This work aimed to evaluate the therapeutic efficacy of clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleic acid (RNA) nanoparticles (NPs) in the therapy of cervical cancer (CC) using ultrasound elastography imaging. Using poly(β-amino esters) (PBAE), CRISPR RNA NPs encapsulating Human Papillomavirus 16 (HPV16) E7, namely Poly(β-amino ester) (PBAE)/CRISPR16E7-GFP and PBAE/shRNA-16E7, were prepared. The characterization of these NPs was conducted using transmission electron microscopy (TEM) and laser diffraction particle size analysis. The cytotoxicity of PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs on CC cell lines SiHa, HeLa, and CaSki was assessed using the cell counting kit-8 (CCK-8) assay. Sixty female Sprague Dawley (SD) rats were rolled into six groups randomlyas follows: the blank Ctrl group (Group A, no treatment), the model group (Group B, CC model), the pSpCas9-GFP plasmid group (Group C, CC model + pSpCas9-GFP), the PBAE/CRISPR-16E7 group (Group D, CC model + PBAE/CRISPR-16E7), the pSIREN-U6-shRNA-CMV-iRFP plasmid group (Group E, CC model + pSIREN-U6-shRNA-CMV-iRFP), and the PBAE/shRNA-16E7 group (Group F, CC model + PBAE/shRNA-16E7), each consisting of 10 rats. The impact of NPs on the expression levels (ELs) of HPV16E7 and RB1 proteins in tumor tissues was assessed using Western Blot (WB) analysis. Additionally, ultrasound elastography imaging was employed to analyze the strain ratio (SR) and shear wave velocity (SWV) in lesions of various rat groups. The results indicated that the PBAE/CRISPR16E7-GFP NPs exhibited a particle size of 125.64 ± 7.8 nm, a zeta potential of 19.17 ± 3.61 mV, and a polydispersity index (PDI) of 0.281 ± 0.03. These NPs demonstrated a regular spherical structure with a compact morphology. The PBAE/shRNA-16E7 NPs displayed a particle size of 112.93 ± 9.1 nm, a zeta potential of 13.54 ± 1.39 mV, and a PDI of 0.185 ± 0.03. They exhibited a uniform distribution of spherical shape with regularity in size. The plasmids within PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs exhibited distinct trends of burst and sustained release. The viability of SiHa, HeLa, and CaSki cells remained unaffected by PBAE/CRISPR16E7-GFP NPs. At various mass ratios, neglectable differences (P > 0.05) were observed in cell viability of SiHa, HeLa, and CaSki cells treated with PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs relative to Ctrl group. Relative to Group B, both Groups C and E exhibited a drastic decrease in tumor volume, tumor mass, and HPV16E7 protein ELs (P < 0.05), whereas Groups D and F showed a notably greater reduction in tumor volume, tumor mass, and HPV16E7 protein ELs (P < 0.01). The HPV16E7 protein ELs, SR, and SWV values greatly increased (P < 0.001) in tumors of Group B rats while the EL of RB1 protein notably decreased (P < 0.001) versus Group A. Groups C and E demonstrated elevated HPV16E7 ELs, SR, and SWV values (P < 0.05), with a marked decrease in RB1 protein EL (P < 0.001). Group F exhibited a notable reduction in HPV16E7 protein levels, SR, and SWV values (P < 0.001).The CRISPRRNA NPs composed of PBAE encapsulating HPV16 E7, namely PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 plasmids, demonstrated a significant role in CC therapy. These NPs hold potential application value in the treatment of HPV-related CC, indicating their importance in addressing this particular disease.
