL74 would also affect virus growth in this background. To address this question, we took advantage of the BAC-cloned virus Merlin-RL13tetO that resembles such clinical isolates by growing cell-associated due to inducible expression of the viral RL13 gene. Stop codons were introduced by seamless mutagenesis into UL74 and/or the UL128 locus to abolish expression of the trimeric or pentameric complex, respectively. Virus mutants were reconstituted by transfection of the respective genomes into cultured cells and analyzed regarding focal growth. When the UL128 locus was intact, deletion of pUL74 did not notably affect focal growth of Merlin, irrespective of RL13 expression. In the absence of UL128 expression, foci were increased compared to wild type, and infectious cell-free virus was produced. Under these conditions, disruption of UL74 completely prevented virus spread from initially transfected cells to surrounding cells. In conclusion the contribution of pUL74 is masked when the UL128 locus is expressed at high levels, and its role in cell-free virus spread is only revealed when expression of the pentameric complex is inhibited

Diversity patterns and community structure of the ground-associated macrofauna along the beach-inland transition zone of small tropical islands

Biodiversity follows distinct and observable patterns. Where two systems meet, biodiversity is often increased, due to overlapping occurrence ranges and the presence of specialized species that can tolerate the dynamic conditions of the transition zone. One of the most pronounced transition zones occurs at shores, where oceans and terrestrial habitat collide, forming the shore–inland transition zone. The relevance of this transition zone in shaping a system’s community structure is particularly pronounced on small islands due to their high shore-to-inland-area ratio. However, the community structure of insular faunas along this transition zone is unknown. Here, we investigated the diversity patterns along the beach–inland transition zone of small islands and tested the hypothesis that species diversity increases toward the transition zone where beach and interior habitat meet. By measuring environmental parameters, resource availability, and ground-associated macrofauna diversity along transects running across the beach–inland transition zone, we show that a gradual change in species composition from beach to the inland exists, but neither taxa richness, diversity, nor overall abundance changed significantly. These findings offer important insights into insular community structure at the transition zone from sea to land that are relevant to better understand the dynamic and unique characteristics of insular ecosystems

The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Transcriptional and Cellular Diversity of the Human Heart

Background: The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low-input RNA sequencing have allowed definitions of cellular transcriptomes at single-cell resolution at scale, we have applied these approaches to assess the cellular and transcriptional diversity of the nonfailing human heart. Methods: Microfluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from 7 human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based on transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic data. Results: We sequenced the transcriptomes of 287 269 single cardiac nuclei, revealing 9 major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses include 2 distinct groups of resident macrophages, 4 endothelial subtypes, and 2 fibroblast subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs but also in subtypes involved in extracellular matrix remodeling and vascularization. Using genetic association data, we identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Intersection of our data set with genes on cardiac clinical testing panels and the druggable genome reveals striking patterns of cellular specificity. Conclusions: Using large-scale single nuclei RNA sequencing, we defined the transcriptional and cellular diversity in the normal human heart. Our identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases