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Continuous wave mud pulse transmission is the most widely used information transmission technology in measurement while drilling (MWD). The increase in transmission distance will cause the signal attenuation and deformation during transmission, the affecting exploration efficiency. The waveform change law of continuous mud pulse wave in the process of downhole transmission, this paper establishes a mathematical analysis model, focuses on the modulation form of continuous wave signal, physical mud characteristics, and drill pipe characteristics, and discusses the transmission rules of various characteristics on continuous pressure wave. A simulation system of drill pipe transmission pressure wave is constructed. The transmission characteristics of continuous wave signals under different modulation forms are discussed. The positive correlation between the amplitude attenuation and waveform distortion of pulse signals caused by increased gas holdup in the mud under bubbly flow patterns is analyzed. The numerical calculation and simulation analysis results show that the viscosity frequency characteristic of mud is the main factor affecting the attenuation of continuous wave signal. The surface roughness, size and other physical characteristics of drill pipe can affect the transmission speed and attenuation of signals in long-distance transmission. The signal is prone to distortion at the position of modulation phase change.

During the operation of Tokamak power system, a large number of low frequency harmonic currents with complex spectrum will be generated. Low-frequency resonance suppressor is an effective solution to suppress this low-frequency harmonic currents. The low-frequency harmonic suppression theory of low-frequency resonance suppressor is analyzed in this paper. Meanwhile, the state space equation of three-phase four-wire neutral-point-clamped rectifier is established in the LFRS. According to the mathematical model, the double closed-loop and zero sequence current control strategies are proposed to improve power factor operation on AC side and neutral point potential balance control on DC side of three-phase four-wire converter. The results show the correctness of the theoretical analysis and provide a technical reference for suppression of low-frequency harmonics of other Tokamak devices.

Implementing power quality analysis of the Experimental Advanced Superconducting Tokamak (EAST) power supply is great significance to the stable operation of the power system and the future development of nuclear fusion power stations. Due to the limited channels and fixed resolution of the existing monitoring equipment in the industry, it is difficult to cover the whole requirements of EAST power quality monitoring. And customized highly personalized equipment will be very expensive. Until now, the EAST power system lacks a multi-functional, high-precision power quality monitoring system. So that it cannot solve the impact fault caused by harmonics and inter-harmonics. Thus, a set of high-precision, multi-channel and real-time harmonic monitoring system with automatic trigger storage is established in this paper. Based on the tri-spectrum line interpolation method and the optional frequency-spectrum function, the spectral resolution can be improved to 1.25Hz. Meanwhile, the horizontal comparison of the data can more accurately locate and measure the characteristics of harmonics and inter-harmonics. Finally, the measurement data of the monitoring system is compared and verified by standard sources.

The past few years have witnessed enormous progresses in the development of antibody-drug conjugates (ADCs). Consequently, comprehensive analysis of ADCs in biological systems is critical in supporting discovery, development and evaluation of these agents. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising and versatile tool for ADC analysis across a wide range of scenarios, owing to its multiplexing ability, rapid method development, as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high, molecular resolution. However, despite this tremendous potential, challenges persist due to the high complexity in both the ADC molecules and the related biological systems. This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.

In order to explore the capture of two types of particles with different refractive-indexes with focused partially coherent Lommel-Gaussian beam (PCLGB), we numerically derived the expressions of the intensity, and its distribution is also simulated. We found that the focused PCLGB is able to capture two high refractive-index particles at different positions on the focal plane and a low refractive-index particle at the focus, respectively. when the orbital angular momentum (OAM)quantum number, lens focal length, asymmetry parameter decreased, and the spatial correlation length and beam waist increased, the transverse gradient force of the focused PCLGB increased; when the OAM quantum number, lens focal length, asymmetry parameter, spatial correlation length decreased and the beam waist increased, the axial gradient force and scattering force of the focused PCLGB increased. We can choose the optimum optical and lens parameters, a large range and stable trapping can be achieved. The obtained results have certain reference value for the focused PCLGB applied in micromanipulation technology and biotechnology.

