Analysis of grain boundary movement analogous to dislocation movement – both with a matrix having precipitates

In the present investigation it has been shown exemplarily for an austenite microstructure containing carbonitrides that the specific restraining force of a grain boundary due to the distribution of precipitates can be described by a modified Orowan's law, so that the grain boundary movement is considered to be analogous to the dislocation movement. This is achieved by using a modified restraining force F_r (corresponding to the cubic geometry of the particles), a detailed thermodynamic analysis of the precipitates (in this case, carbonitrides) and selected relation for the interparticle spacing L_a. The specific restraining force and the interparticle spacing depend on temperature within the austenite range. Each temperature is attached to a couple (F_r/L_a). The plot F_r against shows straight lines for each steel and from their average slope, a shear module G' of grain boundaries, which is about 64300 N·cm^?2, is obtained. Hence, it is possible to describe the specific restraining force of a grain boundary with the help of Orowan's law or as it is conventionally done by using Zener's modell. At a critical temperature T*, which is different for each steel, the specific restraining force is equal to the driving force of the grain boundary. The corresponding values of L_a are also different for each steel and the steel which is the most resistant to grain coarsening is allowed to have the greatest value of L_a which still retains the capacity of impeding grain coarsening.     

Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors

The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature.     

Structural Basis for The Recognition of Deaminated Nucleobases by An Archaeal DNA Polymerase

With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B-family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B-family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’-overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B-family DNA polymerases.     

Processing of High-Density Submicrometer Al2O3 for New Applications

Sintered corundum components with submicrometer grain sizes exhibit properties which enable numerous new applications. Wet powder processing is developed to associate minimum grain sizes at highest densities with the lowest population of macrodefects. A closest ratio of powder particle size and sintered grain size is important for obtaining most fine-grained microstructures. This target was approached best by using powders with particle sizes in the range of 100–200 nm rather than with smaller nanoparticles.     

High Throughput Screening of Low Temperature SCR and SCD De-NOx Catalysts in Scanning Mass Spectrometer

High-throughput synthesis and screening methods have been developed for the discovery of highly active lead compounds for the selective catalytic reduction as well as direct decomposition of NO in the temperature range 200–300 °C. The discovery libraries for primary screening consisted of 16 × 16 catalyst arrays on 4in. square quartz wafers. Catalysts were prepared by robotic liquid dispensing techniques and screened for catalytic activity in Symyx' scanning mass spectrometer. The scanning mass spectrometer is a fast serial screening tool that uses flat wafer catalyst surfaces, local laser heating, a scanning/sniffing nozzle and a quadrupolar mass spectrometer to compare relative catalytic activities. The feed consisted of NO/NH₃ mixtures with optional O₂ cofeed and Kr as the internal standard in Ar carrier gas. QMS detection allowed for tracking of H₂O, N₂, NO, O₂, N₂O and Kr. Screening protocols for catalytic materials encompassed metal precursors and carriers for supported vanadia systems, extensive doping of V₂O₅/TiO₂, and broad screening of mixed redox metal oxides and supported base and noble metal systems. More than 500 samples could be screened in a single day. Active hits (high NO consumption accompanied by corresponding N₂ production) identified in discovery libraries were re-synthesized as focus libraries for lead confirmation and further optimization. These libraries used shallower compositional gradients, for example 56 points (compositions) per ternary, with four 56-point ternaries per 4in. wafer. Broad screening ternaries were generally 8 or 15 points. The focus libraries more clearly reveal the trends and provide guidelines for secondary screening and scale-up. High conversions were achieved in scanning mass spectrometer so the scalability risk is small for the short contact time reactions.     

阳极氧化铝的表面参数对硅酮结构的装锒密封胶长期黏结性的影响(连载一)

硅酮密封胶对阳极氧化铝的黏结质量千差万别.影响黏结性的关键因素是铝材表面的封孔程度、氧化层的着色情况、清洁剂的特性以及基材表面清洁与打胶之间允许的时间间隔.由于清洁剂将有机污染物从阳极氧化铝表面去除的效果不同,所以此效果并不和黏结质量有必然联系.据猜测,吸附在阳极氧化铝表面的清洁溶剂会改善基材表面从而提高硅酮胶的黏结性,但这种改善效果会随着清洁溶剂随时间的的挥发而降低.对于给定的溶剂,最佳的黏结效果取决于材料表面的封孔程度.依照ISO 2143酸刻蚀方法测量材料表面的封孔程度,可以预测未着色的阳极氧化铝基材的黏结性.对于着色的阳极氧化铝表面,依照ISO 2931的测试标准,用电相位漂移方法可以用来预测黏结质量.一种控制阳极氧化铝表面的方法被提了出来,此方法是测量不同频率下基材的电阻抗并将它成功地和硅酮密封胶与该材料表面的长期黏接性联系起来.