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This study explores the fabrication of giant magnetoresistance (GMR) sensors through the microelectromechanical systems (MEMS) process. Moreover, it investigates the magnetic properties of these sensors across various structural parameters. In particular, the study evaluates the effects of variations in four specific parameters of a GMR sensor on magnetic bead signals, aiming to achieve high sensitivity of the sensor and a high signal-to-noise ratio (SNR) output. Dual ac modulation is employed for magnetic bead signal detection. The results indicate that a sensor with a linewidth of $1~\mu $ m and line spacing of $5\mu $ m exhibits the highest signal output and a higher SNR.

Fault location plays a pivotal role in expediting the restoration of systems after faults. However, the necessity for rapid fault isolation in multi-terminal direct current (MTDC) systems dictates that only a few milliseconds of data are available for fault location. Therefore, accurately determining the fault location using an extreme short data window presents a challenge. To address this challenge, a frequency domain fault location method that utilizes data from both ends of lines is proposed. This method accurately considers frequency-dependent and distributed characteristics of line parameters and relies on data collected within 3 ms following a fault occurrence. Initially, the fault location equation is derived. Then, the numerical Laplace transform (NLT) method is introduced to solve this equation, from which the explicit expression for fault distance is obtained. Lastly, the comprehensive fault location scheme is outlined. Numerical simulations demonstrate that this method can accurately locate faults and exhibit good robustness against fault impedance. Additionally, the method features a reduced computational burden, higher accuracy, and stronger noise immunity compared to existing methods.

A hybrid computing system employing the superconductor central processing unit and semiconductor memory is a prospective strategy to boost speed and power performance. Aiming to convert coded signals at room temperature to single-flux-quantum (SFQ) logic signals in a cryogenic environment, this article presents two types of CMOS-to-SFQ interface circuits for return-to-zero (RZ) and nonreturn-to-zero (NRZ) coded signals transformation. One can double the data rate (DDR) of bipolar RZ signals, and the other can decode unipolar and polar NRZ signals. In the simulation using parameters of the SIMIT Nb03 process, both the interface circuits have up to 20 GHz sampling frequency, more than ±30% bias current margin, and tolerance toward 20 dB SNR white noise. The DDR interface circuit can generate SFQ pulses at both edges of 1.4–2.6 mA bipolar RZ signal, and the decoding interface circuit can interpret 0.2–0.6 mA unipolar and polar NRZ signal into SFQ pulses. The test circuits have been fabricated under the SIMIT Nb03 6 kA/cm2 process. In low-frequency measurement, the DDR interface circuit can convert 1.4–2.4 mA bipolar RZ signal, and the decoding interface circuit can convert 0.25–0.5 mA unipolar and polar NRZ signal with more than ±30% bias current margin. In high-frequency measurement, the DDR interface circuit shows an ability to convert a 3.33 GHz input signal.

Accurate fault location with a short data window is crucial and challenging for cable faults in the modular multilevel converter high voltage direct current (MMC-HVdc) system. Aiming at this issue, this article proposes a frequency-domain fault location method, which accurately and comprehensively addresses the frequency dependency and unbalance of the parameter matrices without any approximation while considering the distributed parameters. First, the frequency-domain decoupling is analyzed for dc cables with the metallic sheath and armor grounded at two terminals. Second, a method is proposed to calculate the voltage distribution along the cable using voltages and currents at one side of the cable based on the numerical Laplace transform (NLT). Subsequently, the cable parameter calculation method suitable for the NLT is presented, and a multiround iterative algorithm for voltage distribution calculation is proposed. Ultimately, the complete fault location scheme is presented. Extensive simulations validate that the proposed method can achieve fault location with minor errors using a 20 kHz sampling rate and a 4 ms data window. Besides, high accuracy is maintained even under the influence of large fault impedance and noise. Compared to existing methods, the approach exhibits lower fault location error while requiring less computational complexity.

Bi-based metal-organic frameworks (Bi-MOFs) as efficient catalysts for the CO2electroreduction reaction (CRR) have been extensively investigated. It has been established that Bi-MOFs usually undergo in-situtransformation during the CRR, ultimately converting into Bi nanostructures. However, the effect of the MOF precursors on the structure of the derived Bi catalysts and consequently on their electrocatalytic properties has not been clearly elucidated. In this work, we prepared four variants of a novel Bi-MOF with different morphologies and dimensions, and explored the effects of the precursors on the resulting Bi catalysts and their CRR performance. A precursor-dependent in-situtransformation and its profound impact on tuning the CO2-formate FE towards ∼100% have been revealed. Among the four examined variants, Bi-MOF with nanocube-like morphology (BiMOF-NC) is transformed into thin and flat Bi nanosheets capable of successfully enveloping the fibers of carbon paper (working electrode), while the other three variants with increased size and dodecahedral/octahedral geometry have been transformed into Bi nanoflowers, exposing a fair portion of the carbon fibers in the working electrode. Furthermore, the transformation rate was found to be dependent on the precursors and BiMOF-NC exhibited the highest rate of reconstruction compared with other samples. Consequently, the Bi catalyst derived from BiMOF-NC delivered a selectivity for the formate product of nearly 100% at −1.2 V (vs.reversible hydrogen electrode (RHE)) and of over 95% in a wide potential range due to efficient suppression of the competing hydrogen evolution reaction (HER) over carbon fibers. The in-situtransformed BiMOF-NC also demonstrated equivalently high formate selectivity at large current densities (≽100 mA cm−2) in flow cell reactors as that in H-type reactors, underscoring its potential for industrial applications. This work highlights the necessity of finely tuning the structural features of MOF precursors to achieve optimized electrocatalytic performance.

