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Recent developments in deep learning techniques have offered an alternative and complementary approach to traditional matched filtering methods for the identification of gravitational wave (GW) signals. The rapid and accurate identification of GW signals is crucial for the progress of GW physics and multi-messenger astronomy, particularly in light of the upcoming fourth and fifth observing runs of LIGO-Virgo-KAGRA. In this work, we use the 2D U-Net algorithm to identify the time-frequency domain GW signals from stellar-mass binary black hole (BBH) mergers. We simulate BBH mergers with component masses from 5 to 80 $M_{\odot}$ and account for the LIGO detector noise. We find that the GW events in the first and second observation runs could all be clearly and rapidly identified. For the third observation run, about $80\%$ GW events could be identified and GW190814 is inferred to be a BBH merger event. Moreover, since the U-Net algorithm has advantages in image processing, the time-frequency domain signals obtained through U-Net can preliminarily determine the masses of GW sources, which could help provide the mass priors for future parameter inferences. We conclude that the U-Net algorithm could rapidly identify the time-frequency domain GW signals from BBH mergers and provide great help for future parameter inferences., 11 pages, 9 figures

In the present study, carrot juice prepared was added into skimmed milk before fermentation to produce 10% and 20% (w/w) carrot-fortified skim milk. The influence of carrot juice on the lactic acid content, chemical composition, syneresis, texture, rheology property, and microstructure was evaluated along with a potential of carrot juice as an ingredient with rich dietary fiber and a firm structure with interaction of milk protein and a complex matrix under acidification. The results showed that the pH of yoghurt significantly (P0.05). With 10% and 20% level carrot juice added, the total phenolic content (mg GAEkg−1) increased (37.86 and 38.92, respectively) compared with control (36.91) (P

Deubiquitinating enzyme dysregulation has been linked to the development of a variety of human malignancies, including breast cancer. However, the exact involvement of the deubiquitinating enzyme USP39 in the progression of breast cancer is yet unknown. Cell viability and colony formation analysis was used to assess the effects of USP39 knockdown on breast cancer cells in this study. The interaction between USP39 and FOXM1 was investigated using co-immunoprecipitation (co-IP) and in vitro deubiquitination analysis. The expression of USP39 and FOXM1 in breast cancer tissues was studied using the TCGA database. According to our findings, USP39 deubiquitinates and stabilizes FOXM1, promoting breast cancer cell proliferation, colony formation, and tumor growth in vivo. Furthermore, elevated USP39 expression lowers FOXM1 ubiquitination, resulting in increased transcriptional activity. In addition, the high expression of USP39 reduces the ubiquitination of FOXM1, thereby enhancing the transcriptional activity of FOXM1 and regulating the expression of downstream genes Cdc25b and Plk1. USP39 is positively correlated with the expression level of FOXM1 in breast cancer cells. In general, our research revealed the USP39-FOXM1 axis as a critical driver of breast cancer cell proliferation and provided a theoretical foundation for targeting the USP39-FOXM1 axis for pancreatic cancer treatment.

We propose to develop a wide-field and ultra-high-precision photometric survey mission, temporarily named "Earth 2.0 (ET)". This mission is designed to measure, for the first time, the occurrence rate and the orbital distributions of Earth-sized planets. ET consists of seven 30cm telescopes, to be launched to the Earth-Sun's L2 point. Six of these are transit telescopes with a field of view of 500 square degrees. Staring in the direction that encompasses the original Kepler field for four continuous years, this monitoring will return tens of thousands of transiting planets, including the elusive Earth twins orbiting solar-type stars. The seventh telescope is a 30cm microlensing telescope that will monitor an area of 4 square degrees toward the galactic bulge. This, combined with simultaneous ground-based KMTNet observations, will measure masses for hundreds of long-period and free-floating planets. Together, the transit and the microlensing telescopes will revolutionize our understandings of terrestrial planets across a large swath of orbital distances and free space. In addition, the survey data will also facilitate studies in the fields of asteroseismology, Galactic archeology, time-domain sciences, and black holes in binaries., 116 pages,79 figures

By simulating the X-ray paths and the Chapman Model of a flat multi-channel plate and a curved multi-channel plate in the MATLAB, the field of view, local reflection efficiency, spherical aberration, point-spread function, collection efficiency of incident X-ray and peak-to-background ratio on the focal plane of the two devices were compared. At the same time, the advantages and disadvantages of the flat multi-channel plate and the curved multi-channel plate were compared.

The ultrafast monitoring of deoxyribonucleic acid (DNA) dynamic structural changes is an emerging and rapidly growing research topic in biotechnology. The existing optical spectroscopy used to identify different dynamical DNA structures lacks quick response while requiring large consumption of samples and bulky instrumental facilities. It is highly demanded to develop an ultrafast technique that monitors DNA structural changes with the external stimulus or cancer‐related disease scenarios. Here, we demonstrate a novel photonic integrated graphene‐optofluidic device to monitor DNA structural changes with the ultrafast response time. Our approach is featured with an effective and straightforward design of decoding the electronic structure change of graphene induced by its interactions with DNAs in different conformations using ultrafast nanosecond pulse laser and achieving refractive index sensitivity of ~3 × 10−5 RIU. This innovative technique for the first time allows us to perform ultrafast monitoring of the conformational changes of special DNA molecules structures, including G‐quadruplex formation by K+ ions and i‐motif formation by the low pH stimulus. The graphene‐optofluidic device as presented here provides a new class of label‐free, ultrafast, ultrasensitive, compact, and cost‐effective optical biosensors for medical and healthcare applications.

