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High-precision machining of flexible materials, such as rubber, presents a challenge in manual grinding. The implementation of robotic grinding has the potential to significantly enhance machining precision and efficiency. Normally, an accurate material removal model is needed for precise planning of the robotic grinding parameters. Existing models are mostly built for metal materials, and neglect the large deformation of flexible workpieces, resulting in deficiencies in accuracy and generalization. To this end, a nonlinear dual flexible contact force model is presented, considering the significant deformation of both the tool and the workpiece, to characterize the dual flexible contact mechanism. Then, the contact force model is combined with the Preston equation, yielding the material removal model. The effectiveness and superiority of our contact force model and material removal model are substantiated by force–displacement experiments and robotic grinding experiments, respectively. These experiments show a remarkable reduction of 68.17% in the root-mean-square error (RMSE) for the contact force model and a noteworthy 29.31% decrease in RMSE for the material removal model.

Accurately forecasting the real-time travel demand for dockless scooter-sharing is crucial for the planning and operations of transportation systems. Deep learning models provide researchers with powerful tools to achieve this task, but research in this area is still lacking. This paper thus proposes a novel deep learning architecture named Spatio-Temporal Multi-Graph Transformer (STMGT) to forecast the real-time spatiotemporal dockless scooter-sharing demand. The proposed model uses a graph convolutional network (GCN) based on adjacency graph, functional similarity graph, demographic similarity graph, and transportation supply similarity graph to attach spatial dependency to temporal input (i.e., historical demand). The output of GCN is subsequently processed with weather condition information by the Transformer to capture temporal dependency. Then, a convolutional layer is used to generate the final prediction. The proposed model is evaluated for two real-world case studies in Washington, D.C. and Austin, TX, respectively, and the results show that for both case studies, STMGT significantly outperforms all the selected benchmark models, and the most important model component is the weather information. The proposed model can help micromobility operators develop optimal vehicle rebalancing schemes and guide cities to better manage dockless scooter-sharing operations.

The dominant influence of precession‐induced changes in summer insolation on orbital‐scale variability of the Asian summer monsoon (ASM) during the Holocene has been widely proposed; however, it remains unclear why the decline of the ASM started several thousand years after the peak summer insolation. Through comparisons of climate simulations and proxy records, our study reveals that the abrupt decline in the ASM coincided with an increase in spring insolation at the equator. The reduced spring insolation resulted in a cooler tropical Indian Ocean, which weakened and shifted northward the westerly jet due to decreased meridional thermal gradient. The South Asian high moved northward in conjunction with the westerly jet, causing anomalous upwards over northern South Asia, the Tibetan Plateau, as well as southwestern and northern China. The associated anomalous cyclone over the Tibetan Plateau enhanced the monsoonal moisture transport, subsequently intensifying the ASM circulation and precipitation. The ASM was enhanced by the decrease in spring insolation and was weakened by the opposite. The abrupt decline of the ASM was associated with an increase in spring insolation superimposed on a decrease in summer insolation. Consequently, orbital‐scale ASM variability is dominated by the precession not only via insolation changes in summer but also changes in spring. It is widely acknowledged that orbital‐scale Asian summer monsoon (ASM) variability was controlled by precession‐dominated changes in Northern Hemisphere summer insolation. However, it is still not clear why the ASM did not weaken in response to the initial decrease in summer insolation (e.g., during the early to mid‐Holocene), as evidenced in numerous records. This study explores the underlying dynamics driving the decline of the ASM by comparing climate simulations with proxy records. Our findings reveal that an abrupt decline in the ASM commenced from minimum spring insolation at the equator, lagging the peak summer insolation by several thousand years. Reduced spring insolation had a prolonged impact on cooling of the tropical Indian Ocean in summer, leading to a decrease in meridional thermal gradient. Consequently, both westerly jet and South Asian high shifted northward, intensifying the ASM circulation and precipitation. The decreasing spring insolation slowed down the decline of the ASM, while the rising spring insolation accelerated it. Hence, an abrupt decline in the ASM was driven by increasing spring insolation superimposed on decreasing summer insolation. An abrupt decline in the Asian summer monsoon (ASM) kept pace with the rise in equatorial spring insolationEquatorial spring insolation exerted a prolonged impact on the tropical Indian Ocean in the following summerThe ASM was modulated by the tropical Indian Ocean via shifting the Asian subtropical westerly jet An abrupt decline in the Asian summer monsoon (ASM) kept pace with the rise in equatorial spring insolation Equatorial spring insolation exerted a prolonged impact on the tropical Indian Ocean in the following summer The ASM was modulated by the tropical Indian Ocean via shifting the Asian subtropical westerly jet

How to protect the privacy of training data in deep learning has been the subject of increasing amounts of related research in recent years. Private Aggregation of Teacher Ensembles (PATE) uses transfer learning and differential privacy methods to provide a broadly applicable data privacy framework in deep learning. PATE combines the Laplacian mechanism and the voting method to achieve deep learning privacy classification. However, the Laplacian mechanism may greatly distort the histogram vote counts of each class. This paper proposes a novel exponential mechanism with PATE to ensure the privacy protection. This proposed method improves the protection effect and accuracy through the screening algorithm and uses the differential privacy combination theorems to reduce the total privacy budget. The data-dependent analysis demonstrates that the exponential mechanism outperforms the original Laplace mechanism. Experimental results show that the proposed method can train models with improved accuracy while requiring a smaller privacy budget when compared to the original Pate framework.

ABSTRACTOsteosarcoma (OS) is the most frequent malignant primary bone tumor in children and young adults. Zinc finger Asp-His-His-Cys palmitoyl-acyltransferase 19 (ZDHHC19) is a key enzyme in protein palmitoylation and plays crucial roles in tumor progression. However, its expression profile and biological function in OS have been unclear. In the present study, the expression level of ZDHHC19 in OS cell lines was determined by qRT-PCR and Western blot. The effect of ZDHHC19 in cell growth, invasion and migration was analyzed by CCK8, EDU, transwell, wound healing assay in vitro, and xenograft tumor model in vivo. In addition, bioinformatics analysis was used to explore the potential mechanism of ZDHHC19 in OS. Furthermore, the luciferase reporter assay was conducted to determine the direct binding between miR-940 and ZDHHC19. We discovered that ZDHHC19 was overexpressed in OS cells compared with the normal cells. The functional investigation demonstrated that ZDHHC19 silencing could inhibit proliferation, invasion and migration of OS in vitroand suppress tumorigenicity and lung metastasis in a xenograft model in vivo. Mechanistically, we identified that ZDHHC19 was a direct target of miR-940 and forced ZDHHC19 expressions partially rescue the suppression of proliferation, migration and invasion induced by miR-940. Moreover, bioinformatics analysis combined with validation experiments revealed that activating wnt/β-catenin pathway contributed to the pro-oncogenic effect induced by ZDHHC19. Furthermore, rescue experiments further verified that miR-940/ZDHHC19 axis regulated wnt/β-catenin pathway. Overall, these findings indicated that miR-940/ZDHHC19 axis played a significant role in OS progression and might be considered as a novel target for OS treatment.Abbreviations:OS, osteosarcoma; miRNAs, microRNAs; 3’-UTR, 3’- untranslated region; TARGET, Therapeutically Applicable Research To Generate Effective Treatments; qRT-PCR, quantitative real-time PCR; IHC, Immunohistochemistry; GSVA, Gene Set Variation Analysis; GSEA, Gene Set Enrichment Analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes;

