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Photo-caged benzaldehyde probes using o-nitrophenylethylene glycol were designed for photo-activated electrophile generation.

Aberrantly elevated steroid receptor coactivator-1 (SRC-1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC-1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N-degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC-1 in cells through the N-degron pathway. Importantly, given the ubiquitous expression of the UBR protein in most cells, PROTACs targeting the UBR box could degrade a protein of interest regardless of cell types. We also showed that the SRC-1 degrader significantly suppressed cancer cell invasion and migration in vitro and in vivo. Together, these results demonstrate that the SRC-1 degrader can be an invaluable chemical tool in the studies of SRC-1 functions. Moreover, our findings suggest PROTACs based on the N-degron pathway as a widely useful strategy to degrade disease-relevant proteins.

The high temperature requirement A (HTRA) family of serine proteases mediates protein quality control. These proteins process misfolded proteins in several diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). While their structures and activation mechanisms have been studied, the precise details of the regulation of their activity under physiological conditions have not been completely elucidated, partly due to the lack of suitable chemical probes. In the present study, we developed novel activity-based probes (ABPs) targeting the HTRAs and demonstrated their utility in the monitoring and quantification of changes in enzyme activity in live cells. Using our probes, we found the activity of HTRA1 to be highly elevated in an AD-like cell-based model. We also observed the active HTRA2 in live cells by using a mitochondrion-targeted probe. We believe that our probes can serve as a useful tool to study the role of human HTRAs in neurodegenerative diseases.

Correction for ‘Temporal control of protein labeling by a photo-caged benzaldehyde motif and discovery of host cell factors of avian influenza virus infection’ by Nicholas Asiimwe et al., Chem. Commun., 2022, https://doi.org/10.1039/d2cc04091c.

Isothermal oxidation behavior of NbSi 2 coating grown on Nb substrate was investigated in air at 1000–1450 °C. Oxidation rate of NbSi 2 coating increased with temperature at 1000–1300 °C but opposite trend was observed at 1300–1450 °C. Maximum oxidation rate was obtained at 1300 °C due to the highest porosity of oxide scale. Lowest oxidation rate was observed at 1450 °C due to formation of dense oxide scale by combined effect of volatilization of Nb oxide phase, viscous flow and densification of c-SiO 2 . Oxidation resistance of NbSi 2 coating at these temperatures was governed by some inter-related factors.

4YSZ is generally used as oxygen sensors, fuel cells, thermal barrier and hip and knee joint replacements as a result of these excellent properties with its high biocompatibility, low density, good resistance against corrosion, high ionic conductivity, hard phase and melting point. However, 4YTZ with coarse grain has low resistance to wear and abrasion because of low hardness and low fracture toughness at room temperature. The fracture toughness and hardness of a 4YTZ can be improved by forming nanostructured composites and addition of a second hard phase. In this study, nanostuctured 4YTZ-graphene composites with nearly full density were achieved using high-frequency induction heated sintering for one min at a pressure of 80 MPa. The rapid consolidation and addition of graphene to 4YTZ retained the nano-scale structure of the ceramic by inhibiting grain growth. The grain size of 4YTZ was reduced remarkably by the addition of graphene and the addition of graphene to 4YTZ greatly improved the fracture toughness without decrease of hardness.

The rapid sintering of ultra-fine WC–Al 2 O 3 composites in a short time was investigated with a focus on the mechanical properties and consolidation using pulsed current activated sintering. The advantage of this process is that it allows very quick densification to near theoretical density and prohibition of grain growth in nanomaterials. The addition of Al 2 O 3 to WC can facilitate consolidation and improve mechanical properties. The hardness and fracture toughness of WC–Al 2 O 3 composites outperform those of monolithic Al 2 O 3 .