Passive transmission line (PTL) has been widely applied in rapid single flux quantum (RSFQ) circuits, especially as the first choice of long-distance transmission in large-scale integrated circuits such as arithmetic and logic unit (ALU) and central processing unit (CPU). With the increasing demand of timing regulation, general bias margin is not enough to evaluate the performance of PTL circuits. Timing accuracy including propagation delay of the micro stripe line (MSL) and its delay skew is more critical for clock routine and signal transmission when employing PTL circuits. However, the related reports about the timing information of PTL circuits is limited in the single-value verification of the theoretical MSL's delay. More factors such as bias current, transmission length and system noise should be considered into the evaluation of the PTL circuits. This work focuses on the timing extraction of the designed PTL circuits through different control groups, and evaluates the timing discrepancy between the measurement and simulation. We adopt the method of time accumulation by increasing different lengths of MSL in the loop of the ring oscillator (RO) and subtract each other to evaluate the MSL's propagation delay. We analyzed MSLs of two layers (MSL1 and MSL2). The measured propagation delay of 1 ${\text{mm}}$ MSL is 8.20 ps/mm for MSL1 and 7.66 ps/mm for MSL2, which has a delay skew of 0.30 ${\text{ps}}$ and 0.57 ${\text{ps}}$ from the simulated value (8.23 ${\text{ps}}$). Within MSL transmission length of 5 ${\text{mm}}$, a maximum deviation of 1.2 ${\text{ps}}$ is adopted as time redundancy of PTL circuits applied in ALU and CPU design.

The use of high-frequency input signals from room-temperature microwave sources makes it difficult to scale up the number of quantum bits in universal quantum computers. To address this issue, superconducting single flux quantum (SFQ) integrated circuits are being explored as suitable candidates for qubit manipulation in universal quantum computers. Previously, we designed a low-power SFQ qubit control circuit (SQCC) to produce an equidistant SFQ pulse train without high-frequency input. It was reported that the fidelity of qubit control could be further improved if the pattern of SFQ pulse train could be adjustable. In this paper, we present optimized designs for different pattern requirements of qubit control, building upon the SQCC without high-frequency input. These designs feature segmented frequency modulation circuits, as well as circuits capable of outputting arbitrary patterns. The circuit capable of generating arbitrary patterns currently achieves a maximum adjustable number of 400, with a corresponding frequency output of 20 GHz. It has been successfully fabricated using the SIMIT Nb03 process and has passed functionality measurement tests. The optimized circuit opens up possibilities for improved qubit control and advancements in quantum computing applications.

This article presents a design automation framework for the placement and clock tree synthesis of superconducting rapid single-flux-quantum (RSFQ) logic. The framework includes a global placement method for gate-level-pipelined layout optimization, a clock tree synthesis procedure for HL-tree construction with concurrent-flow and counter-flow schemes, and a detailed placement method for congestion optimization. In the global placer, the optimization problem is reformulated to reduce the run-time cost while maintaining optimization quality; the clock tree synthesis is performed using the bottom-top iterative algorithm, combining synchronizer synthesis and clock tree construction to shrink the size of the clock tree; eventually, the detailed placer performs the algorithm based on Delaunay triangulation and Lloyd iteration, adjusting layout placement under certain constraints. Several benchmarks are used to validate the effectiveness of the proposed framework, and the results show that the framework is capable of maximizing the utilization of layout space and providing a routable layout environment for hybrid routing within a controlled run-time.

Electrochemical hydrogeneration (ECH) of biomass-derived platform molecules, which avoids the disadvantages in utilizing fossil fuel and gaseous hydrogen, is a promising route toward value-added chemicals production. Herein, we reported a CoO/Co heterostructure-supported Pt single atoms electrocatalyst (Pt1-CoO/Co) that exhibited an outstanding performance with a high conversion (>99%), a high Faradaic efficiency (87.6%), and robust stability (24 recyclability) at −20 mA/cm2for electrochemical phenol hydrogenation to high-valued KA oil (a mixture of cyclohexanol and cyclohexanone). Experimental results and the density functional theory calculations demonstrated that Pt1-CoO/Co presented strong adsorption of phenol and hydrogen on the catalyst surface simultaneously, which was conducive to the transfer of the adsorbed hydrogen generated on the single atom Pt sites to activated phenol, and then, ECH of phenol with high performance was achieved instead of the direct hydrogen evolution reaction. This work described that the multicomponent synergistic single atom catalysts could effectively accelerate the ECH of phenol, which could help the achievement of large-scale biomass upgrading.

Rapid single flux quantum (RSFQ) logic is a promising technology to supersede CMOS logic in some specialized areas due to providing ultrafast and energy-efficient circuits. To realize a large-scale integration design, electronic design automation (EDA) tools specialized for RSFQ logic are required due to the divergences in logic type, timing constraints, and circuit structure compared with CMOS logic. Logic synthesis is crucial in converting behavioral circuit description into a circuit netlist, typically combining combinational and sequential circuit synthesis. For the RSFQ logic, the sequential circuit synthesis is challenging, especially, for nonlinear sequential blocks with feedback loops. Thus, this article presents a sequential circuit synthesis algorithm based on finite state machine (FSM) decomposition, which ensures design functionality, lowers costs, and improves the RSFQ circuit performance. Additionally, we present the synthesis processes of the feedback logic and the 2-bit counter to demonstrate how the proposed algorithm operates, and ISCAS89 benchmark circuits reveal our method’s ability to synthesize large-scale sequential circuits.

Along with the improvement of integration and the requirement of high-speed operation, the passive transmission line (PTL) plays a significant role in superconducting integrated circuits due to its intrinsic advantage of extremely low propagation delay and low signal loss in long-distance transmission. Good impedance matching is critical to reduce the signal reflection in the transmission line and maximize the power transferred. Based on the PTL wiring layer selection under SIMIT-Nb03 process, we studied the equivalent input/output impedance for Josephson junction (JJ) at the IO port and explored a method of impedance matching in rapid-single-flux-quantum circuits by adjusting the Stewart McCumber parameter ${\beta }_{\bm{C}}$ of the JJ in the design of the PTL's driver and receiver. Furthermore, the accompanying influence from JJ's modified ${\beta }_{\bm{C}}$ on the performance of the driver and receiver is evaluated to maximize the profit of the functional circuits. The common-used serial resistor is removed to obtain a balanced bias margin for the PTL circuits. The proposed PTL has been designed and tested based on SIMIT-Nb03 fabrication process. In total, $ \pm $30% bias margin for the PTL is achieved at low frequency and high frequency (40 GHz) contrast tests, including operation speed and transmission length as test vector. Additionally, a frequency sweep for 1 mm PTL is performed by the designed ring oscillator on the chip. The maximum working frequency is up to 129 GHz, with a margin duration of 8%.

