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Based on the double-periodic characteristics of a sine waveguide, the dispersion equation, interaction impedance, and transmission losses of slow-wave structures are derived. The dispersion equation indicates that the waves propagating in the sine waveguide should belong to two mode types, which can exist independently rather than as “pseudo-modes.” The dispersion equation, interaction impedance, and transmission losses are obtained using a theoretical model. A 220 GHz traveling wave tube (TWT) is used as an illustrative example to verify the validity of the analytical model. The calculated results show that the dispersion curve is in good agreement with that given by the Ansys high-frequency simulation software over the entire frequency range and that the theoretical numerical calculation time is less than 2% of that of the Ansys software package. In addition, the results demonstrate that the interaction impedance of the symmetric φ0 + π mode is much higher than that of the asymmetric φ0 mode. Therefore, the symmetric φ0 + π mode should be used for propagation in sine waveguide traveling-wave tubes. Moreover, when the conductivity is set at 1.6 × 107 S/m, the loss of the sine waveguide is ∼1.15 dB/cm for 220 GHz. The equivalent conductivity of the metal can be used appropriately in the design of the mm-wave and the THz TWT.

Abstract In this paper, a piecewise sine waveguide (PWSWG) is proposed as the slow-wave structure (SWS) to develop high-power terahertz (THz) traveling wave tubes (TWTs). The PWSWG is an improvement over the rectangular waveguide wherein its two E-planes simultaneously oscillate up and down along the longitudinal direction. The oscillation curve in the H-plane is a piecewise sine curve formed by inserting line segments into the peaks and troughs of the sine curve. The simulation analysis and experimental verification show that the PWSWG offers the advantages of large interaction impedance and excellent electromagnetic transmission performance. Furthermore, the calculation results of beam–wave interaction show that the TWT based on PWSWG SWS can generate a radiated power of 253.1 W at the typical frequency of 220 GHz, corresponding to a gain of 37.04 dB and an interaction efficiency of 6.92%. Compared with the conventional SWG TWTs, the PWSWG TWT has higher interaction efficiency and shorter saturation tube length. In conclusion, the PWSWG proposed in this paper can be considered a suitable SWS for high-power THz radiation sources.

Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular β-amyloid (Aβ) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Aβ pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.

BackgroundAlzheimer’s disease (AD) is the most common form of age-related neurodegenerative disease. Unfortunately, due to the complexity of pathological types and clinical heterogeneity of AD, there is a lack of satisfactory treatment for AD. Previous studies have shown that microRNAs and transcription factors can modulate genes associated with AD, but the underlying pathophysiology remains unclear.MethodsThe datasets GSE1297 and GSE5281 were downloaded from the gene expression omnibus (GEO) database and analyzed to obtain the differentially expressed genes (DEGs) through the “R” language “limma” package. The GSE1297 dataset was analyzed by weighted correlation network analysis (WGCNA), and the key gene modules were selected. Next, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis for the key gene modules were performed. Then, the protein-protein interaction (PPI) network was constructed and the hub genes were identified using the STRING database and Cytoscape software. Finally, for the GSE150693 dataset, the “R” package “survivation” was used to integrate the data of survival time, AD transformation status and 35 characteristics, and the key microRNAs (miRNAs) were selected by Cox method. We also performed regression analysis using least absolute shrinkage and selection operator (Lasso)-Cox to construct and validate prognostic features associated with the four key genes using different databases. We also tried to find drugs targeting key genes through DrugBank database.ResultsGO and KEGG enrichment analysis showed that DEGs were mainly enriched in pathways regulating chemical synaptic transmission, glutamatergic synapses and Huntington’s disease. In addition, 10 hub genes were selected from the PPI network by using the algorithm Between Centrality. Then, four core genes (TBP, CDK7, GRM5, and GRIA1) were selected by correlation with clinical information, and the established model had very good prognosis in different databases. Finally, hsa-miR-425-5p and hsa-miR-186-5p were determined by COX regression, AD transformation status and aberrant miRNAs.ConclusionIn conclusion, we tried to construct a network in which miRNAs and transcription factors jointly regulate pathogenic genes, and described the process that abnormal miRNAs and abnormal transcription factors TBP and CDK7 jointly regulate the transcription of AD central genes GRM5 and GRIA1. The insights gained from this study offer the potential AD biomarkers, which may be of assistance to the diagnose and therapy of AD.

