A TIMM17A Regulatory Network Contributing to Breast Cancer.

BACKGROUND: Translocase of inner mitochondrial membrane 17A (TIMM17A) is overexpressed in breast cancer (BRCA), and upregulation can increase the aggressiveness of BRCA cells. This study examined the influence of the TIMM17A gene network on BRCA outcome. METHODS: Expression levels of TIMM17A were compared between normal and tumor tissues from the OncomineTM database, and the association with patient survival was analyzed using Kaplan-Meier Plotter. Clinical factors influencing TIMM17A expression were studied by UALCAN. cBioPotal was then used to identify genes interacting with TIMM17A, and network relationships were assessed using the R clusterProfiler package. The association between TIMM17A mutation and mRNA expression in BRCA was examined using the LinkFinder application in LinkedOmics, and coexpressed genes were assessed for functional enrichment using the LinkInterpreter application. Furthermore, TIMM17A expression correlation with cell cycle phase distribution was performed by flow cytometry. Finally, the target networks of kinases, microRNAs (miRNAs), and transcription factors were identified using GeneMANIA. The expression and correlation of potential miRNAs and targets were further validated in BRCA cell lines by qRT-PCR. RESULTS: Expression of TIMM17A was significantly elevated in BRCA compared with normal tissue (p < 0.05), and overexpression was associated with both poor overall survival (OS) and shorter distant metastasis-free survival (DMFS) (p < 0.05). Expression of TIMM17A was not associated with age, sex, BRCA subclass, clinical stage, or patient ethnicity. The coexpressed TIMM17A network was enriched in genes targeted by cell cycle regulators such as CDK1, miR-331, and E2F family transcription factors (FDR < 0.001). Furthermore, flow cytometry revealed a strong association between higher TIMM17A expression and faster cell cycle progression in these BRCA cell lines. In addition, expression of TIMM17A protein was correlated with CDK1 protein expression in BRCA cell lines as measured by western blotting. CONCLUSION: Elevated TIMM17A expression accelerates the progression of BRCA, thereby reducing OS and DMFS. The TIMM17A-associated networks identified here provide clues to the molecular pathogenesis of BRCA and potential targets for BRCA treatment.

An Integrated Detection Based on a Multi-Parameter Plasmonic Optical Fiber Sensor.

In this paper, a multi-parameter integrated detection photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) is proposed for its application in detecting temperature, magnetic field, and refractive index. The air holes on both sides of the fiber core were coated with gold film and introduced to the temperature-sensitive medium (PDMS) and magnetic fluid (MF), detecting temperature and magnetic field, respectively. The graphene layer is also presented on the gold film of the D-type side polished surface to improve the sensor sensitivity. The sensor's critical parameters' influence on its performance is investigated using a mode solver based on the finite element method (FEM). Simulation results show when the samples refractive index (RI) detection is a range of 1.36~1.43, magnetic field detection is a range of 20~550 Oe, and the temperature detection is a range of 5~55 °C; the maximum sensor's sensitivity obtains 76,000 nm/RIU, magnetic field intensity sensitivity produces 164.06 pm/Oe, and temperature sensitivity obtains -5001.31 pm/°C.

High Sensitivity Plasmonic Sensor Based on Fano Resonance with Inverted U-Shaped Resonator.

Herein, we propose a tunable plasmonic sensor with Fano resonators in an inverted U-shaped resonator. By manipulating the sharp asymmetric Fano resonance peaks, a high-sensitivity refractive index sensor can be realized. Using the multimode interference coupled-mode theory and the finite element method, we numerically simulate the influences of geometrical parameters on the plasmonic sensor. Optimizing the structure parameters, we can achieve a high plasmonic sensor with the maximum sensitivity for 840 nm/RIUand figure of merit for 3.9 × 105. The research results provide a reliable theoretical basis for designing high sensitivity to the next generation plasmonic nanosensor.

Path following identification of unmanned aerial vehicles for navigation spoofing and its application.

