Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this ...Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this paper,we propose pixelated programmable Si_(3)N_(4)PICs with record-high 20-level intermediate states at 785 nm wavelength.Such flexibility in phase or amplitude modulation is achieved by a programmable Sb_(2)S_(3)matrix,the footprint of whose elements can be as small as 1.2μm,limited only by the optical diffraction limit of anin-house developed pulsed laser writing system.We believe our work lays the foundation for laser-writing ultra-high-level(20 levels and even more)programmable photonic systems and metasurfaces based on phase change materials,which could catalyze diverse applications such as programmable neuromorphic photonics,biosensing,optical computing,photonic quantum computing,and reconfigurable metasurfaces.展开更多
Strict requirement of a coherent spectrum in coherent diffractive imaging(CDI)architectures poses a significant obstacle to achieving efficient photon utilization across the full spectrum.To date,nearly all broadband ...Strict requirement of a coherent spectrum in coherent diffractive imaging(CDI)architectures poses a significant obstacle to achieving efficient photon utilization across the full spectrum.To date,nearly all broadband computational imaging experiments have relied on accurate spectroscopic measurements,as broad spectra are incompatible with conventional CDI systems.This paper presents an advanced approach to broaden the scope of CDI to ultra-broadband illumination with unknown probe spectrum,effectively addresses the key challenges encountered by existing state-ofthe-art broadband diffractive imaging frameworks.This advancement eliminates the necessity for prior knowledge of probe spectrum and relaxes constraints on non-dispersive samples,resulting in a significant extension in spectral bandwidth,achieving a nearly fourfold improvement in bandlimit compared to the existing benchmark.Our method not only monochromatizes a broadband diffraction pattern from unknown illumination spectrum,but also determines the compressive sampled profile of spectrum of the diffracted radiation.This superiority is experimentally validated using both CDI and ptychography techniques on an ultra-broadband supercontinuum with relative bandwidth exceeding 40%,revealing a significantly enhanced coherence and improved reconstruction with high fidelity under ultra-broadband illumination.展开更多
The effects of different treatments on the seedlessness and fruit quality of‘Miguang’table grape was studied by using plant growth regulators,gibberellin acid(GA 3)and forchlorfenuron(CPPU),under different concentra...The effects of different treatments on the seedlessness and fruit quality of‘Miguang’table grape was studied by using plant growth regulators,gibberellin acid(GA 3)and forchlorfenuron(CPPU),under different concentrations and application time.The results showed that the effects of different treatments on the seedlessness and fruit quality were different.Seedless rate,cluster weight,berry weight,berry shape index,soluble solid content,total acid content,soluble solids to acidity ratio,pulling resistance,turgor pressure and flesh firmness without skin were comprehensively evaluated,as a result of which,the optimum treatment on‘Miguang’table grape was to apply with GA 320 mg/L+SM 200 mg/L at one week before bloom and GA 325 mg/L+CPPU 3 mg/L at two weeks after bloom.展开更多
Most electronics such as sensors,actuators and energy harvesters need piezoceramic films to interconvert mechanical and electrical energy.Transferring the ceramic films from their growth substrates for assembling elec...Most electronics such as sensors,actuators and energy harvesters need piezoceramic films to interconvert mechanical and electrical energy.Transferring the ceramic films from their growth substrates for assembling electronic devices commonly requires chemical or physical etching,which comes at the sacrifice of the substrate materials,film cracks,and environmental contamination.Here,we introduce a van der Waals stripping method to fabricate large-area and freestanding piezoceramic thin films in a simple,green,and cost-effective manner.The introduction of the quasi van der Waals epitaxial platinum layer enables the capillary force of water to drive the separation process of the film and substrate interface.The fabricated lead-free film,Ba_(0.85)Ca_(0.15)Zr_(0.1)Ti_(0.9)O_(3)(BCZT),shows a high piezoelectric coefficient d_(33)=209±10 pm V−1 and outstanding flexibility of maximum strain 2%.The freestanding feature enables a wide application scenario,including micro energy harvesting,and covid-19 spike protein detection.We further conduct a life cycle analysis and quantify the low energy consumption and low pollution of the water-based stripping film method.展开更多
Objective: European lung cancer screening studies using computed tomography(CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time(VDT) is more specific for early lung...Objective: European lung cancer screening studies using computed tomography(CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time(VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods: This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol(Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT(a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results: The diagnostic performance of volume-and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions: Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.展开更多
The growing demand for electronic devices, smart devices, and the Internet of Things constitutes the primary driving force for marching down the path of decreased critical dimension and increased circuit intricacy of ...The growing demand for electronic devices, smart devices, and the Internet of Things constitutes the primary driving force for marching down the path of decreased critical dimension and increased circuit intricacy of integrated circuits. However, as sub-10 nm high-volume manufacturing is becoming the mainstream, there is greater awareness that defects introduced by original equipment manufacturer components impact yield and manufacturing costs. The identification, positioning, and classification of these defects, including random particles and systematic defects, are becoming more and more challenging at the 10 nm node and beyond.Very recently, the combination of conventional optical defect inspection with emerging techniques such as nanophotonics, optical vortices, computational imaging, quantitative phase imaging, and deep learning is giving the field a new possibility. Hence, it is extremely necessary to make a thorough review for disclosing new perspectives and exciting trends, on the foundation of former great reviews in the field of defect inspection methods. In this article, we give a comprehensive review of the emerging topics in the past decade with a focus on three specific areas:(a) the defect detectability evaluation,(b) the diverse optical inspection systems,and(c) the post-processing algorithms. We hope, this work can be of importance to both new entrants in the field and people who are seeking to use it in interdisciplinary work.展开更多
