Post mortemRelease of Fish White Muscle α-Actinin as a Marker of Disorganisation

α-Actinin release and its degradation from myofibrils Z-line were studied in post mortem white dorsal muscle from bass and sea trout stored at 4°C and 10°C. Using α-actinin specific antibodies, we show that this protein is rapidly released within the first 24 h for the two species, and reaches a plateau within 4 days. Proteolysis take place very rapidly in bass muscle yielding 80 and 40 kDa fragments from α-actinin as major bands of proteolysis. Sea trout muscle is more resistant, and muscle stored at 4°C is not significantly α-actinin degraded even 10 days after death. In the case of sea trout muscle stored at 10°C, an increasing quantity of 80 and 40 kDa fragment can be observed after the third day. These results show that release and proteolysis of α-actinin are time- and temperature-dependent processes that take place at the early stages of fish storage. Furthermore, we observed that proteolysis of α-actinin seems to be dependent on fish species. In both species studied, the early release of α-actinin comes before the degradation of released molecules, and appears as a biphasic process throughout the disorganisation of post mortem muscle in fish cold-stored above 0°C.     

Quantification of the Immune Content in Neuroblastoma: Deep Learning and Topological Data Analysis in Digital Pathology

We introduce here a novel machine learning (ML) framework to address the issue of the quantitative assessment of the immune content in neuroblastoma (NB) specimens. First, the EUNet, a U-Net with an EfficientNet encoder, is trained to detect lymphocytes on tissue digital slides stained with the CD3 T-cell marker. The training set consists of 3782 images extracted from an original collection of 54 whole slide images (WSIs), manually annotated for a total of 73,751 lymphocytes. Resampling strategies, data augmentation, and transfer learning approaches are adopted to warrant reproducibility and to reduce the risk of overfitting and selection bias. Topological data analysis (TDA) is then used to define activation maps from different layers of the neural network at different stages of the training process, described by persistence diagrams (PD) and Betti curves. TDA is further integrated with the uniform manifold approximation and projection (UMAP) dimensionality reduction and the hierarchical density-based spatial clustering of applications with noise (HDBSCAN) algorithm for clustering, by the deep features, the relevant subgroups and structures, across different levels of the neural network. Finally, the recent TwoNN approach is leveraged to study the variation of the intrinsic dimensionality of the U-Net model. As the main task, the proposed pipeline is employed to evaluate the density of lymphocytes over the whole tissue area of the WSIs. The model achieves good results with mean absolute error 3.1 on test set, showing significant agreement between densities estimated by our EUNet model and by trained pathologists, thus indicating the potentialities of a promising new strategy in the quantification of the immune content in NB specimens. Moreover, the UMAP algorithm unveiled interesting patterns compatible with pathological characteristics, also highlighting novel insights into the dynamics of the intrinsic dataset dimensionality at different stages of the training process. All the experiments were run on the Microsoft Azure cloud platform.     

Higher Tool Productivity due to New Generation of PVD Coatings

PVD coating technology has seen many new developments in the past few years. HIPIMS⁺ is an example of these developments with excellent results on tool productivity and lifespan. The technology combines the advantages of arc evaporation with those of magnetron sputtering and results in a dense and defect‐free coating with tuneable residual stress. The coatings have been tested successfully by international tool manufacturers. Additional developments can be seen in DLC coatings and the hydrogen‐free variety ta‐C. These coatings are suitable for low temperature deposition and machining of special materials.     

The effect of lignin on the structure and characteristics of composite coatings electrodeposited on titanium

Composite coatings based on lignin, obtained by electrophoretic deposition (EPD) on titanium, were investigated. The aim of this work was to produce hydroxyapatite/lignin (HAP/Lig) coatings on titanium and to investigate the effect of the lignin concentration on microstructure, morphology, phase composition, thermal behavior and cytotoxicity of the HAP/Lig coatings. An organosolv lignin was used for the production of the composite coatings studied in this research. The properties of HAP/Lig coatings were characterized using X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FT-IR) and X-ray photoelectron spectroscopy (XPS), as well as the MTT test of cytotoxicity. The results showed that higher lignin concentrations protected the HAP lattice during sintering, thereby improving the stability of the HAP/Lig coatings. The cell survival of peripheral blood mononuclear cells (PBMC) after proliferation indicates that the HAP/Lig coating with 1 wt% Lig electrodeposited on titanium was non-toxic with significant promise as a potential bone-repair material.     