A novel type of superimposed Hermite-Gaussian correlated Schell-model (SHGCSM) laser beam is first represented in terms of theory and then produced experimentally. Similar to a Hermite-Gaussian correlated Schell-model (HGCSM) beam, the SHGCSM beam demonstrates self-splitting features when it propagates in free space, over time the primary single beam spot that is initially seen gradually develops into four or two beam spots when it is in the far-field. The SHGCSM beam splits itself faster than the HGCSM beam when the other beam parameters are fixed, which has lower intensity at the center of beam at an intermediate distance. The four or two spots are more independent with each other, which can be used in attacking multiple targets. Compared with the propagation M2-factor of the HGCSM [Opt. Express 23, 10 (2015)], it has a lower propagation M2-factor in the non-Kolmogorov turbulence. The SHGCSM beam is unaltered to a lesser extent by turbulence compared with a HGCSM beam, which is beneficial for studies on atmospheric optical communications.

Background & Aims: Most targeted therapies against cancer are designed to block growth factor–stimulated oncogenic growth. However, response rates are low, and resistance to therapy is high. One mechanism might relate to the ability of tumor cells to induce growth factor–independent proliferation (GFIP). This project aims to understand how (1) cancer cells preferentially derive a major growth advantage by using critical metabolic products of glucose, such as phosphoenolpyruvate (PEP), to drive proliferation and (2) esophageal squamous cell carcinoma (ESCC) cells, but not esophageal adenocarcinoma cells, can induce GFIP by using glycolysis to activate phosphohistidine (poHis)-mediated signaling through focal adhesion kinase (FAK). Methods: The hypothesis to be tested is that ESCC GFIP induced by glucose is facilitated by PEP-mediated histidine phosphorylation (poHis) of FAK, leading to the possibility that ESCC progression can be targeted by blocking poHis signaling. Biochemical, molecular biological, and in vivo experiments including bromodeoxyuridine/5-ethynyl-2′-deoxyuridine labeling, radioisotope tracing, CRISPR gene editing, and analysis of signaling gene sets in human cancer tissues and xenograft models were performed to define the mechanisms underlying ESCC GFIP. Results: Glucose promotes growth factor–independent DNA replication and accumulation of PEP in ESCC cells. PEP is the direct phospho-donor to poHis58-FAK within a known “HG” motif for histidine phosphorylation. Glucose-induced poHis58 promotes growth factor–independent FAK-mediated proliferation. Furthermore, glucose activates phosphatidylinositol-3′-kinase/AKT via poHis58-FAK signaling. Non-phosphorylatable His58A-FAK reduces xenograft growth. Conclusions: Glucose induces ESCC, but not esophageal adenocarcinoma GFIP via PEP-His58-FAK-AKT signaling. ESCC progression is controlled by actionable growth factor–independent, glucose-induced pathways that regulate proliferation through novel histidine phosphorylation of FAK. Keywords: Esophageal Cancer, Glucose Metabolism, Growth Factors, Cell Adhesion Molecules, Cell Signaling

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Currently, there are no treatments for dry AMD, which is characterized by the death of retinal pigment epithelium (RPE) and photoreceptors. Reports from human donors with AMD suggest that RPE mitochondrial defects are a key event in AMD pathology. Thus, the most effective strategy for treating dry AMD is to identify compounds that enhance mitochondrial function and subsequently, preserve the RPE. In this study, primary cultures of RPE from human donors with (n = 20) or without (n = 8) AMD were used to evaluate compounds that are designed to protect mitochondria from oxidative damage (N-acetyl-l-cysteine; NAC), remove damaged mitochondria (Rapamycin), increase mitochondrial biogenesis (Pyrroloquinoline quinone; PQQ), and improve oxidative phosphorylation (Nicotinamide mononucleotide, NMN). Mitochondrial function measured after drug treatments showed an AMD-dependent response; only RPE from donors with AMD showed improvements. All four drugs caused a significant increase in maximal respiration (p

Summary: In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cardiac troponin I (cTnI) that exceeded the 99th percentile for normal animals 60 min after reperfusion and rose to readily detectable levels 24 h later. Although tissue analysis at 60 min showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24 h. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with apoptosis in the absence of pathological evidence of infarction. Key Words: cardiac troponin I, cardiomyocyte apoptosis, myocardial ischemia, myocardial stunning