Rapid single-flux-quantum (RSFQ) circuit requires an accurate timing scheme to maintain correct function, especially under a very high clock frequency. However, the reported timing regulation schemes have issues, including the bias margin of the circuit being small and the bias margin decrement caused by imprecise timing constraints. This article proposes a new timing regulation scheme based on clock-follow-data clocking that can solve the problems. The scheme uses the unique structure of the RSFQ circuit to eliminate the impact caused by different timing libraries and extend the biasing margin. The simulation results of the XOR gate under various timing regulation schemes demonstrated that the proposed scheme could obtain the maximum static timing analysis (STA) bias margin. Also, the STA bias margin of the 4-b parallel arithmetic logic unit (ALU) designed using the timing regulation scheme proposed in this article was increased by 5%, the PSCAN2 bias margin was increased by 7.4%, and 36 ps reduced latency. The ALU fabricated using the “SIMIT Nb03” process was successfully measured with correct operation at low frequency. It showed this scheme could provide accurate timing constraints range and enhances circuit bias margin.

Arranging atoms in an orderly manner at the atomic scale to create stable polyatomic structures is a very challenging task. In this study, we have developed three-dimensional confinement areas on the two-dimensional surface by creating regional defects. These areas are composed of vertically stacked graphene layers, where Ni and Fe atoms are anchored concentrically to form axial dual atomic sites in high yield. These sites can be used to produce tunable syngas through the electroreduction of CO2. Theoretical calculations indicate that the Ni sites vertically regulate the charge distribution of the adjacent Fe sites in the layer below, resulting in a lower d-band center. This, in turn, weakens the adsorption of the *CO intermediate and inhibits the production of H2at the Fe site. Our research presents a novel approach for concentrated creation of dual atomic sites by building a confinement-selective surface.

In the post-Moore era, slow-growing operating frequency and massive power dissipation make researchers seek new developing directions in integration circuits (ICs). The single flux quantum (SFQ) circuit, a type of superconducting digital circuit, is regarded as an alternative circuit for future computing technology. SFQ circuits are natural gate-level-pipelining synchronous sequential circuits requiring path balancing. However, path balancing may consume enormous resources, as the logic levels of fan-in gates of most gates are different, with the consumption originating from the extra gates (D-Flip-Flops, DFFs) for path balancing and the routing with a much larger clock tree. Hence, in this article, we propose a local optimization method to address the vast consumption problem of the clock tree caused by path balancing in SFQ circuits, primarily relying on self-developed electronic design automation tools for the JSICcomplier for SFQ circuits and using the SIMIT Nb03 cell library. Moreover, we design synchronizer IPs called Dsyn series to replace DFFs in path balancing. The clock nodes and the clocking path consumption are highly reduced by utilizing the proposed strategy, while the new series can be recognized as IPs and easily added to our library, affording scalability. Experiments in a demo S-box circuit demonstrated a percentage of Josephson junctions reduction in clock tree up to 36.48%, while on a few benchmark circuits, the corresponding results are up to 50.69%, demonstrating our method's effectiveness.

The single flux quantum (SFQ) logic family is a novel digital logic as it provides ultrafast and energy-efficient circuits. For large-scale SFQ circuit design, specialized electronic design automation (EDA) tools are required due to the differences in logic type, timing constraints, and circuit architecture, in contrast to the Complementary metal–oxide–semiconductor (CMOS) logic. In order to improve the overall performance of an SFQ circuit, an efficient routing algorithm should be applied during the layout design to perform accurate timing adjustment for fixing hold violations and optimizing critical paths. Thus, a hybrid Josephson transmission line and passive transmission line routing framework is proposed. It consists of four main modules and an exploration of the potential timing performance based on the given layout placement. The proposed routing tool is demonstrated on seven testbench circuits. The obtained results demonstrate that the operating frequency is greatly improved, and all the hold violations are eliminated for each circuit.

The orderly assembly of single atoms into highly periodic aggregates at the nanoscale is an intriguing but challenging process of high-precision atomic manufacturing. Here, we discover that an in-plane film surface shrinkage can induce molecular self-assembly to arrange single atoms with unconventional distribution, contributing them to periodic one-dimensional segregation on carbon stripes (one-dimensional single-atom arrays (SAA)). This originates from the fact that metal phthalocyanine (MPc) molecules gradually aggregate and melt to form a film under a thermal drive and the help of sodium chloride templates, accompanied by surface shrinkage, self-assembly, and deep carbonization. At the nanoscale, these periodic parallel arrays are formed due to MPc molecular interactions by π–π stacking. At the atomic scale, the single atoms are stabilized by the vertical phthalocyanine-derived multilayer graphene. This can significantly modify the electronic structure of the single-atom sites on the outermost graphene (e.g., Fe-based SAA), thus optimizing the adsorption energy of oxygen intermediates and resulting in a superior oxygen reduction reaction (ORR) performance concerning disordered single atoms. Our findings provide a general route for orderly single-atom manufacturing (e.g., Fe, Co, and Cu) and an understanding of the relationship between orderly allocation and catalytic performance.

Background: Although phytoplankton are important primary producers in food webs, they are relatively less studied in large rivers compared to other types of systems. To fill this research gap, we studied phytoplankton taxonomic and functional composition and their relationships with water quality, habitat, climate, and land use across 30 river sections in the middle and lower reaches of the Yangtze River during 2017–2018. Results: Major observed phytoplankton groups were cyanobacteria, bacillariophyta, and chlorophyta. Phytoplankton total abundance, total biomass, and species richness significantly decreased in the dry season compared to the wet season, with the species and functional composition differing significantly between seasons. Phytoplankton species differences between seasons were mainly contributed by Oscillatoriasp., Pseudanabaenasp., and Melosira granulata. The dfferences in phytoplankton functional groups between seasons were mainly contributed by P (including Closteriumsp., Melosirasp.), Lo (including Merismopediasp., Peridiniumsp., Ceratiumsp., and Gymnodiniumsp.), and J (including Pediastrumsp., Tetraedronsp., Crucigeniasp., Scenedesmussp., and Coelastrumsp.). The variance partitioning showed that water quality (NO3-N, total suspended solids, turbidity) and habitat (water flow, river bank and river channel conditions) were critical factors in shaping phytoplankton patterns, followed by climate and land use. Conclusions: Results indicated that there was significant seasonal variation of phytoplankton in the Yangtze River, with water quality and habitat primarily driving phytoplankton patterns. Our study contributes to the understanding of natural and anthropogenic factors that drive seasonal successional processes of phytoplankton in the Yangtze River. These findings have important implications for environmental management as well as towards the ecological restoration of large rivers.

