Stable State Research Articles

Enhancement of phase transition temperature through hydrogen bond modification in molecular ferroelectrics

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.

Destabilization Mechanism and Stability Study of Collapsible Loess Canal Slopes in Cold and Arid Regions

The combination of seasonal shutdowns, water conveyance, cold, and drought can easily lead to the deterioration of the anti-seepage system and loess foundation of the canal, which contributes to the destruction of the slope. To reveal the failure mechanism of the collapsible loess canal slope, this paper is based on the results of laboratory tests and adopts numerical simulations to analyze the stability of the canal slope under different conditions. The results show that the shear strength indexes and elastic modulus E of loess decrease following an exponential pattern with the increase in wetting-drying and freezing-thawing (WD-FT) cycles. The height of the seepage overflow point yields little effect on the water level behind the impermeable membrane, whereas the height of the water level has a significant effect. In the operation period, the slope under any working conditions is in a relatively stable state. However, the slope with a water level of 4.5 m behind the impermeable membrane tends to be unstable after three WD-FT cycles during the shutdown period. By replacing the surface-degraded loess with sand gravel and picking a depth of 0.9–1.2 m, the slope will maintain a long-term stable state.

Ultrafast all-optical toggle writing of magnetic bits without relying on heat

Ultrafast excitation of matter can violate Curie’s principle that the symmetry of the cause must be found in the symmetry of the effect. For instance, heating alone cannot result in a deterministic reversal of magnetization. However, if the heating is ultrafast, it facilitates toggle switching of magnetization between stable bit-states without any magnetic field. Here we show that the regime of ultrafast toggle switching can be also realized via a mechanism without relying on heat. Ultrafast laser excitation of iron-garnet with linearly polarized light modifies magnetic anisotropy and thus causes toggling magnetization between two stable bit states. This new regime of ‘cold’ toggle switching can be observed in ferrimagnets without a compensation point and over an exceptionally broad temperature range. The control of magnetic anisotropy required for the toggle switching exhibits reduced dissipation compared to laser-induced-heating mechanism, however the dissipation and the switching-time are shown to be competing parameters.

Opinion dynamics under double thresholds

In this letter, we introduce a double threshold model to investigate opinion formation in social networks, considering bi-directional binary opinion changes. We derive the law of motion for opinion evolution analytically and explore the conditions for achieving oscillation, convergence, and even consensus comprehensively. Our findings demonstrate that under asymmetric thresholds with synchronous updating, the initial fraction of both opinions tends to approach the respective switching thresholds, facilitating rapid opinion convergence. Additionally, we observe that both lower and higher levels of connectivity promote consensus formation, while moderate connectivity can lead to opinion oscillations. Furthermore, network structures with longer connections or hubs expedite consensus emergence. However, under synchronous updating, both asymmetric and symmetric double thresholds may induce opinion oscillations, impeding stable state attainment. Conversely, with asynchronous updating, opinions consistently converge. Overall, our study enhances understanding of opinion dynamics, providing insights into consensus formation and offering a theoretical foundation to address socio-political issues in diverse communities.

Smart bistable coordination complexes

AbstractSmart molecules have attracted increasing attention due to their transformative role in creating the next generation of smart structures and devices. Smart bistable coordination complexes are a class of functional complexes which have two stable states that can be reversibly switched in response to external stimuli. Such bistable molecules play a vital role in various applications, such as sensors, data storage, spintronics, smart windows, optical switches, information encryption and decryption, displays, actuators, etc. Herein, the recent research studies into the development of these smart bistable metal coordination complexes are reviewed. According to the different external stimuli, these smart bistable coordination systems have been classified and summarized, including light‐responsive systems, thermally‐responsive systems, electrically‐responsive systems, mechanically‐responsive systems, and some other cases. These systems are further subdivided according to the changes in signals (e.g., color, fluorescence, spin state, crystalline phase) under external stimuli. The design principles of each type of smart bistable metal complexes as well as their broad and innovative applications are comprehensively described. Finally, the challenges and opportunities in this field are briefly analyzed and discussed.

Homeostasis and evolution in relation to regeneration and repair.