A thorough examination of PLKs in breast cancer, including their expression and prognosis.With the help of the Oncomine database, the transcript levels of PLKs in breast cancer were examined. The changes in PLKs expression with tumor stage and indeed the relationship between PLKs expression and stage of cancer in women with breast cancer were scrutinized by using the GEPIA database. Based on Kaplan-Meier plots, breast cancer patients were assessed for their prognosis. Breast cancer gene expression and mutations were analyzed within the cBioPortal database.According to Oncomine data, PLK1 and PLK4 mRNA expression levels were dramatically elevated in breast cancer patients while PLK2 and PLK5P levels were significantly downregulated. PLK1 and PLK4 expression were discovered to be greater in breast cancer tissues than in healthy tissues following analysis of the GEPIA database (P 0.05). High levels of PLK1 and PLK4 transcripts have been linked to poor relapse-free survival rates across all patients with breast cancer according to the Kaplan-Meier Plotter database. The high levels of PLK2, PLK3, and PLK5 were associated with a higher recurrence-free survival rate. In the cBioPortal database, PLK was altered in 9.6% of breast cancer samples. Genetic alterations occurred in 15.07% of clinically counted invasive breast cancers, with mutations in 4.11%, gene amplifications in 9.59%, and gene deletion mutations in 1.37%. Additionally, the KEGG database demonstrates that PLKs are crucial for the cell cycle. The findings imply that elevated PLK1 and PLK4 expression in tissues of breast cancer might contribute significantly to the carcinogenesis of breast cancer. Moreover, PLK1 and PLK4 are highly expressed in breast cancer, and their use as molecular markers to identify high-risk subsets from patients with breast cancer is potentially possible.For the precise therapy of breast cancers, PLK1 and PLK4 are potential targets, while PLK2, PLK3, and PLK5 are brand-new biomarkers for predicting the prognosis of breast cancer.

Cong Liu,1 Wei Cheng,1 Yuqin Zeng,1 Zijing Zhou,1 Yiyang Zhao,1 Jiaxi Duan,1 Ran Wang,1 Tian Sun,1 Xin Li,2 Zhi Xiang,3 Ping Chen,1 Si Lei1 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha 410011, Hunan, People’s Republic of China; 2Department of Respiratory Diseases, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha 410007, Hunan, People’s Republic of China; 3Department of Respiratory Diseases, The First People’s Hospital of Huaihua, Affiliated to University of South China, Huaihua 418000, Hunan, People’s Republic of ChinaCorrespondence: Ping Chen; Si Lei Email pingchen0731@csu.edu.cn; leisi0831@csu.edu.cnPurpose: Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is increased in China. Smoking cessation is the first step in COPD management. Data on predictors of smoking cessation are sparse in COPD patients in China. We aim to find the differences in the clinical characteristics between ex-smokers and current smokers with COPD to determine the factors related to smoking cessation.Patients and Methods: From outpatient departments of 12 hospitals in Hunan and Guangxi provinces, a total of 4331 patients were included. Information on demographic and sociological data, lung function, and modified Medical Research Council (mMRC) dyspnea scale scores were recorded. Patients were divided into an ex-smokers group and a current smokers group based on whether they gave up smoking. A logistic regression analysis was performed to analyze the factors associated with smoking cessation.Results: Of the total, the mean age was 62.9± 8.5 years, and 47.3% were ex-smokers. Compared with the current smokers, the ex-smokers were older, and had heavier dyspnea, more severe airflow limitation, fewer pack-years, shorter smoking duration, and a higher proportion of Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups C and D. The logistic regression model showed that smoking cessation was negatively correlated with widowhood, years of smoking, and forced expiratory volume in 1 second (FEV1), but was positively correlated with age, education level, amount smoked, mMRC score, GOLD grades, and GOLD groups.Conclusion: Among patients with COPD, more than half still smoked. In the group of patients who quit smoking, many of them quit rather late in age after they had significant symptoms. Several predictors of smoking cessation were identified, indicating that ex-smokers differ substantially from continuing smokers. This should be taken into account in smoking-cessation interventions.Keywords: COPD, cross-sectional study, ex-smokers and current smokers, smoking cessation

A glass fiber bulk yarn fabric with a graphite coating was produced, with the glass fiber bulk yarn fabric used as the base material, E44 epoxy resin as adhesive, low molecular 650 polyamid...

AST3-2 (the second Antarctic Survey Telescope) is located in Antarctic Dome A, the loftiest ice dome on the Antarctic Plateau. It produces a huge amount of observational data which require a more efficient data reduction program to be developed. Also the data transmission in Antarctica is much difficult, thus it is necessary to perform data reduction and detect variable and transient sources remotely and automatically in Antarctica, but this attempt is restricted by the unsatisfactory performance of the low power consumption computer in Antarctica. For realizing this purpose, to develop a new method based on the existing image subtraction method and random forest algorithm, taking the AST3-2 2016 dataset as the test sample, becomes an alternative choice. This method performs image subtraction on the dataset, then applies the principle component analysis to extract the features of residual images. Random forest is used as a machine learning classifier, and in the test a recall rate of 97% is resulted for the positive sample. Our work has verified the feasibility and accuracy of this method, and finally found out a batch of candidates for variable stars in the AST3-2 2016 dataset.

