The Finemet-type nanocrystalline alloy represents an advanced soft-magnetic metal–metal-type nanocomposite with an eddy-current-determined high- frequency limit. A survey of different heat treatments ...under tensile stress is presented to tailor the hysteresis loop by induced transversal anisotropy. The flattened loop having reduced effective permeability enhances the eddy- current limit in the MHz region; For example, continuous stress annealing in a tubular furnace of 1 m length at 650°C, pulling the ribbon with a velocity of 4 m/min under a tensile stress of 200 MPa, results in a wound core having a permeability of 120 and a frequency limit of 10 MHz. Careful annealing preserves the static coercivity below 10 A/m. The power loss at 0.1 T and 100 kHz is only 82 mW/cm
3
, which is an order of magnitude lower then the values obtained for Sendust™ cores in similar conditions.
Accumulation of semantic or factual knowledge is a major task during development. Knowledge builds through direct experience and explicit instruction as well as through productive processes that ...permit derivation of new understandings. In the present research, we tested the neural bases of the specific productive process of self-derivation of new factual knowledge through integration of separate yet related episodes of new learning. The process serves as an ecologically valid model of semantic knowledge accumulation. We tested structure/behavior relations in 5- to 8-year-old children, a period characterized by both age-related differences and individual variability in self-derivation, as well as in the neural regions implicated in memory integration, namely the hippocampus and prefrontal cortex. After controlling for the variance in task performance explained by age, sex, verbal IQ, and gray-matter volume (medial prefrontal cortex, mPFC, only), we observed relations between right mPFC thickness and memory for information explicitly taught to the children as well as the new information they self-derived; relations with the volume of the right hippocampus approached significance. This research provides the first evidence of the neural substrate that subserves children’s accumulation of knowledge via self-derivation through memory integration, an empirically demonstrated, functionally significant learning mechanism.
In case of the decomposition of foundry artificial resin-bonded moulding materials, the amount and the pressure of the produced gases can have significant effect on the quality of the casting surface ...during the early phases of the solidification. The produced gases can cause casting defects if the casting skin is not solidified before the gas could pass through. The cores were made out of commercially available multi-element (SH33-34) and sieved SH33 sands with phenol no-bake process, with the same resin content. The gas permeability and gas pressure of the released gases were examined. Furthermore, the changes in the gas pressures of the gases released from various resin quality cores at different casting temperatures were also examined.
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly ...broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4–8 μM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.
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•We developed a highly sensitive cell-based Nanoluciferase assay to screen for inhibitors of SARS-CoV-2 main protease.•We provide evidence that the assay is scalable to the 384-well format and robust (z’ factor of 0.8).•The false positive rate is minimized: gain of signal assay, catalytically inactive protease control.•The assay can be adapted to other coronaviruses and viruses which rely on a viral protease.•We report the identification of 2 lead compounds that inhibit nsp5 activity and SARS-CoV-2 replication in cell culture.
Sand cores are used to form the cavities of the castings. The quality of castings is directly affected by the quantity of the gases released from the cores. During our research, the effect of ...different grain sizes and heat input on the pressure of the gases evolved from the cores was investigated. The granulometric properties of the sand used for making the cores have a significant impact on the pressure of the gases. Because of the uneven particle size distribution of multi fraction sands, the gas flow conditions in the cores can be different. The gas pressure in the cores made from sieved sands can be changed between 6 and 9 mbar. According to the recorded cooling curve of the melt, it can be established, that in the case of the presented pouring conditions, a solid metal layer with adequate strength could not be developed before the gas could pass through the core/casting interface. This phenomenon may result in gas blowhole defects on the casting surface.
Whether the growth hormone (GH)/insulin-like growth factor 1(IGF-1) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we ...tested the hypothesis that growth hormone-releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-1 independent fashion. After experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4-week period, either placebo (n = 14), rat recombinant GH (n = 8) or JI-38 (n = 8; 50 μg/kg per day), a potent GHRH agonist. JI-38 did not elevate serum levels of GH or IGF-1, but it markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, and circulating GH and IGF-1, but it did not offset the decline in cardiac structure and function. Whereas both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased antiapoptotic gene expression. The receptor for GHRH was detectable on myocytes, supporting direct activation of cardiac signal transduction. Collectively, these findings demonstrate that within the heart, GHRH agonists can activate cardiac repair after MI, suggesting the existence of a potential signaling pathway based on GHRH in the heart. The phenotypic profile of the response to a potent GHRH agonist has therapeutic implications.
The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1‐INH deficiency (C1‐INH‐HAE) represent one of the oldest unsolved problems of the disease. ...Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12‐46C/T in disease phenotype. We studied 258 C1‐INH‐HAE patients from 113 European families, and we explored possible associations of F12‐46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within‐subject correlation. F12‐46C/T carriers exhibited a significantly delayed disease onset (P < 0.001) and did not need long‐term treatment (P = 0.02). In a GEE linear regression model, the presence of F12‐46C/T was significantly associated with a 7‐year delay in disease onset (P < 0.0001) regardless of SERPING1 mutational status. It is concluded that F12‐46C/T carriage acts as an independent modifier of C1‐INH‐HAE severity.
In situ hysteresis measurements were used to follow the evolution of soft magnetic properties of various Co containing Finemet- and Hitperm-type nanocrystalline materials. This work is aimed at ...obtaining the proper chemical composition of nanocrystalline alloys, which can be applied for highest temperatures and is less affected by the inevitable decoupling phenomena, which is common to all two-phase nanocrystalline systems. Experimental results pointed out that in the Co-added Finemet-type alloys the decoupling temperature can be increased by about 50–70
K as compared to Co-free Finemet alloy. Hitperm alloys, close to equiatomic Fe/Co ratio, have much higher decoupling temperature, but their coercivity is an order of magnitude larger at low temperatures compared to the Co-free alloys so their advantage is evident above 400
°C only.
► U is a good glass former element in Al-based metallic glasses and can replace the usual RE elements. ► Our thermo-mechanical measurements enables determining the true glass transition and fragility ...parameters. ► Good precursor ribbons for preparing bulk samples by hot consolidation.
The thermal stability and viscous flow behavior of three quaternary amorphous alloys Al85Ni5Co2RE8 (RE=Ce, Gd, U) are studied. The viscosity experimental results are interpreted on the basis of the free volume model (FVM). The values of the model parameters obtained are used for estimation of the glass forming ability (GFA) in terms of Angell parameter, and the fracture strength of the alloys based on its correlation with the glass transition temperature. The results show that the amorphous alloys Al85Ni5Co2RE8 (RE=Ce, Gd, U) posses an excellent fracture strength (1.3–1.5GPa). The replacement of RE by U leads to best fracture strength and highest GFA.
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