In eukaryotic cells, macroautophagy is a catabolic pathway implicated in the degradation of long-lived proteins and damaged organelles. Although it has been demonstrated that macroautophagy can selectively degrade specific targets, its contribution to the basal turnover of cellular proteins has not been quantified on proteome-wide scales. In this study, we created autophagy-deficient primary human fibroblasts and quantified the resulting changes in basal degradative flux by dynamic proteomics. Our results provide a global comparison of protein half-lives between wild-type and autophagy-deficient cells. The data indicate that in quiescent fibroblasts, macroautophagy contributes to the basal turnover of a substantial fraction of the proteome at varying levels. As contrasting examples, we demonstrate that the proteasome and CCT/TRiC chaperonin are robust substrates of basal autophagy, whereas the ribosome is largely protected under basal conditions. This selectivity may establish a proteostatic feedback mechanism that stabilizes the proteasome and CCT/TRiC when autophagy is inhibited.

Objectives: Postpartum hemorrhage (PPH) is a common cause of maternal death worldwide, but data on PPH incidence and influencing factors for nulliparous and multiparous women is scarce. So, the study aimed to assess the differences in PPH incidence and influencing factors between nulliparous and multiparous women. Methods: A multicenter retrospective cohort study was conducted among women who gave birth at ≥ 28 weeks of gestation in Hunan Province, China, from January 2017 to December 2018. Logistic regression assessed PPH-influencing factors, and the receiver operating characteristic curve (ROC curve) assessed the predictive performance of identified factors. Results: A total of 144,845 postpartum women were included in the study. The incidence of PPH (blood loss ≥ 500 ml) was 2.1 % and 1.7 % for nulliparous and multiparous women, respectively. Among the nulliparous and multiparous women, similar influencing factors of PPH included erythrocyte suspension transfusion before childbirth, anemia, soft-birth canal avulsion, Cesarean-section, placenta abruption, and general anesthesia administration before birth. Thrombophlebitis was associated [aOR 18.46(1.67–20.31)] with PPH among only the nulliparous women, while instrument-assisted birth [aOR 1.95(1.16–3.28)] and gestational hypertension [aOR 1.57(1.13–2.19)] were associated with PPH among only the multiparous women. The areas under the ROC-curve for the overall-cohort, nulliparous, and multiparous groups were [0.829(0.821–0.838)], [0.828(0.815–0.840)] and [0.833(0.822–0.844)], respectively. Conclusion: PPH incidence is higher among nulliparous women than among multiparous women, but influencing factors vary relatively by parity. The study findings provide new insights into the use of different approaches to PPH prevention for nulliparous and multiparous women in clinical practice.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with poor prognosis. Cancer-testis genes (CTGs) have been vigorously pursued as targets for cancer immunotherapy, but the expressive patterns and functional roles of CTGs remain unclear in ESCC. Methods: A systematic screening strategy was adopted to screen CTGs in ESCC by integrating multiple public databases and RNA expression microarray data from 119 ESCC subjects. For the newly identified ESCC prognosis-associated CTGs, an independent cohort of 118 patients with ESCC was recruited to validate the relationship via immunohistochemistry. Furthermore, functional assays were performed to determine the underlying mechanisms. Findings: 21 genes were recognized as CTGs, in particular, CDCA5 was aberrantly upregulated in ESCC tissues and significantly associated with poor prognosis (HR = 1.85, 95%CI: 1.14–3.01, P = .013). Immunohistochemical staining confirmed that positive CDCA5 expression was associated with advanced TNM staging and a shorter overall survival rate (45.59% vs 28.00% for CDCA5−/+ subjects, P = 1.86 × 10−3). H3K27 acetylation in CDCA5 promoter might lead to the activation of CDCA5 during ESCC tumorigenesis. Functionally, in vitro assay of gain- and loss-of-function of CDCA5 suggested that CDCA5 could promote ESCC cells proliferation, invasion, migration, apoptosis resistance and reduce chemosensitivity to cisplatin. Moreover, in vivo assay showed that silenced CDCA5 could inhibit tumor growth. Mechanistically, CDCA5 knockdown led to an arrest in G2/M phase and changes in the expression of factors that played fundamental roles in the cell cycle pathway. Interpretation: CDCA5 contributed to ESCC progression and might serve as an attractive target for ESCC immunotherapy. Fund: This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20181083 and BK20181496), Jiangsu Top Expert Program in Six Professions (No. WSW-003 and WSW-007), Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2016790 and BE2018746), Jiangsu Medical Young Talent Project (No. QNRC2016566), the Program of Jiangsu Medical Innovation Team (No. CXTDA2017006), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1487) and Jiangsu Province 333 Talents Project (No. BRA2017545). Keywords: Esophageal squamous cell cancer, Cancer-testis gene, CDCA5, Immunotherapy, Biomarker

COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.

