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Fangteng Liu,1,2 Hengyu Wu1 1Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi, 330009, People’s Republic of China; 2Faculty of Medicine, University of Munich, Munich, 80336, GermanyCorrespondence: Hengyu Wu Tel +86-15270280590Email why_wuhengyu0590@163.comBackground: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a high incidence and increased mortality. CC chemokine receptors were participating in the modulation of the tumor microenvironment and involved in carcinogenesis and tumor development. However, the potential mechanistic values of CC chemokine receptors as clinical biomarkers and therapeutic targets in LUAD have not been fully clarified.Methodology: ONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, SurvExpress, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this work.Results: The transcriptional levels of CCR1/10 in LUAD tissues were significantly reduced while the transcriptional levels of CCR3/6/7/8 were significantly elevated, and the expression of CCR1 was the highest in LUAD among these CC chemokine receptors. A significant correlation was found between the expression of CCR2/4/6/7 and the pathological stage of LUAD patients. There were significant associations between CCR2/3/4/5/6/10 expression levels and OS in LUAD, and LUAD patients with high transcriptional levels of CCR3/4 had inferior first-progression survival. In addition, the prognostic values of CC chemokine receptors signature in LUAD were explored in three independent cohorts, the high-risk group displayed unfavorable OS compared with the low-risk group, and the LUAD cases in the high-risk group also suffered inferior RFS than that in the low-risk group. And for the prognostic value of the DNA methylation of CC chemokine receptors, we found 1 CpG of CCR2, 2 CpGs of CCR3, 1 CpG of CCR4, 3 CpGs of CCR6, 3 CpGs of CCR7, 1 CpG of CCR8, and 3 CpGs of CCR9 were significantly associated with prognosis in LUAD patients. However, the DNA methylation signature analysis showed there was no statistically significant association between the high- and low-risk group. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in LUAD were performed, the transcription factor targets, kinase targets, and miRNA targets of CC chemokine receptors were also identified in LUAD. We also found significant correlations among CC chemokine receptors expression and the infiltration of immune cells, the tumor infiltration levels among LUAD with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR1/2/10, B_cell, CD4_Tcell were significantly related to the clinical outcome of LUAD patients.Conclusion: CC chemokine receptors might serve as immunotherapeutic targets and prognostic biomarkers in LUAD.Keywords: CC chemokine receptors, lung adenocarcinoma, prognostic biomarker, immunotherapeutic target, bioinformatics analysis

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. The prognosis of HCC remains poor. Currently, sorafenib is the first-line drug for advanced HCC. Although sorafenib's mechanism of action involving several established cancer-related protein kinase targets is well-characterized, the underlying molecular mechanism is still unclear. Here, we found that sorafenib inhibited viability, proliferation, and migration of HCC cells in a dose-dependent manner. Sorafenib treatment of HCC cells destroyed mitochondrial morphology, accompanied by decreased activity of oxidative phosphorylation, collapse of mitochondrial membrane potential, and reduced synthesis of ATP, with consequent cell death due to ferroptosis. Pharmacological utilization of glutathione (GSH) rescued the sorafenib-induced ferroptosis, eliminated the accumulation of cellular mitochondrial reactive oxygen species (ROS), and lipid peroxide. GSH depletion through cysteine deprivation or cysteinase inhibition exacerbated sorafenib-induced ferroptotic cell death and lipid peroxides generation, and enhanced oxidative stress and mitochondrial ROS accumulation. Collectively, these findings indicate that depletion of cysteine acts synergistically with sorafenib and renders HCC cells vulnerable to ferroptosis, presenting the potential value of new therapeutic combinations for advanced HCC.