Superconducting integrated circuits (ICs) based on Josephson junctions (JJs) and superconducting materials subvert semiconductor ICs at the device level. For over 50 years, superconducting IC technology has realized a technological upgrade from latch logic circuits, which utilize level logic, to single flux quantum (SFQ) ones, which utilize high-speed pulse logic. Only micron-level process nodes are needed to achieve advantages in the speed and power consumption of SFQ circuits. After more than 30 years of development, SFQ logic has become a large family, mainly including rapid single-flux-quantum (RSFQ), reciprocal quantum logic (RQL), energy-efficient single flux quantum technology (ERSFQ), low-voltage RSFQ (LV-RSFQ) and adiabatic quantum flux parametron (AQFP). So far, the maximum number of JJs on a superconductor chip has exceeded 1 million. Applications of SFQ circuits have widely expanded in superconducting computing, such as radio frequency (RF) signal processing and superconducting quantum computing control circuits. Semiconductor ICs have insurmountable technical bottlenecks of speed and power consumption in the sub-10 nm node. Therefore, superconducting ICs have been listed in the international roadmap for devices and systems (IRDS) as a frontier of microelectronics in the post-Moore era. Among all the countries, U.S. and Japan are always at the cutting edge in this field. China has entered the stage of rapid development in superconducting ICs and has realized basic software and hardware platforms for comprehensive research and design of superconducting large-scale SFQ circuits. This paper presents the status of SFQ technology for energy-efficient computing applications and discusses the latest progress in the research and development of SFQ microprocessors.

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Nascent-state manganese dioxide (NSMD) and ferric hydroxide (NSFH) are the main intermediates formed during potassium permanganate and Fenton oxidation processes, respectively, which play an important role in the removal of organic contaminants. This study investigates the removal efficiency in 38 synthetic dye wastewaters by NSMD and NSFH. Results showed that the average removal rates (Rexp) of dyes by NSMD and NSFH were 83.58 ± 5.96% and 43.11 ± 4.17%, respectively. SEM, FT-IR, TGA, XRD and BET analyses revealed that NSMD had a larger specific surface area and more abundant surface hydroxyl groups, resulting in a stronger adsorption capacity than that of NSFH. Besides, the degradation of dyes by NSMD was a combination of adsorption and oxidation; NSFH involved only in the adsorption effect, and thus NSMD had higher removal efficiency than that of NSFH. Additionally, to better illustrate the internal factors that affect the removal efficiency, correlation analyses between Rexpand 28 molecular descriptors, as well as quantitative structure–activity relationship (QSAR) model analysis using Rexpas dependent variables and molecular descriptors as independent variables, were conducted. The optimal QSAR models for NSMD and NSFH systems were Rpre= 1.829–0.460BOx+ 0.017μ− 1.248q(CH+)x+ 0.024ELUMOand Rpre= −0.949 + 0.001MM − 0.017μ+ 4.674f(0)x− 0.072EHOMO− 0.413q(C−)n+ 0.034NN, respectively, which suggested that the maximum value of bond order (BOx) representing oxidation capacity and the relative molecular mass (MM) representing adsorption capacity are the dominant factors affecting the dye removal of NSMD and NSFH, respectively. These findings not only reveal the differences and characteristics of dye removal using NSMD and NSFH, but also provide a rapid way to evaluate the removal efficiency of the two systems.

How to effectively integrate culture into second language teaching has long been of concern in foreign language education. Despite advances in theory and practice for intercultural language teaching, there has been little research to investigate factors influencing teachers’ pedagogical beliefs and perceptions. This study addresses this gap by examining teachers’ perceptions of effective strategies that foster students’ intercultural competence in the teaching of Chinese as a foreign language and factors influencing their beliefs. Twenty-nine school and university teachers in Australia completed a survey and a focus group interview. Quantitative analyses revealed that teachers’ perceptions of the effectiveness of the strategies varied despite an overall positive attitude towards the teaching of culture. Their beliefs were significantly influenced by their years of teaching experience, educational setting, and native language, but not by gender, age group and educational backgrounds. Qualitative analyses attribute the inconsistency in teacher perceptions to teachers’ disparate conceptualisations of culture, teaching experiences, and educational contexts associated with different curricular and pedagogical requirements and learner characteristics. The findings reinforce the necessity for providing teachers with professional training, along with pedagogical guidance and resources in order to facilitate their intercultural language teaching practices.

Background Controversies persist regarding whether exposure to cat or dog increases the risk of asthma and allergic rhinitis.Objective This meta-analysis aimed to assess the associations between exposure to cats or dogs and the development of asthma and allergic rhinitis.Methods A systematic review was performed to identify case-control and cohort studies before May 2019, evaluating the association between exposure to cats and dogs and the risk of asthma and rhinitis. The risk of bias was assessed using the Newcastle–Ottawa Scale. The odds ratios (ORs) and risk ratios (RRs) were pooled for case-control and cohort studies, respectively. Subgroup analyses were performed on prespecified study-level characteristics.Results The meta-analysis of 34 cohort studies showed a protective role of exposure to cats [RR: 0.88, 95% confidence interval (CI): 0.77–0.99] or dogs (RR: 0.85, 95% CI: 0.73–0.97) in the development of asthma. The subgroup analysis of birth cohort (RR: 0.74, 95% CI: 0.56–0.93) and children population (RR: 0.83, 95% CI: 0.70–0.96) also suggested a favorable role of exposure to dogs in the development of asthma. Pooled evidence from 13 case-control studies indicated no significant impact of cats (OR: 1.66, 95% CI: 0.39–2.94) and dogs (OR: 1.22, 95% CI: 0.92–1.52) on the development of asthma. A pooled analysis of five cohort studies showed a favorable effect of exposure to cats (RR: 0.60, 95% CI: 0.33–0.86) or dogs (RR: 0.68, 95% CI 0.44–0.90) on the development of allergic rhinitis.Conclusion The findings indicated a protective effect of exposure to cats and dogs, especially ownership, on the development of asthma and allergic rhinitis.