CARM1 (coactivator-associated arginine methyltransferase 1), which belongs to type I PRMTs (protein arginine methyltransferases), is a potential therapeutic target for treatment of multiple cancers. In this study, we first identified several hit compounds against CARM1 by structure-based virtual screening (IC50= 35.51 ± 6.68 to 68.70 ± 8.12 μM) and then carried out chemical structural optimizations, leading to six compounds with significantly improved activities targeting CARM1 (IC50= 18 ± 2 to 107 ± 6 nM). As a compound with an ethylenediamino motif, the most potent inhibitor, ZL-28-6, also exhibited potent inhibition against other type I PRMTs. Compared to the type I PRMT inhibitor from our previous work (DCPR049_12), ZL-28-6 showed increased potency against CARM1 and decreased activity against other type I PRMTs. Moreover, ZL-28-6 showed better antiproliferation activities toward a series of solid tumor cells than DCPR049_12, indicating its broad spectrum of anticancer activity. In addition, cellular thermal shift and Western blot assays validated that ZL-28-6 could target CARM1 in cells. Taken together, the inhibitor we identified could serve as a potent probe for studying CARM1’s biological functions and shed light on the future design of novel CARM1 inhibitors with stronger activities and selectivities.

Mai-Luo-Shu-Tong pill is an effective traditional Chinese medicine formula for the treatment of superficial thrombophlebitis, but it was insufficiently chemically scrutinized. In this study, the mass spectral data of Mai-Luo-Shu-Tong pill were acquired by ultra-high performance liquid chromatography coupled with Q Exactive hybrid Quadrupole-Orbitrap high resolution mass spectrometry. Then, a data mining strategy combining multiple data processing methods was used to identify chemical constituents in Mai-Luo-Shu-Tong pill by constructing a database of precursor ions and summarizing the mass spectral fragmentation behaviors. As a result, a total of 211 compounds including 70 flavonoids, 56 terpenoids, 37 phenolic acids and 48 others were identified in positive and negative ion modes. Among them, 66 compounds have passed comparison verification with reference standards, 145 compounds were identified based on the data mining strategy combining the characteristic cleavage behaviour of homologous compounds and fragment ions and 4 compounds were potentially new compounds. This study provides a database for quality evaluation and further study of Mai-Luo-Shu-Tong pill in vivo. Moreover, it provides a reference for the characterization of the chemical constituents of other traditional Chinese medicine formulae.

We report a widely tunable optically pumped vertical-external-cavity surface-emitting laser. The multiple quantum wells in the active region of the gain chip are generally designed to form the resonant periodic gain structure, and three different methods are used to tune the oscillating wavelength. The maximum wavelength coverage of 45 nm is obtained when a 2 mm thickness birefringent filter is introduced in a straight-line cavity, while the tuning range of 8 nm is performed by employing a 0.15 mm thickness uncoated Fabry–Perot etalon. For the first time, to the best of our knowledge, we present an 11 nm tuning range by the use of an inserted blade as the tuning element, and the related wavelength tuning mechanism is analyzed.

Glioma is a malignant brain tumor. There is growing evidence that its progression involves altered metabolism. This study’s objective was to understand how those metabolic perturbations were manifested in plasma and urine. Metabolic signatures in blood and urine were characterized by liquid chromatography–tandem mass spectrometry. The results were linked to gene expression using data from the Gene Expression Omnibus database. Genes and pathways associated with the disease were thus identified. Forty metabolites were identified, which were differentially expressed in the plasma of glioma patients, and 61 were identified in their urine. Twenty-two metabolites and five disturbed pathways were found both in plasma and urine. Twelve metabolites in plasma and three in urine exhibited good diagnostic potential for glioma. Transcriptomic analyses revealed specific changes in the expression of 1437 genes associated with glioma. Seventeen differentially expressed genes were found to be correlated with four of the metabolites. Enrichment analysis indicated that dysregulation of glutamatergic synapse pathway might affect the pathology of glioma. Integration of metabolomics with transcriptomics can provide both a broad picture of novel cancer signatures and preliminary information about the molecular perturbations underlying glioma. These results may suggest promising targets for developing effective therapies.

Recently, drug-drug cocrystal attracts more and more attention. It offers a low risk, low-cost but high reward route to new and better medicines and could improve the physiochemical and biopharmaceutical properties of a medicine by addition of a suitable therapeutically effective component without any chemical modification. Having so many advantages, to date, the reported drug-drug cocrystals are rare. Here we review the drug-drug cocrystals that reported in last decade and shed light on the opportunities and challenges for the development of drug-drug cocrystals.

The corrosion process of the ductile iron pipes with different cement mortar lining coverage (lined (100%), unlined (0%), 50%, and 90% lining coverage) in water containing chloride and sulfate were investigated. Electrochemical measurements, including the potentiodynamic polarization curves and electrochemical impedance spectra methods, were carried out to analyze the corrosion mechanisms. Results indicated that the maximum corrosion potential of ductile iron pipes decreased as the increment of ionic strength in a logarithm tendency, while the corrosion current density increased linearly with ionic strength. Additionally, the cement mortar lining coverage affects the inner ductile iron corrosion significantly. The corrosion rate of unlined ductile iron was about 2–5 times higher than that of lined ductile iron pipes. Different from the corrosion rate of lined ductile iron pipes, that of ductile iron pipes with minor defects (90% lining) was higher in the first 10 d, followed by a lower one. The cement mortar lining coverage with significant defects (50% of lining) showed poor protection ability on the iron surface. Moreover, a roughly linear correlation between average corrosion rate (mm a–1) and the relative proportion of bare ductile iron area was fitted.

This paper discusses the issue of impact angle control of an interceptor against stationary targets. Considering the impact angles problem, guidance laws are derived by using terminal sliding mode and finite-time convergence theory. The sliding mode surface is divided into two parts: singularity and nonsingularity. The singularity issue of the terminal sliding mode surface is tackled with a novel control strategy so that it does not consider the absolute value problem of the sliding mode surface any more. It is shown that the state variables of the autonomous underwater vehicle’s guidance system converge to expected states within finite time under the guidance law we proposed. The autopilot dynamics are also taken into account due to its importance. Theoretical analysis and numerical simulation results are presented to validate the performance of the proposed guidance laws.