Objective:To evaluate the correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma(SBA).Methods:46 patients with solitary bronchogenic adenocarci...Objective:To evaluate the correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma(SBA).Methods:46 patients with solitary bronchogenic adenocarcinomas (SBA)(diameter≤4 cm)underwent multi-location dynamic contrast material-enhanced(nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/s by using an autoinjector 90 mL,4×5 mm or 4×2.5 mm scanning mode with stable table were performed)serial CT.Precontrast and postcontrast attenuation on every scan was recorded.Perfusion (PBA),peak height(PHBA),ratio of peak height of the SPN to that of the aorta(BA-to-A ratio)and mean transit time(MTT)were calculated.The correlation between peak height of the aorta(PHA)and parameters of the SBA(PHBA,BA-to-A ratio,PBA,and MTT)and those among parameters of the SBA were assessed by means of linear regression analysis.Regression equation among parameters of the SBA were obtain by means of stepwise regression.Results:The correlation between the SBA peak height(PHBA,36.78 HU±12.02)and the aortic peak height(PHA)was significant(r=0.506,P<0.0001).No significant cor- relation was found between the BA-to-Apeak height ratio(15.33%±4.55)and the aortic peak height(r=0.130,P=0.388> 0.05)as it was between the SBA perfusion(PBA,31.86 mL/min/100 g±9.74)and the aortic peak height(r=0.049,P=0.749 >0.05).The SBA perfusion correlated with the PHBA and the BA-to-A peak height ratio(r=0.394,P=0.007<0.05;r=0.407, P=0.005<0.05).The PHBA correlated positively with the BA-to-A peak height ratio(r=0.781,P<0.0001).Mean transit time was 14.84 s±5.52.PBA=18.500+0.872×BA-to-A ratio.BA-to-A ratio=4.467+0.295×PHBA.Conclusion:The linear correlation between the SBA perfusion and BA-to-Aratio and that between BA-to-Aratio and PHBA can be expressed by equation. It is possible to design a simpler scanning procedure of investigation of bronchogenic adenocarcinoma angiogenesis.展开更多
Objective: To evaluate the correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules and tumor size. Methods: Sixty-eight patients with mal...Objective: To evaluate the correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules and tumor size. Methods: Sixty-eight patients with malignant solitary pulmonary nodules (SPNs) (diameter 〈4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubitai vein at a rate of 4mL/s by using an autoinjector, 4×5 mm or 4×2.5 mm scanning mode with stable table were performed). Precontrast and postcontrast attenuation on every scan was recorded. Blood flow (BF), peak, height (PHSPN), ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio) and mean transit time (MTT) were calculated. The correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules and tumor size were assessed by means of linear regression analysis. Results: No significant correlations were found between the tumor size and each of the peak height (PHSPN) (35.79±10.76 Hu), ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio), (14.27%±4.37) and blood flow (BF) (30.18 mL/min/100 g±9.58) (r=0.180, P=0.142〉0.05; r=0.205, P=0.093〉0.05; r=0.008, P=0.947〉0.05). Conclusion: No significant correlations were found between the tumor size and each of the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules.展开更多
Objective: To evaluate the efficacy of dynamic multi-slice spiral computed tomography (MSCT) for providing quantitative information about blood flow patterns of solitary pulmonary nodules (SPNs). Methods: Sevent...Objective: To evaluate the efficacy of dynamic multi-slice spiral computed tomography (MSCT) for providing quantitative information about blood flow patterns of solitary pulmonary nodules (SPNs). Methods: Seventy-eight patients with SPNs (diameter 〈 4 cm; 68 malignant; 10 active inflammatory) were underwent multi-location dynamic contrast material-enhanced serial CT (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mLJs by using an autoinjector, 4 × 5 mm or 4 × 2.5 mm transverse scanning mode with stable table were performed). Sixteen series CT scans (16 scans each for the first and second series and one scan each for the rest series) were obtained during 9 min scanning period. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion, peak height and ratio of peak height of the SPN to that of the aorta were calculated. Perfusion was calculated from the maximum gradient of the time-attenuation curve and the peak height of the aorta. Results: No statistically significant difference in the peak height was found between malignant (35.79 ± 10.76 Hu) and active inflammatory (39.76 ± 4.59 Hu) (t = 1.148, P = 0.255 〉 0.05). SPN-to-aorta ratio (14.27% ± 4.37) and perfusion value (30.18 mL/min/100 g ± 9.58) in malignant SPNs were significantly lower than those of active inflammatory (18.51% ± 2.71, 63.44 mL/min/100 g ± 43.87) (t = 2.978, P = 0.004 〈 0.05; t = 5.590, P 〈 0.0001). Conclusion: The quantitative information about blood flow patterns of malignant and active inflammatory SPNs is different. SPN-to-aorta ratio and perfusion value are helpful in differentiating malignant nodules from active inflammatory.展开更多