Based on RSCA index, using kernel density estimation, Markov chain transition probability matrix, and survival analysis method, this paper analyzes the dynamics of Chinese export comparative advantage from 2001 to 2020 and draws the following conclusions. Firstly, after 20 years of export trade development, although the comparative advantage of a few commodities of China has weakened and comparative disadvantage has increased, the comparative advantage of most commodities is improving, and the overall distribution of comparative advantage remained unchanged. Secondly, the stability of Chinese comparative advantage is higher than liquidity, and liquidity as a whole shows a good trend. In addition, the viability of Chinese commodities with comparative advantage has performed well in the past 20 years. Therefore, China should optimize export mode based on comparative advantage.

Higher neutron current densities can provide convenience for neutron experiments. Using neutron optical focusing elements, large flux beams transported to sample can be achieved. As one kind of focusing elements, polycapillary lens is very suitable for neutron absorption experiments such as PGAA and NDP technology. At present, a Neutron Physics and Application Spectrometer was in construction in CSNS, which is the first pulsed neutron source in China. To provide some suggestions and ideas for the following design of enhanced PGAA or NDP instrument with polycapillary lens in CSNS, a first neutron focusing experiment using polycapillary lens in CSNS was conducted. For 0.5-12.6 polychromatic beam, a focal spot with FWHM of 800 was obtained. As the value of wavelength increased, the beam size, transmission efficiency and gain increased. For cold neutron, the gain maintained in a level of 7., Comment: 12 pages, 13 figures, 12 references

The x-ray polycapillary lens is an optical device with good optic performance. Similar to the traditional X-ray polycapillary lens, square polycapillary slice lens was regulated on X-ray based on the full reflection principle of X-ray in the capillaries surfaces. According to its geometrical structure model and the X-ray tracing principle, a set of X-ray transmission procedures was established. A complete square polycapillary slice lens with quadratic curve was produced and the optical performance was tested

Background: The MSI/MSS status does not fully explain cancer immunotherapy response in colorectal cancer. Thus, we developed a colorectal cancer-specific method that predicts cancer immunotherapy response.Methods: We used gene expression data of 454 samples (MSI = 131, MSI-L = 23, MSS = 284, and Unknown = 16) and developed a TMEPRE method that models signatures of CD8+ T-cell infiltration and CD8+ T-cell exhaustion states in the tumor microenvironment of colorectal cancer. TMEPRE model was validated on three RNAseq datasets of melanoma patients who received pembrolizumab or nivolumab and one RNAseq dataset of purified CD8+ T cells in different exhaustion states.Results: TMEPRE showed predictive power in three datasets of anti-PD1-treated patients (p = 0.056, 0.115, 0.003). CD8+ T-cell exhaustion component of TMEPRE model correlates with anti-PD1 responding progenitor exhausted CD8+ T cells in both tumor and viral infection (p = 0.048, 0.001). The global pattern of TMEPRE on 454 colorectal cancer samples indicated that 10.6% of MSS patients and 67.2% of MSI patients show biological characteristics that can potentially benefit from anti-PD1 treatment. Within MSI nonresponders, approximately 50% showed insufficient tumor-infiltrating CD8+ T cells and 50% showed terminal exhaustion of CD8+ T cells. These terminally exhausted CD8+ T cells coexisted with signatures of myeloid-derived suppressor cells in colorectal cancer.Conclusion: TMEPRE is a colorectal cancer-specific method. It captures characteristics of CD8+ T-cell infiltration and CD8+ T-cell exhaustion state and predicts cancer immunotherapy response. A subset of MSS patients could potentially benefit from anti-PD1 treatment. Anti-PD1 resistance MSI patients with insufficient infiltration of CD8+ T cells or terminal exhaustion of CD8+ T cells need different treatment strategies.

A few well-documented liquefaction case studies of gravelly soils during major earthquakes have increased concerns regarding the liquefaction susceptibility of gravelly sand soils. Understanding th...

Coccinella septempunctata (ladybird) is one of the foremost natural predators that feed on aphids. Thus, C. septempunctata serves as an effective biological control agent in integrated pest management (IPM) programs. To supplement the activity of biological control agents, IPM programs often incorporate chemical pesticides to bolster crop protection. To evaluate the effects of a potent insecticide, tolfenpyrad, on C. septempunctata, we tested the sublethal effects of tolfenpyrad on all developmental stages of the life cycle of C. septempunctata and its effects on the next generation. For sublethal testing of the parent generation, the LR50 of tolfenpyrad for C. septempunctata was determined to range from 1.04 to 8.43 g a.i. /hm2 within a set exposure period, while the hazard quotient (HQ) values were above our threshold value of 2 during the entire observation period. These data indicated a potential toxicity risk from tolfenpyrad exposure. The no observed effect application rates (NOERs) of tolfenpyrad on parents (F0) were determined for survival (0.485 g a.i. /hm2), developmental time of pupation (0.242 g a.i. /hm2), and fecundity (0.485 g a.i. /hm2). Application of sublethal doses to unexposed progeny (F1) of exposed parents, prolonged the L1 (1st instar of larvae) and L2 (2nd instar of larvae) stage, while the total longevity, intrinsic rate of increase (r), finite rate of increase (γ), net reproductive rate (R0), and mean generation time (T) were significantly reduced. These results demonstrated the negative influence of sublethal concentrations of tolfenpyrad on C. septempunctata and its persistent effects on subsequent generations.

A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2���4 showed weak anti-HIV activities with EC50 values of 11.31 �� 3.29 ��M, 18.77 �� 6.14 ��M and 30.02 �� 3.73 ��M, respectively.