As unmanned aerial vehicles (UAVs) use global navigation satellite systems for positioning, the openness and weak security of satellite navigation signals make these systems easily falsifiable. By leveraging these characteristics, we propose a path following identification algorithm to gain control of UAVs using navigation spoofing as a countermeasure against illegal activities. Our contribution is threefold. First, we redefine the UAV kinematics model by treating the spoofing signal as wind. Subsequently, the relation between the spoofing signal and UAV heading angle is identified based on a path following algorithm, and the relation accuracy is experimentally verified. Finally, we propose the spoofing sparse A* search (SSAS) algorithm, whose effectiveness is verified by simulations of a UAV directed to a designated area while avoiding obstacles and forbidden areas.

Investigation of Anisotropic Subsequent Yield Behavior for 45 Steel by the Distortional Yield Surface Constitutive Model.

The subsequent anisotropic yield behavior of 45 steel was predicted by the distortional yield surface constitutive model, which can describe the anisotropic subsequent yield and the cross effect of metal associating with loading history. The yield characteristics and plastic hardening behaviors of the 45 steel were simulated under three preloading paths including pre-torsion, pre-tension, and pre-tension-torsion. Based on the comparison between the experimental yield stresses and the simulation by the classical Chaboche model, the proposed model can describe the remarkable anisotropic yield behavior related to the loading history, which can effectively describe the sharp point of yield surface in pre-loading direction and the smaller curvature near its opposite direction. It was successfully simulated by the constitutive model proposed that the subsequent distortional yield surface defined by small offset strain and the degradation process of the distortion feature defined by large offset strain.

Improved MAC layer protocol of Wifi for satellite network.

With the development and universal application of satellite technology, an important way to expand the function of satellites is setting up inter-satellite networks to make them work together. Traditional satellite networking methods generally adopt a fixed time slot allocation method, which is not suitable for small satellite groups with low latency and high throughput requirements. In order to solve this problem, it has been proposed to apply the traditional Wifi protocol in satellite networking. As there are differences between satellite networks and terrestrial networks, it's necessary to improve the traditional 802.11 protocol. The Media Access Control (MAC) protocol in 802.11 is improved in this paper, which mainly includes the adaptive algorithm of maximum contention window size and the growth algorithm of Contention Window (CW) size. The maximum contention window is adjusted according to the conflict state of the current network, which makes the network accommodate more satellite nodes. The CW growth algorithm improves the traditional Binary Exponential Back-off (BEB) algorithm, where the CW is designed according to the priority of the data frame or the network load. In this way, high-priority satellite accusation information will have higher reliability or tolerate greater network load.

The Anisotropic Distortional Yield Surface Constitutive Model Based on the Chaboche Cyclic Plastic Model.

Considering the cross effect in the evolution of subsequent yield surfaces for metals, an anisotropic distortional yield surface constitutive model is developed. By introducing an anisotropic distortional hardening function into the isotropic hardening part of the classical Chaboche rate-dependent constitutive model, the plastic-deformation-induced distortional and anisotropic hardening behaviors of subsequent yield surfaces are characterized. The experimental data of distortional yield surfaces for T2 pure copper under three different loading paths, including pre-tension, pre-torsion, and pre-tension-torsion proportional loading of 45-degree, are simulated by implementing the models into a numerical user defined material (UMAT) procedure based on the ABAQUS finite element package. To validate the anisotropic plastic model, the simulated yield surfaces are compared with experimental observations and predicted results for a crystal plasticity model and good agreement are noted. The simulations demonstrate that the proposed model can accurately capture the characteristics of the distortional yield surface and the anisotropic hardening process of the yield surface. Moreover, the distortional shapes of experimental subsequent yield surfaces in loading direction and opposite direction can be better revealed by the anisotropic plastic constitutive model than the crystal plastic constitutive model.

Identification of methylation sites and signature genes with prognostic value for luminal breast cancer.