The chemical stability of cefixime was determined by high-performance liquid chromatography (HPLC) under different conditions, including factors such as pH, solvents, initial concentration, temperature and additives...The chemical stability of cefixime was determined by high-performance liquid chromatography (HPLC) under different conditions, including factors such as pH, solvents, initial concentration, temperature and additives. The degradation process follows the first-order kinetics. A pH-rate profile exhibits the U-shape and shows the maximum stability of cefixime at pH = 6. The stability in different pure solvents is ranked as acetone 〉 ethanol 〉 methanol 〉 water, while the degradation rate of cefixime exists a maximum at the ratio of 0.6 in water + methanol mixtures. In addition, the degradation rate increases with the temperature increasing and the activation energy of degradation was found to be 27.078 kJ. mol- 1 in acetone + water mixed solvents. The addition of different additives was proven to either inhibit or accelerate the degradation. The degradation products were analyzed using HPLC, LC-MS and infrared spectroscopy, and the possible degradation pathways in acid as well as alkaline environment were proposed to help us understand the degradation behavior of cefixime.展开更多
Objective: To investigate the correlations of vascular endothelial growth factor (VEGF)-positive tumor angiogenesis and the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogeni...Objective: To investigate the correlations of vascular endothelial growth factor (VEGF)-positive tumor angiogenesis and the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma. Methods: 30 patients with VEGF-positive bronchogenic adenocarcinomas (diameter ≤ 4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/sec by using an autoinjector) serial CT. The quantifiable parameters (Perfusion, peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and mean transit time) of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma were compared with microvessel densities (MVDs) and VEGF expression by immunohistochemistry. Results: Peak height of VEGF-positive bronchogenic adenocarcinoma was 36.06 HU ± 13.57 HU, bronchogenic adenocarcinoma-to-aorta ratio 14.25% ± 4.92, and perfusion value 29.66 ± 5.60 mL/min/100 g , mean transit time 14.86 s ± 5.84 s, and MVD 70.15 ± 20.03. Each of peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and perfusion correlated positively with MVD (r = 0.781, P < 0.0001; r = 0.688, P < 0.0001; r = 0.716, P < 0.0001; respectively). No significant correlation was found between mean transit time and MVD (r = 0.260, P = 0.200 > 0.05). Conclusion: Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta reflect MVD in VEGF-positive bronchogenic adenocarcinoma. Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta derived with dynamic CT might be index for VEGF-related tumor angiogenesis in bronchogenic adenocarcinoma.展开更多
In order to evaluate the effects of soil depth on the contents of soil organic nitrogen,organic nitrogen forms in apple-pear orchard soil profile were quantified using the method proposed by Bremner in 1965.The result...In order to evaluate the effects of soil depth on the contents of soil organic nitrogen,organic nitrogen forms in apple-pear orchard soil profile were quantified using the method proposed by Bremner in 1965.The results indicated that in addition to the amino sugar-N,all the soil organic N components within the same soil layer in wasteland were more than those in apple-pear orchard soil;with the layer depth increasing,the contents of different organic nitrogen forms in apple-pear orchard soil and wasteland were decreased;and the proportion of each organic N component within total hydrolysable N was different,and the percentages of ammonia N and amino acid-N components within total hydrolysable N were higher,especially the percentage of ammonia N components within total hydrolysable N was the highest.展开更多
Miniaturizing spectrometers for compact and cost-effective mobile platforms is a major challenge in current spectroscopy research,where conventional spectrometers are impractical due to their bulky footprint.Existing ...Miniaturizing spectrometers for compact and cost-effective mobile platforms is a major challenge in current spectroscopy research,where conventional spectrometers are impractical due to their bulky footprint.Existing miniaturized designs primarily rely on precalibrated response functions of nanophotonic structures to encode spectral information captured in a snapshot by detector arrays.Accurate spectrum reconstruction is achieved through computational techniques,but this requires precise component design,high-precision fabrication,and calibration.We propose an ultra-simplified computational spectrometer that employs a one-to-broadband diffraction decomposition strategy facilitated by a numerical regularized transform that depends only on the spectrum of the diffracted radiation.The key feature of our design is the use of a simple,arbitrarily shaped pinhole as the partial disperser,eliminating the need for complex encoding designs and full spectrum calibration.Our spectrometer achieves a reconstructed spectral peak location accuracy of better than 1 nm over a 200 nm bandwidth and excellent resolution for peaks separated by 3 nm in a bimodal spectrum,all within a compact footprint of under half an inch.Notably,our approach also reveals a breakthrough in broadband coherent diffractive imaging without requiring any prior knowledge of the broadband illumination spectrum,assumptions of non-dispersive specimens,or correction for detector quantum efficiency.展开更多
Photoacoustic detection has shown excellent performance in measuring thickness and detecting defects in metal nanofilms.However,existing research on ultrafast lasers mainly focuses on using picosecond or nanosecond la...Photoacoustic detection has shown excellent performance in measuring thickness and detecting defects in metal nanofilms.However,existing research on ultrafast lasers mainly focuses on using picosecond or nanosecond lasers for large-scale material processing and measurement.The theoretical study of femtosecond laser sources for photoacoustic nondestructive testing(NDT)in nanoscale thin film materials receives much less emphasis,leading to a lack of a complete physical model that covers the entire process from excitation to measurement.In this study,we developed a comprehensive physical model that combines the two-temperature model with the acoustic wave generation and detection model.On the basis of the physical model,we established a simulation model to visualize the ultrafast lasermaterial interaction process.The damage threshold of the laser source is determined,and the effect of key parameters(laser fluence,pulse duration,and wavelength)for AlCu nanofilms on the femtosecond photoacoustic NDT process is discussed using numerical results from the finite element model.The numerical results under certain parameters show good agreement with the experimental results.展开更多