Medical physics. Medical radiology. Nuclear medicine, Nuclear engineering. Atomic power
High purity germanium detectors play an increasingly significant role in particle physics and astrophysics, particularly in low-background radiation measurement experiments, due to their exceptional energy resolution, high detection efficiency. These detectors are especially critical in the search for rare events, such as neutrinoless double-beta decay (0vββ) and direct detection of dark matter, as they operate effectively under extremely low-background conditions. To fully leverage the advantages of HPGe detectors, a specifically tailored front-end readout system was required to minimize the contribution of electronic noise from the system itself. This noise minimization is critical to ensure that weak event signals from inside the detector are not obscured by the system’s inherent noise. In this paper, the design of a multi-channel, low-noise charge-sensitive amplifier (CSA) optimized for use with coaxial HPGe detectors was proposed, particularly those with large input capacitance. Large-capacitance detectors tend to introduce significant input noise, which degrades the overall energy resolution of the system. Therefore, higher standards are necessary for the noise performance of front-end electronics in such systems to preserve the excellent resolution that HPGe detectors can achieve. In multi-stage amplification systems, the noise performance is primarily influenced by the first amplification stage, where the noise characteristics of the input transistor play a crucial role. To address this, the input transistor was designed using an optimized noise model, iterative simulations, and a specially engineered layout structure to ensure low noise. However, larger transistor sizes can lead to gate leakage currents, which can alter the baseline of the amplifier output. To address this issue, a low-noise CSA circuit with a feedback resistor module for leakage current compensation was developed. This resistor feedback module mitigates sensitivity to power supply variations, temperature changes, and process deviations, and can compensate for leakage currents up to several micro amperes. Importantly, the circuit is self-biased, eliminating the need for external bias to adjust the feedback resistance value. The proposed amplifier demonstrated a rise time of less than 50 ns when used with a detector capacitance of 10 pF, and no oscillations were observed under these conditions. At low temperatures, the amplifier exhibits outstanding noise performance, with a noise level as low as 5.6 electrons. Additionally, it provides an output conversion gain of 5 mV/fC, a linearity deviation of only 0.15%, and a low static power consumption of 12.5 milliwatts. The performance achieved is sufficient for gamma-ray spectroscopy and pulse shape analysis using coaxial high purity germanium detectors.
There is evidence that the properties of hadrons are modified in a nuclear medium. Information about the medium modifications of the internal structure of hadrons is fundamental for the study of dense nuclear matter and high-energy processes, including heavy-ion and nucleus--nucleus collisions. At the moment, however, empirical information about medium modifications of hadrons is limited; therefore, theoretical studies are essential for progress in the field. In the present work, we review theoretical studies of the electromagnetic and axial form factors of octet baryons in symmetric nuclear matter. The calculations are based on a model that takes into account the degrees of freedom revealed in experimental studies of low and intermediate square transfer momentum $q^2=-Q^2$: valence quarks and meson cloud excitations of baryon cores. The formalism combines a covariant constituent quark model, developed for a free space (vacuum) with the quark--meson coupling model for extension to the nuclear medium. We conclude that the nuclear medium modifies the baryon properties differently according to the flavor content of the baryons and the medium density. The effects of the medium increase with density and are stronger (quenched or enhanced) for light baryons than for heavy baryons. In particular, the in-medium neutrino--nucleon and antineutrino--nucleon cross-sections are reduced compared to the values in free space. The proposed formalism can be extended to densities above the normal nuclear density and applied to neutrino--hyperon and antineutrino--hyperon scattering in dense nuclear matter.
I consider the so-called nuclear polarization correction to the 1S-levels in light to intermediate muonic atoms. An easy to use recipe to compute it is given. The calculation includes the effect of the nucleon polarization, i.e. the contribution from inelastic states in the hadronic range, and Coulomb corrections beyond the leading logarithm approximation to both nuclear and nucleon polarization. I provide numerical estimates for $4\leq Z\leq41$, compare to the estimates in the literature and discuss the need for future improvements.
Large language models (LLMs) have rapidly gained popularity and are being embedded into professional applications due to their capabilities in generating human-like content. However, unquestioned reliance on their outputs and recommendations can be problematic as LLMs can reinforce societal biases and stereotypes. This study investigates how LLMs, specifically OpenAI's GPT-4 and Microsoft Copilot, can reinforce gender and racial stereotypes within the software engineering (SE) profession through both textual and graphical outputs. We used each LLM to generate 300 profiles, consisting of 100 gender-based and 50 gender-neutral profiles, for a recruitment scenario in SE roles. Recommendations were generated for each profile and evaluated against the job requirements for four distinct SE positions. Each LLM was asked to select the top 5 candidates and subsequently the best candidate for each role. Each LLM was also asked to generate images for the top 5 candidates, providing a dataset for analysing potential biases in both text-based selections and visual representations. Our analysis reveals that both models preferred male and Caucasian profiles, particularly for senior roles, and favoured images featuring traits such as lighter skin tones, slimmer body types, and younger appearances. These findings highlight underlying societal biases influence the outputs of LLMs, contributing to narrow, exclusionary stereotypes that can further limit diversity and perpetuate inequities in the SE field. As LLMs are increasingly adopted within SE research and professional practices, awareness of these biases is crucial to prevent the reinforcement of discriminatory norms and to ensure that AI tools are leveraged to promote an inclusive and equitable engineering culture rather than hinder it.