This paper discusses the issue of impact angle control over guidance in scenarios of an interceptor against the maneuvering targets. Inspired by switched nonlinear system, an integral sliding mode manifold is first developed. Then, the impact angle control over guidance is derived by using the integral sliding mode manifold with finite time control. To obtain precise guidance effect, the second-order of extended state observer is proposed in the case of unknown target acceleration. Finally, composited impact angle control over guidance based on extended state observer is developed. The stability analysis of the proposed guidance law is demonstrated by using Lyapunov function, and theoretical proof that the line-of-sight angle and line-of-sight angular rate can converge to the desired value in finite steps, respectively. Numerical simulation results are illustrated to validate the performance of the proposed guidance law.

Access to safe drinking water is among the 17 United Nations sustainable development goals. As the largest developing country, China has confronted large challenges to providing safe and sufficient drinking water to its population of 1.4 billion under the conditions of limited water sources and ubiquitous water contamination.

Chatter is a fast-changing machining fault that needs to be timely diagnosed to avoid the deterioration. However, it is a big challenge to recognize the weak chatter component out of the machining process signal that includes strong disturbances caused by the measurement noise, the machining uncertainty in the early stage. In this paper, an adaptive chatter signal enhancement approach is proposed to improve the signal-to-noise ratio (SNR) based on the principle of statistical resonance. A Fokker-Planck model with smoothly quadratic double well potential is proposed and analytically solved without using the adiabatic approximation. Compared with the recorded double-well models, the superiority of this one mainly lies in its better resolvability and enhancement capacity. The cutting force signals are utilized to prove the efficiency of the approach to enhance and highlight the chatter signal out of strong disturbances for early chatter detection.

The impact angle control over guidance (IACG) law against stationary targets is proposed by using feedback linearization control (FLC) and finite time control (FTC). First, this paper transforms the kinematics equation of guidance systems into the feedbackable linearization model, in which the guidance law is obtained without considering the impact angle via FLC. For the purpose of the line of sight (LOS) angle and its rate converging to the desired values, the second-order LOS angle is considered as a double-integral system. Then, this paper utilizes FTC to design a controller which can guarantee the states of the double-integral system converging to the desired values. Numerical simulation illustrates the performance of the IACG, in contrast to the existing guidance law. [ABSTRACT FROM AUTHOR]

Whether the South Asian summer monsoon (SASM) is controlled by local or remote insolation at the orbital band remains uncertain. Here, we perform a transient simulation forced by Earth's orbital parameters between 400 and 350 ka BP, a period characterized by significant contrast between local and remote insolation, to identify the SASM's response to insolation forcing. Simulation results suggest that the primary driver of orbital‐scale SASM variability is the Northern Hemisphere high‐latitude June insolation, as opposed to local insolation. High June insolation in the Southern Hemisphere might reduce the SASM intensity. Remote insolation influences the SASM by altering the latitudinal thermal gradient and, consequently, the meridional position of the South Asian high (SAH). The SAH is associated with intense convection and hence drives the meridional shift of the intertropical convergence zone and the SASM rain belt. Thus, orbital‐scale SASM variability is strongly related to remote insolation forcing. Because the monsoon is directly related to the movement of the subsolar point, insolation changes are important in regulating the South Asian summer monsoon (SASM) intensity at an orbital timescale. However, it remains unclear whether the SASM is driven by local insolation that directly strikes southern Asia, or remote insolation in the high‐latitude Northern Hemisphere or the Southern Hemisphere at the precession band. We find a time window between 400 and 350 ka BP (ka = thousand years, BP = before present) when local and remote insolations differ significantly, allowing us to determine which insolation dominates the SASM at orbital timescales. We use an Earth system model with orbital forcing to run a transient simulation between 400 and 350 ka BP. Simulations suggest that the SASM is primarily influenced by Northern Hemisphere high‐latitude summer insolation rather than local insolation. Additionally, Southern Hemisphere insolation has a negative impact on orbital‐scale SASM variability. Remote insolation influences the SASM by inducing an anomalous meridional thermal gradient, which moves the South Asian high and thus the Intertropical Convergence Zone. Our findings are significant for future SASM projections because the obvious difference between remote and local insolation will reappear in the next 50 ka. Local insolation is not the direct driver for orbital‐scale variability of the South Asian summer monsoon (SASM)The meridional shift of the South Asian high (SAH) affects orbital‐scale SASM variabilityRemote insolation influences the meridional shift in the SAH through altering the latitudinal thermal contrast Local insolation is not the direct driver for orbital‐scale variability of the South Asian summer monsoon (SASM) The meridional shift of the South Asian high (SAH) affects orbital‐scale SASM variability Remote insolation influences the meridional shift in the SAH through altering the latitudinal thermal contrast

Tibetan chicken is one of the most common and widely distributed highland breeds, and is often used as a model organism for understanding genetic adaptation to extreme environments in Tibet. Despite its apparent geographical diversity and large variations in plumage patterns, the genetic differences within breed were not accounted for in most studies and have not been systematically investigated. In order to reveal and genetically differentiate the current existing TBC sub-populations that might have major implications for genomic research in TBCs, we systematically evaluated the population structure and demography of current TBC populations. Based on 344 whole-genome sequenced birds including 115 Tibetan chickens that were mostly sampled from family-farms across Tibet, we revealed a clear separation of Tibetan chickens into 4 sub-populations that broadly aligns with their geographical distribution. Moreover, population structure, population size dynamics, and the extent of admixture jointly suggest complex demographic histories of these sub-populations, including possible multiple origins, inbreeding, and introgressions. While most of the candidate selected regions found between the TBC sub-populations and Red Jungle fowls were nonoverlapping, 2 genes RYR2 and CAMK2D were revealed as strong selection candidates in all 4 sub-populations. These 2 previously identified high altitude associated genes indicated that the sub-populations responded to similar selection pressures in an independent but functionally similar fashion. Our results demonstrate robust population structure in Tibetan chickens that will help inform future genetic analyses on chickens and other domestic animals alike in Tibet, recommending thoughtful experimental design.

Non-small-cell lung cancer (NSCLC), the most common type of lung canceraccounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine(5hmC) signatures in circulating cell-free DNA(cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkersfor discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E−19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient’s cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.