Artificial ammonia (NH3) synthesis from molecular nitrogen (N2) in aqueous solutions under mild conditions is one of the most attractive and challenging processes in chemistry. In this work, by means of density functional theory (DFT) computations, transition metal (TM) atoms were anchored to porphyrin (Pp) sheets as N2capture (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Nb, Mo, Ru) and reduction catalysts and their catalytic activities were systematically investigated. Among them, the 2D Mo-Pp sheet exhibits the best catalytic performance for N2capture and reduction to NH3. Importantly, the 2D Mo-Pp sheet shows a high thermal stability up to 500 K and thus holds great promise for experimental synthesis. N2can be effectively reduced via the distal reaction pathway with a negative N2adsorption free energy and an energy barrier of 0.58 eV, indicating its good catalytic performance for N2reduction. We believe our work could provide a novel catalyst for electrochemical reduction of N2to NH3at mild conditions.

ObjectiveThis study retrospectively analyzed the risk factors, management strategies, and complications of incomplete stent apposition (ISA) of low-profile visualized intraluminal support (LVIS) stents after initial deployment in the treatment of cerebral aneurysms.MethodsThe clinical characteristics of ISA or wall apposition (WA) of LVIS stent after initial deployment were analyzed. The risk factors of ISA were identified using univariate logistic regression analysis and multivariate logistic regression analysis. The clinical characteristics of ISA following different management strategies were also shown.ResultsThe retrospective study enrolled 303 patients with 315 LVIS stent-assisted aneurysms. Fifty-nine patients with 59 stents showed ISA after initial deployment. At the end of the study, the presence of ISA was only observed in eight patients (2.5%). The stent-subtended arc angle (>90) and the aneurysm of the internal carotid artery (ICA) were associated with ISA. The stent-subtended arc angle (>90) and stent size (4.5*20 mm) were independent risk factors of ISA. The incidence of thromboembolic events in the ISA group was significantly higher than that in the WA group. After the treatment of ISA, there was no significant difference in good outcomes between patients with ISA and those with WA after initial deployment.ConclusionsISA is more likely to occur at tortuous vessels. The stent-subtended arc angle (>90) and LVIS size (4.5*20 mm) were independent risk factors of ISA. ISA led to significantly increased incidence of thromboembolic events. However, ISA after initial deployment did not affect the patient's prognosis.

Hexavalent chromium (Cr(VI)) in soil has received extensive attention because of its harmful effects on the environment. In this study, ball-milled zero-valent iron biochar composites (BM-ZVI/BC) were prepared and used for the remediation of artificial Cr(VI)-contaminated soil. The Cr(VI) in the soil could be reduced from 170.4 mg kg−1to less than 3.0 mg kg−1after 5 days and remained stable in the next 105 days. The immobilization efficiency for Cr(VI) and Cr was close to 100%. In addition, the bioavailability of Cr(VI) and Cr was reduced to 27.9% and 4.6%, respectively. BM-ZVI/BC not only played a role in the transformation of Cr into a more stable chemical form to reduce its toxicity and mobility in the soil, but also affected the soil physicochemical properties. Compared to zero-valent iron biochar composites (ZVI/BC), BM-ZVI/BC had a positive effect on recovering microbial diversity and richness, along with the enhanced growth of low-abundance phyla. The relative abundance of Arthrobacter, Bacillusand Exiguobacteriumrelated to Cr-reduction was also increased in the BM-ZVI/BC remediated soil. BM-ZVI/BC has shown excellent resistance and stability under extreme environmental conditions of acid rain leaching, dry-wet and freeze-thaw cycles. This study demonstrates the potential of ball milling modification in preparing zero-valent iron biochar composites for the remediation of Cr(VI)-contaminated soil.

A Zn-air battery is a potential next-generation energy storage device owing to its extremely high theoretical energy density. Currently, it is important to explore non-precious metal electrocatalysts with high electroactivity and stability in the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) for the development of Zn-air batteries. In this work, porous (Ni,Co)Se2nanosheets were synthesized by selenizing NiCo2O4nanosheets. By regulating the conductivity and morphology of the sample, the prepared porous (Ni,Co)Se2nanosheets show enhanced electrocatalytic activity for OER and ORR compared to NiCo2O4nanosheets. The aqueous Zn-air battery using porous (Ni,Co)Se2nanosheets as the air cathode exhibits superior charge and discharge performance (1.98 V for charging and 1.17 V for discharging), high specific capacity (770 mAh/g), and excellent cycle stability (140 h). These results indicate that the porous (Ni,Co)Se2nanosheets are suitable as a bifunctional electrocatalyst for future Zn-air batteries.

The control of mercury in flue gas is challenging, especially that of elemental mercury (Hg0). Recently, many researchers have focused on various mercury removal technologies. Here, by performing density functional theory (DFT) calculations, we systematically studied the adsorption of Hg0on several experimentally available hexagonal boron nitride (h-BN) nanosheets with no defects, nitrogen vacancies (VN), boron vacancies (VB), and both nitrogen and boron vacancies (VN+B) as well as their structures and electronic properties. Our calculation results show that the presence of VN, VB, and VN+Benhances the adsorption energies of Hg0by 9, 45, and 214 kJ/mol, respectively. Moreover, a more negative potential at the VBand VN+Bsites makes the h-BN-VBand h-BN-VN+Bsurfaces more reactive than those of h-BN and h-BN-VN. The partial density of states analysis reveals that the Hg atom interacts firmly with surface B or/and N atoms through orbital hybridization. The trend of the equilibrium constant implies that adsorption of Hg0on the h-BN-VN+Bsurface is beneficial at low temperature. Our computational studies reveal that defective h-BN nanosheets with VBand VN+Bhave great potential to serve as novel sorbents for the efficient removal of mercury in flue gas.