BACKGROUND: Robust and precise molecular prognostic predictors for luminal breast cancer are required. This study aimed to identify key methylation sites in luminal breast cancer, as well as precise molecular tools for predicting prognosis. METHODS: We compared methylation levels of normal and luminal breast cancer samples from The Cancer Genome Atlas dataset. The relationships among differentially methylated sites, corresponding mRNA expression levels and prognosis were further analysed. Differentially expressed genes in normal and cancerous samples were analysed, followed by the identification of prognostic signature genes. Samples were divided into low- and high-risk groups based on the signature genes. Prognoses of low- and high-risk groups were compared. The Gene Expression Omnibus dataset were used to validate signature genes for prognosis prediction. Prognosis of low- and high-risk groups in Luminal A and Luminal B samples from the TCGA and the Metabric cohort dataset were analyzed. We also analysed the correlation between clinical features of low- and high- risk groups as well as their differences in gene expression. RESULTS: Fourteen methylation sites were considered to be related to luminal breast cancer prognosis because their methylation levels, mRNA expression and prognoses were closely related to each other. The methylation level of SOSTDC1 was used to divide samples into hypo- and hyper-methylation groups. We also identified an mRNA signature, comprising eight transcripts, ESCO2, PACSIN1, CDCA2, PIGR, PTN, RGMA, KLK4 and CENPA, which was used to divide samples into low- and high-risk groups. The low-risk group showed significantly better prognosis than the high-risk group. A correlation analysis revealed that the risk score was an independent prognostic factor. Low- and high- risk groups significantly correlated with the survival ratio in Luminal A samples, but not in Luminal B samples on the basis of the TCGA and the Metabric cohort dataset. Further functional annotation demonstrated that the differentially expressed genes were mainly involved in cell cycle and cancer progression. CONCLUSIONS: We identified several key methylation sites and an mRNA signature for predicting luminal breast cancer prognosis. The signature exhibited effective and precise prediction of prognosis and may serve as a prognostic and diagnostic marker for luminal breast cancer.

Analysis of the miRNA-mRNA-lncRNA network in human estrogen receptor-positive and estrogen receptor-negative breast cancer based on TCGA data.

Estrogen receptor-positive (ER+) and ER-negative (ER-) subtypes of breast cancer have distinct clinical outcomes because they respond differentially to endocrine therapies. We aimed to comprehensively analyze differentially expressed microRNA (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs in different ER subtypes as well as to identify prognosis-related RNAs. The expression levels of miRNAs, lncRNAs, and mRNAs between breast cancer and normal samples were compared using data from The Cancer Genome Atlas database. Differentially expressed miRNAs, lncRNAs and mRNAs between ER+ and ER- samples were also screened. An ER subtype-related miRNA-lncRNA-mRNA network was constructed. lncRNAs and mRNAs in this network were further subjected to an analysis of their associations with patient prognosis. Sets of differentially expressed miRNAs, lncRNAs, and miRNAs between breast cancer and normal samples were identified among which 14 miRNAs, 78 lncRNAs, and 475 mRNAs were differentially expressed between ER subtypes. Relationships between these RNAs were analyzed. The resultant ER subtype-related miRNA-lncRNA-mRNA network consisted of 14 nodes, among which LINC0092 and chromosome 2 open reading frame 71 (C2orf71) were correlated with better prognosis of breast cancer. LINC0092 was co-expressed with SFRP1 and RGMA and regulated by hsa-miR-449a and hsa-miR-452-5p. C2orf71 was co-expressed with LINC00511 and regulated by hsa-miR-184. Cross-talk among differentially expressed miRNAs, lncRNAs, and miRNAs may be an important feature in ER+ and ER- subtypes of breast cancer. LINC0092 and C2orf71, two of these cross-talking RNAs, may serve as novel prognostic predictor of breast cancer because of their close associations with prognosis.

Serum cytokine profile in patients with breast cancer.