For the developmental and risk-evaluation phases of next-generation nuclear power platforms — specifically those utilizing liquid metal as a coolant — the availability of high-resolution thermo-hydraulic computational frameworks is indispensable. This paper details the implementation and validation of a second-order Total Variation Diminishing (TVD) scheme within the thermal-hydraulic analysis module of the Fast Reactor Transient Analysis Code (FRTAC), a system analysis software developed by the China Institute of Atomic Energy. The primary objective was to enhance the code’s predictive accuracy by mitigating the numerical diffusion inherent in the original first-order upwind scheme. The research involved a comprehensive reconstruction of the underlying solver, incorporating a robust flux limiter to suppress numerical oscillations at sharp gradients while preserving high-order accuracy in smooth flow regions. The newly developed module was systematically validated against two internationally recognized benchmark cases. For transient analysis, the module’s simulation of the Edwards blowdown experiment demonstrated good agreement with experimental data for the rapid depressurization process. For steady-state heat transfer analysis, simulations of the U.S. Energy Technology Engineering Center steam generator test cases A5 and A7 yielded outlet temperature predictions with a maximum relative deviation of less than 1.65% from experimental values. The validation results confirm that the enhanced module possesses the requisite accuracy and versatility for handling both severe transient and steady-state thermal-hydraulic phenomena, establishing it as a more reliable tool for reactor safety analysis.
Shivani Chaudhary, Akanksha Gupta, Sakshi Singh
et al.
The Stopping Power Ranges of Ions in Matter (SRIM) and the Transport of Ions in Matter (TRIM) package are used to study ion irradiation and deceleration. The SRIM package provides insights into expected range and energy deposition through Monte Carlo simulations, while the TRIM package focuses on ion deceleration, sputtering events, atom recoils, and damage investigations. This manuscript investigates damages induced by a diverse range of ions, spanning from 10keV to 100 keV and 1MeV and 2 MeV Au ions on a 5nm thin layer of tungsten carbide using comprehensive TRIM computations with the Full Cascade Collisions. The research shows that nuclear stopping power is more prominent in deeper places, while electronic stopping is more prevalent near the surface. Low-energy ions lose a larger fraction of their energy to recoils than high-energy ions. The study also examines ion range features, damage profiles, flaws, and the damage range and production rate for various atomic species. The results greatly affect material engineering and ion beam applications.
BackgroundEtched track dosimeters (ETDs) based on CR-39 foils are the most frequently used passive detectors for neutron personal dosimetry at various nuclear facilities. That applying a pre-treatment in carbon dioxide (hereafter, CO2 pre-treatment) can improve the CR-39 detection sensitivity and enlarge the tracks is extremely valuable and warrants further investigation.PurposeThis study aims to investigate the effect of CO2 pre-treatment on the sensitivity and the track size distributions of CR-39 detectors, and to obtain an optimal CO2 pre-treatment condition.MethodsA parametric study was conducted to evaluate the effect of CO2 pre-treatments at different pressures and durations on CR-39 detectors. The detectors were firstly irradiated by a standard 252Cf neutron source, delivering a personal dose equivalent Hp(10) of 2 mSv. Then, the detectors were subjected to carbon dioxide treatment prior to undergoing chemical etching for durations ranging from 6 h to 168 h at partial pressures varying between 0.1 MPa to 1.6 MPa. Finally, the correlation between detector sensitivity and pre-treatment condition was obtained by analyzing the number of registered tracks and track size distribution under each pre-treatment condition.ResultsThe obtained results indicate that the CO2 pre-treatment significantly improves sensitivity and maximum track size, with the sensitivity increasing by up to 870% and the maximum track size expanding from 20 μm to 40 μm. The sensitivity increases linearly with pre-treatment pressures, and the saturation point of the maximum track size appears around 40 μm. As the time and pressure continue to increase, the neutron spectrometry information contained in the track size distributions will be erased, the optimal sensitivity for CR-39 to retain the spectral information in the track size distributions is 6.25 tracks·mm-2·mSv-1.ConclusionsThis study is of significance for improving the sensitivity of CR-39 detectors in neutron dosimetry and selecting CO2 pre-treatment conditions, providing a processing method to enhance the track readability whilst preserving the spectral information in the track distributions for practical applications of CR-39 detectors in neutron dosimetry and spectrometry.
