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Roughness surfaces likely present on high-speed flight vehicles due to ablation can greatly impact the laminar-turbulent transition process. In this work, effects of a randomly distributed roughness patch with roughness Reynolds number R e k k = 474 on the stability and transition in a Mach 6.5 boundary-layer flow over a flat plate have been investigated via stability analyses and direct numerical simulation (DNS). The roughness patch induces several streamwise streaks downstream. The streaks slightly stabilize the Mack mode instability, yet sustain strongly unstable shear-layer modes, achieving a significantly larger integrated growth rate than the smooth case. The most amplified shear-layer mode extracts energy primarily through the spanwise velocity gradient and develops nonlinearly into hairpin vortices residing on the strongest low-speed streak. The hairpin vortices eventually contaminate the whole flowfield, leading to a fully turbulent state. We further assess the influences of wall-temperature ratio and the roughness geometry on the flowfield and the pertaining instability characteristics. The results reveal that the high wall-temperature ratio weakens the streak amplitudes and shear-layer instabilities; while randomly distributed roughness tends to induce larger-amplitude streaks than the regular counterpart with the same R e k k , the flowfield of the former one can even be more stable than the latter. We find that the spanwise gradient of streamwise velocity should also be considered along with the streak amplitude in determining the strength of shear-layer instabilities. [ABSTRACT FROM AUTHOR]

Nonmodal linear stability analysis results are presented for hypersonic flow over a cone at 6° angle of attack complementing earlier modal stability analysis. Based on the parallel flow assumption, singular value decomposition is applied to obtain the optimal linear combination of global crossflow modes. The optimal disturbance exhibits significant transient growth in the initial short distance and progressively follows the path of the most unstable mode downstream. The largest transient energy gain is observed for disturbances at around 40 kHz close to the most amplified modal frequency and tends to increase with the Reynolds number. The optimal disturbance initially exhibits two amplitude peaks in the azimuthal direction, one lying in the leeward region where the unstable crossflow modes reside and the other in the windward region where the adjoint modes exist. As the optimal disturbance travels downstream, the second amplitude peak rapidly shifts toward the leeward side and reaches the optimal energy gain when it eventually merges with the first amplitude peak. The evolution process of the optimal disturbance indicates that the optimal disturbance might have exploited the locally crossflow instability through traveling from the windward side to the leeward side. [ABSTRACT FROM AUTHOR]

Identifying new targets for overcoming radioresistance is crucial for improving the efficacy of lung cancer radiotherapy, given that tumor cell resistance is a leading cause of treatment failure. Recent research has spotlighted the significance of Musashi2 (MSI2) in cancer biology. In this study, we first demonstrated that MSI2 plays a key function in regulating the radiosensitivity of lung cancer. The expression of MSI2 is negatively correlated with overall survival in cancer patients, and the knockdown of MSI2 inhibits tumorigenesis and increases radiosensitivity of lung cancer cells. Cellular radiosensitivity, which is closely linked to DNA damage, is influenced by MSI2 interaction with ataxia telangiectasia mutated and Rad3‐related kinase (ATR) and checkpoint kinase 1 (CHK1) post‐irradiation; moreover, knockdown of MSI2 inhibits the ATR‐mediated DNA damage response pathway. RNA‐binding motif protein 17 (RBM17), which is implicated in DNA damage repair, exhibits increased interaction with MSI2 post‐irradiation. We found that knockdown of RBM17 disrupted the interaction between MSI2 and ATR post‐irradiation and increased the radiosensitivity of lung cancer cells. Furthermore, we revealed the potential mechanism of MSI2 recruitment into the nucleus with the assistance of RBM17 to activate ATR to promote radioresistance. This study provides novel insights into the potential application of MSI2 as a new target in lung cancer radiotherapy. [ABSTRACT FROM AUTHOR]

The interaction problem of waves with a body floating near the marginal ice zone is studied, where the marginal ice zone is modeled as an array of multiple uniformly sized floating ice sheets. The linear velocity potential theory is applied for fluid flow, and the thin elastic plate mode is utilized to describe the ice sheet deflection. A hybrid method is used to solve the disturbed velocity potential; i.e., around the floating body, a boundary integral equation is established, while in the domain covered by ice sheets, the velocity potential is expanded into an eigenfunction series, and in the far-field with a free surface, a similar eigenfunction expansion is used to satisfy the radiation condition. The boundary integral equation and the coefficients of the eigenfunction expansions are solved together based on the continuous conditions of pressure and velocity on the interface between the sub-domains. Extensive results for the equivalent Young's modulus of the ice sheet array and hydrodynamic force on the body are provided, and the effect of individual ice sheet length as well as wave parameters are investigated in detail. [ABSTRACT FROM AUTHOR]