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women’s overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

The demand for highly flexible and self-powered wearable textile devices has increased in recent years. Graphene coated textile-based wearable devices have been used for energy harvesting and storage due to their outstanding mechanical, electrical and electronic properties. However, the use of metal based nanocomposites is limited in textiles, due to their poor bending, fixation, and binding on textiles. We present here reduced graphene oxide (rGO) as an n-type and conductive polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as a p-type material for a wearable thermoelectric nanogenerator (TEG) using a (pad–dry–cure) technique. We developed a reduced graphene oxide (rGO) coated textile-based wearable TEG for energy harvesting from low-grade human body heat. The conductive polymer (PEDOT:PSS) and (rGO) nanocomposite were coated using a layer by layer approach. The resultant fabric showed higher weight pickup of 60–80%. The developed textile based TEG device showed an enhanced Seebeck coefficient of (25–150 μV K−1), and a power factor of (2.5–60 μW m−1 K−1). The developed TE device showed a higher potential to convert the low-grade body heat into electrical energy, between the human body temperature of (36.5 °C) and an external environment of (20.0 ± 5 °C) with a temperature difference of (2.5–16.5 °C). The wearable textile-based TEG is capable of producing an open circuit output voltage of 12.5–119.5 mV at an ambient fixed temperature of (20 °C). The rGO coated textile fabric also showed reduced electrical sheet resistance by increasing the number of dyeing cycles (10) and increased with the number of (20) washing cycles. The developed reduced graphene oxide (rGO) coated electrodes showed a sheet resistance of 185–45 kΩ and (15 kΩ) for PEDOT:PSS–rGO nanocomposites respectively. Furthermore, the mechanical performance of the as coated textile fabric was enhanced from (20–80 mPa) with increasing number of padding cycles. The thermoelectric performance was significantly improved, without influencing the breath-ability and comfort properties of the resultant fabric. This study presents a promising approach for the fabrication of PEDOT:PSS/rGO nano-hybrids for textile-based wearable thermoelectric generators (TEGs) for energy harvesting from low-grade body heat.

Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control. Recent work identifies a population of poorly differentiated TCF-1(+)PD-1(+)CD8(+)T cells as precursors of the terminally exhausted CTL pool. These "predysfunctional" CTLs are suggested to respond to PD-1 targeted therapy by giving rise to a pool of functional CTLs. Supported by gene expression analyses, we present a model in which lack of CD4(+)T cell help during CD8(+)T cell priming results in the formation of predysfunctional CTLs. Our model implies that predysfunctional CTLs are formed during priming and that the remedy for CTL dysfunction is to provide "help" signals for generation of optimal CTL effectors. We substantiate that this may be achieved by engaging CD4(+)T cells in new CD8(+)T cell priming, or by combined PD-1 blocking and CD27 agonism with available immunotherapeutic antibodies.

Qingliang Shao,1 Zhiqiang Zhang,1 Rongxian Cao,2 Hui Zang,1 Wanting Pei,2 Tian Sun2 1Department of General Surgery, The Peoples’ Hospital of Liaoning Province, Shenyang City, Liaoning Province, People’s Republic of China; 2Graduate School of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Hui Zang Email Drzanghui0320@163.comBackground: Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified.Materials and Methods: We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro.Results: CPA4 was overexpressed in clinical PC samples that was positively related with tumor size (P=0.026), T stage (P=0.011), lymph-node metastasis (P=0.026) and a worse prognosis for PC patients (P=0.001). Interestingly, CPA4 was inversely correlated with E-cadherin (r=− 0.372, P=0.003) in clinical samples and PC cell lines which cooperatively contributed to a worse prognosis (P=0.005) for PC patients. CPA4 overexpression enhanced EMT in AsPC-1 and Capan-2 cells, which promoted EMT-like cellular morphology and cell invasion and migration. Meanwhile, CPA4 overexpression activated EMT and PI3K-AKT-mTOR signaling, following with the downregulation of E-cadherin and β-catenin, and the upregulation of N-cadherin, vimentin, p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448). However, PI3K inhibitor LY294002 reversed CPA4 overexpression-stimulated EMT in vitro. Moreover, CPA4 was co-immunoprecipitated with AKT in two PC cells with CPA4 high expression. Conversely, CPA4 silencing inhibited EMT in PANC-1 cells. CPA4 overexpression or silencing promoted or inhibited cell proliferation and drug resistance in Capan-2 and PANC-1 cells via regulating Bcl2/Bax and cleaved-caspase3 signaling. However, LY294002 reversed CPA4 overexpression-stimulated cell proliferation and drug resistance in vitro in Bcl2/Bax and caspase3-dependent apoptosis.Conclusion: CPA4 overexpression contributes to aggressive clinical stage of PC patients and promotes EMT in vitro via activation of PI3K-AKT-mTOR signaling.Keywords: CPA4, EMT, pancreatic cancer, PI3K-AKT-mTOR signaling

Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) “exhaustion”, i.e., loss of effector function and disease control. Recent work identifies a population of poorly differentiated TCF-1+PD-1+ CD8+ T cells as precursors of the terminally exhausted CTL pool. These “predysfunctional” CTLs are suggested to respond to PD-1 targeted therapy by giving rise to a pool of functional CTLs. Supported by gene expression analyses, we present a model in which lack of CD4+ T cell help during CD8+ T cell priming results in the formation of predysfunctional CTLs. Our model implies that predysfunctional CTLs are formed during priming and that the remedy for CTL dysfunction is to provide “help” signals for generation of optimal CTL effectors. We substantiate that this may be achieved by engaging CD4+ T cells in new CD8+ T cell priming, or by combined PD-1 blocking and CD27 agonism with available immunotherapeutic antibodies.