Interindividual and interethnic variability of drug responses could be attributed to the differences of genetic polymorphisms in the drug metabolizing enzymes and transporters genes among the populations. Here we reviewed the studies of genetic variations in Uyghur Chinese of fifteen CYP450 genes including CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP2W1, CYP3A4, CYP3A5, CYP4A11, and CYP17A1, which totally covered 277 variants. We also collected the data of 277 variants covered in our study in two extensive population sequencing projects, the International HapMap Project (Hap-Map) and the 1000 Genomes Project and compared them with the data of Uyghur Chinese. The results suggested that remarkable differences of variants allele frequencies of CYP450 genes were existed among Uyghur Chinese and other world populations and drug doses should be adjusted clinically in Uyghur in contrast to Han Chinese and Caucasians.

An optimization method for calibrating cutting force coefficients and cutter runout parameters is developed in this study. The optimization technique works by minimizing the difference between the measured force and predicted force for all force components. Formulation of the instantaneous uncut chip thickness demonstrates that the total measured cutting forces can be separated into a nominal component independent of cutter runout and a perturbation component induced by cutter runout. Based on the differential evolution algorithm, the cutting force coefficients are identified via the nominal components of cutting forces, then the cutter runout parameters are determined from the perturbation components of cutting forces. The experimental results indicate that, compared with the linear-edge force model, the cutting forces predicted by the proposed method agree better with the measured forces both in magnitude and in waveform distribution.

Comprehensive control of regulated trihalomethanes (THMs) and haloacetic acids (HAAs), as well as nitrosamines, is needed to address forthcoming regulations. The formation potentials (FPs) of these disinfection by-products (DBPs) with chlorination (Cl2) and chloramination (NH2Cl) were investigated along the treatment train of a conventional and ozone-biologically active carbon (O3-BAC) process. The nitrosamines FP-NH2Cl, THM FP-Cl2, and HAA FP-Cl2in heavily impacted source water in China were as high as 333 ng/L, 307 µg/L, and 247 µg/L, respectively, indicating that there was a high risk of DBP formation in the finished water. A combination of conventional and O3-BAC processes reduced nitrosamine FP-NH2Cl to 39 ng/L, achieving an 88% removal. This process also reduced THM FP-Cl2and HAA FP-Cl2to 197 and 174 µg/L, with fairly low removals of 36 and 29.5%, respectively. The strategy for this water was to apply conventional and O3-BAC processes to substantially eliminate nitrosamine precursors and then apply chloramination to control THMs and HAAs.

Quantitative information regarding the long-term variability of precipitation and vegetation during the period covering both the Late Glacial and the Holocene on the Qinghai-Tibetan Plateau (QTP) is scarce. Herein, we provide new and numerical reconstructions for annual mean precipitation (PANN) and vegetation history over the last 18,000 years using high-resolution pollen data from Lakes Dalianhai and Qinghai on the northeastern QTP. Hitherto, five calibration techniques including weighted averaging, weighted average-partial least squares regression, modern analogue technique, locally weighted weighted averaging regression, and maximum likelihood were first employed to construct robust inference models and to produce reliable PANN estimates on the QTP. The biomization method was applied for reconstructing the vegetation dynamics. The study area was dominated by steppe and characterized with a highly variable, relatively dry climate at ~18,000–11,000 cal years B.P. PANN increased since the early Holocene, obtained a maximum at ~8000–3000 cal years B.P. with coniferous-temperate mixed forest as the dominant biome, and thereafter declined to present. The PANN reconstructions are broadly consistent with other proxy-based paleoclimatic records from the northeastern QTP and the northern region of monsoonal China. The possible mechanisms behind the precipitation changes may be tentatively attributed to the internal feedback processes of higher latitude (e.g., North Atlantic) and lower latitude (e.g., subtropical monsoon) competing climatic regimes, which are primarily modulated by solar energy output as the external driving force. These findings may provide important insights into understanding the future Asian precipitation dynamics under the projected global warming. New pollen-inferred precipitation estimates are provided for the northeastern Qinghai-Tibetan Plateau (QTP) during the past 18,000 yearsA multitechnique methodology was tested for the first time for biological proxy-based numerical paleoclimatic reconstructions on the QTPPrecipitation was low in Late Glacial period, increased in early Holocene, obtained a maximum in middle Holocene, and declined to present

The causes of the decreased intensity of the East Asian summer monsoon (EASM) over the past 150 years are still not fully understood, although several studies have linked the monsoon weakening to the warming of tropical oceans. Here, we use pine tree‐rings to reconstruct the precipitation total for April–August from 1810 to 2018, in south‐central Shandong Province, in the EASM region. The reconstruction accounts for 41.8% of the instrumental precipitation variance during 1965–2018. The EASM precipitation reconstruction shows extreme pluvial conditions in 1832, 1833, 1886, and 1998, and extreme droughts in 1878, 1901, and 1910, which correspond precisely to extreme climatic events recorded in historical documents. The reconstructed precipitation reveals a drying trend since the 1870s, which matches well with the decreasing trend of the EASM inferred from stalagmite oxygen isotope (δ18O) records and climate simulations. The trend of decreasing precipitation since the 1870s, indicated by our reconstruction, is significantly correlated with the spring sea surface temperature (SST) of the North Atlantic Ocean, which suggests that the EASM weakening was linked to North Atlantic SST variations during the past 150 years. This potential role of North Atlantic SST variability is supported by climate sensitivity simulations of the Community Earth System Model. North Atlantic SST variability induces two teleconnections of Rossby‐like wave propagation from the North Atlantic into East Asia, resulting in anomalous precipitation in this region. A 209‐year precipitation reconstruction was established from the south‐central Shandong, the monsoonal eastern China used pine tree ringsSeveral historical severe droughts are captured by the reconstructed precipitation, and 20th century was dominated by dry conditionsThe trend of decreasing precipitation since the 1870s correlates significantly with spring sea surface temperature in the North Atlantic A 209‐year precipitation reconstruction was established from the south‐central Shandong, the monsoonal eastern China used pine tree rings Several historical severe droughts are captured by the reconstructed precipitation, and 20th century was dominated by dry conditions The trend of decreasing precipitation since the 1870s correlates significantly with spring sea surface temperature in the North Atlantic