Breast cancer is the leading cause of cancer-related death among women, with a more 20% 5-year survival rate after metastases. It is therefore critical to improve early diagnosis in order to improve disease prognosis. This study investigates cytokine profiles of breast cancer serum with the aim of identifying biomarkers for early diagnosis. A solid-phase antibody array was used for screening 274 biomarkers in serum from breast cancer patients. ELISA assay was carried out to identify biomarkers with differential expression. The serum levels of IL-8, MIP-1 alpha, MIP-1 beta, MMP-8, Resistin, FLRG, and BCAM were significantly higher in breast cancer patients, but LAP and TSH-ß levels were lower. ELISA assay results confirmed those of the antibody array. Our results suggest that these cytokines, screened by antibody array, might serve as novel inflammatory markers in breast cancer patients. Whether these biomarkers are specific for breast cancer and can help to improve diagnoses and prognoses of breast cancer needs further investigation.

Uplink Scheduling of Navigation Constellation Based on Immune Genetic Algorithm.

The uplink of navigation data as satellite ephemeris is a complex satellite range scheduling problem. Large-scale optimal problems cannot be tackled using traditional heuristic methods, and the efficiency of standard genetic algorithm is unsatisfactory. We propose a multi-objective immune genetic algorithm (IGA) for uplink scheduling of navigation constellation. The method focuses on balance traffic and maximum task objects based on satellite-ground index encoding method, individual diversity evaluation and memory library. Numerical results show that the multi-hierarchical encoding method can improve the computation efficiency, the fuzzy deviation toleration method can speed up convergence, and the method can achieve the balance target with a negligible loss in task number (approximately 2.98%). The proposed algorithm is a general method and thus can be used in similar problems.

The Availability of Space Service for Inter-Satellite Links in Navigation Constellations.

Global navigation satellite systems (GNSS) are widely used in low Earth orbit (LEO) satellite navigation; however, their availability is poor for users in medium Earth orbits (MEO), and high Earth orbits (HEO). With the increasing demand for navigation from MEO and HEO users, the inadequate coverage of GNSS has emerged. Inter-satellite links (ISLs) are used for ranging and communication between navigation satellites and can also serve space users that are outside the navigation constellation. This paper aims to summarize their application method and analyze their service performance. The mathematical model of visibility is proposed and then the availability of time division ISLs is analyzed based on global grid points. The BeiDou navigation constellation is used as an example for numerical simulation. Simulation results show that the availability can be enhanced by scheduling more satellites and larger beams, while the presence of more users lowers the availability. The availability of navigation signals will be strengthened when combined with the signals from the ISLs. ISLs can improve the space service volume (SSV) of navigation constellations, and are therefore a promising method for navigation in MEO/HEO spacecraft.

Correlational study on mitochondrial DNA mutations as potential risk factors in breast cancer.

The presented study performed an mtDNA genome-wide association analysis to screen the peripheral blood of breast cancer patients for high-risk germline mutations. Unlike previous studies, which have used breast tissue in analyzing somatic mutations, we looked for germline mutations in our study, since they are better predictors of breast cancer in high-risk groups, facilitate early, non-invasive diagnoses of breast cancer and may provide a broader spectrum of therapeutic options. The data comprised 22 samples of healthy group and 83 samples from breast cancer patients. The sequencing data showed 170 mtDNA mutations in the healthy group and 393 mtDNA mutations in the disease group. Of these, 283 mtDNA mutations (88 in the healthy group and 232 in the disease group) had never been reported in the literature. Moreover, correlation analysis indicated there was a significant difference in 32 mtDNA mutations. According to our relative risk analysis of these 32 mtDNA mutations, 27 of the total had odds ratio values (ORs) of less than 1, meaning that these mutations have a potentially protective role to play in breast cancer. The remaining 5 mtDNA mutations, RNR2-2463 indelA, COX1-6296 C>A, COX1-6298 indelT, ATP6-8860 A>G, and ND5-13327 indelA, whose ORs were 8.050, 4.464, 4.464, 5.254 and 4.853, respectively, were regarded as risk factors of increased breast cancer. The five mutations identified here may serve as novel indicators of breast cancer and may have future therapeutic applications. In addition, the use of peripheral blood samples was procedurally simple and could be applied as a non-invasive diagnostic technique.