Tian Sun,1,2 Xiaoyun Li,3 Wei Cheng,1,2 Yating Peng,1,2 Yiyang Zhao,1,2 Cong Liu,1,2 Yuqin Zeng,1,2 Yan Chen,1,2 Shan Cai,1,2 Ping Chen1,2 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510000, People’s Republic of ChinaCorrespondence: Ping ChenDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86-13873115563Fax +86 731-85295848Email pingchen0731@csu.edu.cnBackground: The morning is the most troublesome time of day for patients with chronic obstructive pulmonary disease (COPD). However, the association of morning symptoms and COPD exacerbations in longitudinal follow-up has not been studied. In this study, we mainly aimed to investigate the relationship between morning symptoms and exacerbations over a one-year follow-up period. And the secondary aim was an investigation of the association between morning symptoms and baseline clinical features.Patients and Methods: Ninety-two patients with stable COPD provided the baseline information. Morning symptoms were assessed with the Chinese version of Chronic Obstructive Pulmonary Disease Morning Symptom Diary (Ch-COPD-MSD); the median morning symptoms score was used as a cut-off to separate the study cohort in two groups. Modified Medical Research Council (mMRC), COPD assessment test (CAT), and Clinical COPD Questionnaire (CCQ) were used and exacerbation history of the previous year was recorded. Seventy-eight patients (84.8%) completed the longitudinal follow-up of exacerbations.Results: The median morning symptoms score was 30 in stable COPD patients. Morning symptoms severity was different between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups (p< 0.001). Patients with high morning symptoms (score > 30) had higher scores of mMRC, CAT, and CCQ (p< 0.05). CAT score was an independent risk factor of morning symptoms. During follow-up, 41% of patients experienced ≥ 1 exacerbation. The frequency of severe exacerbations was higher in patients with high morning symptoms compared to patients with low morning symptoms (p< 0.005). The Ch-COPD-MSD score could predict future severe exacerbations; the area under the ROC curve was 0.751 (95% CI: 0.633– 0.868, p=0.002).Conclusion: Worse health status and more dyspnea symptom were associated with increased severity of morning symptoms. Morning symptoms were most strongly related to future severe exacerbations and could predict future exacerbations in patients with COPD.Keywords: chronic obstructive pulmonary disease, morning symptoms, future exacerbations

BackgroundFOLFOX is a combination of drugs that is widely used to treat colorectal cancer. The response rate of FOLFOX in colorectal cancer(CRC) is 30-50%. We develop a method that analyzes mechanisms of FOLFOX resistance and predicts whether a patient will benefit from FOLFOX.MethodsGene expression data of 83 stage IV CRC tumor samples (FOLFOX responder n=42, non-responder n=41) were used to develop a supervised learning method IML and analyze subgroups of FOLFOX resistance mechanism. Datasets of 32 FOLFOX treated stage IV CRC patients and 55 FOLFOX treated stage III CRC patients were used as independent validations.ResultsAn iterative supervised learning (IML) method identified two distinct subgroups of CRC patients who resist FOLFOX. Each subgroup relies on different types of DNA damage repair proteins and they are mutually exclusive. Protein-protein networks showed the main mechanism might be the synergistic effect of resisting apoptosis and an altered cell cycle. IML method was validated in two independent validation sets, one FOLFOX treated stage IV CRC patients(HR=2.6, p-value=0.02, 3-years survival rate of the predicted responder group 61.9%, predicted nonresponder group 18.8%) and one FOLFOX treated stage III CRC patients (estimated HR=2.36, p-value=0.02). A subgroup of mesenchymal subtype patients shows the pattern as FOLFOX responders.ConclusionsIML method reflects the underlying biology of FOLFOX resistance and predicts FOLFOX response.

Background: Acupuncture has been widely used to treat primary dysmenorrhea (PD) with satisfactory outcomes. Sanyinjiao (SP6) is the most commonly used acupoint for PD. Different needling techniques may influence the effect of SP6, and its underlying mechanism needs to be explored. This randomized controlled parallel trial is designed to evaluate the immediate analgesic effect and hemodynamic responses in uterine arterial blood flow of perpendicular needling and transverse needling at SP6 in patients with PD of cold-dampness stagnation pattern using color doppler ultrasonography. Methods: Forty-eight patients who meet inclusion criteria will be randomized in a ratio of 1:1 to either perpendicular needling or transverse needling groups. Every participant will receive 1 session of acupuncture treatment for 10 minutes at bilateral SP6. In the perpendicular needling group, needles will be inserted vertically 1 to 1.2 cun and will be manipulated to achieve needling sensation. In transverse needling group, the needles will be inserted transversely 1 to 1.2 cun toward the abdomen without any manipulation to avoid needling sensation. Color doppler ultrasonography will be performed before, during, and after needling. The primary outcome measure is visual analog scale for pain. The secondary outcome measures include the uterine artery blood flow changes by measuring pulsatility index, resistance index values, and ratio of systolic peak and diastolic peak, the Hamilton anxiety scale, blood pressure, and heart rate. Adverse events in both groups also will be recorded. Discussion: This trial will be the first study protocol designed to explore the influence of needling techniques on the analgesia effect of solo acupoint and its hemodynamic responses for PD. It will promote more widespread awareness of the benefits of using suitable needling techniques in acupuncture clinical setting and provide a further explanation of the underlying hemodynamic mechanism. Trial registration: This study protocol was registered at the Chinese clinical trial registry (ChiCTR1900026051).

