The solid-state transformation of delta-ferrite to austenite (gamma) dictates the final solidified microstructure of austenitic stainless steels. This study examines the impact of undercooling on the mechanism of the delta to gamma transformation. By coupling precise temperature measurements with in-situ radiographic imaging and Laue diffraction analysis, we observed that the degree of undercooling profoundly influences the transformation behavior. At small undercoolings, the transformation is slow and diffusion-controlled with significant partitioning of Ni and Cr. However, at large undercoolings, the mechanism changes to fast and interface-controlled (massive or massive-like) growth, resulting in a chemically homogeneous and partitionless austenite phase. We found that the magnitude of the undercooling, rather than the cooling rate, fundamentally controls the transformation mechanism and the subsequent chemical homogeneity of the microstructure.

The mechanisms of thermal stress build-up and thermal crack formation were investigated in ferritic high-Si and austenitic high-Mn steels (HS and HM). The thermal stress was evaluated by measuring stress under a fixed crosshead during the continuous temperature drop to room temperature. The thermal stress of HS was higher than that of HM, despite its lower thermal contraction. Unlike HM, thermal cracking occurred in the HS-1 during the thermal stress test. However, thermal cracking was suppressed when active deformation twinning formed during the cooling of the HS-2 specimen. Electron channeling contrast and transmission electron microscopy images revealed significant pile-up dislocations around the grain boundary and deformation twins in HS after the thermal stress test. The intensified normal stress due to dislocation pile-up approached the theoretical decohesion stress of HS-1, thereby accounting for its higher susceptibility to thermal cracking. HS-2, with a high twin density formed during cooling, showed much lower intensified normal stress than the theoretical decohesion stress due to the twin's grain refinement effect. The findings of this study provide insights into the matrix-structure-dependent mechanisms of thermal stress build-up and thermal crack formation during the continuous cooling of steels.

p97/VCP ATPase uses adenosine triphosphate (ATP) hydrolysis to remodel protein assemblies and unfold substrates across diverse cellular processes, including protein quality control, membrane fusion, and chromatin regulation. Although cryogenic structural studies have provided valuable snapshots of distinct nucleotide states, they often suppress the conformational variations that are intrinsic to the protein function. Here, we present a comparative structural analysis of the ADP-bound human p97 ND1 hexamer using room-temperature X-ray free-electron laser (XFEL) and cryogenic synchrotron crystallography. While the fundamental hexameric architecture is conserved across both conditions, the room-temperature XFEL structure reveals significantly enhanced conformational variability. Notably, the N-terminal domain exhibits increased flexibility and positional variations. Furthermore, the room-temperature structure reveals an extended, ordered active-site water network that connects the nucleotide-binding pocket to the bulk solvent, a feature absent under cryogenic conditions. Interestingly, the ADP ribose undergoes a pucker transition from a canonical C2'endo to a C3'-endo conformation, revealing altered active-site conformations. Together, these structures highlight the intrinsic conformational flexibility of the p97 ND1 fragment using room-temperature XFEL crystallography as a powerful approach for identifying temperature-dependent structural flexibility of ATPases.

The liquid-liquid phase separation (LLPS) behavior during solidification of Cu-Fe immiscible alloys with various Fe contents was observed in real time using in-situ X-ray imaging techniques. The coarsening and agglomeration behavior of Fe-rich droplets during LLPS was successfully visualized and compared with previously proposed coarsening mechanisms in immiscible alloys. This research revealed that the Fe-rich droplets move toward higher temperature regions to reduce their interfacial energy and that the linear relationship between speed and size causes collisions. In contrast, the buoyancy-driven movement and the diffusional coarsening were observed to play minor roles in coarsening and agglomeration during LLPS. Coalescence after droplet collision was found to be an additional source of droplet movement, causing an immediate displacement equivalent to the counterpart droplet's radius. Based on our observations, we modeled the agglomeration behavior with two simple equations and analyzed the time evolution of droplet size with various volume fractions of droplets and linear coefficients of droplet movement. Our investigation through real-time observation provides an immediate understanding of the microstructure evolution mechanism and an insight into critical factors affecting the degree of droplet agglomeration, which are useful for designing immiscible alloys.