Understanding millennial‐scale East Asian summer monsoon (EASM) variability is critical for climate projection in East Asia in the context of slowing Atlantic Meridional Overturning Circulation (AMOC) caused by global warming. This study performs two groups of sensitivity experiments at 8.2 and 4.2 ka BP, both forced by the same North Atlantic freshwater hosing and corresponding orbital parameters using the Community Earth System Model, to explore the orbital effect on millennial‐scale EASM variability. Our simulations reveal that EASM variability differs significantly between these two cold events. During the 8.2 ka BP (4.2 ka BP) (0 BP = 1950 AD) cold event, North Atlantic freshwater forcing weakens the EASM, generating a meridional tripole (dipole) pattern of EASM precipitation anomalies. Furthermore, the same freshwater discharge causes a greater decline in the EASM, contrasting to a slight weaker AMOC slowdown, at 4.2 ka BP than at 8.2 ka BP. This suggests orbital parameters significantly influence the EASM response to North Atlantic cold events. The East Asian subtropical westerly jet, whose meridional position and intensity are controlled by summer insolation on an orbital timescale, plays a key role in this orbital effect. The westerly jet's meridional position determines the spatial pattern of EASM precipitation anomalies, while its intensity affects the amplitude of the EASM's response to freshwater forcing. Because of a larger EASM decline due to freshwater hosing with lower summer insolation, we anticipate a profound declining EASM precipitation in the future with low summer insolation if the AMOC continues to weaken. Millennial‐scale East Asian summer monsoon (EASM) variability is modulated by Earth's orbital parametersThe EASM weakens more pronounced in response to North Atlantic freshwater forcing under lower summer insolationSummer insolation influences the EASM response to North Atlantic freshwater forcing via the westerly jet Millennial‐scale East Asian summer monsoon (EASM) variability is modulated by Earth's orbital parameters The EASM weakens more pronounced in response to North Atlantic freshwater forcing under lower summer insolation Summer insolation influences the EASM response to North Atlantic freshwater forcing via the westerly jet

ABSTRACTDEK is associated with DNA replication and break repair, mRNA splicing, and transcriptional regulation, which had been studied in humans and mammals. The function of DEK in plants was poorly understood. In this study, GhDEK2D was identified in Gossypium hirsutumby genome-wide and post-translational modifications. GhDEK2D had been phosphorylated, acetylated and ubiquitylated under Verticillium dahliae(Vd) challenge. The GhDEK2D-silenced cotton decreased resistance against Vd. In GhDEK2D-silenced cotton plants, the reactive oxygen species was activated, the callose, xylogen, hypersensitive reaction (HR) and expression levels of defense-related genes were reduced. Homozygous overexpressing-GhDEK2D transgenic Arabidopsislines were more resistant to Verticillium wilt (Vw). We propose that GhDEK2D was a potential molecular target for improving resistance to Vw in cotton.

Epidermal growth factor receptor (EGFR) is one of the most important targets in anticancer therapy. Till date, a large number of first and second generation EGFR tyrosine kinase inhibitors (TKIs) have been marketed or advanced into clinical studies. However, the occurrence of TKI-resistant mutations has led to the loss of efficacy of these inhibitors. In the purpose of overcoming resistant mutations and reducing side effects, lots of third generation EGFR inhibitors are explored with promising potencies against EGFR mutations while sparing wild-type EGFR. This review outlines the current landscape of the development of third generation EGFR inhibitors, mainly focusing on the biological properties, clinical status and structure-activity relationships.

AbstractA study was conducted to study the effects of feeding desalinated seawater (DSW) to an existing distribution system and subsequent effects on red water formation due to iron release. Iron release from existing pipe scales was investigated using pipe section reactors filled with the DSW containing different chloride concentrations. Iron release was linearly correlated to desalted seawater chloride concentration. When chloride concentration increased from 50 to 240 mg/L, the total iron concentration after 8 h stagnation increased from 1.50 to 6.50 mg/L, respectively. A mechanistic explanation for iron release based on chloride was proposed, wherein it was concluded that chloride could penetrate and disrupt stable tubercles existing on the pipe wall. “Red water” was shown to be controlled by adjusting the pH, alkalinity, and hardness of the desalted permeate; enhancements were seen when phosphate inhibitors were added to the desalinated permeate. It is suggested that water quality targets for the distribution of DSW into an existing cast iron pipeline include maintaining the pH above 7.7, alkalinity over 80 mg/L, hardness more than 80 mg/L, and providing 0.25–0.50 mg/L blended phosphate inhibitor.

A new approach was developed for the simultaneous separation and determination of 18 active components (including one new component) in traditional Chinese medicines, Fructus Alpinia oxyphylla, by ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) with positive–negative conversion multiple reaction monitor (+/−MRM) technology. The chromatographic separation was performed on a Waters ACQUITY UPLC® HSS C18column (2.1 mm × 50 mm, 1.8 μm) with gradient elution using 0.1% formic acid aqueous solution (A) and acetonitrile (B) at a flow rate of 0.3 mL min−1. This is the first report of the simultaneous determination of 18 bioactive constituents in Alpinia oxyphyllaextract by UPLC-MS/MS. Good linear behaviors over the investigated concentration ranges were observed with the values of rhigher than 0.998 for all the analytes. The method was reproducible with intra-and inter-day variation less than 3.0% and the recovery of the assay was in the range of 95.5% to 104.6%. The validated method was successfully applied for the analysis of 18 bioactive compounds in Fructus Alpinia oxyphyllaextract from different sources and the analysis results were classified by hierarchical cluster analysis (HCA). This study provides a powerful and practical guidance to be used for the comprehensive quality control of Alpinia oxyphyllaand lays the foundation for further research of Alpinia oxyphylla.

Paleoclimatic records reveal spatially asynchronous changes of East Asian summer monsoon (EASM) precipitation during the Holocene, but the underlying mechanisms are not fully understood. This study explores the role of the zonal shift of the Asian westerly jet (AWJ) core on the spatial‐temporal variability of EASM precipitation based on Holocene climate simulations using the KCM and CESM forced by orbital variations. We analyzed the composite differences of summer precipitation and associated atmospheric circulations between the early (middle) and middle (late) Holocene. Simulations suggest a dipole pattern of summer precipitation with increasing (decreasing) precipitation in central (southern) China from the early to late Holocene, which was shaped by the eastward shift of the AWJ core. The eastward shift of the AWJ core and the accompanied eastward movement of the upper‐level convergence over the AWJ's right exit region weakened the low‐level downward motions over central China. Meanwhile, the low‐level upward motions over southern China were weakened by the concurrent eastward (westward) migration of the South Asian High (western Pacific subtropical High) during the Holocene. Consequently, summer precipitation increased (decreased) in central (southern) China from the early to late Holocene. The eastward shift of the AWJ core was primarily driven by amplified meridional insolation gradient at middle latitudes via strengthening upper‐level westerly intensity during the Holocene. In addition, land cover difference between East Asia and central Asia caused a greater enhancement of westerlies intensity in East Asia, further modulating the eastward movement of the AWJ core during the Holocene. Our simulations reveal a dipole pattern of summer precipitation between central and southern China during the HoloceneThe dipole precipitation pattern was strongly modulated by zonal shift of the Asian westerly jet coreInsolation variation and land cover caused the eastward shift of the Asian westerly jet core during the Holocene Our simulations reveal a dipole pattern of summer precipitation between central and southern China during the Holocene The dipole precipitation pattern was strongly modulated by zonal shift of the Asian westerly jet core Insolation variation and land cover caused the eastward shift of the Asian westerly jet core during the Holocene