The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity ...The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.展开更多
With the continued shrinking of the critical dimensions(CDs)of wafer patterning,the requirements for modeling precision in optical proximity correction(OPC)increase accordingly.This requirement extends beyond CD contr...With the continued shrinking of the critical dimensions(CDs)of wafer patterning,the requirements for modeling precision in optical proximity correction(OPC)increase accordingly.This requirement extends beyond CD controlling accuracy to include pattern alignment accuracy because misalignment can lead to considerable overlay and metal-via coverage issues at advanced nodes,affecting process window and yield.This paper proposes an efficient OPC modeling approach that prioritizes pattern-shift-related elements to tackle the issue accurately.Our method integrates careful measurement selection,the implementation of pattern-shift-aware structures in design,and the manipulation of the cost function during model tuning to establish a robust model.Confirmatory experiments are performed on a via layer fabricated using a negative tone development.Results demonstrate that pattern shifts can be constrained within a range of+1 nm,remarkably better than the original range of±3 nm.Furthermore,simulations reveal notable differences between post OPC and original masks when considering pattern shifts at locations sensitive to this phenomenon.Experimental validation confirms the accuracy of the proposed modeling approach,and a firm consistency is observed between the simulation results and experimental data obtained from actual design structures.展开更多
In recent years,the demand for real-time data processing has been increasing,and various stream processing systems have emerged.When the amount of data input to the stream processing system fluctuates,the computing re...In recent years,the demand for real-time data processing has been increasing,and various stream processing systems have emerged.When the amount of data input to the stream processing system fluctuates,the computing resources required by the stream processing job will also change.The resources used by stream processing jobs need to be adjusted according to load changes,avoiding the waste of computing resources.At present,existing works adjust stream processing jobs based on the assumption that there is a linear relationship between the operator parallelism and operator resource consumption(e.g.,throughput),which makes a significant deviation when the operator parallelism increases.This paper proposes a nonlinear model to represent operator performance.We divide the operator performance into three stages,the Non-competition stage,the Non-full competition stage,and the Full competition stage.Using our proposed performance model,given the parallelism of the operator,we can accurately predict the CPU utilization and operator throughput.Evaluated with actual experiments,the prediction error of our model is below 5%.We also propose a quick accurate auto-scaling(QAAS)method that uses the operator performance model to implement the auto-scaling of the operator parallelism of the Flink job.Compared to previous work,QAAS is able to maintain stable job performance under load changes,minimizing the number of job adjustments and reducing data backlogs by 50%.展开更多
Hydride ion(H^(-))has high polarizability(α_(H^(-))=10.17A^(3))and high redox potential(H^(-)/H_(2):-2.3 V),and therefore is an attractive energy carrier[1,2].The H^(-)superconductors play a crucial role in the devel...Hydride ion(H^(-))has high polarizability(α_(H^(-))=10.17A^(3))and high redox potential(H^(-)/H_(2):-2.3 V),and therefore is an attractive energy carrier[1,2].The H^(-)superconductors play a crucial role in the development of high-density energy storage and chemical conversion technologies[3].展开更多
Disodium 5′-ribonucleotide,which is composed of disodium 5′-inosine(IMP)and disodium 5′-guanosine(GMP),is an important food additive.The lack of kinetic studies of it causes a lack of clarity in understanding the c...Disodium 5′-ribonucleotide,which is composed of disodium 5′-inosine(IMP)and disodium 5′-guanosine(GMP),is an important food additive.The lack of kinetic studies of it causes a lack of clarity in understanding the complicated multi-solute crystallization of IMP+GMP in ethanol-water.In this work,process analytical technology tools were used to obtain the thermodynamics and kinetic data from the experiments,the kinetic parameters of anti-solvent and cooling crystallization were investigated.The crystal form of IMP+GMP mixed crystal was determined,which was consistent with the IMP whether crystallized from pure water or ethanol-water.The effects of different anti-solvent addition rates and cooling rates on the metastable zone widths were studied,and the opposite effect on metastable zone width was found.The modified exponential empirical function was developed to correlate nucleation and growth kinetic equations under different conditions.The kinetic data were well fitted with adjusted correlation coefficient(adj-R^(2)>0.7),which is sufficient to provide a valid reference for process design and control.展开更多
基金funded by the National Nature Science Foundation of China(Grant Nos.52175509 and 52130504)National Key Research and Development Program of China(2017YFF0204705)2021 Postdoctoral Innovation Research Plan of Hubei Province(0106100226)。
文摘Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this paper,we propose pixelated programmable Si_(3)N_(4)PICs with record-high 20-level intermediate states at 785 nm wavelength.Such flexibility in phase or amplitude modulation is achieved by a programmable Sb_(2)S_(3)matrix,the footprint of whose elements can be as small as 1.2μm,limited only by the optical diffraction limit of anin-house developed pulsed laser writing system.We believe our work lays the foundation for laser-writing ultra-high-level(20 levels and even more)programmable photonic systems and metasurfaces based on phase change materials,which could catalyze diverse applications such as programmable neuromorphic photonics,biosensing,optical computing,photonic quantum computing,and reconfigurable metasurfaces.