Sensory and physicochemical evolution of tropical cooked peeled shrimp inoculated by Brochothrix thermosphacta and Lactococcus piscium CNCM I-4031 during storage at 8°C

This study investigated the sensory quality and physicochemical evolution (pH, glucose, l-lactic acid, biogenic amine, free amino-acids and volatile compounds) during storage at 8 °C of cooked peeled shrimp inoculated with the specific spoilage bacteria Brochothrix thermosphacta alone or mixed with the protective strain Lactococcus piscium CNCM I-4031. Growth of both bacteria was monitored at regular intervals during storage by microbial counts and the thermal temperature gradient gel electrophoresis (TTGE) technique. Bacterial counts showed that L. piscium and B. thermosphacta inoculated at 7 log CFU/g and 3 log CFU/g were well adapted to shrimp, reaching a maximum level of 9 log CFU/g after 4 days and 10 days respectively. In mixed culture, the growth of B. thermosphacta was reduced by 3.2 ± 0.1 log CFU/g. The TTGE technique allowed monitoring the colonisation of the strains on the shrimp matrix and confirming the dominance of L. piscium in mixed culture throughout the experiment. Sensory analysis confirmed that B. thermosphacta spoiled the product after 11 days, when its cell number attained 8 log CFU/g with the emission of strong butter/caramel off-odours. This sensory profile could be linked to the production of 2,3 butanedione, cyclopentanol, 3-methylbutanol, 3-methylbutanal, 2-methylbutanal, 4-methyl-3-chloro-3-pentanol and ethanol, which were produced in more significant quantities in the B. thermosphacta batch than in the batches in which the protective strain was present. On the contrary, TVBN and TMA were not suitable as quality indicators for B. thermosphacta spoilage activity. In the products where the protective L. piscium strain was present, no adverse effect on sensory quality was noted by the sensory panels. Moreover, biogenic amine assessment did not show any histamine or tyramine production by this strain, underlining its safety profile. Both strains produced lactic acid (1850 mg/kg in L. piscium and B. thermosphacta batch on days 3 and 10 respectively; 3830 mg/kg on day 7 in mixed culture) and the pH decrease from 6.6 ± 0.0 to 5.9 ± 0.1 was similar in all batches. Lactic acid production or competition for free amino-acid was not involved in the inhibition mechanism; however rapid glucose consumption by L. piscium could partially explain the growth limitation of the spoilage micro-organism. This study demonstrated the spoilage characteristic of B. thermosphacta and the usefulness of L. piscium as a bioprotective culture for tropical cooked peeled shrimp without any adverse effect on the sensory quality of the product.     

Development of ultra-fine grained dual phase microalloyed steels through severe cold rolling and intercritical annealing

A Nb-microalloyed structural steel with ferrite-pearlite microstructure was subjected to cold rolling and intercritical annealing to produce ultra-fine grained dual phase microstructure. Optical and transmission electron microscopy techniques were employed to characterise the microstructure. Initial results showed that the intercritical annealing (at 790°C for 90s) of samples rolled to a true strain of 2.4 resulted in a significant grain refinement from the average initial grain size of 20 μm to 1–2 microns. The microstructure primarily consisted of UFG ferrite matrix with homogeneously distributed islands of plate martensite with volume fraction of 27%.     

NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.     

汽液两相流自调节液位控制装置在电厂的应用

介绍了汽液两相流自调节液位控制装置的工作原理和应用 ,并列举大量事实说明火电厂高压加热器使用汽液两相流自调节液位控制装置的优越性 ,以及该装置在火电厂的节能和安全生产方面取得的显著效果