Myasthenia gravis (MG) is an autoimmune disorder characterized by antibodies directed against components of the neuromuscular junction. Currently, the diagnosis and therapeutic evaluation rely on the serum acetylcholine receptor (AchR) antibody titer, which is not reliable for monitoring. The disruption of the menus had been implicated in many immunological disorders, including MG. A quantitative PCR was used to evaluate the miR-20b level. ELISA was used to determine the levels of IL-8 and IL-25 in serum. QuantitativeMGscores (QMGS) were used to examine the clinical manifestations. Here, we report that miR-20b, an immune- and cancer-related miRNA, is decreased in the serum ofMGpatients and correlates negatively with QMGSs in the pretreatment stage. Furthermore, after treatment with prednisone acetate, levels of miR-20b recover but remain negatively correlated with the QMGS. We also identified that IL-8 and IL-25 are targets of miR-20b via the luciferase reporter system. Both of these are increased in MG and correlate negatively with miR-20b. Furthermore, IL-8 and IL-25 levels are decreased following treatment with prednisone acetate. Our data suggest that miR-20b might be a potential biomarker for MG.

Biological activated carbon (BAC) can effectively remove nitrosamine (NA) precursors. However, the relative significance of adsorption and biotreatment in the NA removal process remains unclear. In this study, organic matter in the influent of a pilot‐scale BAC plant was separated into four fractions that were adsorbable, biodegradable, or both. Bench‐scale tests showed that 70% of the N‐nitrosodimethylamine formation potential was biodegradable and 42% was adsorbable. In addition, 45% of the N‐nitro sodiethylamine formation potential was biodegradable and 59% was adsorbable. Biological treatment included two consecutive actions: biosorption, which was quick and accounted for 10% of the removal of NA formation potential, and biodegradation, which accounted for 70% of the removal of NA formation potential but took up to seven days to maximize. Activated carbon adsorption during bench‐scale tests was capable of effectively removing NA formation potential in 7 h, but its performance was impaired in pilot‐scale tests because of declining adsorption capacity after extended operation and shorter contact time in the BAC filter.

Proxy records of the oxygen isotopic composition of meteorological precipitation (δ18Op) preserved in archives such as ice cores, lacustrine carbonates and stalagmite calcite are important for paleoclimatic studies. Therefore, knowledge of the variations and controlling mechanisms of modern δ18Opon different time scales is necessary. Here, we investigate the linear correlations between δ18Opand corresponding temperature and precipitation on monthly and inter-annual timescales, using data from the Urumqi (1986–2003) and Hotan stations of the Global Network of Isotopes in Precipitation (GNIP), and δ18O data from 4 ice cores in the adjacent Tianshan Mountains. Consistent with previous reported results, modern δ18Opvariations on a seasonal time scale in the Tianshan region are mainly controlled by a ‘temperature effect’ (indicated by a significant positive correlation between δ18Opand temperature), with more positive δ18Opvalues occurring in summer. However, on an inter-annual timescale, there is a weak inverse correlation between weighted average annual δ18Opand annual average temperature at Urumqi station. This finding is supported by the inversely varying trends of δ18O data from 4 ice cores in the central and eastern Tianshan Mountains compared to annual average temperatures in the same region during the past 40–50 years. The data from Urumqi station and the 4 ice cores demonstrate that there is inverse correlation between δ18Opand temperature on inter-annual to decadal time scales. Analysis of water vapor sources and pathways for the warm year of 1997 and the cold year of 1988 reveal that relatively more water vapor for the Tianshan region was derived from long-distance transport from high-latitude sources than during the warm year of 1997; and that more water vapor was transported from more proximal sources from mid- to low-latitude areas during the cold year of 1988. In addition, the δ18Opvalues are more negative in the high latitude areas than those in mid- to low-latitude areas in the Eurasian continent at the upper wind direction of Tianshan Mountains region, according to the weighted averaged warm season (May to September) δ18Opvalues for 14 GNIP stations in the years 1997 and 1988. Due to the distribution of δ18Opwithin the Eurasian continent, the relative shift of water vapor sources between warm and cold years convincingly explains the observed variations of δ18Opin the Tianshan Mountains region. Therefore, we conclude that variations in δ18Opin this region are mainly controlled by changes in water vapor sources which are ultimately caused by northward and southward shifts in the Westerly circulation.

The East Asian winter monsoon (EAWM) is one of the most active components of the global climate system. Climate anomalies associated with the EAWM differ between extratropical and tropical regions due to the EAWM's meridional extent. Spatial differences in the EAWM variability on centennial and millennial time scales during the Holocene have not been well understood. This study describes Holocene spatiotemporal features of the EAWM based on comparisons of proxy records and climate simulations. The analysis specifically compared four proxy records located throughout China to assess the EAWM's spatial variability during the Holocene. These records indicate a stronger EAWM during the early Holocene than that during the late Holocene. The EAWM also shows a rapid, asynchronous decline from northwestern to southeastern China. The EAWM declined in northwestern China from 10 to 7.5 ka B.P., whereas the decline did not occur in southern China and the eastern Tibetan Plateau until 6–4.5 ka B.P. Coupled equilibrium and transient simulations of climate evolution during the Holocene indicate that the decline of the EAWM from 10 to 7.5 ka B.P. was probably caused by melting of Northern Hemisphere (NH) ice sheets and enhanced Atlantic meridional overturning circulation (AMOC). The decline of the EAWM from 6 to 4.5 ka B.P. over the eastern Tibetan Plateau and southern China is related to an abrupt increase in sea surface temperatures (SSTs) of the tropical western Indian Ocean. We therefore argue that the regional shift in EAWM intensity was probably related to a distinguishing response to high‐latitude (NH ice sheets and AMOC) and low‐latitude (tropical SSTs) forcings. Spatiotemporal features of Holocene East Asian winter monsoonHigh‐latitude forcing of the EAWM in northwestern ChinaLow‐latitude forcing of the EAWM on eastern Tibetan Plateau and in southern China

The term “westerlies-dominated climatic regime” describes the pattern of precipitation/moisture variations between westerlies-dominated arid Central Asia (ACA) and mid-latitude monsoon-dominated Asia on decadal to multi-millennial time scales. However, no attempts have been made to define its core region and the possible physical mechanisms responsible during the period of instrumental observations. The present study investigates the spatiotemporal variations of summer and winter precipitation on interannual to decadal time scales over mid-latitudes of the Eurasian continent using Empirical Orthogonal Function (EOF) analysis. Our results suggest the existence of an opposing pattern of summer precipitation variations between ACA and mid-latitude monsoon-dominated Asia and Mediterranean on decadal time scales. Based on these results, the core region influenced by the westerlies is outlined, including arid central Asia and Xinjiang in China (36°–54°N, 50°–90°E). By using monthly NCEP-NCAR reanalysis, the relationship between the “westerlies-dominated climatic regime” and atmospheric circulation were also analyzed. The combination of the zonal climatic teleconnection pattern and anomalous Indian summer monsoon precipitation (ISMP) causes the precipitation characteristics of the “westerlies-dominated climatic regime” precipitation pattern. In addition, the Atlantic Multidecadal Oscillation (AMO) may also have an important effect on the “westerlies-dominated climatic regime”.