基金the technical support from the Experiment Centre for Advanced Manufacturing and Technology in School of Mechanical Science&Engineering of HUSTsupported by the Natural Science Foundation of China(52130504)+4 种基金Key Research and Development Program of Hubei Province(2021BAA013)Innovation Project of Optics Valley Laboratory(OVL2023PY003)Natural Science Foundation of Hubei Province(2021CFB322)Fundamental Research Funds for the Central Universities(2021XXJS113)Guangdong Basic and Applied Basic Research Foundation(2023A1515030149).
文摘Strict requirement of a coherent spectrum in coherent diffractive imaging(CDI)architectures poses a significant obstacle to achieving efficient photon utilization across the full spectrum.To date,nearly all broadband computational imaging experiments have relied on accurate spectroscopic measurements,as broad spectra are incompatible with conventional CDI systems.This paper presents an advanced approach to broaden the scope of CDI to ultra-broadband illumination with unknown probe spectrum,effectively addresses the key challenges encountered by existing state-ofthe-art broadband diffractive imaging frameworks.This advancement eliminates the necessity for prior knowledge of probe spectrum and relaxes constraints on non-dispersive samples,resulting in a significant extension in spectral bandwidth,achieving a nearly fourfold improvement in bandlimit compared to the existing benchmark.Our method not only monochromatizes a broadband diffraction pattern from unknown illumination spectrum,but also determines the compressive sampled profile of spectrum of the diffracted radiation.This superiority is experimentally validated using both CDI and ptychography techniques on an ultra-broadband supercontinuum with relative bandwidth exceeding 40%,revealing a significantly enhanced coherence and improved reconstruction with high fidelity under ultra-broadband illumination.
基金Supported by Basic Research Funds of Hebei Academy of Agriculture and Forestry Sciences(2023020103)Domestic Training Program for Young Scientific and Technological Talents of Agriculture and Forestry Sciences+3 种基金Hebei Agriculture Research System(HBCT2023150202)Key R&D Program Project of Hebei Provincial Department of Science and Technology(20326813D)The innovation project of modern seed technology(21326310D)HAAFS Science and Technology Innovation Special Project(2022KJCXZX-CGS-1).
文摘The effects of different treatments on the seedlessness and fruit quality of‘Miguang’table grape was studied by using plant growth regulators,gibberellin acid(GA 3)and forchlorfenuron(CPPU),under different concentrations and application time.The results showed that the effects of different treatments on the seedlessness and fruit quality were different.Seedless rate,cluster weight,berry weight,berry shape index,soluble solid content,total acid content,soluble solids to acidity ratio,pulling resistance,turgor pressure and flesh firmness without skin were comprehensively evaluated,as a result of which,the optimum treatment on‘Miguang’table grape was to apply with GA 320 mg/L+SM 200 mg/L at one week before bloom and GA 325 mg/L+CPPU 3 mg/L at two weeks after bloom.
基金supported by General Research Grant(Project No.11212021,No.11210822)Early Career Scheme(Project No.CityU 21210619)from the Research Grants Council of the Hong Kong Special Administrative Regionthe Innovation and Technology Fund(ITS/065/20,GHP/096/19SZ)from the Innovation and Technology Commission of the Hong Kong Special Administrative Region.
文摘Most electronics such as sensors,actuators and energy harvesters need piezoceramic films to interconvert mechanical and electrical energy.Transferring the ceramic films from their growth substrates for assembling electronic devices commonly requires chemical or physical etching,which comes at the sacrifice of the substrate materials,film cracks,and environmental contamination.Here,we introduce a van der Waals stripping method to fabricate large-area and freestanding piezoceramic thin films in a simple,green,and cost-effective manner.The introduction of the quasi van der Waals epitaxial platinum layer enables the capillary force of water to drive the separation process of the film and substrate interface.The fabricated lead-free film,Ba_(0.85)Ca_(0.15)Zr_(0.1)Ti_(0.9)O_(3)(BCZT),shows a high piezoelectric coefficient d_(33)=209±10 pm V−1 and outstanding flexibility of maximum strain 2%.The freestanding feature enables a wide application scenario,including micro energy harvesting,and covid-19 spike protein detection.We further conduct a life cycle analysis and quantify the low energy consumption and low pollution of the water-based stripping film method.
基金a part of NELCIN-B3 project. The NELCIN-B3 project is funded by The Royal Netherlands Academy of Arts and Sciences (Grant No. PSA_SA_BD_01)Ministry of Science and Technology of the People’s Republic of China+1 种基金National Key R & D Program of China (Grant No. 2016YFE0103000)the financial support from China Scholarship Council (CSC file No. 201708340072)
文摘Objective: European lung cancer screening studies using computed tomography(CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time(VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods: This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol(Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT(a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results: The diagnostic performance of volume-and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions: Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.