Study on the constitutive model for jointed rock mass.

A new elasto-plastic constitutive model for jointed rock mass, which can consider the persistence ratio in different visual angle and anisotropic increase of plastic strain, is proposed. The proposed the yield strength criterion, which is anisotropic, is not only related to friction angle and cohesion of jointed rock masses at the visual angle but also related to the intersection angle between the visual angle and the directions of the principal stresses. Some numerical examples are given to analyze and verify the proposed constitutive model. The results show the proposed constitutive model has high precision to calculate displacement, stress and plastic strain and can be applied in engineering analysis.

Detection of mitochondrial DNA mutations by high-throughput sequencing in the blood of breast cancer patients.

Mitochondrial DNA mutations have been identified in serveral types of cancer. In breast cancer, germline and somatic mitochondrial DNA (mtDNA) mutations have been identified. A number of mtDNA mutations in breast cancer have been identified in protein-coding regions (in protein-coding genes, such as ND2, COX3, ND4, ND5 and CytB). Mutations in these structure proteins cause impaired electron transport function and lead to electron leakage and increased reactive oxygen species (ROS) production, which in turn increases oxidative stress and oxidative damage to the mitochondria, as well as to cells. These data establish an association between mtDNA mutations and breast cancer; however, there is no reliable prediction of breast cancer predisposition or progression based on mtDNA mutation patterns thus far. In this study, we used high-throughput sequencing to detect mtDNA mutations in the blood of breast cancer patients. Some of these mutations may be used as potential markers for breast cancer diagnosis.

[Changes of microRNA expression profiles in Vero cells induced by HSV-2 LAT overexpression].

OBJECTIVE: To investigate the changes in the microRNA expression profile of Vero cells induced by HSV-2 LAT overexpression. METHODS: The full-length open reading frame of HSV-2 LAT was synthesized and cloned into pRetroQ- AcGFP1-C1 vector, and the recombinant retrovirus expressing HSV-2 LAT was packaged. Using a microRNA microarray, the microRNA expression profile changes in Vero cells were analyzed after infection with the recombinant retrovirus. RESULTS: In Vero cells infected with the recombinant retrovirus for stable HSV-2 LAT overexpression, 5 microRNAs (hsa-miR-23a*, kshv-miR-K12-3, hsa-miR-943, hsa-miR-634, and hsa-miR-1270) were up-regulated and 5 (hsa-miR-181a-2*, hsa-miR-450b-5p, hsa-miR-31, hsa-miR-24, and kshv-miR-K12-12*) were down-regulated. CONCLUSION: The expression of HSV-2 LAT can induce changes in microRNA expression profile in Vero cells.

[Preparation of a monoclonal antibody against fusion protein preM/EIII of WNV].

OBJECTIVE: To prepare a monoclonal antibody (mAb) against the fusion protein preM/EIII of West Nile virus (WNV) for clinical detection of WNV. METHODS: Sp2/0 cells were fused with the spleen cells of BALB/c mice immunized with the recombinant fusion protein preM/EIII expressed in E. coil to obtain the hybridoma cell line that secreted preM/EIII mAb. The hybridoma cells were injected into the peritoneal cavity of BALB/c mice and the ascites was collected and purified. The specificity and titer of the obtained mAb were determined using ELISA and Western blotting. RESULTS: One hybridoma cell line secreting preM/EIII mAb, named ME1, was obtained. The titer of the purified mAb was 10(-6). Identified as a mAb of the Ig subclass IgG1, ME1 was capable of specific reactions with preM/EIII protein and WNV without cross-reactions with other viruses such as JEV, SLEV, YFV and DENV. The accuracy of clinical testing of MNV with ME1 was 97.78%. CONCLUSION: The mAb against preM/EIII obtained have a high specificity and accuracy in clinical testing of MNV and can be used in clinical diagnosis of MNV infection.