In this paper, a laminated planar feed structure has been proposed to excite the omnidirectional radiation modes of a dielectric resonator (DR): TM01δ, TM011+δ and TM012+δ. The resonant frequencies of the three modes are 2.44, 2.78 and 3.10 GHz respectively. By combining three resonant frequencies, the proposed band-notched dielectric resonator antenna (DRA) achieves a wide impedance bandwidth and stable omnidirectional radiation pattern in the whole passband. The simulated passbands of the proposed band-notched DRA are 2.23–2.56 GHz and 2.71–3.17 GHz. The laminated planar feed structure also can produce an adjustable radiation null (RN) at the upper edge of the passband, improving the skirt selectivity. To suppress in-band interference, four metal patches have been plated on the side walls of the DR and another adjustable RN (notched frequency) is generated within the passband. By changing the size of the metal patch, the notched band can be adjusted. In a word, the proposed DRA has numerous advantages such as wideband, stable omnidirectional radiation, filtering and band-notched functions. A prototype has been fabricated and measured for demonstration, and the measured results are coincided with the simulated ones.

A dual-band omnidirectional coupled-fed monopolar filtering antenna is designed in this paper. The proposed filtering antenna consists of three stacked circular substrates. A via-loaded annular ring and an annular ring are fabricated on the top of bottom and middle substrates respectively. Four adjustable resonant modes are introduced by this way, which are combined in pairs to generate two independently controllable operating bands. Meanwhile, each resonant mode can produce corresponding omnidirectional radiation, making the proposed filtering antenna have omnidirectional radiation function. There are four adjustable radiation nulls (RNs) located at the both sides of two passbands realized by the coupled-fed via-loaded annular ring and the circular patch printed on the uppermost substrate. Hence, high skirt selectivity can be obtained. The proposed dual-band filtering antenna is simulated, fabricated and measured. The simulation and measurement are in excellent agreements. It is proved that the proposed filtering antenna realizes a stable omnidirectional radiation pattern in the azimuth plane with the cross-polarization level of lower than 20 dB. Additionally, the measured results display that the 10-dB impedance bandwidths are 6.3 % (2.47–2.63 GHz) and 6 % (5.38–5.71 GHz), respectively. The maximum realized gains are 2.6 and 5.2 dBi for two working bands with the out-of-band suppression of more than 15 dB.

Numerous moundy reflections were found at the Upper Meishan Formation in southern Qiongdongnan Basin, South China Sea which are suspected reefs. However, no common understanding on the seismic and geologic interpretation was acquired. Based on seismic reflection identification, geometrical configuration description, wave impedance inversion, forward simulation, analysis of reef-building sedimentary environments and pseudomorph identification, these suspected-reef moundy reflections were studied in details. Three types of reefs were recognized, i.e., patch reef, platform-edge reef, and pinnacle reef. They have some typical characteristics of reefs, including moundy or lenticular shape, clear outline with crest and canal, internal foreset bedding, bidirectional uplap between limbs, and strong reflection at top and bottom. The patch reefs are of moundy seismic facies, with moderate–strong amplitude and moderate frequency, and distribute at the higher part of southern slope belt. Fore-reef and back-reef of patch reefs are slightly asymmetrical being perpendicular to palaeo-bathymetric orientation; while symmetrical to slightly asymmetrical being parallel to the palaeo-bathymetric orientation, and the wave impedance value is about 7 kg/m3×m/s. Platform-edge reefs are of flat-moundy seismic facies with strong amplitude and moderate frequency, which develop at the carbonate platform edge of higher part of southern slope belt, and the wave impedance value is about 7.5 kg/m3×m/s. Pinnacle reefs grow up on volcanic cones, forming the complex of pinnacle reef and volcanic cone. The Miocene Meishan Formation reefs in southern Qiongdongnan Basin, northern South China Sea, with high quality source–reservoir–seal assemblages, have good petroleum exploration prospects.