Stability in a Mach 4.5 boundary layer over backward-facing steps (BFSs) is investigated using numerical methods. Two types of cases are considered with different laminar inflow conditions, imposed with single-frequency or broadband-frequency modes, respectively. Compared with the typical K-type transition over a flat plate, the boundary layer transition initiated by 90 kHz-frequency second mode appears to follow the same pattern but with a noticeable delay over the step. A larger step height leads to a better inhibition of the downstream Λ-vortices and thus a later transition, providing the step height is smaller than the local boundary layer thickness. Moreover, both the frequency weighted power spectral density and the root mean square of the streamwise velocity indicate the presence of Kelvin–Helmholtz (K–H) instability when the step height is equivalent to the thickness of the nearby boundary layer. There may exist an optimal step height for suppressing single-frequency (90 kHz) mode without exciting significant K–H modes. Similar to the previous studies on roughness, BFS can act as an amplifier for the low-frequency second modes and a suppressor for the high-frequency second modes. The critical frequency is equal to that of the unstable mode whose synchronization point is exactly located at the step corner. Additionally, the correction effects of the step induce the change of the phase speed of the fast mode, which correspondingly results in the movement of the synchronization point. Generally, the BFS is not able to completely alleviate the transition initiated by the broadband-frequency second modes but can still delay the boundary layer transition in a certain degree by suppressing the high-frequency unstable waves. [ABSTRACT FROM AUTHOR]

Gametogenesis is an essential step for malaria parasite transmission and is activated in mosquito by signals including temperature drop, pH change, and mosquito-derived xanthurenic acid (XA). Recently, a membrane protein gametogenesis essential protein 1 (GEP1) was found to be responsible for sensing these signals and interacting with a giant guanylate cyclase α (GCα) to activate the cGMP-PKG-Ca2+ signaling pathway for malaria parasite gametogenesis. However, the molecular mechanisms for this process remain unclear. In this study, we used AlphaFold2 to predict the structure of GEP1 and found that it consists of a conserved N-terminal helical domain and a transmembrane domain that adopts a structure similar to that of cationic amino acid transporters. Molecular docking results showed that XA binds to GEP1 via a pocket similar to the ligand binding sites of known amino acid transporters. In addition, truncations of this N-terminal sequence significantly enhanced the expression, solubility, and stability of GEP1. In addition, we found that GEP1 interacts with GCα via its C-terminal region, which is interrupted by mutations of a few conserved residues. These findings provide further insights into the molecular mechanism for the XA recognition by GEP1 and the activation of the gametogenesis of malaria parasites through GEP1-GCα interaction. [ABSTRACT FROM AUTHOR]

Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs (1). Menin interacts with many proteins and is involved in a variety of cellular processes (2-8). Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity (2,9). Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription (2,10). Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyl-transferase, and functions as an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis (5,7,11,12). A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins (13). Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1., The amino-terminal region of MLL1 interacts with menin (12,14,15). Isothermal titration calorimetry measurements showed that the menin-binding motif (residues 6-25) of MLL1 (MLL1MBM) is necessary and sufficient for menin binding [...]

A systematic parametric study is presented on the modal global linear instability of Mach 6 boundary-layer flow over an inclined cone at a 6° angle of attack under typical wind tunnel conditions. The analysis is performed using the spatial BiGlobal theory. Results reveal two classes of global instabilities in the outboard region away from the leeward plane: high-frequency (hundreds of kHz) second mode instabilities and low-frequency (tens of kHz) crossflow instabilities. In the global eigenvalue spectra of the second mode instability, two distinct branches of significantly unstable modes are identified, namely, an approximately continuous spectrum (branch S) and a few discrete points (branch D). The branch D modes peak at the windward centerline, while branch S modes lie at a certain distance away from the windward meridian. The global stability characteristics of the crossflow instability over a conical configuration are uncovered for the first time. In the global eigenvalue spectra of the crossflow instability, many unstable modes emerge and form a complex pattern, with the most amplified frequency of around 30 kHz. The unstable crossflow modes are mainly distributed on the leeward side and wave angles obviously increase toward the leeward centerline. The peak growth rates are slightly smaller than those of second modes, and yet the most amplified frequency varies rather mildly along the streamwise direction so that they may achieve larger integrated growth rates than second modes do. [ABSTRACT FROM AUTHOR]