This study focused on evaluating the efficiency of powdered activated carbon (PAC) adsorption process and tackling chlorobenzenes and chlorophenols spill in drinking water source. The adsorption kinetics and PAC’s capacities for five chlorobenzenes and three chlorophenols at drinking water contamination levels were studied in order to determine the influence of different functional groups on the adsorption behavior. The results showed that PAC adsorption could be used as an effective emergency drinking water treatment process to remove these compounds. The adsorption kinetics took 30 min to achieve nearly equilibrium and could be described by both pseudo first-order and pseudo second-order models. A mathematic relationship was developed between the pseudo first-order adsorption rate constant, k1, and the solutes’ properties including lgKow, polarizability and molecular weight. The Freundlich isotherm equation could well describe the adsorption equilibrium behaviors of chlorinated aromatics with r2from 0.920 to 0.999. The H-bond donor/acceptor group, hydrophobicity, solubility and molecular volume were identified as important solute properties that affect the PAC adsorption capacity. These results could assist water professionals in removing chlorinated aromatics during emergency drinking water treatment.

Arsenic (As) spills occurred more frequently and sometimes polluted water sources in recent years in China. It is as urgent need to develop emergency treatment technologies to address the arsenic threat for large-scale water treatment plants. In response, we developed a chemical sedimentation technology to remove arsenic contaminants for water treatment plants. Bench-scale experiments were conducted to investigate the efficiency of arsenic removal and the influencing factors of the chemical sedimentation treatment process. The influencing factors included the choice and dosage of coagulants, the valence of arsenic and pH value of solution. The As(V) contaminants can be almost completely removed by ferric or alum coagulants. The As(III) contaminants are more recalcitrant to chemical sedimentation, 75% for ferric coagulant and 40% for alum coagulant. The quantitative results of arsenic removal load by different ferric or alum coagulants were presented to help determine the parameters for arsenic treatment technology. The dominant mechanism for arsenic removal is static combination, or adsorption of negative arsenic species onto positive ferric hydroxide or alum hydroxide flocs. The efficiency of this treatment technology has also been demonstrated by a real production test in one water treatment plant with arsenic-rich source water and one emergency response. This technology was verified to be quick to set-up, easy to operate and highly efficient even for high concentration of arsenic.

Frequent pattern mining discovers sets of items that frequently appear together in a transactional database; these can serve valuable economic and research purposes. However, if the database contains sensitive data (e.g., user behavior records, electronic health records), directly releasing the discovered frequent patterns with support counts will carry significant risk to the privacy of individuals. In this paper, we study the problem of how to accurately find the top-kfrequent patterns with noisy support counts on transactional databases while satisfying differential privacy. We propose an algorithm, called differentially private frequent pattern (DFP-Growth), that integrates a Laplace mechanism and an exponential mechanism to avoid privacy leakage. We theoretically prove that the proposed method is (λ, δ)-useful and differentially private. To boost the accuracy of the returned noisy support counts, we take consistency constraints into account to conduct constrained inference in the post-processing step. Extensive experiments, using several real datasets, confirm that our algorithm generates highly accurate noisy support counts and top-kfrequent patterns.

Some N‐nitrosamines are probable human carcinogens and disinfection by‐products. This study focused on a wastewater‐affected drinking water supply in the Yangtze River Delta, China, that was highly dominated by low‐molecular‐weight organic matter, aromatic proteins, and soluble microbial products (SMPs) and low in humic substances. The study water presented a unique opportunity to investigate treatment processes for controlling an array of nitrosamines because it contained precursors for five N‐nitrosamines [N‐nitrosodimethylamine (NDMA), N‐nitrosodiethylamine (NDEA), N‐nitrosopiperidine, N‐nitrosomorpholine, and N‐nitrosopyrrolidine] whereas only NDMA precursors have been detected in most North American waters. Although conventional processes removed only low levels of precursors, advanced treatment processes effectively removed precursors as well as aromatic proteins and SMPs. Ozone destroyed and/or transformed precursors (e.g., median of 45% for NDMA and 22% for NDEA). Granular activated carbon proved more effective in removing precursors (e.g., median of 88% for NDMA and 83% for NDEA) than in removing bulk dissolved organic carbon (median ~ 60%).

A red water phenomenon occurred in several communities few days after the change of water source in Beijing, China in 2008. In this study, the origin of this problem, the mechanism of iron release and various control measures were investigated. The results indicated that a significant increase in sulphate concentration as a result of the new water source was the cause of the red water phenomenon. The mechanism of iron release was found that the high-concentration sulphate in the new water source disrupted the stable shell of scale on the inner pipe and led to the release of iron compounds. Experiments showed that the iron release rate in the new source water within pipe section was over 11-fold higher than that occurring within the local source water. The recovery of tap water quality lasted several months despite ameliorative measures being implemented, including adding phosphate, reducing the overall proportion of the new water source, elevating the pH and alkalinity, and utilizing free chlorine as a disinfectant instead of chloramine. Adding phosphate was more effective and more practical than the other measures. The iron release rate was decreased after the addition of 1.5 mg·L−1orthophosphate-P, tripolyphosphate-P and hexametaphosphate-P by 68%, 83% and 87%, respectively. Elevating the pH and alkalinity also reduced the iron release rate by 50%. However, the iron release rate did not decreased after replacing chloramine by 0.5–0.8 mg·L−1of free chlorine as disinfectant.

