Cells trigger the assembly of stress granules (SGs) under various stress conditions. Among the many proteins recruited to SGs are RNA-binding proteins and transcription regulators. Here, we report ...the translocation of human (h)Cdc73, a component of the PAF1 transcription complex, to cytosolic SGs in response to arsenic stress. The hCdc73 protein possesses a long intrinsically disordered region (IDR) from amino acids 256-416, the presence of which is required for the translocation of hCdc73 to cytosolic SGs. The purified hCdc73 IDR formed droplets in vitro, and the light-activated assembly of hCdc73-IDR-mCherry-CRY2 was verified. For translocation of hCdc73 to SGs, physical interactions with SG carrier proteins, such as FMR1, are also needed. Previously, we reported that the cytosolic hCdc73-eEF1Bγ complex controls the stability of p53 mRNA. Under arsenic stress, selective sequestration of cytosolic hCdc73, but not eEF1Bγ (EEF1G) or p53 (TP53) mRNA, was detected. As a result, a transient increase in p53 mRNA at the post-transcriptional level was observed. In conclusion, we propose that the availability of mRNAs for stress-responsive genes can be controlled by restraining their negative regulators within SGs.
In this investigation, annealed Cu–0.13Sn alloys
i.e
., as-received samples were subjected to room-temperature rolling (RTR) at reduction ratios (RR) of 40 and 75 pct. Electron backscattered ...diffraction (EBSD) and transmission electron microscopy (TEM) was used to discuss the microstructure evolution in the as-received and RTR samples. RTR deformation resulted in the formation of Copper-type shear bands (SBs). An unusual phenomenon of static recrystallization (SRX) at room-temperature (RT)/self-annealing was observed in the severely deformed Cu–0.13Sn alloy. SBs and deformed grain boundaries (GBs) were the main sites with high levels of stored energy (SE), and new grains were nucleated in those regions
via
discontinuous SRX (DSRX) in the RTR samples. Continuous SRX (CSRX) was observed in grains nucleated inside the deformed grains. The fraction of SBs was increased with increases in the RR, and visco-plastic self-consistent (VPSC) modelling was used to predict the texture of the SBs in the severely deformed Cu–0.13Sn alloy. Microstructural heterogeneities had a significant effect on the evolution of the crystallographic texture in as-received and RTR samples. Under low strain (40 pct RR), a Copper-type texture was observed, whereas the severely deformed sample (75 pct RR) showed strong Copper and S components, but weak Brass component. Self-annealed grains in the SB regions and in the deformed GB regions led to the evolution of strong Copper and Rotated Cube components, but weak Brass component.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A capacitive synaptic transistor (synaptor) compatible with the fabrication process of conventional Flash memory is proposed for compute-in-memory (CIM) array cells to support energy-efficient ...inference operations. This synaptor demonstrates the highly reliable endurance characteristic of program/erase (P/E) due to overturned charge injection occurring between a control gate (CG) and a floating gate (FG) rather than between the FG and a channel. On- and off- state capacitances (<inline-formula> <tex-math notation="LaTeX">{C}_{\text {on}} </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">{C}_{\text {off}}{)} </tex-math></inline-formula> are determined by the area ratio of CG and FG. After optimizing the pulse conditions, we achieved the P/E endurance of at least 107 cycles and retention time of 104 sec.
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Antibody-protein conjugates have been useful tools for studying biological systems and also played important roles in developing therapeutics and diagnostics. In particular, because ...of the increased interest in therapeutics of complexity higher than monoclonal antibodies, various methods have been reported for generating bispecific antibodies, immunotoxins, and antibody-enzyme conjugates in which antibodies are site-specifically conjugated with other proteins. Compared with conjugating antibodies with synthetic molecules, controlling the modification sites is difficult in the antibodies conjugated with protein cargos due to the presence of several reactive groups in both molecules. Enzymatic reactions are often used to generate antibody-protein conjugates owing to their high specificity for both reactants and products. Chemical modifications involving genetic introduction of natural or unnatural amino acid residues have also been used for site-specific conjugation of antibodies. Recent studies have developed methods to modify native antibodies using peptides having affinity for antibodies, and these methods do not need antibody engineering for conjugation reactions. In this review, we have summarized enzymatic and chemical approaches to generate site-specific antibody-protein conjugates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Conjugation of antibody has expanded its applications in therapeutics and diagnostics, and various methods have been developed based on chemical or enzymatic reactions. However, the majority of them ...have focused on synthetic molecules such as small molecules, nucleic acids, or synthetic materials, but site-specific conjugation of antibody with protein cargo has rarely been demonstrated. In this Communication, we report a PEptide-DIrected Photo-cross-linking (PEDIP) reaction for site-specific conjugation of IgG with protein using an Fc-binding peptide and a photoreactive amino acid analogue, and demonstrate this method by developing an immunotoxin composed of a Her2-targeting IgG (trastuzumab) and an engineered Pseudomonas exotoxin A (PE24). The ADP-ribosylation of eukaryotic elongation factor-2 by the bacterial toxin inhibits the ribosomal translation of protein, and the trastuzumab-PE24 conjugate exhibited the cytotoxicity toward Her2-overexpressing cell lines. The PEDIP reaction can also be applied for many other types of cargo with slight modifications of the method.
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IJS, KILJ, NUK, PNG, UL, UM
We developed a method to analyze amino acids using a personal glucose meter (PGM). In this method, the principles of protein biosynthesis were interfaced with the sensing mechanism of a PGM to enable ...simple and ubiquitous measurement of amino acids. A reaction mixture for cell-free protein synthesis was designed to synthesize a bacterial invertase in response to exogenous addition of a specific amino acid. The invertase synthesized upon addition of an assay sample containing the amino acid of interest was used to convert sucrose into glucose, which was detected using a PGM. The titers of the amino acid in assay samples were precisely represented by the readouts of a PGM. In addition to the convenience provided by use of a PGM, the accuracy and reproducibility of this method were comparable to those of standard high-performance liquid chromatography based methods.