In this paper, a method of ball milling and sieving is proposed for recovery of high-grade copper from waste printed circuit boards (WPCBs). The effects of the milling time on the metals grade and recovery of the Cu, Sn and Pb during mechanical treatment were investigated. The results showed that, after 3 cycles of ball milling and sieving, the content of Cu was enriched to 94.72 wt.% from the initial 74.22 wt.% with a high recovery rate of 86.78%. Moreover, the contents of Sn and Pb were enriched to 28.27 wt.% and 18.86 wt.% from 10.13 wt.% and 6.63 wt.% in the by-products, respectively. However, excessive grinding occurred when the milling time was longer than 3 h and led to a sharp decrease in Cu recovery. The X-ray diffraction (XRD) patterns indicated that the metal phases mainly comprised pure Cu, Sn, Pb in the WPCB particles, while a Cu-Sn alloy was formed during the milling process, and the Cu-Sn alloy was also enriched in the tailings. The results presented here establish that ball milling and sieving is an alternative approach to recovering high-grade copper from WPCBs. [ABSTRACT FROM AUTHOR]

Boundary layer transition (BLT) can cause a sharp rise in heat flux and skin friction, which can seriously affect the flight performance and safety of hypersonic flight vehicles. Therefore, the mechanism, prediction and control of transition have become important issues that must be dealt with for the development of advanced flight vehicles, and it is also a research hotspot of particular interest to major aerospace countries. Compared to other transition research approaches, model flight tests can better present the transition problems under real flight conditions, thus have been carried out extensively over the past 30 years. The United States, Germany, France, Australia, and other countries have carried out transition research based on flight tests, such as the Pegasus wing-glove crossflow transition and the Hypersonic Boundary Layer Transition (HyBOLT) transition control flight test of the United States, the joint research project of the Hypersonic International Flight Research and Experimentation-1 (HIFiRE-1) circular cone and the HIFiRE-5 elliptic cone transition flight tests between the United States and Australia, the flight test of compression surface transition of the scramjet forebody (LEA) in France and so on. Although these flight tests suffered various setbacks, they still obtained valuable transition data. Recently, the United States is carrying out the concave-surface transition flight tests of Hypersonic Boundary Layer Transition (BOLT) and BOLT-II. Since its first model flight test mission for verification purpose launched successfully in 2015, several hypersonic BLT flight tests have been conducted by China Aerodynamics Research and Development Center (CARDC). The flight tests have measured valid transition data under flight conditions, obtained the transition front and its dynamical variation on blunt cones at various angles of attack and a lifting body Hypersonic Transition Research Vehicle (HyTRV). The crossflow traveling waves in high-altitude flight were measured for the first time, and our understanding of hypersonic BLT has been greatly improved. [ABSTRACT FROM AUTHOR]

The receptivity of the second mode for Mach 6 flow over a blunt wedge with a nose radius of 0.258 mm is investigated numerically. When a plane slow acoustic wave is imposed on the freestream, the receptivity process of the boundary layer goes through three stages, with the development of an entropy-layer mode, a fast mode, and nonmodal external disturbances, before exciting the second mode. The first two dominant modes can be obtained by linear stability theory in the entropy layer and the boundary layer, respectively, whereas the third is a complicated type of disturbance whose shape function peaks in the entropy layer. The results show that the nonmodal disturbances in the entropy layer play a leading role in the excitation of the second mode, which suggests that the growth of nonmodal disturbances could dominate nonmodal amplification, eventually leading to boundary-layer transition. [ABSTRACT FROM AUTHOR]

Understanding crossflow instabilities in three-dimensional boundary layers triggered by either traveling crossflow waves or stationary crossflow vortices is of great importance for modeling, predicting, and controlling hypersonic laminar-turbulent transition. However, due to very limited available flight experiment data, the crossflow instability under real flight conditions is still far from fully understood. To gain further insight, the raw data of a recent model flight experiment conducted by China Aerodynamics Research and Development Center have been thoroughly analyzed in the present study. The instrumented model is an inclined blunt cone mounted with several pressure sensors. Distinct low-frequency signals detected by these pressure sensors are peaked at about 10 kHz, which are in good agreement with the traveling-crossflow-wave frequencies with the largest N factors predicted by the eN method. Moreover, propagation velocities and wave angles of these signals obtained from correlation analysis also agree with the results from linear stability theory. The present study confirms that the detected low-frequency signals are traveling crossflow waves and provides the first evidence of traveling crossflow waves under real flight conditions. [ABSTRACT FROM AUTHOR]