ZHANG Kaihui, ZHUANG Kun, ZHANG Xinxin, WANG Senshan, DENG Lina, WANG Yongzhan, WANG Yingzhen
Space heat pipe reactors have the advantages of miniaturization, long life, and strong environmental adaptability, and have broad application prospects in the aerospace field. This study focused on a high-enrichment space heat pipe reactor KRUSTY-HEU proposed by Los Alamos National Laboratory. While maintaining the reactivity, the volume was optimized by adding moderator materials to reduce the control rod’s volume and the reflector thickness to decrease spacecraft launch costs and launch loads. In terms of moderator selection, zirconium hydride was selected by comparing the moderator materials commonly used in space reactor with yttrium hydride. For moderator configuration, three schemes including a moderator located inside the core, in the middle, and dispersed in fuel were proposed, and reactivity and safety were analyzed. Three schemes added the same amount of moderator, and the scheme with the largest initial excess reactivity was selected. The results show that the scheme of moderator located inside the core is better than the other two schemes, and the minimum reflector thickness is 8.69 cm, which is 3.11 cm less than before, and the volume is reduced by about 30%. And the reactor remains subcritical state when the control rod is fully inserted and in an unexpected dropping accident. The neutronics and thermal-mechanics were carried out for the optimized scheme. The results show that the fuel temperature has little influence on the reactivity, besides the reactivity do not change with the change of moderator temperature. Moving reflector can control the reactivity effectively, the differential value of the reflector control is highest when the radial reflector moves about 20 cm. The reactivity caused by burnup is small, when the reactor runs for 15 years, the reactivity is basically unchanged, due to the low power of 4.3 kW. During normal operation, the core temperature and thermal displacement are not much different from before, and the maximum thermal stress is about 200 MPa at the interface of moderator and core, which exceeds the yield limit of core material. The thermal stress is effectively reduced to about 63.3 MPa within the yield limit of the material by adding a gap between the moderator and the core. Single pipe failure analysis shows that core temperature, displacement and thermal stress have changed, but it do not affect its safety. In summary, the moderator located inside the core scheme proposed in this study can effectively reduce the volume of KRUSTY-HEU, and the thermal-mechanical coupling characteristics show that the optimized core still has high safety and stability.
ZOU Hang1,2, CHEN Ying3, ZHANG Qian4, CAO Wei4, ZHANG Jinchao5, LIANG Liang6, SONG Peitao7, LIU Jie1,2
The purpose of this study is to investigate the impact of neutron anisotropic scattering on critical experimental setups and to develop a MOC (method of characteristic) program capable of handling anisotropic scattering, along with a high-performance heterogeneous parallel algorithm for high-order scattering transport calculations. In the initial stages, the physical calculations of the critical experimental setup were analyzed, revealing that neutron anisotropic scattering can significantly affect the calculation results, particularly when a thicker water reflector is present. Building upon the P1 anisotropic scattering MOC, a specialized MOC program was developed to address this issue. To validate the accuracy of the newly developed program for critical experimental simulations, the researchers selected the LCT011 critical experimental benchmark for neutronic calculations. A comprehensive comparison was performed between the results obtained from the MOC program and a Monte Carlo program, serving as a benchmark for verification. One notable challenge encountered during the study was the substantial increase in computation time and memory consumption caused by the presence of anisotropic sources. This created a significant memory burden, especially on heterogeneous systems. Consequently, the researchers conducted a thorough performance analysis of the high-order scattering transport solver employed in the program. The numerical results obtained from the study showcase that the MOC program achieves comparable accuracy to the Monte Carlo program under conditions involving high-order scattering computations. Furthermore, the researchers observed that the developed program exhibited remarkable computational efficiency, making it a promising alternative to the Monte Carlo method. By effectively addressing the impact of neutron anisotropic scattering and providing accurate results with enhanced computational efficiency, the developed MOC program holds great potential for advancing critical experimental simulations. This research significantly contributes to the field of physical calculations by offering a reliable and efficient solution for handling anisotropic scattering in high-order transport calculations. In conclusion, this study presents the purposeful investigation of neutron anisotropic scattering in critical experimental setups, resulting in the development of a specialized MOC program and a high-performance heterogeneous parallel algorithm. The validation process, conducted using the LCT011 critical experimental benchmark, confirms the accuracy of the program. The performance analysis showcases the computational efficiency of the developed program, thus establishing its viability for critical experimental simulations involving anisotropic scattering effects. This research underscores the importance of accurate neutron anisotropic scattering calculations and offers an innovative solution to address the associated challenges in the field of reactor core physical calculations.