Motor activities during daily life always involve simultaneous control of multiple degrees of freedom (DOFs), which has not yet been fully explored in myoelectric control due to difficulty in sufficiently decoding the complex neural control information. This study presents a novel framework for simultaneous myoelectric control based on pattern recognition incorporated with a muscle synergy motor control strategy for each DOF. An experiment for discriminating 18 dexterous finger movement tasks was designed to evaluate the performance of the framework for the simultaneous control of 5 DOFs. Task discrimination was assessed with 18 neurologically intact subjects, and the framework exhibited high accuracy (96.79% ±2.46%), outperforming three other methods, including the routine myoelectric pattern-recognition approach for conventional sequential control (p<0.001). Furthermore, the feasibility of the proposed framework is also demonstrated with data from paretic muscles of two stroke subjects. This study offers a feasible solution for simultaneous myoelectric control of multiple DOFs, which has great potential for natural implementation in prosthetic hand devices and robotic training systems, especially for dexterous finger movements.

Engineering the site density of single-atom catalysts (SACs) on a confined catalyst surface has great potential to improve catalytic performances. Especially, the dispersed status of single metal atoms and optimal site distributions are crucial during the catalytic process. Here, using integrated theoretical and experimental approaches, we demonstrate an optimal single Pt site coverage (about 0.34 Pt/nm2) over a CdS-confined Pt single-atom-layer surface for high-effective hydrogen evolution. A volcanic-type relation between hydrogen products and Pt site densities is found when progressively increasing Pt concentrations. Further theory calculations show the individual Pt monomer within the CdS matrix could trigger an effect radius (about 8.6 Å) to weaken the hydrogen adsorption of neighbor S atoms and enhance hydrogen products. This radial range will lead into an optimal density distribution of 0.33 Pt/nm2to maximally activate the whole surface. Furthermore, the interactions between overly dense Pt monomers will deteriorate the adsorption and desorption behaviors of hydrogen.

ABSTRACTThe reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing. Menin, the product of the MEN1gene, has been shown to physically interact with the KMT2A and KMT2B histone methyltransferases. Both the KMT2Aand MEN1genes are located on chromosome 11q, which frequently undergoes loss of heterozygosity (LOH) in PanNETs. We report herein that inactivation of Kmt2ain Men1-deficient mice accelerated pancreatic islet tumorigenesis and shortened the average life span. Increases in cell proliferation were observed in mouse pancreatic islet tumors upon inactivation of both Kmt2aand Men1. The Kmt2a/Men1double knockout mouse model can be used as a mouse model to study advanced PanNETs.

A nonwoven fabric has been widely used in geotextile engineering in recent years; its tensile strength is an important behaviour. Since the fibre distributions in nonwoven fabrics are random and discontinuous, the unit-cell model of a nonwoven fabric cannot be developed to simulate its tensile behaviour. This article presents our research on using finite element method (FEM) to study the tensile behaviour of a nonwoven fabric in macro-scale based on the classical laminate composite theory. The laminate orientation was considered with orientation distribution function of fibres, which has been obtained by analysing the data acquired from scanning electron microscopy with Hough Transform. The FE model of a nonwoven fabric was developed using ABAQUS software; the required engineering constants of a nonwoven fabric were obtained from experimental data. Finally, the nonwoven specimens were stretched along with machine direction and cross direction. The experimental stress-strain curves were compared with the results of FE simulations. The approximate agreement proves the validity of an FE model, which could be used to precisely simulate the stress relaxation, strain creep, bending and shear property of a nonwoven fabric.

Rapid single flux quantum (RSFQ) circuits have the advantages of high speed and low power consumption. The typical frequency of the RSFQ circuits is tens of GHz. Therefore, it is necessary to reliably test the high-frequency performance of RSFQ circuits simply and effectively. This paper proposes a new on-chip high-frequency testing method, which uses pseudo-random sequences generated by linear feedback shift register (LFSR) as the test vectors, and the output shift registers (SRs) to store the last piece of high-frequency testing result and read out it at low-frequency. Unlike the traditional high-frequency demonstration method of using the Input/Output SRs, our testing system can automatically generate a large number of test vectors to test the circuit at high frequency at low cost, making the whole high-frequency demonstration more reliable and convincing. On the other hand, this method is also a feasible and straightforward on-chip high-frequency test method for various RSFQ circuits. This work verified the proposed method, and the highest test frequency can reach 54 GHz while the circuit shows good operating margins.

AbstractThis study investigates the effects of linguistic difficulty and task type on the use of Chinese baconstruction by second language learners. One hundred and ten adult learners completed four tasks orally (i.e., an oral production task prompted by video clips, an oral imitation task, a grammaticality judgement task and a correction task), as well as a background questionnaire and a one-on-one post-task interview. Twenty-two native speakers of Chinese served as baseline. Results demonstrate that the variable type of the Chinese baconstruction which is subject to functional constraints is harder to learn than the obligatory type which is subject to obligatory syntactic constraints, and that the oral tasks were more challenging to perform than the metalinguistic tasks. The findings suggest that a series of factors including functional value and discourse context contribute to the linguistic difficulty of Chinese grammar features. The processing constraints of completing tasks and their interaction with linguistic characteristics explain the learning difficulty of the two types of the baconstruction.

Abstract: In this paper, the sterilization of surfactin and iturin to Salmonella enteritidis was observed, and the optimization of the inactivation of surfactin and iturin to S. enteritidis in meat by a response surface methodology was studied. Results showed that surfactin and iturin had high sterilization to S. enteritidis, whose minimal inhibitory concentration was 6.25 and 12.50 μM respectively. The optimization result indicated that S. enteritidis could be inactivated by five orders of magnitude when the temperature was 4.83°C, the action time was 17.20 h, and the concentration (surfactin/iturin molar ratio 1:2) was 0.69 MIC.

Abstract: In this paper, the sterilization of surfactin and fengycin to Bacillus cereus was observed, and the optimization of the inactivation of surfactin and fengycin to spores of B. cereus by a response surface methodology was studied. Results showed that surfactin and fengycin had high sterilization to B. cereus, whose minimal inhibitory concentration was 31.25 μM and 62.5 μM respectively. The optimization result indicated that spores of B. cereus could be inactivated by two orders of magnitude when the temperature was 20.41°C, the action time was 21.13 h, and the concentration (surfactin/fengycin molar ratio 1:1) was 54.20 μM.