A multi-layered plate with robust interfacial strength composed of high-Cr martensitic stainless steel was produced via repetitive hot roll bonding (RHRB) at elevated temperature. The minimum processing temperature required for the production of multi-layered plates turned out to be in the two-phase region between the A1 and A3 temperatures of stainless steel. Decarburization took place on the surface layer of each process cycle and multi-layered plates were produced with a carbon content that fluctuated along the thickness direction that constitutes a composite plate. The multi-layered composite structure revealed an effective combination of strength and ductility. Also, strong bonding results at each interface were validated via tensile testing with in-situ observation from the sides of the specimens during deformation.

The rapid sintering of nanostructured Al 2 O 3 and Al 2 O 3 to Al 2 SiO 5 composites was investigated by a high-frequency induction heating sintering process. The advantage of this process is that it allows very quick densification to near theoretical density and inhibition of grain growth. Highly dense nanostructured Al 2 O 3 and Al 2 O 3 to Al 2 SiO 5 composites were produced with simultaneous application of a 80 MPa pressure and induced output current of a total power capacity (15 kW) within 3 min. The sintering behavior, grain size and mechanical properties of Al 2 O 3 and Al 2 O 3 to Al 2 SiO 5 composites were investigated.

Highly ordered TiO2 nanotube arrays were prepared using a self-templating multi-step anodic oxidation process in a fluoride-containing electrolyte. The microstructures, chemical compositions, and phases of the self-organized TiO2 nanotube arrays were analyzed by FESEM, XPS, and XRD, respectively. Hexagonal packing density in TiO2 nanotube arrays significantly improved after the the multi-step anodic oxidation. The area densities of the hexagonal TiO2 nanotube arrays increased approximately 3 times from the first to second step in the anodic oxidation steps process (4.9 μm−2 to 16.4 μm−2), but there was no difference between the second and third step (16.4 μm−2 to 16.0 μm−2). The as-anodized TiO2 nanotube array had an amorphous structure and it transformed to an anatase phase during the annealing process at 450 °C for 1 h. The as-anodized TiO2 nanotube arrays adsorbed the fluoride, hydrocarbon groups (CH), hydroxyl groups (OH, C-OH), and carboxyl groups (O = C-OH) on their surfaces.

Growth kinetics of the W 5 Si 3 layer in the WSi 2 /W diffusion couple was investigated using optical microscopy, field-emission scanning electron microscopy, cross-sectional transmission electron microscopy, and X-ray diffraction. The 62 μm WSi 2 /0.3 μm–W 5 Si 3 /W diffusion couple was made by chemical vapor deposition (CVD) of Si on a W substrate. When the diffusion couple was annealed at temperatures between 1300 and 1500 °C in an argon atmosphere, the W 5 Si 3 layer was simultaneously formed both at the surface of the WSi 2 layer and at the interface between the WSi 2 layer and the W substrate. The W 5 Si 3 layer observed at the surface of WSi 2 layer was formed by loss of Si released from the decomposition of WSi 2 phase into the W 5 Si 3 and Si phases. The growth kinetics of W 5 Si 3 layer formed at the interface between the WSi 2 layer and the W substrate obeyed a parabolic rate law, indicating the diffusion-controlled growth. From the change of columnar diameter and texture of W 5 Si 3 grains, the dominant diffusion element and growth mechanism of the W 5 Si 3 layer was found. The integrated interdiffusion coefficients in the W 5 Si 3 phase were determined.

In this paper, we investigate an active vibration control of a translating tensioned steel strip in the zinc galvanizing line. The dynamics of the moving strip is modeled as a Euler-Bernoulli beam with non-linear tension. The control objective is to suppress the transverse vibrations of the strip via boundary control. A right boundary control law based upon the Lyapunov second method is derived. It is revealed that a time-varying boundary force and a suitable passive damping at the right boundary can successfully suppress the transverse vibrations. The exponential stability of the closed-loop system is proved. The effectiveness of the control laws proposed is demonstrated via simulations.