Fangteng Liu,1,2 Hengyu Wu1 1Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang 330009, Jiangxi, People’s Republic of China; 2Faculty of Medicine, University of Munich, Munich 80336, GermanyCorrespondence: Hengyu Wu Tel +86-15270280590Email why_wuhengyu0590@163.comBackground: Janus kinases (JAKs) are a family of non-receptor tyrosine kinases involved in multiple malignancies. However, clinical values of JAKs as prognostic markers and potential mechanism as molecular targets in breast invasive carcinoma (BC) are not completely clarified.Methodology: TIMER, UALCAN and GEPIA were used to assess the expression and methylation levels of JAKs in BC. Kaplan–Meier Plotter, bc-GenExMiner, SurvExpress, TRGAted, MethSurv, and SurvivalMeth were used to assess the multilevel prognostic significance of JAKs in breast cancer patients. And cBioPortal, TIMER, STRING, GeneMANIA, NetworkAnalysis, LinkedOmics, DAVID 6.8, and Metascape were applied for multilayer networks and functional enrichment analyses. Correlations between immune cell infiltrates/their gene markers and JAKs were evaluated by TIMER.Results: We first explored the expression and methylation level of JAKs in breast cancer and found significantly reduced JAK1 and JAK2 expression at mRNA and protein levels, significantly higher JAK3 protein expression, and significantly increased TYK2 expression at mRNA level but decreased at protein level. In addition, hypermethylation of JAK3 and TYK2 and hypomethylation of JAK1 were found in tumor samples. In terms of prognostic values of JAKs in BC patients, low transcriptional levels of JAK1, JAK2, JAK3, and TYK2 indicated worse OS/DMFS/PPS/RFS/DFS, inferior DFS, worse RFS, and shorter OS/DMFS/RFS, respectively. The mRNA signature analysis showed that high-risk group had unfavorable OS/RFS/MFS. Low JAK2 protein level indicated unfavorable DSS/PFS in BC patients. Five CpGs of JAK1, four CpGs of JAK2, 20 CpGs of JAK3, and 13 CpGs of TYK2 were significantly associated with prognosis in BC patients. The DNA methylation signature analysis also suggested worse prognosis in the high-risk group. For potential biological roles of JAKs, interaction analyses, functional enrichment analyses for biological process, cellular component, molecular function, and KEGG pathway analyses of JAKs and their neighbor genes in BC were conducted. Kinase targets, gene–miRNA interactions, and transcription factor–gene interactions of JAKs were also identified. Furthermore, JAKs were found to be significantly related to immune infiltrates as well as the expression levels of multiple immune markers in BC.Conclusion: JAKs showed multilevel prognostic value and important biological roles in BC. They might serve as promising prognostic markers and possible targets in breast cancer.Keywords: Janus kinase, breast cancer, prognosis, immunity, biomarker, target

Background GKN2, as a secretory protein, is involved in the inflammation and immune modulation, and its aberrant expression is closely related to tumorigenesis. However, integrated studies on the value of GKN2 as a promising clinical biomarker and immunotherapy target in multiple tumors are still rare. Methodology Multiple online databases, including ONCOMINE, SEGreg, UALCAN, GEPIA, K-M Plotter, cBioPortal, MethSurv, CellMarker, and Timer, were applied to assess the clinical significance of GKN2 and its correlation with tumor-infiltrating immune cells in differentially expressed cancers. Results Several databases confirmed that GKN2 was significantly down-regulated in lung and gastric cancers compared that in normal samples. GKN2 was altered in 3%, 5%, and 4% of the LUAD, LUSC, and STAD samples, respectively. Hyper-methylation of GKN2 was found in LUAD and LUSC samples. For the clinical values of GKN2, we found that the low transcription level of GKN2 was associated with worse OS in lung cancer, and inferior FP and PPS in gastric cancer, and the relationships between GKN2 expression and clinical variables regarding OS/FP/PPS in lung and gastric cancers were assessed. Moreover, the prognostic value of the DNA methylation patterns of GKN2 in LUAD, LUSC, and STAD was identified. Furthermore, GKN2 expression was found to be significantly correlated with the infiltrating multiple tumor immune cells, and statistically significant differences in the correlation between GKN2 expression and multiple markers of neutrophils and macrophage polarization were observed in LUAD, LUSC, and STAD. Conclusion The study revealed the prognosis and risk factors for deterioration in patients with low expression of GKN2. GKN2 may be used as a valuable prognostic biomarker and therapeutic target in lung and gastric cancers.