Supplemental material, sj-pdf-1-tar-10.1177_1753466620977376 for Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease by Yi-yang Zhao, Cong Liu, Yu-qin Zeng, Ai-yuan Zhou, Jia-xi Duan, Wei Cheng, Tian Sun, Xin Li, Li-bing Ma, Qi-mi Liu, Ying-qun Zhu, Ming Chen, Mei-ling Zhou and Ping Chen in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-2-tar-10.1177_1753466620977376 for Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease by Yi-yang Zhao, Cong Liu, Yu-qin Zeng, Ai-yuan Zhou, Jia-xi Duan, Wei Cheng, Tian Sun, Xin Li, Li-bing Ma, Qi-mi Liu, Ying-qun Zhu, Ming Chen, Mei-ling Zhou and Ping Chen in Therapeutic Advances in Respiratory Disease

To understand the effect of f-functions in predicting the right reaction mechanism for hypervalent iodine reagents, we adopt the Ahlrichs basis set family def2-SVP and def2-TZVP to revisit the potential energy surfaces of IBX-mediated oxidation and Togni I's isomerisation. Our results further prove that f-functions (in either Pople, Dunning, or Ahlrichs basis set series) are indispensable to predict the correct rate-determining step of hypervalent iodine reagents. The f-functions have a significant impact on the predicted reaction barriers for processes involving the I-X (X = O, OH, CF$_3$, etc.) bond cleavage and formation, e.g. in the reductive elimination step or the hypervalent twist step. We furthermore explore two hypervalent twist modes that account for the different influences of f-functions for IBX and Togni I. Our findings may be helpful for theoretical chemists to appropriately study the reaction mechanism of hypervalent iodine reagents., Comment: 12 pages, 5 figures

Supplemental material, sj-pdf-3-tar-10.1177_1753466620977376 for Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease by Yi-yang Zhao, Cong Liu, Yu-qin Zeng, Ai-yuan Zhou, Jia-xi Duan, Wei Cheng, Tian Sun, Xin Li, Li-bing Ma, Qi-mi Liu, Ying-qun Zhu, Ming Chen, Mei-ling Zhou and Ping Chen in Therapeutic Advances in Respiratory Disease

Based on the basic structure of the intelligent production line, the indicator hierarchy is established according to the basic ideas of the analytic hierarchy process; combining its intelligent features, we can complete the extraction and screening of indicators at each level. The expert consultation method is used to construct the judgment matrix for various indicators under the same level, and the consistency test is completed. The weight of each index is determined by the eigenvalue method. Finally, according to the intelligent manufacturing capability maturity model, the scoring rules and comprehensive calculation models of each indicator are formulated, and the evaluation of the total target score is completed. Compared with the score range of the intelligent level, we can judge the level of the intelligent level of the production line at the present stage, and analyze the development direction and improvement measures in the later stage.

In order to more reasonable analyze the dynamic reliability of aero-engine blade with coupling failure mode. A fuzzy intelligent multiple extremum response surface method (FIMERSM) was proposed. Considering the coupling effect of temperature load and centrifugal load, the maximum stress point, the maximum strain point and the minimum life point on blade were found by deterministic analysis. Then, the density of blade, rotor speed, elastic modulus, blade-tip temperature, blade-root temperature, fatigue strength coefficient, fatigue strength exponent, fatigue ductility coefficient, fatigue ductility exponent, blade width, blade thickness, blade torsion angle, and blade height as input random variables. By using Latin hypercube sampling technique, the sample values of the input random variables were acquired and finite element basic equation was calculated for each samples which obtained the corresponding dynamic output response of their stress, strain, and low cycle fatigue life within the analysis time domain. By taking the entire maximum values of the dynamic output response in the analysis time domain as new output response, the fuzzy intelligent multiple extremum response surface function (FIMERSF) was established. Finally, the dynamic reliability of the blade structure were obtained by using the Monte Carlo method (MCM) large amount linkage sampling of the input random variables and take it into the FIMERSF to calculate the output response. The results imply that the comprehensive reliability of blade is 99.46%. Through the comparison of MCM, Multiple extremum response surface method (MERSM) and FIMERSM, the computational results show that the FIMERSM has high computational precision and computational efficiency.

The integrated navigation system is used to estimate the position, velocity, and attitude of a vehicle with the output of inertial sensors. This paper concentrates on the problem of the INS/GPS integrated navigation system design and simulation. The structure of the INS/GPS integrated navigation system is made up of four parts: 1) GPS receiver, 2) Inertial Navigation System, 3) Extended Kalman filter, and 4) Integrated navigation scheme. Afterwards, we illustrate how to simulate the integrated navigation system with the extended Kalman filter by measuring position, velocity and attitude. Particularly, the extended Kalman filter can estimate states of the nonlinear system in the noisy environment. In extended Kalman filter, the estimation of the state vector and the error covariance matrix are computed by steps: 1) time update and 2) measurement update. Finally, the simulation process is implemented by Matlab, and simulation results prove that the error rate of statement measuring is lower when applying the extended Kalman filter in the INS/GPS integrated navigation system.