Homeostasis constitutes a key concept in physiology and refers to self-regulating processes that maintain internal stability when adjusting to changing external conditions. It diminishes internal entropy constituting a driving force behind evolution. Natural selection might act on homeostatic regulatory mechanisms and control mechanisms including homeodynamics, allostasis, hormesis and homeorhesis, where different stable stationary states are reached. Regeneration is under homeostatic control through hormesis. Damage to tissues initiates a response to restore the impaired equilibrium caused by mild stress using cell proliferation, cell differentiation and cell death to recover structure and function. Repair is a homeorhetic change leading to a new stable stationary state with decreased functionality and fibrotic scarring without reconstruction of the 3-D pattern. Mechanisms determining entrance of the tissue or organ to regeneration or repair include the balance between innate and adaptive immune cells in relation to cell plasticity and stromal stem cell responses, and redox balance. The regenerative and reparative capacities vary in different species, distinct tissues and organs, and at different stages of development including ageing. Many cell signals and pathways play crucial roles determining regeneration or repair by regulating protein synthesis, cellular growth, inflammation, proliferation, autophagy, lysosomal function, metabolism and metalloproteinase cell signalling. Attempts to favour the entrance of damaged tissues to regeneration in those with low proliferative rates have been made; however, there are evolutionary constraint mechanisms leading to poor proliferation of stem cells in unfavourable environments or tumour development. More research is required to better understand the regulatory processes of these mechanisms.

Electrical and optical properties of environmental friendly Li(1‐x)Smx/3NbO3 ceramics for high‐temperature energy storage applications

AbstractThis research article delves into the synthesis and characterization of Li(1‐x)Sm(x/3)NbO3 ceramic, employing a high‐energy ball milling process. The investigation explores the incorporation of Sm3+ at the Li+1 site across a range of compositions (x = 0, 0.01, 0.02, 0.03, 0.04, 0.05). Structural analysis, using x‐ray diffraction (XRD) and Rietveld structural refinement, establishes that within the investigated composition range, no significant changes in the crystal structure are evident. The x‐ray photoelectron spectroscopy revealed the presence of oxygen vacancies as well as the stable oxidation state of different elements like O2−, Nb5+, Sm3+, and Li1+. At sintering temperature 1050°C, the average grain sizes vary approximately from 1.5 to 3.8 μm for different compositions with regular grain morphology. The UV‐Vis analysis reveals a noteworthy reduction in the band gap to 3.09 eV for the x = 0.01 composition. Photoluminescence studies exhibit distinct green, orange, and red bands, with the highest intensity observed for x = 0.01, showcasing promising optical properties. The dielectric permittivity of Sm‐substituted compositions surpasses the response of pure LiNbO3, demonstrating an increasing trend with temperature in the frequency range 100 Hz‐1 MHz intriguingly, no Curie temperature is observed up to 500°C for any composition. The polarization vs electric field hysteresis loop response highlights better polarization characteristics at the room temperature and maximum polarization is 0.66 μC/cm2 for the composition x = 0.05. The energy storage response of the developed compositions is investigated, which reveals a maximum efficiency of 46.64% for x = 0.04 in Li(1‐x)Sm(x/3)NbO3. The tunable optical properties, enhanced dielectric response, and notable energy efficiency of these high TC ceramics suggest their utility across diverse applications. These findings not only contribute to the understanding of functional ceramic materials but also pave the way for their optimized utilization in advanced technological applications, particularly in energy storage devices under nonambient conditions at high temperatures.

#1779 Assessment of inflammation score in immune cells of atypical hemolytic uremic syndrome using single-cell sequencing analysis

