Thermally sprayed hardmetal coatings have a typical thickness within the range 100–500μm. Thus, thermal spray enables the functionality of hardmetals to be realized on the surface of large parts, ...which cannot be produced by powder metallurgy for technical and economical reasons. This article reviews the different types of thermal spray processes, with particular focus on the high velocity HVOF and HVAF deposition techniques which are of most relevance to the application of hardmetal coatings. Feedstock powder preparation technologies are presented. The majority of hardmetal thermal spray coatings are based either on WC or Cr3C2 or hard phases appearing as a result of their interaction. As an alternative, TiC-based compositions are most intensively studied. Thermal spraying generates significant changes in the hardmetal chemical and phase compositions between the feedstock powder to the sprayed coating. Coating formation and microstructures as well as selected properties, such as hardness, the effect of heat treatments and the oxidation in service, as well as corrosion resistance are discussed. As an example for wear protection applications, abrasion wear resistance is shortly discussed.
This paper is a partly updated and condensed version of the chapter: “Coatings by thermal spray” in the book “Comprehensive Hard Materials”, V.K. Sarin (Editor-in-Chief) & D. Mari & L. Llanes (Vol. Ed.), Vol. 1 (pp. 471–506), Elsevier, 2014.
•Thermal spray as a technology for hardmetal coating preparation is reviewed.•Hardmetal compositions for thermal spray coating preparation are analyzed.•Spray processes and hardmetal feedstock powders are reviewed.•Metallurgical processes during spraying and coating formation are discussed.•Coating microstructures and selected properties are presented.
Alzheimer's disease (AD) involves brain neuropathologies such as amyloid plaque and hyperphosphorylated tau tangles and is accompanied by cognitive decline. Identifying the biological mechanisms ...underlying disease onset and progression based on quantifiable phenotypes will help understand disease etiology and devise therapies.
Our objective was to identify molecular pathways associated with hallmark AD biomarkers and cognitive status, accounting for variables such as age, sex, education, and APOE genotype.
We introduce a pathway-based statistical approach, extending the gene set likelihood ratio test to continuous phenotypes. We first analyzed independently each of the three phenotypes (amyloid-β, tau, cognition) using continuous gene set likelihood ratio tests to account for covariates, including age, sex, education, and APOE genotype. The analysis involved 634 subjects with data available for all three phenotypes, allowing for the identification of common pathways.
We identified 14 pathways significantly associated with amyloid-β; 5 associated with tau; and 174 associated with cognition, which showed a larger number of pathways compared to biomarkers. A single pathway, vascular endothelial growth factor receptor binding (VEGF-RB), exhibited associations with all three phenotypes. Mediation analysis showed that among the VEGF-RB family genes, ITGA5 mediates the relationship between cognitive scores and pathological biomarkers.
We presented a new statistical approach linking continuous phenotypes, gene expression across pathways, and covariates like sex, age, and education. Our results reinforced VEGF RB2's role in AD cognition and demonstrated ITGA5's significant role in mediating the AD pathology-cognition connection.
Recent studies of HVOF-sprayed WC–(W,Cr)2C–Ni coatings indicated an applicability at temperatures above 600°C. Therefore, in the present paper the dry sliding wear behaviour of coatings prepared from ...one selected feedstock powder was studied up to 750°C and compared to a WC–10%Co–4%Cr coating as reference.
Coatings were prepared onto stainless steel substrates by a liquid-fueled high velocity oxygen-fuel (HVOF) spray process. A Cr–W–Ni–C “mixed” matrix phase and chromium-rich large (W,Cr)2C grains were formed as a result of metallurgical reactions between the components WC, Cr3C2 and Ni during spraying; therefore, the resulting coating can be better designated as WC–(W,Cr)2C–Ni.
The dry unidirectional sliding wear behaviour of the coatings, studied according to ASTM G99 against Al2O3 counterbodies at four different temperatures (25°C, 400°C, 600°C, 750°C) and at two sliding speeds, was interpreted on the basis of their microstructure, micromechanical properties and oxidation behaviour. The morphology and composition inside the wear scars were also studied by SEM and micro-Raman spectroscopy. The results show that the WC–(W,Cr)2C–Ni coating exhibits good wear resistance up to 750°C, whereas WC–CoCr, in spite of its very mild wear at low temperature, suffers from catastrophic oxidation at 750°C.