[Study on the changing regularity of special antibody and expression of stomach and enteric involvement on SARS-coronavirus infection in the recovery period of severe acute respiratory syndrome].

OBJECTIVE: To study the change of special antibodies titer IgG, IgM and nucleocapsid to SARS coronavirus (CoV) and observing the expression of stomach and enteric involvement on SARS-CoV infection by monoclonal antibody against N protein of SARS-CoV in the 7-year recovery period among family clustering cases of severe acute respiratory syndrome. METHODS: Special antibody titer to SARS-CoV of 14 patients from 5 different families and their 10 kinfolks continuously tested by IFA and antigen-capturing ELISA methods. Samples were taken in the 1(st) - 7(th) year periods after SARS patients infected by SARS-CoV, being diluted and measured on it titers of three kinds of antibodies. Immunochemical staining with monoclonal antibody (mAb) against N protein of SARS-CoV was used to determine the stomach and enteric tissues among 5 SARS patients with their nucleocapsid antibody titer ascended obviously after 1(st)-7(th) year. RESULTS: When testing the IgG antibody titer of the 14 SARS patients by IFA method, the average titer was 1/71 (95%CI: 1/58 - 1/85) in the 1(st) year, but began to descend in the following years, and the IgG antibody of the most SARS patients disappeared in the 7(th) year. Regarding the IgM titer, it disappeared in most of the SARS patients 1 year later. The average value of nucleocapsid antibody titer was 1/146 (95%CI: 1/122 - 1/171) in the 1(st) year, and it descended as the IgG antibody titer did. In 5 cases, differences appeared. The nucleocapsid antibody titer was between 1/156 and 1/210 in 3 cases, and 2 cases were normal. Immunochemical staining with mAb against N protein of SARS-CoV was identified in the stomach and enteric tissues of 5 SARS patients with the nucleocapsid antibody titer increased significantly, 1(st)-7(th) year later. The five patients were detected by gastroscopy detection and cell immunohistochemistry test. 3 cases showed N protein antibody positive in the serum, and positive immunohistochemical expression in most of the cytoplasm in the gastric tissue mucous gland epithelial cells. 1 case also expressed in the intestinal tissue slurry columnar epithelium and interstitial cells. The other two cases showed negative on both serum N protein antibody and immunohistochemical expression. The biopsy results of the 5 patients were as follows: 1 case diagnosed as "signet-ring cell carcinoma of the stomach and rectum multiple transfer", 1 case of gastric polyp, 1 case of superficial antral gastritis and 2 cases were normal. CONCLUSION: By testing the special IgG, IgM, nucleocapsid antibody to SARS-CoV of the 14 family clustering cases, we found that they all decreased in the 7(th) year, and most of them disappeared. The nucleocapsid antibody titer was related to pathogenetic condition. SARS-CoV was proved to be still present in stomach and enteric tissues of SARS patients with the nucleocapsid antibody titer increased significantly after the 7(th) year.

[The use of kidney-shaped pressure bandage to prevent postoperative salivary fistula].

PURPOSE: To evaluate the usefulness of pressure bandage with kidney-shaped cotton pad in parotidectomy and the relevant factors of parotid salivary fistula occurring after parotidectomy. METHODS: One hundred and ninety-six patients with parotid benign tumor or tumor-like lesions were randomly divided into two groups, 100 cases in the kidney-shaped cotton pad group and 96 cases in the traditional management group. The incidence of postoperative salivary in relation to surgical procedure, main parotid duct ligation, and parotid salivary fistula was analyzed. SPSS13.0 software package was used for Chi-square test. RESULTS: The incidence of parotid salivary fistula in the kidney-shaped cotton pad group was 1%, and the incidence in the traditional management group was 13.54%. The difference between the two groups was significant(P<0.01); Different surgical procedure, ligating the main parotid duct or not, had no effect on salivary fistula(P>0.05). CONCLUSIONS: The kidney-shaped cotton pad pressure bandaging can effectively prevent the occurrence of postoperative salivary fistula and has certain value in clinical application.