In order to investigate the phase transformation behavior of peritectic steels, we devise an integrated facility for X-ray transmission imaging combined with Laue diffraction analysis and precise temperature control. This integrated facility can measure the temperature at which the delta phase transforms into the gamma phase during solidification with continuous cooling. The investigation of four alloys with different carbon content reveals the dependence of carbon content on the minimum undercooling required for gamma phase formation. As carbon content increases, the amount of undercooling for the peritectic transformation decreases, and the gamma phase onset temperature necessarily increases. X-ray transmission images, which present the growing dendrites and moving delta-to-gamma interface, confirm that the peritectic reaction is likely to occur with high carbon content, leading to the gamma phase formation before the end of solidification. On the contrary, the low carbon content suppresses the gamma phase formation, and the solid delta and liquid phase exist under equilibrium peritectic temperature. Once after the gamma phase nucleation, the phase change occurs rapidly with increasing undercooling. The delay in gamma phase formation results in massive phase transition and rapid change of interface velocity with a slight variation of undercooling. The fast kinetic of solid phase transformation is associated with a corresponding increase of internal stress, leading to the degradation of slab quality.

Boron-induced unique precipitation behavior at the grain boundary (GB) and its effect on the brittle fracture were studied in a Fe-Mn-Al-C austenitic lightweight alloy. Adding 50 ppm wt.% of B promoted the GB segregation of boron at the early aging stage at 550 degrees C. The segregated boron forms the M23B6 at the GBs during further aging treatment. The initial M23B6 evolves the M23C6 by the replacement of boron to carbon during prolonged aging. Meanwhile, the M23B6 promotes the catalytic reaction that sequential formation of alpha-ferrite and x-carbide, which results in the accelerated coverage of the GB cellular precipitates. The ductility of the alloy drops faster by cracking of GB alpha-ferrite and x-carbide under the applied stress as the cellular precipitate covers the GB. This study provides new insights into the role of boron addition between the GB strengthener and the embrittler in a Fe-Mn-Al-C austenitic lightweight steel.

Fe-12Mn alloy possesses one of the most interesting microstructures - a blocky alpha ' martensitic structure with twinning relationships and sub-micrometer grain size. Although these indicate the possibility of a very desirable grain refinement effect, this alloy shows low yield stress and is inherently brittle; its ductile-to-brittle transition temperature (DBTT) occurs around ambient temperature, causing poor impact toughness at subzero temperatures. Here, we fabricated a composite-like Fe-12Mn alloy that exhibits an ultrahigh yield strength (similar to 1 GPa) and a DBTT of - 50 degrees C. Such an excellent strength-impact toughness combination is achieved by utilizing the synergistic effect of chemical heterogeneity and metastability engineering concepts, e.g., transformation-induced plasticity effect from a unique two-step gamma ->epsilon ->alpha ' martensitic transformation. The feasibility of this newly designed alloy lies in its sustainability, i.e., containing an impurity amount of carbon yet exhibiting exceptional properties, and its economic potential as an alternative to other high-cost alloys for extreme environments.

Recent in-situ studies on carbon steel solidification have shown that the & ouml; to gamma transformation can occur at a high degree of undercooling, even in the single gamma-phase region, a transformation referred to as massive or massive-like by researchers. In this study, the & ouml; to gamma phase transformation of two experimental TRIP steels was investigated using a setup that integrates X-ray imaging, Laue diffraction, and precise temperature measurement. Steel T1, a hypo-peritectic alloy (0.1% C-1.23% Mn-1.97% Si), and Steel T2, a hyper-peritectic alloy (0.23% C-1.55% Mn1.87% Si), were compared. The results reveal that the & ouml; to gamma transformation in both steels occurred within the single gamma-phase region, but at significantly different rates. Compared to carbon steels with lower Mn and Si content, these steels exhibit differences in behavior, as discussed in the results section. The thermodynamic and interface kinetic of the & ouml; to gamma transformation were investigated to gain deeper insights into this transformation behavior. Thermodynamic analysis reveals that the transformation in both steels is strongly dependent on undercooling from the T0 temperature, rather than the equilibrium peritectic temperature. Using a diffuse interface model of massive transformation, the kinetics of the & ouml; to gamma transformation were analyzed. The results showed two distinct regimes in the relationship between interface velocity and thermodynamic driving force: a low-velocity regime with partitioning of C, Mn, and Si, and a high-velocity regime with almost no partitioning of Mn and Si. The massive transformations observed in these steels occurred in the low and high-velocity regimes, respectively.

This study focuses on understanding the complex interactions between the initial cold-rolled microstructure and the heating rate, and how these factors influence the post-annealed microstructure, particularly the fraction of polygonal ferrite, in the Nb-Ti microalloyed steel. Key findings include that increasing the heating rate from 3 degrees C/s to 30 degrees C/s enhances the kinetics of reverse transformation to austenite, resulting in a larger fraction of new ferrite and thus a higher proportion of polygonal ferrite in the post-annealed microstructure in most cases. Interestingly, in scenarios where recrystallization can occur by altering the initial microstructure, the combined evolution of recrystallized and new ferrite enlarges the fraction of polygonal ferrite at slower heating rates of 3 degrees C/s. It indicates that the contribution of recrystallization and reverse transformation on the evolution of polygonal ferrite depends on the interplay between initial microstructure and the heating rate. Further, the calculations of the austenite/ferrite interface velocity suggest that the accelerated reverse transformation to austenite, facilitated by increased heating rates, is little affected by kinetic transitions.