XIANG Huawei1, 2, , , RONG Hua1, 2, 3, FAN Xinglang2, GENG Yan1, BAI Linhong4
For concrete, the strain tends to grow when the stress is kept at a constant level. This phenomenon is usually referred to as creep. Creep is an important physical property of concrete. For a prestressed concrete containment, creep could lead to prestress losses, stress redistribution, additional displacements, and even cracking. In general, the stress-strain relation of creep is nonlinear, but the principal stresses of concrete remain within the service stress range which is below 40% to 50% of the uniaxial strength. Therefore, the superposition principle can be utilized in linear elasticity, which works with the current values of stress and strain. Based on the theory of linear viscoelasticity, the principle of superposition can be used to characterize creep at a constant stress and the compliance function is used to describe the concrete creep mathematically, which facilitates numerical calculations. However, when the exponential algorithm is used to solve the creep effect of concrete, it is necessary to express the concrete creep compliance function by Dirichlet series and the calculation of the Dirichlet series corresponding to the compliance function is the key to implementing the exponential algorithm. The Weeks method for the inverse Laplace transform was used to approximate the Dirichlet series based on the continuous retardation spectrum method. The problem of approximating the concrete creep compliance function by the Weeks method was examined. First, the process of using the Weeks method to solve the continuous retardation spectrum was introduced. By taking the CEB MC90 creep model commonly used in engineering as an example, the equations for solving the concrete creep compliance function were derived by the Weeks method. The idea for improving the performance of the Weeks method was proposed. Based on this idea, the ranges of the various parameters that play a role in this solution were proposed. The numerical integration formula for the time-dependent term in the compliance function was derived. The results show that the calculation relative error with this method is no larger than ±1% when the duration is larger than 10 days. The validity of the algorithm was checked by comparing the numerical algorithm with the exact solution. This method is well suited for calculating the concrete creep compliance function for a long-term duration. The solution based on the Weeks method only requires the first-order derivative of the concrete creep compliance function to obtain the explicit function in the time domain, avoiding the complex computations of high-order derivatives and the low computational efficiency. Finally, the efficient Weeks method developed for the concrete creep model of CEB MC90 can also be extended and applied to other concrete creep models such as ACI 209R-92, JSCE, and GL2000.
BackgroundAn electrolyte waste salt containing LiCl and various products is generated during the pyroprocessing of spent nuclear fuel in metal fast reactors. Separating metal impurities from waste salt can purify molten salt, facilitate salt recycling, and reduce the amount of waste salt, achieving waste minimization.PurposeThis study aims to investigate the effects of key factors on the application of the cold finger crystallization method used for removal of Sr and Ba from molten LiCl salt.MethodsA homemade cold finger experimental apparatus was applied to the experimental removal of two alkaline earth metals, Sr and Ba, from molten LiCl salt, and Fluent software was employed to simulate the application of cold finger crystallization equipment during dry reprocessing. The effects of crystal growth time, initial crystallization temperature, and initial SrCl2/BaCl2 concentrations on the removal ratio of the crystalline salt during the process were analyzed.ResultsThe initial temperature of molten salt is a critical factor that influences cold finger separation efficiency. When the initial temperature reaches 660 ℃, the removal efficiency improves. Moreover, when the impurity contents of Sr and Ba in molten salt are lower than 0.55%(w/w), the removal efficiency of the cold finger crystallization method can exceed 80%. Further analysis shows that the removal effects of different parts of molten salt crystals differ. The solvent salt at the top of the molten salt crystal is better, and the removal ratio of the bottom and inner salts is lower. Therefore, the optimal conditions for removing Sr and Ba from LiCl crystalline salt require an initial temperatures of 660~670 ℃, an airflow intensity of 10 L·min-1, and a growth time of 20 min. Under these optimal conditions, the removal ratio can reach 90%.ConclusionsThe proposed approach is feasible for purifying solvent salts from electrolyte waste molten salt via cold finger crystallization. This study provides a reference for purifying waste salt and reusing molten salt.