Objective: To determine whether acute alcohol ingestion raises estradiol (E2) and estrone (E1) levels in a randomized, controlled, crossover study on postmenopausal women using transdermal E2. Methods: Healthy, non-smoking postmenopausal women (n = 7) using no medications were enrolled. Transdermal E2, 0.15 mg, was applied 13 hours before the subjects ingested alcohol (1 mL/kg 95% ethanol) or isocaloric carbohydrate punch. Serum samples were obtained for 40 minutes before drink ingestion and 6 hours afier drink ingestion and were assayed for E2 and E1. Results: Ethanol levels peaked 60 minutes afier the start of ethanol-drink ingestion, at 25.4 mmol/L (117 mg/dL). Estradiol levels rose significantly above the mean baseline of 657 pmol/L (179 pg/mL) afier ethanol-drink ingestion (P ?.01), with a mean peak of 804 pmol/L (219 pg/mL) 35 minutes after the start of drink ingestion, and were significantly greater than the E2 levels that followed the carbohydrate drink (P ?.0001). There were no significant changes in E2 or E1 levels afier carbohydrate-drink ingestion. Conclusions: We conclude that ethanol ingestion may acutely raise circulating E2 concentrations in women using transdermal E2.

ABSTRACTBased on conserved expression patterns, three members of the GATA family of transcriptional regulatory proteins, GATA-4, -5, and -6, are thought to be involved in the regulation of cardiogenesis and gut development. Functions for these factors are known in the heart, but relatively little is understood regarding their possible roles in the regulation of gut-specific gene expression. In this study, we analyze the expression and function of GATA-4, -5, and -6 using three separate but complementary vertebrate systems, and the results support a function for these proteins in regulating the terminal-differentiation program of intestinal epithelial cells. We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal fatty acid-binding protein (xIFABP) gene, which is a marker for differentiated enterocytes. This is the first direct demonstration of a target for GATA factors in the vertebrate intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at least in part by a defined proximal IFABP promoter element. The expression patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal villus axis. Transcript levels for cGATA-4 increase along the axis toward the villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal tip containing differentiated cells. In contrast, the pattern of cGATA-6 transcripts is complementary to cGATA-5, with highest levels detected in the region of proliferating progenitor cells. Undifferentiated and proliferating human HT-29 cells express hGATA-6 but not hGATA-4 or hGATA-5. Upon stimulation to differentiate, the transcript levels for hGATA-5 increase, and this occurs prior to increased transcription of the terminal differentiation marker intestinal alkaline phosphatase. At the same time, hGATA-6 steady-state transcript levels decline appreciably. All of the data are consistent with evolutionarily conserved but distinct roles for these factors in regulating the differentiation program of intestinal epithelium. Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP.

A new marine dinoflagellate, Scrippsiella minima sp. nov., is described from the Atlantic Ocean. It is tear-shaped, with a mean length of 20 μm and a mean width of 15 μm. The plate tabulation is po, x, 4', 3a, 7'', 6c, 5s, 5''' and 2''''. When it is induced to undergo sexual reproduction, resting cysts are formed which are ovoid in shape, about 34 μm long × 29 μm wide and have a thick organic wall covered with small calcareous verrucae. Ultrastructural observation shows that S. minima is of typical dinoflagellate organization. The pusule consists of a group of large vesicles connecting with a collecting chamber. The fibrous structures in the area of the apical pore and subthecal microtubular system have been examined and compared with those in other dinoflagellates. A comparison of the ultrastructure with other Scrippsiella species is also presented.

Native isocitrate lyase from castor bean and a C-terminally truncated variant were expressed in Saccharomyces cerevisiae under the control of a galactose-inducible promoter. Both forms of isocitrate lyase were targeted to the yeast peroxisomes. They co-fractionated with catalase on sucrose-density-gradient centrifugation of a post-nuclear supernatant prepared from cells grown on oleic acid plus galactose, but were found in the cytosolic fractions when the cells were grown under conditions that repress peroxisome formation. The endogenous S. cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even under growth conditions that induce peroxisome proliferation. This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. Although the heterologous enzyme was transported to peroxisomes it was not enzymically active. Immunocytochemical studies provide independent evidence that the plant enzyme is imported into the matrix of yeast peroxisomes.

Objective:To determine whether acute alcohol ingestion raises estradiol (E2) and estrone (E1) levels in a randomized, controlled, crossover study on postmenopausal women using transdermal E2.Methods:Healthy, non-smoking postmenopausal women (n = 7) using no medications were enrolled. Transdermal E2, 0.15 mg, was applied 13 hours before the subjects ingested alcohol (1 mL/kg 95% ethanol) or isocaloric carbohydrate punch. Serum samples were obtained for 40 minutes before drink ingestion and 6 hours after drink ingestion and were assayed for E2 and E1.Results:Ethanol levels peaked 60 minutes after the start of ethanol-drink ingestion, at 25.4 mmol/L (117 mg/dL). Estradiol levels rose significantly above the mean baseline of 657 pmol/L (179 pg/mL) after ethanol-drink ingestion (P ≤ .01), with a mean peak of 804 pmol/L (219 pg/mL) 35 minutes after the start of drink ingestion, and were significantly greater than the E2 levels that followed the carbohydrate drink (P ≤ .0001). There were no significant changes in E2 or E1 levels after carbohydrate-drink ingestion.Conclusions:We conclude that ethanol ingestion may acutely raise circulating E2 concentrations in women using transdermal E2.

The application of in situatomic-resolution scanning tunneling microscopy (STM) to the elucidation of local structure and potential-induced phase transitions within ordered adlayers on monocrystalline metal electrodes is discussed, and illustrated primarily for compressed CO adlayers on Pt(111). The value of the additional structural information on adsorbate binding sites that can be obtained from infrared reflection-absorption spectroscopy (IRAS) as well as from potentiodynamic STM imaging tactics is emphasized. The atomic-level and nanoscale structural alterations wrought upon the Pt(111)/CO adlayer by bismuth predosing are described as a further illustration of the synergetic value of the spatial and surface-bonding information provided by STM and IRAS. A comparison is made between the potential-dependent adlayer characteristics of the compressed CO adlayers with iodide adlayers on gold and platinum low-index electrodes. Possible reasons for the marked differences in the phase-transition behavior of these nonmetallic adlayers are briefly discussed, along with comparisons with analogous adlayers in ultrahigh vacuum environments.