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IJS, KILJ, NUK, PNG, UL, UM
Toll-like receptors (TLRs) belong to a class of pattern-recognition receptors that play an important role in host defense against pathogens by recognizing a wide variety of pathogen-associated ...molecular patterns (PAMPs). Besides driving inflammatory responses, TLRs also regulate cell proliferation and survival by expanding useful immune cells and integrating inflammatory responses and tissue repair processes. TLR signaling, which is centrally involved in the initiation of both innate and adaptive immune responses, has been thought to be restricted to immune cells. However, recent studies have shown that functional TLRs are expressed not only on immune cells, but also on cancer cells, thus implicating a role of TLRs in tumor biology. Increasing bodies of evidence have suggested that TLRs act as a double-edged sword in cancer cells because uncontrolled TLR signaling provides a microenvironment that is necessary for tumor cells to proliferate and evade the immune response. Alternatively, TLRs can induce an antitumor immune response in order to inhibit tumor progression. In this review, we summarize the dual roles of TLRs in tumor cells and, more importantly, delve into the therapeutic potential of TLRs in the context of tumorigenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Strain localizations (SLs) were observed preferentially in Copper-type grains in the CR Cu-Fe-P specimens.•Self-annealing at room temperature was observed at the deformed GBs and at SLs in the CR ...specimens.•TEM and TKD confirms that DSRX and CSRX were responsible for the self-annealing phenomena in the CR specimens.•CPFEM simulation was showing the nearby predictions for average grain size (GSavg) and texture fraction.•Activation of single-slip system in the Copper and S oriented grains was the primary cause of SLs formations.
Deformation of Cu-Fe-P alloys at cryogenic temperature (CT) leads to the evolution of a complex microstructure, which includes deformed and recrystallized grains, strain localizations (SLs), and heterogeneous deformation. In this study, specimens of Cu-Fe-P alloy were subjected to cryogenic rolling (CR) at reduction ratios (RR) of 20, 40, 60, and 80%. The microstructural evolution of the CR specimens was characterized using electron back-scattered diffraction (EBSD) and high-resolution transmission electron microscopy (HR-TEM). Severely deformed CR specimens showed SLs, which formed predominantly in the Copper and S oriented grains. After deformation, the CR specimens exhibited self-annealing behavior, which is also referred to as static recrystallization (SRX). Self-annealing at room temperature (RT) caused grain nucleation at the deformed grain boundaries (GBs) and at the SLs. The nucleation of new grains was attributed to both discontinuous SRX (DSRX) and continuous SRX (CSRX) phenomena. The characteristics of DSRX and CSRX grains were analyzed based on transmission Kikuchi diffraction (TKD) and HR-TEM investigations. DSRX grains were surrounded by high-angle GBs, whereas CSRX grains showed sub-boundaries with no dislocations inside. The as-received Cu-Fe-P specimen showed a weak plane-strain texture that intensity increased with an increase in the RR. The CR-80 specimen showed the highest-intensity for plane-strain texture components. SRX at the SLs showed preferential formations of Copper, Brass and S-nucleated grains in the CR-80 specimen. In this study, crystal plasticity finite element method (CPFEM) was used to calculate the stored energy, relative slip activity and texture fractions for the CR specimens. Copper and S oriented grains showed the occurrence of predominant single-slip systems near the severely deformed regions which was the primary cause of SLs formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Systematic study of welding parameters on microstructure in laser-welded steel and V using EBSD and FEA.•Better surface appearance was achieved at higher welding speeds.•Hardness was mainly driven ...by microstructural distribution around the weldment.•FEA results were validated against the dimensional variations of FZ and HAZ observed experimentally.•FEA used to study cooling rate impact on HAZ microstructure in laser welding.
This study delves into the influence of laser welding parameters on the microstructural evolution, surface roughness, and hardness of dissimilar lap joints formed by welding 340BH steel (upper) to cold-rolled pure vanadium (bottom) in an attempt to successfully develop metal membranes by adopting a novel technological route. Specifically, we examined power levels of 0.3 kW and 0.4 kW combined with varying welding speeds (40 mm/s, 50 mm/s, and 60 mm/s). The results indicate that defect-free joints were achievable at the higher welding speed of 60 mm/s. This conclusion is supported by the observed surface roughness profile. Elemental interdiffusion and temperature play pivotal roles in the formation of these dissimilar joints. These factors determine the dimensions of the heat-affected zone (HAZ) and the fusion zone (FZ) under all welding conditions. Notably, the high cooling rates during laser welding hindered the formation of intermetallic phases both in the FZ and at the interface between the metals. Microstructural examination of the HAZ/FZ on the Fe side showed a coarser microstructure when using a power of 0.4 kW, in contrast to the lath martensite observed at 0.3 kW. These observations align with the cooling curve derived from finite element analysis (FEA). FEA was also used to estimate temperature profiles throughout the welded area, and the results were consistent with experimental data. Further microstructural analysis using electron backscattered diffraction (EBSD) revealed a significant phenomenon: the formation of recrystallized grains of vanadium in the HAZ near the FZ on the vanadium side. Microhardness tests, conducted to gauge joint quality, displayed varying hardness levels across the base metal (BM), HAZ, and FZ interfaces. At a power of 0.3 kW, the HAZ displayed greater hardness than the FZ and BM due to the formation of lath martensite. Conversely, at a power setting of 0.4 kW, a reduction in hardness was observed within the HAZ, attributable to coarser ferrite formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
