Grain fracture in rapid particulate media deformation and a particulate media research roadmap from the PMEE workshops

It is well known that grain fracture plays an important role in quasi-static compaction of particulate media (e.g. civil engineering applications). Grain fracture is frequently the energy-minimizing path which enables particulate media to support large stresses. Less well known is the role that fracture plays in higher-rate particulate media systems. This paper discusses grain-scale & macro-scale evidence for the role of fracture in high-pressure/rate particulate media deformation events. It also presents (Appendix) a related particulate materials research roadmap developed by feedback from the Particulate Materials in Extreme Environments (PMEE) workshops. Experimental evidence is presented from recent sand fracture experiments performed by launching hemispherical-nose projectiles into specially-prepared beds of sand. Particle size analysis, SEM images of virgin & fractured media, and images from the bulk sand fracture & flow are used to illustrate the role of sand fracture. It is shown that as-poured sand exhibits a dilatational response and that mechanically compacted sand exhibits a compaction response when each is stimulated by a high-speed hemi-nose projectile. For compacted sand, particle size analysis suggests that particles near the rear of the target (lower projectile velocities and pressures) are reduced more in size. Fractured sand is shown to exhibit abrasion, attrition and fracture modes with visual self-similarity limited to specific particle size range roughly divided into classes larger or smaller than ~50 microns. Initial particulate media density affects the bulk response to high-pressure/rate events. Varying the density can transition the flow from dilation to compaction-dominated, likely as a function of inter-grain stresses from compaction. Substantial particle fracture is an artifact of both flow cases.     

Engaging High‐Sensation Seekers: The Dynamic Interplay of Sensation Seeking,Message Visual‐Auditory Complexity and Arousing Content

This study extends the research on message‐sensation value (MSV) by treating it as a dynamic stream of complex visual‐auditory information and arousing content (MSV‐d). Real‐time attentional and emotional responses to this dynamic stream during the PSA viewing process are indicated by psychophysiological measures. Dynamic models are used to systematically examine endogenous and exogenous influences on message processing to more accurately understand the effects of MSV‐d variables and individuals' sensation seeking tendencies during the processing of the PSAs. An important finding is that generally, increasing visual‐auditory complexity activates an approach tendency in those with high sensation‐seeking tendencies but activates an avoidance tendency in those with low sensation‐seeking tendencies, and this response pattern is moderated by arousing content.     

The Natural Course of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.     

Study of the Effects of LAS and Zein Concentrations on Protein Solubilization

The effects of both linear alkylbenzene sulfonate (LAS) and zein protein concentrations on protein solubilization were investigated to better understand the influence of increasing concentration of the surfactant on protein denaturation and skin irritation. Different methods have been used for the determination of the amount of protein dissolved. A wide range of LAS concentrations and zein amounts were used. The results confirm that protein solubilization increases with LAS concentration increase and demonstrate that a minimum LAS/Zein ratio exists for all the zein to be dissolved.     

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation.     

Modularisierung von Gaswäschern für die CO2‐Entfernung aus Biogas

Modularization has been identified as one of the research fields of the ?50 % idea”?. A development methodology for modules must consider both the economies of scale for investment costs and costs of operation and maintenance. In this paper, the impact of an absorber module, which is offered as discretized diameter scaling, on the total process is investigated at the example of the CO₂ separation from biogas. The simulation shows the effect of this approach to the stripper diameter and the energy demand of the process. The calculations form the basis for applying cost models.     

Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis

Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.     

Optical properties of γ-irradiated synthetic sapphire and yttria-stabilized zirconia spectroscopic windows

Synthetic sapphire and yttria-stabilized zirconia single-crystals were irradiated by increasing doses of γ-radiation to study the changes of their optical properties. The optical transparency of -Al₂O₃ was nearly constant up to the γ-radiation dose of 150 kGy for the spectral range of 400–1000 nm, while yellowish-brown coloration of (Zr_0.89Y_0.11)O_1.94 appeared for irradiation above 1 kGy. However, after a short-term heating in the temperature of 210^oC stable discoloration of zirconia can be achieved.     

Druggability Assessment for Selected Serine Proteases in a Pharmaceutical Industry Setting

Target druggability assessment is an integral part of the early target characterization and selection process in pharmaceutical industry. Here, we investigate a set of five different serine proteases from the blood coagulation cascade. The aim of this study is twofold. Firstly, leveraging the wealth of available in-house high-throughput screening (HTS) data, we analyze HTS hit rates and discuss their predictive value for the development of small molecule (SMOL) candidates. Purely structure-activity relationship (SAR) based druggability ratings are compared with computational protein-structure based druggability assessments. Secondly, we evaluate the impact of using conformational ensembles from molecular dynamics (MD) simulations instead of single static crystal structures as basis for computational druggability assessments. Based on this study, we recommend incorporating molecular dynamics routinely into the early target characterization process, especially if only a single X-ray structure is available.