In this paper, a W-band traveling-wave tube (TWT) is proposed by combining the slotted sine waveguide (SSWG) slow-wave structure (SWS) with the cylindrical electron beam. The dispersion properties and interaction impedances of the SSWG SWS are analyzed by using the numerical simulation and compared to the conventional sine waveguide (SWG) SWS. The interaction impedances of the SSWG SWS are much higher than the SWG SWS over the entire operating frequency band. The whole high frequency system, which consists of the SSWG SWS, the coupler, and the attenuator, is designed suitably. From the particle-in-cell simulation results, the maximum output power of the SSWG TWT at the typical frequency of 94 GHz can reach 284.5 W with the cylindrical electron beam of 20.6 kV and 180 mA. Compared to the SWG TWT, the SSWG TWT possesses the higher beam–wave interaction efficiency and the shorter saturated tube length.

Despite that immune responses play important roles in acute myeloid leukemia (AML), immunotherapy is still not widely used in AML due to lack of an ideal target. Therefore, we identified key immune genes and cellular components in AML by an integrated bioinformatics analysis, trying to find potential targets for AML. Eighty-six differentially expressed immune genes (DEIGs) were identified from 751 differentially expressed genes (DEGs) between AML patients with fair prognosis and poor prognosis from the TCGA database. Among them, nine prognostic immune genes, including NCR2, NPDC1, KIR2DL4, KLC3, TWIST1, SNORD3B-1, NFATC4, XCR1, and LEFTY1, were identified by univariate Cox regression analysis. A multivariable prediction model was established based on prognostic immune genes. Kaplan–Meier survival curve analysis indicated that patients in the high-risk group had a shorter survival rate and higher mortality than those in the low-risk group (P < 0.001), indicating good effectiveness of the model. Furthermore, nuclear factors of activated T cells-4 (NFATC4) was recognized as the key immune gene identified by co-expression of differentially expressed transcription factors (DETFs) and prognostic immune genes. ATP-binding cassette transporters (ABC transporters) were the downstream KEGG pathway of NFATC4, identified by gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). To explore the immune responses NFATC4 was involved in, an immune gene set of T cell co-stimulation was identified by single-cell GSEA (ssGSEA) and Pearson correlation analysis, positively associated with NFATC4 in AML (R = 0.323, P < 0.001, positive). In order to find out the immune cell types affected by NFATC4, the CIBERSORT algorithm and Pearson correlation analysis were applied, and it was revealed that regulatory T cells (Tregs) have the highest correlation with NFATC4 (R = 0.526, P < 0.001, positive) in AML from 22 subsets of tumor-infiltrating immune cells. The results of this study were supported by multi-omics database validation. In all, our study indicated that NFATC4 was the key immune gene in AML poor prognosis through recruiting Tregs, suggesting that NFATC4 might serve as a new therapy target for AML.

Electrical gating has been typically used for Graphene-based devices to deliver high performance with superior electrical controllability. In this study, we utilize direct electron beam irradiation to attain the electrical controllability of graphene. The newly established system combines terahertz time-domain spectroscopy (TDS) with scanning electron microscopy (SEM). We experimentally demonstrate the precise localized tuning of graphene terahertz metamaterials, as the size and position of the electron beam generated by SEM are highly controllable. Furthermore, graphene metamaterials with different chemical potentials are simulated, and the results are highly consistent with the experiments.

Remodeling of adipocyte morphology and function plays a critical role in prostate cancer development. We previously reported that leukemia cells secrete growth differentiation factor 15 (GDF15)，which remodels the residual bone marrow (BM) adipocytes into small adipocytes and is associated with a poor prognosis in acute myeloid leukemia (AML) patients. However, little is known about how GDF15 drives BM adipocyte remodeling. In this study, we examined the role of the transient receptor potential vanilloid (TRPV) channels in the remodeling of BM adipocytes exposed to GDF15. We found that TRPV4 negatively regulated GDF15-induced remodeling of BM adipocytes. Furthermore, transforming growth factor-β type II receptor (TGFβRII) was identified as the main receptor for GDF15 on BM adipocytes. PI3K inhibitor treatment reduced GDF15-induced pAKT, identifying PI3K/AKT as the downstream stress response pathway. Subsequently, GDF15 reduced the expression of the transcription factor Forkhead box C1 (FOXC1) in BM adipocytes subjected to RNA-seq screening and Western blot analyse. Moreover, it was also confirmed that FOXC1 combined with the TRPV4 promoter by the Chip-qPCR experiments, which suggests that FOXC1 mediates GDF15 regulation of TRPV4. In addition, an AML mouse model exhibited smaller BM adipocytes, whereas the TRPV4 activator 4α-phorbol 12,13-didecanoate (4αPDD) partly rescued this process and increased survival. In conclusion, TRPV4 plays a critical role in BM adipocyte remodeling induced by leukemia cells, suggesting that targeting TRPV4 may constitute a novel strategy for AML therapy.