•Reaction mechanisms for the particular WC–20%Cr3C2–7%Ni feedstock powder are proposed.•Sliding wear of WC–(W,Cr)2C–Ni and WC–CoCr HVOF-sprayed coatings studied up to 750°C.•WC–(W,Cr)2C–Ni has mild wear rates increasing gradually up to 10−5mm3/(Nm) at 750°C.•Up to 600°C, harder, tougher WC–CoCr exhibits lower wear rates than WC–(W,Cr)2C–Ni.•At 750°C, WC–(W,Cr)2C–Ni forms a tribofilm whilst WC–CoCr oxidises catastrophically.
High velocity thermal spray Cr3C2–NiCr coatings are widely used to mitigate wear at high temperatures and in corrosive environments due to their superior oxidation and corrosion resistance relative ...to WC-Co coatings. This work explored a novel two–step process of first depositing a coating from feedstock particles having a high liquid phase content by shrouded plasma spraying (SPS), followed by controlled precipitation of the carbide grains through heat treatment. The appearance of additional melt from peritectic decomposition of Cr3C2, protection from oxidation by the shroud, as well as absence from water vapour of hydrocarbon combustion, created a new quality of microstructure. Heat treatment generated uniquely novel coating microstructures of continuous carbide within which pools of Ni alloy formed, in direct contrast to the conventional coating microstructure of isolated carbide grains encapsulated within a continuous Ni binder. The variation in the as-sprayed chemical and phase compositions between the SPS and HVOF coatings played a direct role in the dramatic microstructural variation seen with heat treatment. The mechanism of compositional and microstructural development with heat treatment in the SPS coating is contrasted to that in conventional HVOF coatings. Microhardness values above 1000 VHN300 demonstrate the potential of this new type of coating.
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•Novel two-step Cr3C2–NiCr carbide composite microstructure formation mechanism.•Initially form a supersaturated Ni binder through in-flight carbide dissolution.•Heat treatment used to generate controlled carbide precipitation.•Ceramic matrix structure formed compared to traditional metal matrix composite.
Influenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can ...serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate poorly in most mammalian hosts. Importantly, IAV polymerases from avian strains function poorly in mammalian cells but host adaptive mutations can restore activity. The 2009 pandemic H1N1 (H1N1pdm09) virus acquired multiple mutations in the PA gene that activated polymerase activity in mammalian cells, even in the absence of previously identified host adaptive mutations in other polymerase genes. These mutations in PA localize within different regions of the protein suggesting multiple mechanisms exist to activate polymerase activity. Additionally, an immunomodulatory protein, PA-X, is expressed from the PA gene segment. PA-X expression is conserved amongst many IAV strains but activity varies between viruses specific for different hosts, suggesting that PA-X also plays a role in host adaptation. Here, we review the role of PA in the emergence of currently circulating H1N1pdm09 viruses and the most recent studies of host adaptive mutations in the PA gene that modulate polymerase activity and PA-X function.
A systems-based model of Alzheimer's disease Tang, Yi; Lutz, Michael W.; Xing, Yi
Alzheimer's & dementia,
January 2019, 2019-01-00, 20190101, Letnik:
15, Številka:
1
Journal Article
Recenzirano
The new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease has been developed to accelerate drug discovery and offer a common structure and ...language to construct new Alzheimer's disease conceptual models. However, as a “complex” disease, a model based on systems-level understanding is needed to accommodate the complex, interacting etiologic pathways and the system-level changes associated with Alzheimer's disease pathogenesis and interventions that are currently known and which will be identified in the future. To accomplish this, the evolution of the structure of the research framework itself should be encouraged.
Abstract
Objectives
Genetic risks for cognitive decline are not modifiable; however their relative importance compared to modifiable factors is unclear. We used machine learning to evaluate ...modifiable and genetic risk factors for Alzheimer’s disease (AD), to predict cognitive decline.