This paper studies the option valuation problem of non-Gaussian and asymmetric GARCH models from a state-space structure perspective. Assuming innovations following an infinitely divisible distribution, we apply different estimation methods including filtering and learning approaches. We then investigate the performance in pricing S&P 500 index short-term options after obtaining a proper change of measure. We find that the sequential Bayesian learning approach (SBLA) significantly and robustly decreases the option pricing errors. Our theoretical and empirical findings also suggest that, when stock returns are non-Gaussian distributed, their innovations under the risk-neutral measure may present more non-normality, exhibit higher volatility, and have a stronger leverage effect than under the physical measure.

In this paper, a ray sampling method for calculating the luminance maps of light sources and compressing the ray files is proposed. The approach can directly derive luminance maps ofa light...

In this study, a common-path compensation method is proposed for the laser beam drift resulting from the air parameters to enhance the stability of small-angle measurement in laser autocollimation....

CISD2, a NEET protein that coordinates 2Fe-2S clusters through its CDGSH domain, is critical for normal development and iron homeostasis. CISD2 plays an important role in Fe-S cluster transfer and promotes cancer proliferation. However, its specific role in the development of non-small cell lung cancer (NSCLC) remains unclear. Bioinformatics of pan-cancer analysis from The Cancer Genome Atlas show that CISD2 has an aberrant expression in most types of human cancers. Moreover, CISD2 expression is associated with a higher hazard ratio and exhibits significantly poorer overall survival in lung adenocarcinoma (LUAD), uveal melanoma, head and neck squamous cell carcinoma, brain lower grade glioma, kidney chromophobe, and liver hepatocellular carcinoma. Further investigation revealed that CISD2 is highly expressed in LUAD and LUSC, which is associated with clinical pathological stages. In addition, survival data collected from GSE31210 and GSE13213, two datasets from the NCBI Gene Expression Omnibus, also confirmed that high CISD2 expression is associated with unfavorable survival in patients with LUAD. A cell-based assay indicated that the knockdown of CISD2 inhibited proliferation, invasion, and migration in A549 cells. Additionally, CISD2 knockdown accelerated the accumulation of cellular and mitochondrial reactive oxygen species, destroying the mitochondrial morphology and function. Moreover, CISD2 inhibition activated the iron starvation response, thus, accelerating iron accumulation in A549 cells. Pretreatment with DFO, the iron chelator, blocked mitochondrial dysfunction in CISD2-knockdown cells. Collectively, the present study provides novel insights into the regulatory role of CISD2 in NSCLC and presents a potential target to improve antitumor activity based on oxidative stress.

With the development of web technology, the communication based on C/S transmission mode is gradually replaced by B/S communication mode. The updating of intrusion technology and web source code visibility and, and the construction of joint query statements based on SQL database query language make the web penetration mode based on SQL injection become a direct database-oriented penetration mode. This paper analyses the principle of SQL injection, completes the verification test on the target machine, and puts forward a new direction for the development of SQL injection.

To eliminate axial misalignment-induced measurement errors of discrete light-emitting diode arrays in the far-field condition, a robust and effective method for correcting the measured luminous intensity distribution is proposed. The precision of the correction can be determined beforehand by setting a criterion which can also be used to determine the required test distance. To validate the feasibility and practicability of the proposed approach, numerical simulations of light-emitting diode arrays with three kinds of typical luminous intensity distributions were performed. In addition, the test distances as a function of the light-emitting diode luminous intensity distribution, packing density and dimensions under translational misalignment were analysed. Some beneficial operating methods and rules for practical application are summarised. Finally, physical measurements of several experimental examples were collected. The correction results agreed with the desired data and again proved the utility of the presented method.

The entrance optic is an important part of the photometer head. It can match the directional response of the photometer to the cosine function. In this paper, an entrance optic consisting of a free-form diffuser, a shadow ring, and an integrating cavity is introduced. An iterative optimization algorithm is presented to design a free-form diffuser that exhibits better cosine response characteristics. Diffusers of different materials and sizes are designed in a simulation experiment. After a finite number of iterations, in the absence of the shadow ring, the integral cosine error of the free-form diffuser is less than 1%. The directional cosine error is less than 3% for incidence angles between 0° and 70°. After adding a shadow ring to correct the directional response of the incident angle greater than 80°, for incident angles between 0° and 85°, the cosine errors are typically less than 3%, except that the cosine errors of very few large incident angles are close to 5%. The experimental results show the effectiveness and robustness of the proposed method. In addition, the influence of an important percentage constant σ on iterative optimization is studied. It is found that the larger the parameter σ, the fewer the number of iterations, and the directional cosine error may be slightly larger but still acceptable. The wide range of values of σ further embodies the versatility and flexibility of the proposed method.