Uranium metal and alloys can be easily oxidized by the O-containing species such as O2 and H2O, etc. in atmosphere. Furthermore, the existence of H2 may also accelerates the oxidation of uranium metal. To prevent the corrosion of these materials, many techniques, such as alloying, coating, surface recrystallization, surface modification, etc. were developed to prevent this material from oxidation. In the surface modification processes, such as ion implantation, plasma nitriding and pulsed laser nitriding, UNx(U2N3+x or UN) layers are always formed on the metal surfaces to prevent the contact of the metal surfaces with the surrounding atmospheres. Thus the compatibilities of the as-prepared UNx layers with the surrounding atmospheres, especially O2, H2O and H2 molecules there, can play important role on the corrosion resistance of the modified layers, and thus are important topics in the nuclear industry. Here the compatibilities of UNx with O2, H2O and H2 molecules are reviewed, respectively. From the previous results, it seems that the as-prepared UNx, neither U2N3+x nor UN layers can directly prevent the diffusion of O2 into the solid phase. Instead, the surface of the modified layers can be easily oxidized to form UO2 or UO2Nx layers. For a UNx layer in which x is smaller than 1, it can be oxidized to a final product of UO2. However, under environmental temperature, for a layer in which x is no less than 1, only a thin layer(about several tens of nm) of UO2 can be formed on the layer surface. Moreover, a gradient layer in which the O content gradually decreases while the N content gradually increases from the surface to the deeper layer may effectively prevent the continuous diffusion of O into the substrate, and thus the modified layer presents excellent anticorrosion property against O2. However, the modified layers can not effectively prevent the diffusion of O2 under high temperature. For the hydrolysis process, the surface UO2 layers may restrain the hydrolysis of UNx under environmental temperature. However, the hydrolysis process of UNx can be effectively accelerated under high temperature, and the gaseous products during hydrolysis vary greatly with temperature and more research are needed on this topic. A very interesting phenomena during both the oxidation and hydrolysis processes is that N-rich layers can be always found under the oxide layers after oxidation or hydrolysis, and more research is needed to uncover the mechanism of this phenomena. For the compatibility of UNx with H2, it’s concluded that H2 has little effect on the layers. However, When there are defects in the layers, H2 can easily diffuses to the interface of the modified layers and the substrates and destroy the integrity of the layers. Thus, the uniformity and integrality of the modified layers are very important for the long-term storage of uranium metal.
Nuclear engineering. Atomic power, Chemical technology
A. Pérez-Obiol, S. Masot-Llima, A. M. Romero
et al.
Quantum entanglement offers a unique perspective into the underlying structure of strongly-correlated systems such as atomic nuclei. In this paper, we use quantum information tools to analyze the structure of light and medium-mass berillyum, oxygen, neon and calcium isotopes within the nuclear shell model. We use different entanglement metrics, including single-orbital entanglement, mutual information, and von Neumann entropies for different equipartitions of the shell-model valence space and identify mode-entanglement patterns related to the energy, angular momentum and isospin of the nuclear single-particle orbitals. We observe that the single-orbital entanglement is directly related to the number of valence nucleons and the energy structure of the shell, while the mutual information highlights signatures of proton-proton and neutron-neutron pairing, as well as nuclear deformation. Proton and neutron orbitals are weakly entangled by all measures, and in fact have the lowest von Neumann entropies among all possible equipartitions of the valence space. In contrast, orbitals with opposite angular momentum projection have relatively large entropies, especially in spherical nuclei. This analysis provides a guide for designing more efficient quantum algorithms for the noisy intermediate-scale quantum era.