Lipid membrane coated nanoparticles as model system to investigate glycoprotein-independent targeting of human immune cells and mimic viral uptake and trafficking

Nanoparticles (NPs) are becoming increasingly popular as a new tool for the investigation of virus trafficking pathways and the delivery of therapeutic agents into targeted recipient cells. However, one general challenge for applications of NPs in the biological context is that a broad variety of different proteins can adsorb to the NP surface. The resulting formation of a so-called “corona” around NPs impacts the fate and distribution of NPs both in vitro and in vivo due to nonspecific opsonization and scavenging. Inspired by the surface compositions of living cells and enveloped viruses, here in this dissertation, a NP passivation strategy based on a self-assembled lipid membrane containing phospholipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) is developed and evaluated. The effect of the DPPC / DOPS ratio on corona formation is systematically analyzed. After inclusion of monosialoldihexosyl-ganglioside GM3, which binds selectively to CD169 (Siglec-1) expressed by myeloid cells such as macrophages and dendritic cells, into the membrane coating, NPs are found to target CD169 expressing macrophages in mouse lymph nodes in vivo. Combined in vitro and in vivo studies show that lipid-wrapped NPs represent a versatile platform for utilizing specific lipid–receptor interactions for targeting purposes. Presentation of GM3 on NPs achieves a recapitulation of the intracellular distribution observed for human immunodeficiency virus type 1 (HIV-1) in CD169 expressing macrophages and dendritic cells. Therefore, membrane-wrapped NPs are referred to as artificial virus nanoparticles (AVN). We demonstrate that AVN can accumulate in virus containing compartments (VCC), which are deep plasma membrane invaginations in macrophages that provide evasion for HIV-1 from the immune system and anti-viral therapeutics. Intriguingly, the ability to target VCC depended exquisitely on the GM3/DOPS ratio in the AVN membrane. Exchange of gold NPs with mesoporous silica NPs provides a new class of AVN whose core can serve as matrix and also carry therapeutic agents. We show using rilpivirine (RPV), a FDA approved second-generation non-nucleoside reverse transcriptase inhibitor of HIV-1 infection, that AVN with mesoporous NP core achieve significantly enhanced HIV-inhibition effects compared with soluble RPV or long-acting nanocrystalline formulation of RPV.2019-11-27T00:00:00

Behavior of wire arc additively manufactured 316L austenitic stainless steel single shear bolted connections

This paper aims to investigate the behavior of single shear bolted connections made of wire arc additively manufactured 316L austenitic stainless steel. A set of 44 wire arc additive manufacturing (WAAM) 316L austenitic stainless steel single shear bolted connections were included with consideration of various bolt positions, surface conditions and loading orientations respective to the printing layer direction. The geometric dimensions of the WAAM austenitic stainless steel plates were measured with the assistance of non-contact 3D laser scanning prior to tensile testing. Monotonic tensile tests were carried out to investigate the load-deformation responses, failure patterns and resistances determined by both the deformation and strength criteria of the single shear bolted connections. The effects of geometric and printing parameters on the single shear bolted connections were analyzed. Due to the absence of codified design provisions for WAAM austenitic stainless steel bolted connections, the suitability of the existing design rules originally developed for traditionally manufactured carbon steel and stainless steel bolted connections was examined. Design resistances calculated by the Eurocode 3 (prEN 1993-1-8 and prEN 1993-1-4), the American Specification (ANSI/AISC 370-21) as well as the prevalent design recommendations proposed in existing literature were compared with the obtained experimental results. It is shown that the abovementioned design methods offer conservative predictions for the resistances of WAAM 316L austenitic stainless steel single shear bolted connections. Further study is needed to improve the accuracy of design resistance predictions

Power dissipation of an inductively coupled plasma torch under E mode dominated regime

This paper focuses on the power dissipation of a plasma torch used for an optical surface fabrication process. The process utilizes an inductively coupled plasma (ICP) torch that is equipped with a De-Laval nozzle for the delivery of a highly collimated plasma jet. The plasma torch makes use of a self-igniting coil and an intermediate co-axial tube made of alumina. The torch has a distinctive thermal and electrical response compared to regular ICP torches. In this study, the results of the power dissipation investigation reveal the true efficiency of the torch and discern its electrical response. By systematically measuring the coolant parameters (temperature change and flow rate), the power dissipation is extrapolated. The radio frequency power supply is set to 800 W, E mode, throughout the research presented in this study. The analytical results of power dissipation, derived from the experiments, show that 15.4% and 33.3% are dissipated by the nozzle and coil coolant channels, respectively. The experiments also enable the determination of the thermal time constant of the plasma torch for the entire range of RF power