Methods
Health and Retirement Study participants, aged 65–90 years, with DNA and >2 cognitive evaluations, were included (n = 7,142). Predictors included age, body mass index, gender, education, APOE ε4, cardiovascular, hypertension, diabetes, stroke, neighborhood socioeconomic status (NSES), and AD risk genes. Latent class trajectory analyses of cognitive scores determined the form and number of classes. Random Forests (RF) classification investigated predictors of cognitive trajectories. Performance metrics (accuracy, sensitivity, and specificity) were reported.
Results
Three classes were identified. Discriminating highest from lowest classes produced the best RF performance: accuracy = 78% (1.0%), sensitivity = 75% (1.0%), and specificity = 81% (1.0%). Top ranked predictors were education, age, gender, stroke, NSES, and diabetes, APOE ε4 carrier status, and body mass index (BMI). When discriminating high from medium classes, top predictors were education, age, gender, stroke, diabetes, NSES, and BMI. When discriminating medium from the low classes, education, NSES, age, diabetes, and stroke were top predictors.
Discussion
The combination of latent trajectories and RF classification techniques suggested that nongenetic factors contribute more to cognitive decline than genetic factors. Education was the most relevant predictor for discrimination.
We investigate the functioning of the ocean’s biological pump by analyzing the vertical transfer efficiency of particulate organic carbon (POC). Data evaluated include globally distributed time ...series of sediment trap POC flux, and remotely sensed estimates of net primary production (NPP) and sea surface temperature (SST). Mathematical techniques are developed to compare these temporally discordant time series using NPP and POC flux climatologies. The seasonal variation of NPP is mapped and shows regional‐ and basin‐scale biogeographic patterns reflecting solar, climatic, and oceanographic controls. Patterns of flux are similar, with more high‐frequency variability and a subtropical‐subpolar pattern of maximum flux delayed by about 5 days per degree latitude increase, coherent across multiple sediment trap time series. Seasonal production‐to‐flux analyses indicate during intervals of bloom production, the sinking fraction of NPP is typically half that of other seasons. This globally synchronous pattern may result from seasonally varying biodegradability or multiseasonal retention of POC. The relationship between NPP variability and flux variability reverses with latitude, and may reflect dominance by the large‐amplitude seasonal NPP signal at higher latitudes. We construct algorithms describing labile and refractory flux components as a function of remotely sensed NPP rates, NPP variability, and SST, which predict POC flux with accuracies greater than equations typically employed by global climate models. Globally mapped predictions of POC export, flux to depth, and sedimentation are supplied. Results indicate improved ocean carbon cycle forecasts may be obtained by combining satellite‐based observations and more mechanistic representations taking into account factors such as mineral ballasting and ecosystem structure.
Alzheimer's disease (AD) is a common neurodegenerative disease and mild cognitive impairment (MCI) is considered as the prodromal stage of AD. Previous studies showed that changes in the neurotrophin ...signaling pathway could lead to cognitive decline in AD. However, the association of single nucleotide polymorphisms (SNPs) in genes that are involved in this pathway with AD progression from MCI remains unclear.
We investigated the associations between SNPs involved in the neurotrophin signaling pathway with AD progression.
We performed single-locus analysis to identify neurotrophin-signaling-related SNPs associated with the AD progression using 767 patients from the Alzheimer's Disease Neuroimaging Initiative study and 1,373 patients from the National Alzheimer's Coordinating Center study. We constructed polygenic risk scores (PRSs) using the identified independent non-APOE SNPs and evaluated its prediction performance on AD progression.
We identified 25 SNPs significantly associated with AD progression with Bayesian false-discovery probability ≤0.8. Based on the linkage disequilibrium clumping and expression quantitative trait loci analysis, we found 6 potentially functional SNPs that were associated with AD progression independently. The PRS analysis quantified the combined effects of these SNPs on longitudinal cognitive assessments and biomarkers from cerebrospinal fluid and neuroimaging. The addition of PRSs to the prediction model for 3-year progression to AD from MCI significantly increased the predictive accuracy.
Genetic variants in the specific genes of the neurotrophin signaling pathway are predictors of AD progression. eQTL analysis supports that these SNPs regulate expression of key genes involved in the neurotrophin signaling pathway.
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