Efficient pre-processing is essential to the mechanical recovery of waste printed circuit boards (WPCBs). In this work, a thermal shock pretreatment was utilized to damage the interface between metals and nonmetals of single-sided copper clad laminates (SSCCLs), which are usually employed as the base material of printed circuit boards (PCBs). The effects of three thermal shock treatment parameters—i.e., peak temperature, holding time, and thermal shock cycle times—on the adhesion strength of SSCCLs were evaluated by orthogonal experiments. Microstructures and peel resistance of SSCCLs before and after thermal shock were characterized by scanning electron microscopy (SEM) and 90° peel test, respectively. Our results showed that the impact of three major factors that influence liberation efficiency was in the sequence of peak temperature > shock cycle times > holding time. Furthermore, the optimal thermal shock level could be achieved when the peak temperature was 300°C with the soaking time of 30 min and three cycle times. In the meantime, the corresponding peel strength of the SSCCLs (0.065 N/mm) was sharply decreased by 94% in comparison with those without thermal shock treatment. The manual dismantling experimental data verified the good feasibility of the optimal thermal shock process, suggesting that the copper foil could be readily dismantled from the substrate by hand after pretreatment, with a successful separation rate of 100% and a peeling efficiency of ~ 30 seconds per piece. Therefore, the optimal thermal shock process could notably improve liberation of metals and nonmetals, which would be helpful for efficient recycling of WPCBs. Implications: The interface between copper foil and laminate dielectric in a PCB can be weakened significantly via efficient thermal shock method. Thus, a good liberation could be achieved after thermal shock. In this work, a manual peeling of copper foil from the SSCCL substrates was achieved efficiently after optimal thermal shock pretreatment, confirming the feasibility of a shorter process of metal recovery from scrap SSCCLs without pulverization. The results will be useful for the pretreatment of recovery of the WPCBs. [ABSTRACT FROM AUTHOR]

Soil multifunctionality is the consequence of biotic interactions that drive decomposition, nutrient cycling and net primary production. Energy flux describes the energy consumed and transferred among multitrophic groups in the soil food web, which are logically linked to multifunctionality. In a subtropical agroecosystem with an annual sweet potato-oilseed rape rotation, we explored how biochar and synthetic fertilizer jointly affected agroecosystem multifunctionality (e.g., crop production, soil carbon storage and nutrient cycling) and the energetic structure of the nematode food web during two consecutive years. Results showed that biochar increased soil multifunctionality by 37–110% mainly by promoting a uniform energy flow through the soil nematode food web, which was largely due to increased energy fluxes of fungivores and omnivores-carnivores at the expense of decreased energy flux through herbivores. Applying a lower rate of synthetic fertilizer led to non-uniform energy flow in the soil nematode food web, suggesting that nitrogen limitation could offset the stimulatory effect of biochar on soil multifunctionality. This was because biochar induced oligotrophic conditions (a stoichiometry-induced nitrogen limitation), effectively warranting that continuous biochar application would aggravate nutrient limitations to crops, especially when low rates of synthetic fertilizer are applied. Notably, soil nutrient impoverishment could lead to resource reallocation from aboveground shoot to belowground root production, thereby fueling the energy flow through the herbivore channel. Our findings highlight the importance of balancing biochar and synthetic fertilizer applications to sustain a stable energetic structure in soil nematode food webs, which are associated with greater crop production and soil health in subtropical region. • Biochar increased the energy flow uniformity and arable soil multifunctionality. • Energy flow uniformity was positivity related to multifunctionality. • Biochar stimulatory effects were weakened when reducing synthetic fertilizer input. • Sustaining multifunctionality needs complementary input of both biochar and nutrients. [ABSTRACT FROM AUTHOR]

Summary Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates. [ABSTRACT FROM AUTHOR]

In the present work, the effect of yttrium (Y) addition (0, 0.15, 0.3, 0.5 and 0.7 wt%) on the microstructure and tensile properties of recycled A356 cast alloys containing 1.0 wt% Fe has been studied systematically. With the addition of Y, despite no transformations of β-Fe (Al 5 FeSi) phases into α-Fe phases, the acicular β-Fe phases were refined remarkably, and the volume fraction of β-Fe phases were decreased evidently. With addition of 0.3 wt% Y, the average length of β-Fe phase decreased from ~78 µm to ~20 µm and the finest β-Fe phases were obtained, in the meantime, the eutectic silicon particles were present in fully modified form, and the secondary dendrite arm spacing (SDAS) reached the lowest value. In addition, it was proposed that according to the microstructural analysis, the Al 2 Si 2 Y intermetallic phases might be responsible for the refinement of the β-Fe phases. With addition of 0.3 wt% Y, the maximum improvement of quality index was achieved, approximately 32% in both as-cast and T6 heat treated alloys, and the corresponding Y-modified alloys in T6 heat treated condition obtained the best tensile properties compared with other experimental alloys, with the corresponding ultimate tensile strength (UTS) and elongation (EL) values being 383.86 MPa and 4.85%, respectively. Furthermore, the tensile properties of 0.3 wt% Y modified recycled Al–7Si–0.3Mg–1.0Fe alloys (T6) exceed the minimum properties standard for ZL101A alloy (JB, T6), approximately 30.12% for UTS value and 61.67% for EL value, suggesting it can be a good candidate for the commercial applications. [ABSTRACT FROM AUTHOR]