The origin of the dynamic transition of internal oxides was clarified in Fe-2.4Mn-0.4Si-0.13C-based steel during decarburization annealing at 1073 K. High dew point with H2 gas leads to the formation of deep decarburized ferrite layers containing grain boundary internal oxides. Microstructural characterization reveals the oxide transition from Mn2SiO4 to alpha-SiO2 at the tip of the internal oxidation layer and from alpha-SiO2 to Mn2SiO4 at the middle range of the internal oxidation layer. The dynamic transition between Mn2SiO4 and alpha-SiO2 is understood by the depletion in Mn contents and change of oxygen content, which change the normalized driving force of both oxides. The study gives a detailed mechanism of internal oxide formation and growth in multi-phase steel during high dew point annealing. Impact statement: During high dew-point decarburization annealing, the fluctuation of Mn contents affects the driving force to form an internal oxide, resulting in the dynamic transition between Mn2SiO4 and alpha-SiO2.

This study proposes a novel method for accelerating bainitic transformation by utilizing Mn heterogeneity. The process involves intercritical annealing to create a heterogeneous distribution of Mn prior to full austenitizing. Heterogeneous Mn distribution leads to the rapid nucleation of bainitic ferrite in the Mn-depleted austenite region, and the rapidly formed bainitic ferrite acts as a nucleation site for Mn-enriched austenite region. Consequently, the required austempering time to achieve a similar fraction of bainitic ferrite is nearly halved compared to conventional process. The effectiveness of Mn heterogeneity in accelerating the transformation is comparable to other acceleration methods, such as prior austenite grain refinement and introducing prior martensite. Moreover, the proposed method has an additional advantage in increasing the fraction of retained austenite. The retained austenite is stabilized not only by C partitioning during austempering but also by pre-partitioned Mn during intercritical annealing.

The combination of X-ray free-electron lasers (XFELs) with serial femtosecond crystallography represents cutting-edge technology in structural biology, allowing the study of enzyme reactions and dynamics in real time through the generation of `molecular movies'. This technology combines short and precise high-energy X-ray exposure to a stream of protein microcrystals. Here, the XFEL structure of carbonic anhydrase II, a ubiquitous enzyme responsible for the interconversion of CO2 and bicarbonate, is reported, and is compared with previously reported NMR and synchrotron X-ray and neutron single-crystal structures.

Despite the technical importance of δ/γ phase transition in steel alloys, conventional thermal analysis techniques like calorimetry lack precise kinetics measurement. This study introduces an integrated approach combining X-ray topographic imaging, diffraction, and precise temperature measurement to overcome these limitations. This methodology allows for the accurate quantification of recalescence due to release of latent heats from solidification and solid-state phase transformation. It also enables tracking of the fractional volume changes of the δ phase during continuous cooling. We demonstrate that in Ultra-Low Carbon steels, the δ to γ transformation occurs rapidly in the single γ phase region far below the solidus temperature in the phase diagram, and this transformation accelerates further in the higher cooling rate. Furthermore, it can be inferred that in phase transformation, its rate becomes a critical factor in the temperature increase resulting from the released latent heat, overshadowing the influence of undercooling during continuous cooling.

The correlation between internal oxidation and surface crack was investigated in high Mn steel. Time- and temperature-dependent internal oxidation behaviors are examined in the temperature ranges of 1000- 1250 degrees C, revealing faster and deeper oxidation along grain boundaries than in grain. Oxides at the internal oxidation layer are confirmed to be MnO and MnAl2O4. The grain boundary penetration depths of the internal oxide increase from 13 to 34 mu m as the temperature increases. The tensile crack on the surface of the specimen was evaluated after 5 % straining with 10(-3)/s strain. Temperature-dependent crack formation probability (L-AC/L-T) increases also from 0.4 to 1.6 % as the temperature increases. The evolution of the internal oxidation layer during the hot compression test was investigated to clarify its role in surface crack formation. The transition of the internal oxide layer to the external oxide layer was observed. Exfoliation of the external oxidation layer was also confirmed by further compression. Driving force calculation on the internal and external oxides reveals that the abundant oxygen supply originating from the cracking of oxide and thickness reduction of the internal oxide layer transforms the internal oxide layer to scale during the compression. High-resolution analysis of the grain boundary crack reveals the cracking of grain boundary MnAl2O4. The comparison between the grain boundary oxides' penetration depth and the crack formation behavior clarifies the grain boundary internal oxide's crucial role in the surface crack formation in a high Mn steel. This study provides vital insights into the surface crack formation mechanism in a Fe-Mn-Al-C-based high Mn steel during hot-rolling processes, highlighting the significance of grain boundary internal oxidation in production.