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening form of thrombotic microangiopathy (TMA) characterized by a complex interplay of genetic and immunological factors. Historically, research into aHUS has primarily focused on genes associated with complement activation and coagulation pathways. Our previous studies, employing single cell sequencing analysis, have revealed a significant association between aHUS and various immune cell types [1]. The clinical manifestation of aHUS is often initiated by infections, autoimmune diseases, or pregnancy, with many instances not reverting to a stable state even after the elimination of these triggering factors. Additionally, a significant portion of patients, despite lacking identifiable anomalies in complement or coagulation genes, respond positively to anti-complement therapy. This observation suggests a potential role for inflammation-related genes in the pathogenesis of aHUS. Given the extensive array of genes linked to inflammation, our study is designed to quantitatively assess inflammation gene expression, converting these measures into an inflammation score for each immune cell type in aHUS patients, their nuclear families, and healthy controls. This approach allows for a detailed comparison of disease activity variations within aHUS cases, aiming to deepen our understanding of aHUS and explore new avenues for therapeutic intervention. Method This study enrolled 13 aHUS patients, 3 nuclear families without aHUS, and 4 healthy subjects from Taiwan. Peripheral blood samples were collected for single-cell RNA sequencing analysis. aHUS patients were categorized into stable and unstable groups. The definition of stable disease activity is characterized by consistent TMA-related organ involvement and normal markers of hemolysis. Single-cell RNA sequencing data was processed using CellRanger and analyzed using the Seurat package in R. We obtained inflammatory genes from the Molecular Signatures Database, and we used the AddModuleScore function in Seurat to calculate inflammation score (IS). Results Our analysis demonstrated that non-switch memory B cells, classical monocytes, intermediate monocytes, non-classical monocytes, low-density basophils, naïve CD8 T cells, central memory CD8 T cells, terminal effector CD4 T cells, Th1 cells, Th17 cells, Th1/Th17 cells, and follicular helper T cells had the highest IS in aHUS patients, followed by aHUS patients' nuclear family members without aHUS and healthy control subjects. Furthermore, we observed that the IS of classical monocytes, non-switch memory B cells (Fig. 1), intermediate monocytes, non-classical monocytes, naïve CD8 T cells, central memory CD8 T cells, non-vd2 gd T cells, terminal effector CD4 T cells, Th17 cells, and follicular helper T cells were highest in aHUS patients with unstable disease activity, followed by aHUS patients with stable disease activity, aHUS patients' nuclear family members without aHUS, and healthy control subjects. Conclusion Our study underscores a pivotal link between elevated inflammation scores and aHUS severity aHUS. This finding not only emphasizes the critical role of inflammation in disease progression but also opens new avenues for therapeutic intervention, particularly in cases of unstable aHUS. By highlighting inflammation as a key factor in aHUS pathophysiology, our research offers fresh insights for disease management and future investigations. Moreover, exploring anti-inflammatory pathways presents promising therapeutic possibilities, potentially leading to improved patient outcomes and enhanced management strategies for aHUS.

Preparation, structure and spectral characteristics of Zinc tellurite glasses system doped with different concentrations of Tm3+

Gallium-tellurite glass is a new optical material with good transmittance in the infrared region up to 6.5[Formula: see text][Formula: see text]. Three different tellurate glasses were prepared: TeO2–ZnO–Ga2O3(TZG), TeO2–ZnO–La2O3(TZL) and TeO2–ZnO–B2O3(TZB). X-ray diffraction indicates that no crystal precipitates in the three glass systems, which maintain a stable glass state. Raman scattering experiments and fluorescence emission spectroscopy measurements were carried out on the tellulate glasses doped with the same concentration of Tm[Formula: see text]. It was found that the phonon energy of TZG(TeO2–ZnO–Ga2O3)-doped thulium glass is the lowest, and the emission light at 1380[Formula: see text]nm is the strongest with [Formula: see text][Formula: see text]nm fluorescence FWHM. These results show that Tm-doped TZG glass is a good luminescent material. Refractive indices were measured by the minimum deviation method. Sellmeier dispersion equation is obtained, which can be used to calculate the refractive index within visible and near-infrared spectral range. Furthermore, different Tm[Formula: see text] concentrations (0.4%, 0.8%, 1.2% and 2%) TZG glasses were prepared, the emission spectra and fluorescence lifetime were measured, and the emitted light was strongest when the thulium ion doping concentration is 1.2%. All the results suggest that these newly developed ternary tellurite glass systems are promising candidates for near/mid-infrared laser glass fibers, fiber amplifiers, or lasers.