基金funded by the National Natural Science Foundation of China(Grant Nos.52175509 and 52130504)the National Key Research and Development Program of China(2017YFF0204705)+1 种基金the Key Research and Development Plan of Hubei Province(2021BAA013)the National Science and Technology Major Project(2017ZX02101006-004)。
文摘The growing demand for electronic devices, smart devices, and the Internet of Things constitutes the primary driving force for marching down the path of decreased critical dimension and increased circuit intricacy of integrated circuits. However, as sub-10 nm high-volume manufacturing is becoming the mainstream, there is greater awareness that defects introduced by original equipment manufacturer components impact yield and manufacturing costs. The identification, positioning, and classification of these defects, including random particles and systematic defects, are becoming more and more challenging at the 10 nm node and beyond.Very recently, the combination of conventional optical defect inspection with emerging techniques such as nanophotonics, optical vortices, computational imaging, quantitative phase imaging, and deep learning is giving the field a new possibility. Hence, it is extremely necessary to make a thorough review for disclosing new perspectives and exciting trends, on the foundation of former great reviews in the field of defect inspection methods. In this article, we give a comprehensive review of the emerging topics in the past decade with a focus on three specific areas:(a) the defect detectability evaluation,(b) the diverse optical inspection systems,and(c) the post-processing algorithms. We hope, this work can be of importance to both new entrants in the field and people who are seeking to use it in interdisciplinary work.
文摘Objective:To evaluate the correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma(SBA).Methods:46 patients with solitary bronchogenic adenocarcinomas (SBA)(diameter≤4 cm)underwent multi-location dynamic contrast material-enhanced(nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/s by using an autoinjector 90 mL,4×5 mm or 4×2.5 mm scanning mode with stable table were performed)serial CT.Precontrast and postcontrast attenuation on every scan was recorded.Perfusion (PBA),peak height(PHBA),ratio of peak height of the SPN to that of the aorta(BA-to-A ratio)and mean transit time(MTT)were calculated.The correlation between peak height of the aorta(PHA)and parameters of the SBA(PHBA,BA-to-A ratio,PBA,and MTT)and those among parameters of the SBA were assessed by means of linear regression analysis.Regression equation among parameters of the SBA were obtain by means of stepwise regression.Results:The correlation between the SBA peak height(PHBA,36.78 HU±12.02)and the aortic peak height(PHA)was significant(r=0.506,P<0.0001).No significant cor- relation was found between the BA-to-Apeak height ratio(15.33%±4.55)and the aortic peak height(r=0.130,P=0.388> 0.05)as it was between the SBA perfusion(PBA,31.86 mL/min/100 g±9.74)and the aortic peak height(r=0.049,P=0.749 >0.05).The SBA perfusion correlated with the PHBA and the BA-to-A peak height ratio(r=0.394,P=0.007<0.05;r=0.407, P=0.005<0.05).The PHBA correlated positively with the BA-to-A peak height ratio(r=0.781,P<0.0001).Mean transit time was 14.84 s±5.52.PBA=18.500+0.872×BA-to-A ratio.BA-to-A ratio=4.467+0.295×PHBA.Conclusion:The linear correlation between the SBA perfusion and BA-to-Aratio and that between BA-to-Aratio and PHBA can be expressed by equation. It is possible to design a simpler scanning procedure of investigation of bronchogenic adenocarcinoma angiogenesis.
文摘Objective: To evaluate the correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules and tumor size. Methods: Sixty-eight patients with malignant solitary pulmonary nodules (SPNs) (diameter 〈4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubitai vein at a rate of 4mL/s by using an autoinjector, 4×5 mm or 4×2.5 mm scanning mode with stable table were performed). Precontrast and postcontrast attenuation on every scan was recorded. Blood flow (BF), peak, height (PHSPN), ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio) and mean transit time (MTT) were calculated. The correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules and tumor size were assessed by means of linear regression analysis. Results: No significant correlations were found between the tumor size and each of the peak height (PHSPN) (35.79±10.76 Hu), ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio), (14.27%±4.37) and blood flow (BF) (30.18 mL/min/100 g±9.58) (r=0.180, P=0.142〉0.05; r=0.205, P=0.093〉0.05; r=0.008, P=0.947〉0.05). Conclusion: No significant correlations were found between the tumor size and each of the quantifiable parameters of blood flow pattern derived with dynamic CT in malignant solitary pulmonary nodules.
文摘Objective: To evaluate the efficacy of dynamic multi-slice spiral computed tomography (MSCT) for providing quantitative information about blood flow patterns of solitary pulmonary nodules (SPNs). Methods: Seventy-eight patients with SPNs (diameter 〈 4 cm; 68 malignant; 10 active inflammatory) were underwent multi-location dynamic contrast material-enhanced serial CT (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mLJs by using an autoinjector, 4 × 5 mm or 4 × 2.5 mm transverse scanning mode with stable table were performed). Sixteen series CT scans (16 scans each for the first and second series and one scan each for the rest series) were obtained during 9 min scanning period. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion, peak height and ratio of peak height of the SPN to that of the aorta were calculated. Perfusion was calculated from the maximum gradient of the time-attenuation curve and the peak height of the aorta. Results: No statistically significant difference in the peak height was found between malignant (35.79 ± 10.76 Hu) and active inflammatory (39.76 ± 4.59 Hu) (t = 1.148, P = 0.255 〉 0.05). SPN-to-aorta ratio (14.27% ± 4.37) and perfusion value (30.18 mL/min/100 g ± 9.58) in malignant SPNs were significantly lower than those of active inflammatory (18.51% ± 2.71, 63.44 mL/min/100 g ± 43.87) (t = 2.978, P = 0.004 〈 0.05; t = 5.590, P 〈 0.0001). Conclusion: The quantitative information about blood flow patterns of malignant and active inflammatory SPNs is different. SPN-to-aorta ratio and perfusion value are helpful in differentiating malignant nodules from active inflammatory.