Mass spectrometry-based metabolomics plays a vital role in discovering new markers and revealing the unpredictable biological effects of external stimuli. However, the current metabolomics research on materials is still in its infancy, and in-depth research on possible toxic mechanisms is lacking. In this study, a nanocomposite of gold nanoparticles (AuNPs)-zeolite-imidazole framework-8 (ZIF-8) (Au@ZIF-8) was designed to investigate its effects on metabolism in mouse RAW 264.7 macrophages. The successful synthesis of Au@ZIF-8 was confirmed by transmission electron microscopy (TEM) and elemental analysis. The changes in the metabolic activity of mouse RAW 264.7 macrophages at different concentrations of Au@ZIF-8 and different treatment times were investigated, and their influence on the morphological changes and behavior of RAW 264.7 cells was discussed. In addition, ultrahigh-performance liquid chromatography quadrupole-orbital high-resolution mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to study the metabolic effects of Au@ZIF-8 on RAW 264.7 cells, and the results showed different metabolites being expressed at different reaction times. After 4, 8 and 24 h of treatment, the differential expression of 14, 16, and 16 metabolites, respectively, was detected. Twenty-five candidate key metabolites were identified from the results of the expression patterns and metabolic pathways. These metabolites are related to glutamine metabolism, the tricarboxylic acid cycle and glycolytic metabolic pathways, which may provide insight into the treatment of diseases caused and progressed by glutamine metabolism. This study also indicates the effectiveness of high-resolution LC-MS in revealing the nanotoxicity mechanism of Au@ZIF-8.

High-efficiency hybrid solar cells (HSCs) based on electrospun titanium dioxide (TiO2) nanofibers plus poly(3-hexylthiophene) (P3HT) are fabricated by means of both the pretreatment using tetrahydrofuran (THF) vapor and the surface modification using n-type antimony chalcogenide (Sb2S3) on the TiO2nanofibrous networks. It is revealed that the THF pretreatment not only reinforces the interfacial physical contact but also suppresses the interfacial recombination. The Sb2S3modification improves the light absorption and charge transfer. Given that the active layer of the HSCs is as thin as 300 nm, it is demonstrated that the power conversion efficiency (PCE) is enhanced over 175%, exhibiting a PCE of 2.32%.

The formation of cancinogenic nitrosamines, esp. N-nitrosodimethylamine (NDMA) in water and wastewater treatment plants has drawn much attention in recent years. Dissolved organic matter from the transported Luan River water as water source of Tianjin was fractionated with different XAD resins and a series of ultra-filtration membranes with molecular weight (MW) cut-offs of 5k Da, 3k Da, and 1k Da, respectively. The NDMA yields from the raw water and each fraction were measured to investigate their role in NDMAyield. Results indicated that the hydrophilic fraction had a higher NDMA yield than those of hydrophobic fraction and transphilic fraction. The fraction with MW below 1k Da had a higher NDMAyield than that with larger MW. NDMA formation increased as the dissolved organic carbon (DOC) to dissolved organic nitrogen (DON) ratio decreased, which indicated that DON might serve as the real important precursor for NDMA. The correlation between NDMA yield and specific ultraviolet absorbance at 254 nm (SUVA254) suggested that the latter might not represent the specific precursors for NDMA in the water. Besides the water quality, the influences of pH, disinfectant dosage, and disinfection contact time on the formation of NDMA were also examined. These results will help water treatment plants establish measures to control this harmful disinfection by-product.

N-nitrosodimethylamine (NDMA) and several other N-nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatographytandem mass spectrometry method with solid phase extraction sample preparation was developed to study the occurrence of N-nitrosamines in several water treatment plants and distribution systems in China. Isotope labeled N-nitrosodi-n-propylamine-d14 (NDPA-d14) was selected as the internal standard for quantification. The solid phase extraction procedures including pH, enrichment process and MS/MS parameters including capillary voltage, cone gas flow, cone voltage, collision energy were optimized to give average recoveries of 26% to 112% for nine N-nitrosamine species. The instrument detection limits were estimated to range from 0.5 to 5 µg·L-1for the nine N-nitrosamine species. NDMA and several other N-nitrosamines were found at fairly high concentrations in several water treatment plants and distribution systems. NDMA was found in all locations, and the highest concentrations in cities B, G, T, and W were 3.0, 35.7, 21.3, and 19.7 ng·L-1, respectively. A wide range of N-nitrosamines concentrations and species were observed in different locations. Higher concentrations of N-nitrosamines were detected in distribution systems that were further away from the treatment plants, suggesting that the contact time between the residual disinfectant and natural organic matter may play an important role in the formation of these compounds.N-nitrosodimethylamine (NDMA) and several other N-nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatographytandem mass spectrometry method with solid phase extraction sample preparation was developed to study the occurrence of N-nitrosamines in several water treatment plants and distribution systems in China. Isotope labeled N-nitrosodi-n-propylamine-d14 (NDPA-d14) was selected as the internal standard for quantification. The solid phase extraction procedures including pH, enrichment process and MS/MS parameters including capillary voltage, cone gas flow, cone voltage, collision energy were optimized to give average recoveries of 26% to 112% for nine N-nitrosamine species. The instrument detection limits were estimated to range from 0.5 to 5 µg·L-1for the nine N-nitrosamine species. NDMA and several other N-nitrosamines were found at fairly high concentrations in several water treatment plants and distribution systems. NDMA was found in all locations, and the highest concentrations in cities B, G, T, and W were 3.0, 35.7, 21.3, and 19.7 ng·L-1, respectively. A wide range of N-nitrosamines concentrations and species were observed in different locations. Higher concentrations of N-nitrosamines were detected in distribution systems that were further away from the treatment plants, suggesting that the contact time between the residual disinfectant and natural organic matter may play an important role in the formation of these compounds.

Abstract: This paper focuses on the development of an efficient semi-analytical solution of chatter stability in milling based on the spectral method for integral equations. The time-periodic dynamics of the milling process taking the regenerative effect into account is formulated as a delayed differential equation with time-periodic coefficients, and then reformulated as a form of integral equation. On the basis of one tooth period being divided into a series of subintervals, the barycentric Lagrange interpolation polynomials are employed to approximate the state term and the delay term in the integral equation, respectively, while the Gaussian quadrature method is utilized to approximate the integral term. Thereafter, the Floquet transition matrix within the tooth period is constructed to predict the chatter stability according to Floquet theory. Experimental-validated one-degree-of-freedom and two-degree-of-freedom milling examples are used to verify the proposed algorithm, and compared with existing algorithms, it has the advantages of high rate of convergence and high computational efficiency.

Abstract: This paper analyzes the stability of milling with variable pitch cutter and tool runout cases characterized by multiple delays, and proposes a new variable-step numerical integration method for efficient and accurate stability prediction. The variable-step technique is emphasized here to expand the numerical integration method, especially for the low radial immersion cases with multiple delays. First, the calculation accuracy of the numerical integration method is discussed and the variable-step algorithm is developed for milling stability prediction for single-delay and multiple-delay cases, respectively. The milling stability with variable pitch cutter is analyzed and the result is compared with those predicted with the frequency domain method and the improved full-discretization method. The influence of the runout effect on the stability boundary is investigated by the presented method. The numerical simulation shows that the cutter runout effect increases the stability boundary, and the increasing stability limit is verified by the milling chatter experimental results in the previous research. The numerical and experiment results verify the validity of the proposed method.