Learning the Optimal Control for Evolving Systems with Converging Dynamics

We consider a principle or controller that can pick actions from a fixed action set to control an evolving system with converging dynamics. The actions are interpreted as different configurations or policies. We consider systems with converging dynamics, i.e., if the principle holds the same action, the system will asymptotically converge (possibly requiring a significant amount of time) to a unique stable state determined by this action. This phenomenon can be observed in diverse domains such as epidemic control, computing systems, and markets. In our model, the dynamics of the system are unknown to the principle, and the principle can only receive bandit feedback (maybe noisy) on the impacts of his actions. The principle aims to learn which stable state yields the highest reward while adhering to specific constraints (i.e., optimal stable state) and to immerse the system into this state as quickly as possible. A unique challenge in our model is that the principle has no prior knowledge about the stable state of each action, but waits for the system to converge to the suboptimal stable states costs valuable time. We measure the principle's performance in terms of regret and constraint violation. In cases where the action set is finite, we propose a novel algorithm, termed Optimistic-Pessimistic Convergence and Confidence Bounds (OP-C2B), that knows to switch an action quickly if it is not worth waiting until the stable state is reached. This is enabled by employing "convergence bounds" to determine how far the system is from the stable states, and choosing actions through maintaining a pessimistic assessment of the set of feasible actions while acting optimistically within this set. We establish that OP-C2B can ensure sublinear regret and constraint violation simultaneously. Particularly, OP-C2B achieves logarithmic regret and constraint violation when the system convergence rate is linear or superlinear. Furthermore, we generalize our algorithm OP-C2B to the case of an infinite action set and demonstrate its ability to maintain sublinear regret and constraint violation. We finally show two game control problems including mobile crowdsensing and resource allocation that our model can address.

Comparative Analysis of the Slope Stability Using Slide and Plaxis 2D Software: A Case Study of Tombel Pozzolan Quarry (South-West Cameroon)

The presented study attempted to use coupled finite element numerical (FEM) and analytical limit equilibrium (LEM) procedures to provide comparative graphical charts demonstrating the geometry, the groundwater condition, the safety factor, and the characteristics of the support, which were implemented in the Dangote Pozzolan quarry at Tombel to preventing the slope instability’s occurrence. Field and laboratory work have been carried out to collect and characterize data. The results obtained with the LEM procedure via Slide 2D showed a safety factor of 0.87, indicating an unstable slope compared to a safety factor of 1.0 obtained with the FEM procedure via Plaxis 2D corresponding to a limited equilibrium state of the slope. The characteristics of the support that can be used to stabilize the slopes are geotextile support of 100% strip coverage, a tensile strength of 100 kN/m, an adhesion property of 4 kPa, and a frictional angle of 40°. The geotextile is anchored at the slope surface. After the support has been introduced, and the new safety factor calculated, the support automatically increased the safety factor value from 0.87 to 1.51 by using Slide 2D and from 1.0 to 1.98 by using Plaxis 2D, which is from an unstable state to a very stable state.

Structural stability, electronic, magnetic, thermoelectric, optical and thermodynamic properties of CoTiFeGe and Co2Fe0.25Mn0.75-xTixGe alloys

Density Functional Theory (DFT) calculations are performed using full potential linearized augmented plane wave (FP-LAPW) method to study CoTiFeGe and Co2Fe0.25Mn0.75-xTixGe (x = 0, 0.25, 0.50, 0.75) systems through GGA and mBJ-GGA formalisms. The lattice equilibrium optimization was conducted to determine the stable magnetic phase state of these systems. It was found that the systems exhibit stability in a ferromagnetic nature, with the exception of the Co2Fe0.25Mn0.75Ge compound, which displays ferrimagnetic behavior. Electronic band structures and density of states for our systems show a half-metallic character using mBJ-GGA, except the Co2Fe0.25Mn0.75Ge system, which exhibits metallic behavior. Furthermore, the studied systems adhere to the Slater-Pauling rule condition for half-metallicity of alloys Mtot = ZV-24. Optoelectronic properties have been analyzed using optical parameters, confirming semiconducting behavior. Optical reflections with minimal loss and the existence absorption are observed in the infrared and visible areas suggest that the studied systems are suitable for optoelectronic devices. Additionally, a comprehensive assessment of the thermodynamic properties of the systems was carried out to investigate their thermodynamical stability against temperature and pressure change. The transport properties of these systems were systematically investigated, revealing that our alloys present the poor thermoelectric matter.