Atmospheric ducts are horizontal layers that occur under certain weather conditions in the lower atmosphere. Radio signals guided in atmospheric ducts tend to experience less attenuation and spread much farther, i.e, hundreds of kilometers. In a large-scale deployed TD-LTE (Time Division Long Term Evolution) network, atmospheric ducts cause faraway downlink wireless signals to propagate beyond the designed protection distance and interfere with local uplink signals, thus resulting in a large outage probability. In this paper, we analyze the characteristics of ADI atmospheric duct interference (Atmospheric Duct Interference) by the use of real network-side big data from the current operated TD-LTE network owned by China Mobile. The analysis results yield the time varying and directional characteristics of ADI. In addition, we proposed an SVM (Support Vector Machine)-classifier based spacial prediction method of ADI by machine learning over combination of real network-side big data and real meteorological data. Furthermore, an implementation of ADMM (Alternating Direction Methods of Multipliers) framework is proposed to implement a distributed SVM prediction scheme, which reduces data exchange among different regions/cities, maintains similar prediction accuracy and is thus of a more practical use to operators.

Recently, a new emerging field about heavily-doped colloidal plasmonic nanocrystals (NCs) has attracted great attention due to their lower and expediently adjustable free carrier densities, lower and tunable LSPR band in the spectral range from NIR to MIR and higher optical nonlinearity. These new kinds of plasmonic materials will show huge potential and opportunities for nonlinear optical applications, such as ultrafast switching, nonlinear sensing and pulse laser generation. In this work, we demonstrate that high-quality mode-locking and Q-switching pulses at 1560 nm can both be generated by using controllable concentration of Cu3-xP NCs solution and fabricating evanescently interacted saturable absorbers. Furthermore, the plasmonic NCs material has good reproduction for fabricating SA devices and promising potential for large-scale industrial production. Our results may attract great attention for further investigations of heavily-doped plasmonic NCs as next generation, cheap and solution-processed element for fascinating applications in optoelectronic devices., 16 pages, 4 Figures

Undrained cyclic loading patterns and consolidation states can significantly affect the deformation features of medium-dense saturated fine-grained sand. A series of undrained cyclic loading tests with different consolidation states, i.e., various mean effective consolidation stresses ( p 0 ), principal stress direction angles ( α 0 ), ratios ( R 0 ) of major and minor principal stresses, and relative magnitudes of intermediate principal stress ( b 0 ), were performed on saturated micaceous fine sand specimens with a relative density of 50% corresponding to a wide strain range in the order of 10 − 5 to 10 − 2 . The patterns of cyclic axial, torsional, and axial–torsional combined loadings were applied in a hollow cylinder apparatus. The small-strain shear modulus G 0 , the reference shear strain γ r , curves for shear modulus reduction G / G 0 , the damping ratio λ and Poisson's ratio υ with increasing strain were determined. The results of the cyclic axial–torsional combined tests showed a close relationship between G 0 , γ r , and υ as well as the consolidation state parameters p 0 , R 0 , α 0 , and b 0 . The G 0 and γ r increased nearly linearly with increasing p 0 and with decreasing α 0 or b 0 . The υ is strain dependent and increases as the p 0 decreases. Tests indicated that the reduction of G with increasing shear strain γ became more pronounced as p 0 increased. The relationship for the G / G 0 versus γ / γ r was approximately independent of the cyclic loading patterns and the various values of parameters p 0 , R 0 , α 0 , and b 0 . A slight difference is noted between the damping ratios λ t and λ z , corresponding to vertical and torsional deformations. An empirical model was proposed for the dependence of the increase in damping ratio characteristics on the deviatoric strain.

The paper presents a simple one-bath template-free solution method to develop the conductive poly (3, 4-ethylenedioxythiophene) (PEDOT) with controlled morphological structures using various monomer to oxidant (PEDOT: FeCl 3 ) ratio of 1:3, 1:6 and 1:9 respectively for the preparation and growth on textile substrate. The results of the structural analysis showed that the polymerization process affected the formation of different shapes from nanofibers, nanotubes, and nanocubes. The spherical nanotubes changed their size and shape into 3D nanocubes at monomer/oxidant ratio of 1:6. The resultant structure considerably influenced the electrical conductivity, and thermoelectric performance of PEDOT coated textile substrate towards potential energy harvesting textile based thermoelectric Nanogenerator for energy harvesting from human body heat. This study demonstrates the new systematic approach for textile-based energy harvesting TE generator with enhanced thermoelectric performance.

A variety of fabrication methods for van der Waals heterostructures have been demonstrated; however, their wafer-scale deposition remains a challenge. Here we report few-layer van der Waals PtS2/PtSe2 heterojunction photodiodes fabricated on a 2" SiO2/Si substrate that is only limited by the size of work chamber of the growth equipment, offering throughputs necessary for practical applications. Theoretical simulation results show that the bandgap of PtS2 is shrunk to half of its original size in the PtS2/PtSe2 heterostructures, while PtSe2 exhibits a limited response to the coupling. Both PtSe2 and PtS2 layers in the coupled system are still semiconductors. Dynamic photovoltaic switching in the heterojunctions is observed at zero-volt state under laser illuminations of 532 to 2200 nm wavelengths. The PtS2/PtSe2 photodiodes show excellent characteristics in terms of a high photoresponsivity of 361 mAW-1, an external quantum efficiency (EQE) of 84%, and a fast response speed (66 ms). The wafer-scale production of 2D photodiodes in this work accelerates the possibility of 2D materials for practical applications in the next-generation energy-efficient electronics.

In this work, we show a solvent-free "explosive" synthesis (SFES) method for the ultrafast and low-cost synthesis of metal-formate frameworks (MFFs). A combination of experiments and in-depth molecular modelling analysis - using grand canonical Monte Carlo (GCMC) simulations - of the adsorption performance of the synthesized nickel-formate framework (Ni-FA) revealed extremely high quality products with permanent porosity, prominent CH4/N2 selectivity (ca. 6.0), and good CH4 adsorption capacity (ca. 0.80 mmol g-1 or 33.97 cm3 cm-3) at 1 bar and 298 K. This performance is superior to those of many other state-of-the-art porous materials.