NAD(P)-dependent steroid dehydrogenase-like (NSDHL), an essential enzyme in human cholesterol synthesis and a regulator of epidermal growth factor receptor (EGFR) trafficking pathways, has attracted interest as a therapeutic target due to its crucial relevance to cholesterol-related diseases and carcinomas. However, the development of pharmacological agents for targeting NSDHL has been hindered by the absence of the atomic details of NSDHL. In this study, we reported two X-ray crystal structures of human NSDHL, which revealed a detailed description of the coenzyme-binding site and the unique conformational change upon the binding of a coenzyme. A structure-based virtual screening and biochemical evaluation were performed and identified a novel inhibitor for NSDHL harboring suppressive activity towards EGFR. In EGFR-driven human cancer cells, treatment with the potent NSDHL inhibitor enhanced the antitumor effect of an EGFR kinase inhibitor. Overall, these findings could serve as good platforms for the development of therapeutic agents against NSDHL-related diseases.

The formation and evolution of centerline carbides in a martensitic stainless steel slab are investigated using various characterization techniques. The intensive formation of carbides was observed close to the shrinkage cavity at the centerline of the slab. Carbide structures include a complex eutectic-like mixture of delta-ferrite and M7C3 phases with M6C carbides at the delta/M7C3 interface. Nano-sized M7C3 particles also precipitate in the delta holding the orientation relationship of ((1) over bar 10)(delta). (100) M7C3; [111](delta) parallel to [100]M7C3.This complex structure was surrounded by the retained gamma. The decomposition of the coarse M7C3 was investigated after the reheating treatment to 1200, 1250, and 1300 degrees C. It was found that by increasing the reheating temperature, coarse M7C3 carbide completely decomposed, whereas delta-ferrite islands enlarged due to the thermodynamic stability of delta-ferrite at high temperatures. At the same time, the retained austenite reduces because of homogenizing of the segregated solutes. The new formation of M23C6 and the growth of M6C were identified after reheating to 1200 degrees C, while all carbides were fully decomposed at 1250 and 1300 degrees C. The effect of reheating temperature on the decomposition process of coarse carbide was further discussed.

The influence of reheating temperatures on hot ductility is investigated in two Ni‐, Mo‐, and Cu‐containing low‐carbon steels. The effects of solution treatment conditions at 1623, 1673 K, and remelting at 1803 K on the reduction in area (RA) are analyzed. The results show an RA trough in the range of 973–1173 K in all experimental conditions. At 973 K, which is close to the Ae3 temperature of both steel grades, ductility drop is caused by the formation of the thin ferrite film at the prior austenite grain boundary. Higher RA values are achieved after reheating to 1623 K, mainly due to smaller austenite grain size by the action of preformed precipitation throughout the matrix. In contrast, increased reheating temperatures result in relatively poor RA values because of the large austenite grain size due to the dissolution of preformed precipitate and reprecipitation at the grain boundaries during cooling. A comparison between two steel grades shows that better ductility at 973 K is achieved in low Ni‐containing steel due to the relatively thick ferrite film. The effects of alloy composition and preformed precipitate's existence on hot ductility are further discussed based on the matrix strengthening and reprecipitation behavior.

Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF 1 R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF 1 R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists—BMK-C203 and BMK-C205—and determined the CRF 1 R/BMK-C203 and CRF 1 R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF 1 R.

The role of sulfide growth behavior on the sulfur segregation at the grain boundary was studied in high-nickel steel. The alloy shows recrystallization, grain growth, and M(Ca, Mn)S growth during the holding at 800-1100 & DEG;C after applying rapid heating of 50 & DEG;C/s. As the annealing temperature increases, faster grain refinement (recrystallization) of the matrix and the growth behavior of MS are confirmed by electron backscatter diffraction and electron probe X-ray microanalyzer analyses. The segregation behavior of sulfur at the grain boundary was analyzed using Auger electron spectroscopy. The kinetics of intergranular sulfur segregation after holding at 800 & DEG;C showed time-dependent enrichment behavior, but sulfur seemed to be less segregated time-dependently during annealing at 900-1100 & DEG;C. Based on McLean's theory, a semi-quantitative calculation on the grain boundary sulfur segregation was applied without considering the sulfur-scavenging of MS and with thinking about the sulfur-scavenging of MS. The calculated result considering the sulfur-scavenging of MS better explained the experimental tendency of the grain boundary sulfur segregation at 800 & DEG;C. However, the difference between both calculations was negligible at 900-1100 & DEG;C due to the critical contribution of grain refinement.