Validation of Ecology and Energy Parameters of Diesel Exhausts Using Different Fuel Mixtures, Consisting of Hydrogenated Vegetable Oil and Diesel Fuels, Presented at Real Market: Approaches Using Artificial Neural Network for Large-Scale Predictions

Machine learning models have been used to precisely forecast emissions from diesel engines, specifically examining the impact of various fuel types (HVO10, HVO 30, HVO40, HVO50) on the accuracy of emission forecasts. The research has revealed that models with different numbers of perceptrons had greater initial error rates, which subsequently reached a stable state after further training. Additionally, the research has revealed that augmenting the proportion of Hydrogenated Vegetable Oil (HVO) resulted in the enhanced precision of emission predictions. The use of visual data representations, such as histograms and scatter plots, yielded significant insights into the model’s versatility across different fuel types. The discovery of these results is vital for enhancing engine performance and fulfilling environmental regulations. This study highlights the capacity of machine learning in monitoring the environment and controlling engines and proposes further investigation into enhancing models and making real-time predictive adjustments. The novelty of the research is based on the determination of the input interface (a sufficient amount of input parameters, including chemical as well as technical), which characterizes the different regimes of the diesel engine. The novelty of the methodology is based on the selection of a suitable ANN type and architecture, which allows us to predict the required parameters for a wide range of input intervals (different types of mixtures consisting of HVO and pure diesel, different loads, different RPMs, etc.).

Nonlinear dynamic characteristics of mechatronics integrated planetary gears considering wear and temperature effects

The electromechanical planetary gear system has high work efficiency and long service life, but factors such as heat, wear, and electrical signals can affect the transmission performance of electromechanical planetary gears. This article comprehensively considers factors such as temperature, tooth surface wear, lubrication, current and voltage, damping ratio, etc. Based on the principle of thermal deformation, Archard wear model, and equivalent circuit principle, a dynamic model of electromechanical planetary gears is established. The existing literature has not comprehensively analyzed the effects of temperature, wear, and electrical signal changes on the nonlinear characteristics of electromechanical planetary gear systems. The results show that when the motor current is between 7 A and 18 A and the voltage is lower than the rated voltage, the system is in a stable state; as the temperature rises, the system tends to stabilize; the gear wear exceeds 30 μm, and the bifurcation characteristics of the system are more pronounced.

Combined Effect of Underlayer and Deposition Solution to Optimize the Alignment of Hematite Photoanodes.

This study investigates the optimization of hematite (α-Fe2O3) photoanodes for enhanced photoelectrochemical (PEC) performance and reproducibility, which are crucial for photocatalytic applications. Despite hematite's potential, hindered by inherent limitations, significant improvements were realized by introducing a titanium dioxide (TiO2) underlayer and ethanol-modified deposition. The influence of the deposition methods was understood by potential-dependent photoelectrochemical impedance spectroscopy analysis. The introduction of the TiO2 underlayer effectively increased the density of states, preferable for the electron transport in the bulk hematite, and the ethanol deposition on a TiO2 underlayer led to a stable surface state formation (S1 state) for the photoexcited hole transfer. This analysis illuminated the intricate interplay between electron transport in the bulk and photogenerated hole transfer at the solution interface, thereby facilitating smoother charge transfer. These findings underscore the viability of surface engineering and meticulous process optimization in addressing critical challenges in photocatalyst development.

Thermal-Stabilized Protonated TiO2 for Heat-Accelerated Photoelectrochemical Water Splitting.

Enhancing the charge separation efficiency is a big challenge that limits the energy conversion efficiency of photoelectrochemical (PEC) water splitting. Surface states generated by protonation of TiO2 are the efficient charge separation passageways to massively accept or transfer the photogenerated electrons. However, a challenge is to avoid the deprotonation of a protonated TiO2 photoelectrode at the operation temperature. Here, we found that the terminal hydroxyl group (OHT) as surface states on the TiO2 surface generated via electrochemical protonation of TiO2 at 90 °C [90-TiO2-x-(OH)x] is thermally stable. As a result, the thermally enhanced photocurrent of the 90-TiO2-x-(OH)x electrode reached 1.05 mA cm-2 under 80 °C, and the stability was maintained up to 10 h with a slight photocurrent decrease of 3%. The thermally stable surface states as charge separation paths provide an effective method to couple the heat field with the PEC process via thermal-stimulating hopping of polarons.