Realisation of a multi-sensor framework for process monitoring of the wire arc additive manufacturing in producing Ti-6Al-4V parts

Wire arc additive manufacturing (WAAM) is arc welding-based additive manufacture which is providing a major opportunity for the aerospace industry to reduce buy-to-fly ratios from 20:1 with forging and machining to 5:1 with WAAM. The WAAM method can build a wide range of near net shapes from a variety of high-grade (metallic) materials at high deposition speeds without the need for costly moulds. However, current WAAM methods and technologies are unable to produce parts reliably and with consistent structural material properties and required dimensional accuracy. This is due to the complexity of the process and the lack of process control strategies. This article makes a brief review on monitoring methods that have been used in WAAM or similar processes. The authors then identify the requirements for a WAAM monitoring system based on the common attributes of the process. Finally, a novel multi-sensor framework is realised which monitors the system voltage/current, part profile and environmental oxygen level. The authors provide a new signal process technique to acquire accurate voltage and current signal without random noises thereby significantly improving the quality of WAAM manufacturing

Breast Cancer Immunohistochemical Image Generation: a Benchmark Dataset and Challenge Review

For invasive breast cancer, immunohistochemical (IHC) techniques are often used to detect the expression level of human epidermal growth factor receptor-2 (HER2) in breast tissue to formulate a precise treatment plan. From the perspective of saving manpower, material and time costs, directly generating IHC-stained images from hematoxylin and eosin (H&E) stained images is a valuable research direction. Therefore, we held the breast cancer immunohistochemical image generation challenge, aiming to explore novel ideas of deep learning technology in pathological image generation and promote research in this field. The challenge provided registered H&E and IHC-stained image pairs, and participants were required to use these images to train a model that can directly generate IHC-stained images from corresponding H&E-stained images. We selected and reviewed the five highest-ranking methods based on their PSNR and SSIM metrics, while also providing overviews of the corresponding pipelines and implementations. In this paper, we further analyze the current limitations in the field of breast cancer immunohistochemical image generation and forecast the future development of this field. We hope that the released dataset and the challenge will inspire more scholars to jointly study higher-quality IHC-stained image generation.Comment: 13 pages, 11 figures, 2table

Effects of Modified Atmosphere Packaging with Various CO2 Concentrations on the Bacterial Community and Shelf-Life of Smoked Chicken Legs

The effects of modified atmosphere packaging (MAP) with various CO2 concentrations on the bacterial community and shelf-life of smoked chicken legs during 25 d of storage at 4 °C were evaluated herein. Four treatments were stored in pallets (PAL) and MAP under 20% (M20), 60% (M60), and 100% (M100) CO2, respectively. The results indicated that the MAP treatments provided the legs with higher redness and hardness and lower yellowness, luminance, and lipid oxidation, compared with the PAL treatment. In addition, the MAP treatments effectively inhibited the growth of viable bacteria, delayed bacterial spoilage, and extended the shelf-life of the samples. The M60 and M100 treatments had a better inhibition effect on bacteria. In terms of bacterial community, Carnobacterium, Pseudomonas, Brochothrix, and Lactococcus were the most predominant genera in the 25 d-stored MAP samples, with Carnobacterium maltaromaticum, Pseudomonas fragi, Shewanella baltica, and Lactococcus piscium being the dominant species. However, while the inhibition effects of the M60 and M100 treatments on the bacterial community at Day 25 were similar, the outer package of the M100 treatment collapsed. Overall, the M60 treatment may be a promising approach to improving the quality and extending the shelf-life of smoked chicken legs

Purification and Characterization of the Protease from <i>Staphylococcus xylosus</i> A2 Isolated from Harbin Dry Sausages

The protease generated from Staphylococcus (S.) xylosus A2, which was isolated from Harbin dry sausages, was purified and characterized. The molecular weight of the purified protease was approximately 21.5 kDa, and its relative activity reached the highest at pH 6.0 and 50 °C. At pH 4.0–8.0 and temperatures of 20–50 °C, the protease was stable. Its activity was significantly improved by Ca2+ and Zn2+ ions (p S. xylosus A2 protease and its future application in fermented meat products