Abstract Background The adipocyte remodeling, including of the morphological change, might indicate special pathological function. Our previous study found that the morphological remodeling of larger marrow adipocytes into small marrow adipocytes correlates with a poor prognosis for acute myeloid leukemia (AML) patients. However, the mechanisms contributed to the marrow adipocyte remodeling are still poorly understood. Methods GDF15 expression was analyzed by RT-qPCR and western blotting assays in the leukemic cells. The enhancing and antibody neutralization tests in vitro were employed to evaluate the effect of GDF15 on the morphology of mature adipocytes. CCK8 test was used to detect the proliferation of leukemic cells after co-cultivation with small marrow adipocytes. Flow cytometry was used to analysis the proportion of cell cycle of leukemic cells. Immunofluorescence staining and linear analysis were applied to verify the GDF15 expression and the relationship between GDF15 and small marrow adipocytes in AML patients. Results In this study, we found that leukemic cell lines not only expressed significantly higher growth differentiation factor 15 (GDF15) than the other three cytokines associated with adipocyte differentiation in RNA level but also secreted GDF15 factor. Furthermore, the in vitro experiments demonstrated that GDF15 was involved in the conversion of small marrow adipocytes from larger marrow adipocytes. Correspondingly, the leukemic cells proliferated more rapidly through regulating the cell cycle when co-cultured with GDF15-induced small marrow adipocytes. The immunofluorescence staining on the bone marrow sections of AML patients further exhibited that GDF15 was partly produced by leukemic cells. The positive correlation between the concentration of GDF15 in the marrow aspirates and the number and the volume of small marrow adipocytes might suggest the contribution of GDF15 in AML patients (r = 0.72, r = 0.67). Conclusions GDF15 secreted by leukemic cells was involved in the morphological remodeling of marrow adipocytes, which can in turn promote leukemic cell growth, indicating that GDF15 may be a promising treatment target for AML patients.

Background/Aims: Chemotherapy is still the main strategy used to prevent the relapse of acute myeloid leukaemia (AML). As the most abundant stromal component in bone marrow (BM), marrow adipocytes have been previously shown to promote leukaemogenesis. The present study was designed to further validate whether marrow adipocytes exert synergistic effects on strengthening chemotherapeutic efficacy and evaluate the underlying mechanism. Methods: A retrospective study of BM biopsies from 80 patients with AML in remission and 71 control subjects was applied to quantitatively analyse the marrow adipocyte volume. Toxicity tests were used to assess the effect of chemotherapy drugs on BM cells. The possible mechanisms by which chemotherapy regulated the reduced marrow adipocyte content were investigated using antibody neutralization experiments, with an emphasis on growth differentiation factor 15 (GDF15). Results: In our study, the marrow adipocyte content was obviously reduced in the AML- complete remission (CR) group compared with the control group (P

A double-ridge-loaded folded waveguide (DRL-FW) travelling wave tube (TWT) based on period-tapered structure is proposed. Through analysing the dispersion characteristics of the DRL-FW slow wave structure (SWS), the physical mechanism of the band-edge oscillation is obtained. Period-tapered SWS is proposed and analysed for verifying the feasibility in suppressing upper-band-edge oscillation and increasing the output power. Then the electromagnetic characteristics and the beam-wave interaction of TWT based on the period-tapered DRL-FW SWS are investigated. The calculation results predict that it potentially could provide continuous wave power over 600W from 29 GHz to 32 GHz without upper-band-edge oscillation. The bandwidth expands from 29-31GHz to 29-32GHz and electron efficiency is increased from more than 8.3% to more than 11%, while the range of operating voltage expands from 22kV-22.5kV to 22kV-24kV. The corresponding saturated gain can reach over 36.8 dB. In addition, we have carried out experimental tests on the transmission characteristics of period-tapered DRL-FW SWS. The cold test results show that the voltage stand-wave ratio (VSWR) is below 1.8 in the range of 29-32GHz. Good transmission characteristics greatly reduce the risk of reflection wave oscillation, thus improving the stability of DRL-FW TWT.