Möbius group actions in the solvable chimera model

We study actions of Möbius group on two sub-populations in the solvable chimera model proposed by Abrams et al. Dynamics of global variables are given by two coupled Watanabe–Strogatz systems, one for each sub-population. At the first glance, asymptotic dynamics in the model seem to be very simple. For instance, in the stable chimera state distributions of oscillators perform a simple rotation after a certain (sufficiently large) moment. However, a closer look unveils that dynamics are subtler that what can be observed from evolution of densities of oscillators’ phases. In order to gain the full picture, one needs to investigate dynamics on the transformation group that acts on these densities. Such an approach emphasizes impact of the “hidden” variable that is not visible on macroscopic level. More precisely, we demonstrate that the chimera model is an intriguing example of the classical system that exhibits the holonomy in fiber bundles of the group of Möbius transformations.

ELECTRONIC PARAMETERS OF CONFORMATIONAL STATES OF ABETA-AMYLOID PEPTIDE (25-35)

ELECTRONIC PARAMETERS OF CONFORMATIONAL STATES OF ABETA-AMYLOID PEPTIDE (25-35)

Unraveling the interplay between the leucine zipper and forkhead domains of FOXP2: Implications for DNA binding, stability and dynamics.

FOXP2 is a transcription factor associated with speech and language. Like other FOX transcription factors, it has a DNA binding region called the forkhead domain (FHD). This domain can exist as a monomer or a domain swapped dimer. In addition to the FHD, the leucine zipper region (LZ) of FOXP2 is also believed to be associated with both DNA binding and oligomerization. To better understand the relationship between DNA binding and oligomerization of FOXP2, we investigated its structure, stability and dynamics, focusing specifically on the FHD and the LZ. We did this by using two constructs: one containing the isolated FHD and one containing both the LZ and the FHD (LZ-END). We demonstrate in this work, that while the FHD maintains a monomeric form that is capable of binding DNA, the LZ-END undergoes a dynamic transition between oligomeric states in the presence of DNA. Our findings suggest that FOXP2's LZ domain influences DNA binding affinity through a change in oligomeric state. We show through hydrogen exchange mass spectroscopy that certain parts of the FHD and interlinking region become less dynamic when in the presence of DNA, confirming DNA binding and oligomerization in these regions. Moreover, the detection of a stable equilibrium intermediate state during LZ-END unfolding supports the idea of cooperation between these two domains. Overall, our study sheds light on the interplay between two FOXP2 domains, providing insight into the protein's ability to respond dynamically to DNA, and enriching our understanding of FOXP2's role in gene regulation.

SHP2-EGFR States in Dephosphorylation Can Inform Selective SHP2 Inhibitors, Dampening RasGAP Action.

SHP2 is a positive regulator of the EGFR-dependent Ras/MAPK pathway. It dephosphorylates a regulatory phosphorylation site in EGFR that serves as the binding site to RasGAP (RASA1 or p120RasGAP). RASA1 is activated by binding to the EGFR phosphate group. Active RASA1 deactivates Ras by hydrolyzing Ras-bound GTP to GDP. Thus, SHP2 dephosphorylation of EGFR effectively prevents RASA1-mediated deactivation of Ras, thereby stimulating proliferation. Despite knowledge of this vital regulation in cell life, mechanistic in-depth structural understanding of the involvement of SHP2, EGFR, and RASA1 in the Ras/MAPK pathway has largely remained elusive. Here we elucidate the interactions, the factors influencing EGFR's recruitment of RASA1, and SHP2's recognition of the substrate site in EGFR. We reveal that RASA1 specifically interacts with the DEpY992LIP motif in EGFR featuring a proline residue at the +3 position C-terminal to pY primarily through its nSH2 domain. This interaction is strengthened by the robust attraction of two acidic residues, E991 and D990, of EGFR to two basic residues in the BC-loop near the pY-binding pocket of RASA1's nSH2. In the stable precatalytic state of SHP2 with EGFR (DADEpY992LIPQ), the E-loop of SHP2's active site favors the interaction with the (-2)-position D990 and (-4)-position D988 N-terminal to pY992 in EGFR, while the pY-loop constrains the (+4)-position Q996 C-terminal to pY992. These specific interactions not only provide a structural basis for identifying negative regulatory sites in other RTKs but can inform selective, high-affinity active-site SHP2 inhibitors tailored for SHP2 mutants.