基金Supported by the National Natural Science Foundation of China(81361140344 and21376164)National High Technology Reseach and Development Program of China(863Program,2015AA021002)Major National Scientific Instrument Development Project(21527812)
文摘The chemical stability of cefixime was determined by high-performance liquid chromatography (HPLC) under different conditions, including factors such as pH, solvents, initial concentration, temperature and additives. The degradation process follows the first-order kinetics. A pH-rate profile exhibits the U-shape and shows the maximum stability of cefixime at pH = 6. The stability in different pure solvents is ranked as acetone 〉 ethanol 〉 methanol 〉 water, while the degradation rate of cefixime exists a maximum at the ratio of 0.6 in water + methanol mixtures. In addition, the degradation rate increases with the temperature increasing and the activation energy of degradation was found to be 27.078 kJ. mol- 1 in acetone + water mixed solvents. The addition of different additives was proven to either inhibit or accelerate the degradation. The degradation products were analyzed using HPLC, LC-MS and infrared spectroscopy, and the possible degradation pathways in acid as well as alkaline environment were proposed to help us understand the degradation behavior of cefixime.
文摘Objective: To investigate the correlations of vascular endothelial growth factor (VEGF)-positive tumor angiogenesis and the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma. Methods: 30 patients with VEGF-positive bronchogenic adenocarcinomas (diameter ≤ 4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/sec by using an autoinjector) serial CT. The quantifiable parameters (Perfusion, peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and mean transit time) of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma were compared with microvessel densities (MVDs) and VEGF expression by immunohistochemistry. Results: Peak height of VEGF-positive bronchogenic adenocarcinoma was 36.06 HU ± 13.57 HU, bronchogenic adenocarcinoma-to-aorta ratio 14.25% ± 4.92, and perfusion value 29.66 ± 5.60 mL/min/100 g , mean transit time 14.86 s ± 5.84 s, and MVD 70.15 ± 20.03. Each of peak height, ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta and perfusion correlated positively with MVD (r = 0.781, P < 0.0001; r = 0.688, P < 0.0001; r = 0.716, P < 0.0001; respectively). No significant correlation was found between mean transit time and MVD (r = 0.260, P = 0.200 > 0.05). Conclusion: Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta reflect MVD in VEGF-positive bronchogenic adenocarcinoma. Perfusion, peak height and ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta derived with dynamic CT might be index for VEGF-related tumor angiogenesis in bronchogenic adenocarcinoma.
文摘In order to evaluate the effects of soil depth on the contents of soil organic nitrogen,organic nitrogen forms in apple-pear orchard soil profile were quantified using the method proposed by Bremner in 1965.The results indicated that in addition to the amino sugar-N,all the soil organic N components within the same soil layer in wasteland were more than those in apple-pear orchard soil;with the layer depth increasing,the contents of different organic nitrogen forms in apple-pear orchard soil and wasteland were decreased;and the proportion of each organic N component within total hydrolysable N was different,and the percentages of ammonia N and amino acid-N components within total hydrolysable N were higher,especially the percentage of ammonia N components within total hydrolysable N was the highest.
基金supported by the National Natural Science Foundation of China(52130504)Key Research and Development Program of Hubei Province(2021BAA013)+3 种基金Innovation Project of Optics Valley Laboratory(OVL2023PY003)Natural Science Foundation of Hubei Province(2021CFB322)Fundamental Research Funds for the Central Universities(2021XXJS113)Guangdong Basic and Applied Basic Research Foundation(2023A1515030149).
文摘Miniaturizing spectrometers for compact and cost-effective mobile platforms is a major challenge in current spectroscopy research,where conventional spectrometers are impractical due to their bulky footprint.Existing miniaturized designs primarily rely on precalibrated response functions of nanophotonic structures to encode spectral information captured in a snapshot by detector arrays.Accurate spectrum reconstruction is achieved through computational techniques,but this requires precise component design,high-precision fabrication,and calibration.We propose an ultra-simplified computational spectrometer that employs a one-to-broadband diffraction decomposition strategy facilitated by a numerical regularized transform that depends only on the spectrum of the diffracted radiation.The key feature of our design is the use of a simple,arbitrarily shaped pinhole as the partial disperser,eliminating the need for complex encoding designs and full spectrum calibration.Our spectrometer achieves a reconstructed spectral peak location accuracy of better than 1 nm over a 200 nm bandwidth and excellent resolution for peaks separated by 3 nm in a bimodal spectrum,all within a compact footprint of under half an inch.Notably,our approach also reveals a breakthrough in broadband coherent diffractive imaging without requiring any prior knowledge of the broadband illumination spectrum,assumptions of non-dispersive specimens,or correction for detector quantum efficiency.
基金funded by the National Natural Science Foundation of China(Grant Nos.52375541,52022034,52130504,and 62175075)the National Key Research and Development Plan of China(Grant No.2022YFF0709104)+2 种基金the Key Research and Development Plan of Hubei Province,China(Grant No.2020BAA8)the Interdisciplinary Research Program of Huazhong University of Science and Technology,China(Grant No.2023JCYJ047)the Innovation Project of Optics Valley Laboratory,China(Grant No.OVL2023PY003).