The formation process and microstructural evolution of Ni-silicide layers formed by chemical vapour deposition (CVD) of Si on Ni substrate at deposition temperatures between 900 and 1050 °C using horizontal hot-wall reactor and SiCl 4 –H 2 gas mixtures was investigated. The Ni-silicide layers grew sequentially in a series of γ-Ni 5 Si 2 , δ-Ni 2 Si and θ-Ni 2 Si layers with increasing deposition time. After an incubation time necessary for nucleation of each Ni-silicide phase, the growth kinetics of each layer obeyed a parabolic rate law and was controlled by solid-state diffusion of Ni leading to void formation at the interface of the Ni-silicide layers and the Ni substrate. The growth rates of γ-Ni 5 Si 2 and δ-Ni 2 Si layers were faster at the early deposition stage than those at the later deposition stage. The formation process and microstructures of each Ni-silicide layer was influenced by the effect of deposition parameters especially on the difference between the Si flux supplied by CVD process and the Ni flux diffusing through each Ni-silicide layer.

In this paper, a kinematic optimal design of a new parallel-type rolling mill based upon two Stewart platform manipulators is investigated. To provide the end-effector (work roll) with sufficient d.o.f. and to achieve the structural stability of each stand, a parallel manipulator with six legs is considered. The objective of this new parallel-type rolling mill is to pursue an integrated control of the strip thickness, strip shape, pair-crossing angle, uniform wear of the rolls and strip tension. By splitting the weighted Jacobian matrices into two parts, the linear velocity, angular velocity, force and moment transmissibilities are analyzed. A manipulability measure, as the ratio of the manipulability ellipsoid volume and the condition number of a split Jacobian matrix, is defined. The two kinematic parameters, the radius of the base and the angle between two neighboring joints, are optimally designed by maximizing the global force manipulability measure defined in the entire workspace. The maximum exerti...

This paper reports the results of experimental studies on the relationship between grain boundary character distribution and the fracture toughness in the polycrystalline NiAl. The fracture toughness has been investigated by the ring on ring disk bend test in conjunction with the acoustic emission (AE) measurement, and the grain boundary character distribution is measured by the electron back-scatter diffraction pattern (EBSD or EBSP) technique. The fracture toughness of the annealed specimen (1473 K, 20 h) is 6.42±0.88 (MPa m−1/2) and that of the forged (1473 K) and annealed (1473 K, 20 h) specimen is 5.08±0.36 (MPa m−1/2). The strong boundary and weak boundary were decided by comparing the distribution of grain boundary characteristics at the intergranular cracks to the distribution in general population. Σ1, Σ3 and Σ5 boundaries have strong and the good crack resistance, but Σ7, Σ11, Σ13, Σ21 and Σ23 boundaries are relatively weak boundary in the polycrystalline NiAl. Consequently, the annealing process makes the fraction of Σ1 and Σ5 boundaries higher than forging and annealing process. The high fraction of Σ1 and Σ5 boundaries that have the good crack resistance seem to affect the increase of fracture toughness in the annealed specimen.

In this study, under the viscous glide creep condition of Al-3 at. pct Mg solid solution alloy, which is the power-law creep condition with stress exponent n=3, [9,10] surface void nucleation due to GBM (grain boundary migration) and evaporation of magnesium is investigated

Molecular dynamics simulations of the interaction between a screw dislocation and a 3.5 nm diameter bcc Cu precipitate in bcc Fe have been performed in the twinning and antitwinning direction between 10 and 400 K. The results indicate a significant temperature dependence in the antitwinning direction, whereby the screw dislocation bypasses the Cu precipitate by Orowan looping below 200 K, but shears the precipitate above 300 K. The transition in interaction mechanism is caused by a screw dislocation assisted martensitic transformation of the Cu precipitate, which significantly diminishes above 300 K. The screw dislocation shears the precipitate at all temperatures between 10 and 400 K in the twinning direction. Thus, transformation of the precipitate induces additional precipitate strengthening below 200 K in the antitwinning direction, which drastically decreases with increasing temperature above 300 K.