Many Fourier ptychography microscopy techniques have been proposed to achieve higher recovery accuracy in the past few years, yet it is little known that their reconstructed quality is also dependent on the choice of recovery sequence, which is important for fast solution convergence during the Fourier ptychography reconstruction process. In this paper, we propose to use the Hilbert fractal curve, which is one of the most representative of classic space-filling curves, as a new kind of recovery sequence of mesh LED arrays and validate its effectiveness and robustness with both simulated and real experiments. Results show that the Hilbert fractal curve as the recovery sequence is a better choice for periodic LED arrays, compared with raster line, spiral line, and wave-shaped-curve three-recovery sequences.

Since computer controlled optical surfacing (CCOS) processes were proposed in the 1960s, many processes were developed for precision optics successfully. In this present work, a novel approach, the precessions process, is proposed and used for large segments fabrication. The removal function of the bonnet polisher based on velocity and pressure distribution, which are obtained from the geometry of the process tool-motion and Hertzian contact theory respectively, are simulated. A finite element analysis (FEA) model is constructed to optimize process parameters. At last, detailed experimental studies are carried out to verify the optimal parameters.

For structured light technique using commercial digital projector, gamma distortion is an inevitable factor affects the accuracy and resolution of the final measurement result seriously. This paper presents a gamma correction method based on the response function of the whole system, which is calculated from the input and output grayscale, and then the actual projected fringe patterns could be got. Through projecting these corrected fringes, the measurement error induced by gamma distortion would be reduced. At the same time, a low-pass filter has been designed to eliminate the residual high order harmonics in the deformed fringe patterns captured by a camera, in the basis of a mathematical model of the high order harmonics which are caused by gamma nonlinearity. Both computer simulation and experiment have been conducted to demonstrate the validity of this method.

To meet the special demands in small-scale discontinuous optical surface fabrication, the integrated magnetorheological jet polishing (IMJP) tool with multiple motion degrees is introduced in this paper. Four jetting models are implemented and investigated by means of the IMJP tool for practical manufacture. To ensure steady jetting in a long distance, ideal distribution characteristics of the magnetic field in the structure is proposed, based on electromagnetic theory. The magnetic field distribution is simulated subsequently using the finite element analysis method, and three key parameters in the IMJP tool structure are optimized through the simulations. The actual magnetic flux density is measured and spot polishing experiments are conducted in different standoff distances, verifying the effectiveness of the optimization. A processing experiment of a millimeter scale structure with milling tool marks located on a surface with nonuniform curvatures was conducted using the IMJP tool. The roughness of the polishing region converged to 4.86 nm Ra from a low initial quality after processing, and the tool marks have been efficiently removed. The experimental results reveal the reliability of the setup design and the remarkable roughness convergence ability of the IMJP tool for small complex structures.

Because the traditional BP neural network slow convergence speed, easily falling in local minimum and the learning process will appear oscillation phenomena. This paper introduces a tolerance analog circuit hard fault and soft fault diagnosis method based on adaptive learning rate and the additional momentum algorithm BP neural network. Firstly, tolerance analog circuit is simulated by OrCAD / Pspice circuit simulation software, accurately extracts fault waveform data by matlab program automatically. Secondly, using the adaptive learning rate and momentum BP algorithm to train neural network, and then applies it to analog circuit hard fault and soft fault diagnosis. With shorter training time, high precision and global convergence effectively reduces the misjudgment, missing, it can improve the accuracy of fault diagnosis and fast. DOI: http://dx.doi.org/10.11591/telkomnika.v11i9.3301

This paper develops the ARMA-GARCH model and obtain the historical filtered noise sequence based on time series analysis of Shanghai Composite Index (SHI). Then, it estimates the parameters of noise using method of moments estimation and simulates TS measure applying sequence representation method. Further, it fits the noise distribution and tailed distribution employing normal distribution and a - stable distribution, classical tempered stable (CTS) distribution and rapidly decreasing tempered stable (RDTS) distribution, respectively. The empirical results are as follows. Firstly, the random residual noise sequence presents leptokurtic, skewed and heavy-tailed characteristics in Chinese financial markets. Secondly, tempered stable (TS) distribution fits tailed distribution well under the method of moments estimation and exhibits the characteristics of rapidly decreasing jump. Thirdly, the probability of extreme events is 5 times in TS process than that of the normal process, which is in line with markets and be closed to the annual average frequency of Chinese financial markets' turmoils.