文摘Photoacoustic detection has shown excellent performance in measuring thickness and detecting defects in metal nanofilms.However,existing research on ultrafast lasers mainly focuses on using picosecond or nanosecond lasers for large-scale material processing and measurement.The theoretical study of femtosecond laser sources for photoacoustic nondestructive testing(NDT)in nanoscale thin film materials receives much less emphasis,leading to a lack of a complete physical model that covers the entire process from excitation to measurement.In this study,we developed a comprehensive physical model that combines the two-temperature model with the acoustic wave generation and detection model.On the basis of the physical model,we established a simulation model to visualize the ultrafast lasermaterial interaction process.The damage threshold of the laser source is determined,and the effect of key parameters(laser fluence,pulse duration,and wavelength)for AlCu nanofilms on the femtosecond photoacoustic NDT process is discussed using numerical results from the finite element model.The numerical results under certain parameters show good agreement with the experimental results.
基金the National Key Research and Development Program of China(2021YFC2300101).
文摘The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.
基金funded by the National Natural Science Foundation of China(Grant Nos.52130504,52305577,and 52205592)the Key Research and Development Plan of Hubei Province,China(Grant No.2022BAA013)+2 种基金the Major Program(JD)of Hubei Province,China(Grant No.2023BAA008-2)the Innovation Projection of Optics Valley Laboratory,China(Grant No.OVL2023PY003)the Postdoctoral Fellowship Program(Grade B)of the China Postdoctoral Science Foundation(Grant No.GZB20230244).
文摘With the continued shrinking of the critical dimensions(CDs)of wafer patterning,the requirements for modeling precision in optical proximity correction(OPC)increase accordingly.This requirement extends beyond CD controlling accuracy to include pattern alignment accuracy because misalignment can lead to considerable overlay and metal-via coverage issues at advanced nodes,affecting process window and yield.This paper proposes an efficient OPC modeling approach that prioritizes pattern-shift-related elements to tackle the issue accurately.Our method integrates careful measurement selection,the implementation of pattern-shift-aware structures in design,and the manipulation of the cost function during model tuning to establish a robust model.Confirmatory experiments are performed on a via layer fabricated using a negative tone development.Results demonstrate that pattern shifts can be constrained within a range of+1 nm,remarkably better than the original range of±3 nm.Furthermore,simulations reveal notable differences between post OPC and original masks when considering pattern shifts at locations sensitive to this phenomenon.Experimental validation confirms the accuracy of the proposed modeling approach,and a firm consistency is observed between the simulation results and experimental data obtained from actual design structures.
基金supported by the National Key Research and Development Program of China(2020YFB1506703)the National Natural Science Foundation of China(Grant No.62072018)+1 种基金the State Key Laboratory of Software Development Environment(SKLSDE-2021ZX-06)the Fundamental Research Funds for the Central Universities.
文摘In recent years,the demand for real-time data processing has been increasing,and various stream processing systems have emerged.When the amount of data input to the stream processing system fluctuates,the computing resources required by the stream processing job will also change.The resources used by stream processing jobs need to be adjusted according to load changes,avoiding the waste of computing resources.At present,existing works adjust stream processing jobs based on the assumption that there is a linear relationship between the operator parallelism and operator resource consumption(e.g.,throughput),which makes a significant deviation when the operator parallelism increases.This paper proposes a nonlinear model to represent operator performance.We divide the operator performance into three stages,the Non-competition stage,the Non-full competition stage,and the Full competition stage.Using our proposed performance model,given the parallelism of the operator,we can accurately predict the CPU utilization and operator throughput.Evaluated with actual experiments,the prediction error of our model is below 5%.We also propose a quick accurate auto-scaling(QAAS)method that uses the operator performance model to implement the auto-scaling of the operator parallelism of the Flink job.Compared to previous work,QAAS is able to maintain stable job performance under load changes,minimizing the number of job adjustments and reducing data backlogs by 50%.
文摘Hydride ion(H^(-))has high polarizability(α_(H^(-))=10.17A^(3))and high redox potential(H^(-)/H_(2):-2.3 V),and therefore is an attractive energy carrier[1,2].The H^(-)superconductors play a crucial role in the development of high-density energy storage and chemical conversion technologies[3].
基金Financial supports from the National Natural Science Foundation of China (Nos.22178121 and 21908254)are greatly appreciated.
文摘Disodium 5′-ribonucleotide,which is composed of disodium 5′-inosine(IMP)and disodium 5′-guanosine(GMP),is an important food additive.The lack of kinetic studies of it causes a lack of clarity in understanding the complicated multi-solute crystallization of IMP+GMP in ethanol-water.In this work,process analytical technology tools were used to obtain the thermodynamics and kinetic data from the experiments,the kinetic parameters of anti-solvent and cooling crystallization were investigated.The crystal form of IMP+GMP mixed crystal was determined,which was consistent with the IMP whether crystallized from pure water or ethanol-water.The effects of different anti-solvent addition rates and cooling rates on the metastable zone widths were studied,and the opposite effect on metastable zone width was found.The modified exponential empirical function was developed to correlate nucleation and growth kinetic equations under different conditions.The kinetic data were well fitted with adjusted correlation coefficient(adj-R^(2)>0.7),which is sufficient to provide a valid reference for process design and control.