A W-band sheet electron beam (SEB) traveling-wave tube (TWT) based on flat-roofed sine waveguide slow-wave structure (FRSWG-SWS) is proposed. The sine wave of the metal grating is replaced by a flat-roofed sine wave around the electron beam tunnel. The slow-wave characteristics including the dispersion properties and interaction impedance have been investigated by using the eigenmode solver in the 3-D electromagnetic simulation software Ansoft HFSS. Through calculations, the FRSWG SWS possesses the larger average interaction impedance than the conventional sine waveguide (SWG) SWS in the frequency range of 86-110 GHz. The beam-wave interaction was studied and particle-in-cell simulation results show that the SEB TWT can produce output power over 120 W within the bandwidth ranging from 90 to 100 GHz, and the maximum output power is 226 W at typical frequency 94 GHz, corresponding electron efficiency of 5.89%.

Meander lines (MLs) in two configurations are presented to reduce the mutual coupling (MC) between two microstrip patch antenna elements. Inserting a slot in the ground plane between the antenna elements is a simple method to reduce the MC, while adding the MLs in the slot of the ground can further reduce the MC. In the first configuration, one ML is inserted in the slot of the ground and a maximum MC reduction of 39 dB throughout the −10 dB bandwidth is achieved. What’s more, the radiation patterns are not changed compared with the dual-element microstrip antenna array with a slotted ground. For the second configuration, two MLs are added in the slot of the ground. It is found that a maximum isolation of 53 dB can be obtained. However, the radiation patterns are slightly changed compared with the dual-element microstrip antenna array with a slot in the ground. Meanwhile, the measured peak gain and efficiency of the dual-element microstrip antenna array in the two configurations are given. Along with this paper, several prototypes have been fabricated and measured. The simulated results are in good accordance with the measurements, which are presented to verify that MC reduction can be achieved between microstrip antenna elements by adding the MLs in the slotted ground.

Nonlinear effects of large power millimeter wave on critical chips for the T/R module of phased array radar is experimental studied and analyzed in this paper. A multifunction amplifier chip is selected for our experiments. A solid continuous wave (CW) source and a large power pulsed magnetron are both employed to generate the Ka-band microwave. The input-output characteristics, the degradation and destroy threshold of the chips are obtained through a series of experimental tests. At last, the results are given by figures and analyzed theoretically.

A theoretical model for calculation of the high frequency characteristics of the sine waveguide slow-wave structure (SWS) is proposed. The formulas of dispersion and interaction impedances of the hybrid modes are obtained by combining the Helmholtz equation with the appropriate boundary conditions. Using the full wave analysis method, it is proved that the periodic structures with a half-period shift followed leads to a pairwise closing of passbands characteristic of adjacent mode. The sine waveguide SWS for 0.22THz traveling wave tube (TWT) is chosen as an illustrative example to verify the validity of the theoretical model, and the calculation results of the dispersion curve and interaction impedance curve are consistent with the HFSS simulation results. In addition, the influences of dimensions of sine waveguide on the high frequency characteristics of +1st spatial harmonic wave are investigated by numerical calculation. The study indicates that the appropriate SWS parameters are helpful for improving the bandwidth and increasing output power of TWT.

Deep-sea permanent magnet motor equipped with fluid compensated pressure-tolerant system is compressed by the high pressure fluid both outside and inside. The induced stress distribution in stator core is significantly different from that in land type motor. Its effect on the magnetic properties of stator core is important for deep-sea motor designers but seldom reported. In this paper, the stress distribution in stator core, regarding the seawater compressive stress, is calculated by 2D finite element method (FEM). The effect of compressive stress on magnetic properties of electrical steel sheet, that is, permeability, BH curves, and BW curves, is also measured. Then, based on the measured magnetic properties and calculated stress distribution, the stator iron loss is estimated by stress-electromagnetics-coupling FEM. At last the estimation is verified by experiment. Both the calculated and measured results show that stator iron loss increases obviously with the seawater compressive stress.