To effectively and precisely drive industrial cameras to photograph and then sort long bamboo battens, a surface-defect and color detection device and a sorting device are designed. Further, a sectionalized photography program and sorting program design is proposed. The overall machine employs STM32 as the core master controller, which is connected to the relay drive plate, the photoelectric switch, the industrial camera, etc., for control, to photograph bamboo battens of different lengths in sections, and to sort six types of bamboo batten according to the bamboo-batten category signal sent by the upper computer. Devices for improving bamboo-product processing system efficiency and enhancing the level of automation of modern agricultural products, such as the proposed design, are of considerable importance.

This article reviewed the effect of climate changes on the variation of agricultural climate resources, characteristics of agricultural disaster and the response of the main crops in Northeast China under the condition of global warming. The results showed that there were ad-vantages and disadvantages to the effects of climate warming on agriculture of China. The growing temperature in main crop season in North-east China, the increasing of heat resources, the extended growth period and the expansion of region suitable for crop, which were potential possible for raising the output of crop production and light-temperature potential productivity. Because of the light and the limitation of water resources and the increase of CO2 concentration which were caused by the greenhouse effect, the yield and quality of the crop had a negative effect. With extreme weather events increasing, agricultural ecological environment deterioration, drought, flood and waterlogging, salinization speed, the most obvious effect was drought disaster in Northeast China, especially for the effect of global warming in recent years. With the to-tal amount of precipitation reduction and precipitation uneven distribution, the Northeast China became one of the most sensitive and vulner-able areas affected by climate change.

Simultaneous improvement in adsorption selectivity and capacity for single adsorbents is challenging but counting for much in adsorptive separations. To this end, a formate metal-organic framework and activated carbon fiber composite was synthesized in our work by a simple two-step process, involving homogeneous precipitation of a MOF precursor on an activated carbon fiber and subsequent template replication. The resultant core-shell composite, ACF@[Ni3 (HCOO)6 ], exhibited optimized adsorption performance both in selectivity and capacity for the separation of CH4 /N2 to most of state-of-the-art adsorbents.

In most colorectal cancer (CRC) patients, outcome cannot be predicted because tumors with similar clinicopathological features can have differences in disease progression and treatment response. Therefore, a better understanding of the CRC biology is required to identify those patients who will benefit from chemotherapy and to find a more tailored therapy plan for other patients. Based on unsupervised classification of whole genome data from 188 stages I–IV CRC patients, a molecular classification was developed that consist of at least three major intrinsic subtypes (A-, B- and C-type). The subtypes were validated in 543 stages II and III patients and were associated with prognosis and benefit from chemotherapy. The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in high mutation frequency associated with microsatellite instability and cellular proliferation. A-type tumors, observed in 22% of the patients, have the best prognosis, have frequent BRAF mutations and a deficient DNA mismatch repair system. C-type patients (16%) have the worst outcome, a mesenchymal gene expression phenotype and show no benefit from adjuvant chemotherapy treatment. Both A-type and B-type tumors have a more proliferative and epithelial phenotype and B-types benefit from adjuvant chemotherapy. B-type tumors (62%) show a low overall mutation frequency consistent with the absence of DNA mismatch repair deficiency. Classification based on molecular subtypes made it possible to expand and improve CRC classification beyond standard molecular and immunohistochemical assessment and might help in the future to guide treatment in CRC patients.

BRAF(V600E) mutant colon cancers (CCs) have a characteristic gene expression signature that is also found in some tumors lacking this mutation. Collectively, they are referred to as "BRAF-like" tumors and represent some 20% of CCs. We used a shRNA-based genetic screen focused on genes upregulated in BRAF(V600E) CCs to identify vulnerabilities of this tumor subtype that might be exploited therapeutically. Here, we identify RANBP2 (also known as NUP358) as essential for survival of BRAF-like, but not for non-BRAF-like, CC cells. Suppression of RANBP2 results in mitotic defects only in BRAF-like CC cells, leading to cell death. Mechanistically, RANBP2 silencing reduces microtubule outgrowth from the kinetochores, thereby inducing spindle perturbations, providing an explanation for the observed mitotic defects. We find that BRAF-like CCs display far greater sensitivity to the microtubule poison vinorelbine both in vitro and in vivo, suggesting that vinorelbine is a potential tailored treatment for BRAF-like CCs.

To optimize the architecture of weighted average multiresolution image fusion algorithm,an extended weighted average multiresolution image fusion model to control the decision map only with the match measure is presented based on the Piella pixel-level multiresolution image fusion framework.The extended model changes the fusion pattern that the decision factor must be decided by both activity measure and match measure in the conventional weighted average multiresolution image fusion model.Since the activity measure is removed in the extended model,the corresponding algorithm architecture is rather simpler.By taking the correlated signal intensity ratio as the match measure,a weighted average multiresolution image fusion method based on the extended model is proposed.The experiment on fusing infrared and visible images shows that the proposed method is able to produce better fusion results than the conventional ones and its Edge Fusion Quality Index(EFQI) and Weight Fusion Quality Index(WFQI)has increased by 2.9% and 1.8%,respectively.Moreover,it achieves much lower computational complexity for the decision factor with decreased multiplication and addition times of 66.7% and 33.3%,respectively.