The atomic and nanoscale structures of high-index gold surfaces in aqueous perchloric acid electrolyte as revealed by in-situ scanning tunneling microscopy (STM) under electrode potential control are reported with the objective of ascertaining the terrace-step morphology and superstructures as a function of the crystallographic orientation. Six faces, Au(221), (331), (533), (311), (210), and (410), two each lying in the three main zones of the unit projected stereographic triangle, were selected to investigate the role of the step orientation and terrace width for non-vicinal faces. Data for the low-index surface Au(llO) are included for comparison with Au(331) and (221), since all three feature formally a n(111)−(111) terrace-step structure. Measurements of the double-layer capacitance as a function of the electrode potential, E, in dilute perchloric acid were also undertaken in order to evaluate the potential of zero charge (Epzc) for each surface and to check the potential-dependent surface stability. The two surfaces in the (111)−(100) zone, Au(533) and (311), both display essentially (1 × 1) (i.e. bulk-termination) atomic structures at positive electrode charges (i.e. for E>E), yet exhibit significant surface relaxation at negative charges involving edge-atom depression and row buckling. For Au(221) and (331), lying in the (111)−(110) zone, however, such surface relaxation is seen even at positive electrode charges. This behavioral distinction can be understood on the basis of the differing step structures. Moreover, Au(331) undergoes a reversible (1 × 2) reconstruction at negative charges, involving row pairing. This reconstruction is compared with that observed for Au(110), which also involves “row pairing” but for which several distinct local microstructures can be distinguished. The faces in the (100)−(110) zone, Au(210) and (410), exhibit locally ordered atomic arrangements indicative of an essentially bulk-termination structure. The longer-range superstructures for the high-index faces, specifically involving domain-edge propagation across monoatomic steps, exhibit systematic trends consistent with an effectively attractivestep-step interaction at distances within ca. 5 Å.

ABSTRACTBased on conserved expression patterns, three members of the GATA family of transcriptional regulatory proteins, GATA-4, -5, and -6, are thought to be involved in the regulation of cardiogenesis and gut development. Functions for these factors are known in the heart, but relatively little is understood regarding their possible roles in the regulation of gut-specific gene expression. In this study, we analyze the expression and function of GATA-4, -5, and -6 using three separate but complementary vertebrate systems, and the results support a function for these proteins in regulating the terminal-differentiation program of intestinal epithelial cells. We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal fatty acid-binding protein (xIFABP) gene, which is a marker for differentiated enterocytes. This is the first direct demonstration of a target for GATA factors in the vertebrate intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at least in part by a defined proximal IFABP promoter element. The expression patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal villus axis. Transcript levels for cGATA-4 increase along the axis toward the villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal tip containing differentiated cells. In contrast, the pattern of cGATA-6 transcripts is complementary to cGATA-5, with highest levels detected in the region of proliferating progenitor cells. Undifferentiated and proliferating human HT-29 cells express hGATA-6 but not hGATA-4 or hGATA-5. Upon stimulation to differentiate, the transcript levels for hGATA-5 increase, and this occurs prior to increased transcription of the terminal differentiation marker intestinal alkaline phosphatase. At the same time, hGATA-6 steady-state transcript levels decline appreciably. All of the data are consistent with evolutionarily conserved but distinct roles for these factors in regulating the differentiation program of intestinal epithelium. Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP.

The spin state of antibonding orbital (eg) occupancy in LaCoO3is recognized as a descriptor for its oxygen electrocatalysis. However, the Co(III) cation in typical LaCoO3(LCO) favors low spin state, which is mediocre for absorbing oxygen-containing groups involved in oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), thus hindering its further development in electrocatalysis. Herein, both experimental and theoretical results reveal the enhancement of bifunctional electrocatalytic activity in LaCoO3by N doping. More specifically, electron energy loss spectroscopy and superconducting quantum interference devices magnetic analysis demonstrate that the Co(III) cation in N-doped LaCoO3(LCON) achieves a moderate egoccupancy (≈1) compared with its low spin state in LaCO3. First-principle calculation results reveal that N dopants play a bifunctional role of tuning the spin-state transition of Co(III) cations and increasing the electrical conductivity of LCO. Thus, the optimized LCON exhibits an OER overpotential of 1.69 V at the current density of 50 mA/cm2(1.94 V for pristine LCO) and yields an ORR limiting current density of 5.78 mA/cm2(4.01 mA/cm2for pristine LCO), which offers a new strategy to simultaneously modulate the magnetic and electronic structures of LCO to further enhance its electrocatalytic activity.

Nuclear or cell number, and the mitotic index, were recorded in endosperms of Triticum aestivum cv. Mardler to test if a particular stage of endosperm development was critical in determining the final grain weight. The basal four florets of emasculated spikelets (controls), and the third and fourth florets of spikelets where the two basal ovaries were removed (ovary-removed), were sampled at various times up to 360 h after hand-pollination. The coenocytic phase in endosperms ended about 84 h after pollination regardless of both grain position and the treatment. The onset of the cellular stage was characterized by the final large fluctuations in the mitotic index reflecting the culmination of the synchronous nuclear division of the coenocytic stage. Thereafter, the mitotic index fluctuated with smaller amplitudes and, by 216 h after pollination, was < 1%. Neither floret position in the spikelet nor the treatment affected the pattern of alteration to the mitotic index. However, ovary removal from first and second florets resulted in significantly heavier grains and higher endosperm cell number in the 3rd and 4th florets compared with the controls. In all florets, mean endosperm cell number peaked at 280 h but decreased by 360 h after pollination. At this time, the mean cell numbers in endosperms of the 3rd and 4th florets of ovary-removed spikelets were significantly higher than in the corresponding endosperms in the controls. Thus, a key contributory factor in determining the final endosperm cell number may be the number of cells which are lost during the late period of the cellular stage of endosperm development.