It firstly analyzes effects of price shocks in ECX CER spot market and futures markets applying VAR model and Impulse Response Analysis. The results are found that price shocks of CER spot price with Cholesky one standard deviation innovations to itself and futures prices of Dec09 CER, Dec10 CER, Dec11 CER and Dec12 CER show high positive effects while price shocks of CER futures prices to themselves and CER spot price exhibit low positive effects, even negative effects. Besides, it respectively fits characteristics of returns series in CER futures markets and spot market using t-GARCH model, Gaussian-GARCH model, t-GJR model and Gaussian-GJR model. It displays that t-GARCH (1, 1) model is the optimal model to fit the returns series. Meanwhile, we suggest the use of Markov regime-switching model for ECX CER stochastic modeling, indicating that both CER spot market and futures markets exhibit high stochastic behavior in the returns.

It analyzes the non-linear term structure of interest rates of Treasury in Shanghai Stock Exchange, using two-factor Vasicek model and Kalman filter in the state-space framework. The observation errors of one-year and 20-year interest rates are extracted and estimated applying the Archimedean copulas and mixture copula by maximum likelihood estimation. It has shown that the Gumbel copula and mixture copula could be more proper to capture their dependence structure. It is also found that Gumbel copula is superior over Gaussian copula, Frank copula, Clayton copula and mixture copula to test the VaR of Treasury portfolio by Monte Carlo simulation, for the latter four categories of copulas would underestimate the risks of portfolio.

As people have higher and higher requirement on PCB drilling efficiency and hole position accuracy, the drill bit is becoming smaller and smaller and its blade is becoming shorter and shorter. Usually, the dust-attachment phenomenon arises in case that the hole diameter is not greater than 0.4mm (mainly Φ0.35mm), the stack height is equal to or greater than 4.8mm and the drill bit that has been re-sharpened for over 3 times (re-sharpened for 4 or 5 times) is used. In this paper, by taking the following measures, the dust-attachment phenomenon can be basically eliminated: improving the material of pressure foot, properly choosing entry board and back-up board, using suitable pressure foot, reasonably set the dust suction pressure and the pressure of pressure foot, correctly selecting drilling tools and taking strict control on the quality of their re-sharpening.

Under the network environment,the Network topologies will change which leads to the changes of the routes for the moving characteristic of the nodes.We analyze the effects on TCP RQB caused by the changes of the routes in AD hoc and present the modified methods for TCP RQB, which is called TCP RQB-R,on the basis of the theory above. By identifying dynamically the changes of routes in the method of cross-layer and updating the RTTmax and RTTmin in time,TCP RQB-R can make a right judgment of the degree of congestions and control the congestions effectively.Based on the simulation experiment of NS2,the improved TCP RQB-R has a better performance than TCP RQB.

Presented is a street lights control system based on AT89S52 as control core. It is a combined product of the following technologies: a digital clock, a timer, a Liquid Crystal Display (LCD), a statistics of traffic flowing magnitude, a photosensitive induction, an infrared control and alarm function. This street light system also includes a time cut-out function, and an automatic control pattern for even more electricity conserving, namely when vehicles pass by, the light will turn on automatically, later turn off. This design can save a great amount of electricity compared to streetlamps that keep alight during nights. The design implements traffic flow magnitude statistics without adding any hardware, facilitating transportation condition information collecting. Furthermore, this system has auto-alarm function which will set off if any light is damaged and will show the serial number of the damaged light, thus it is easy to be found and repaired the damaged light.

The system is a nucleus model on the main control of single chip computer 78F9234, using DS18B20 temperature sensor to collect temperature data and digital tube monitor to show temperature data, with up-and-down limitation of temperature control key to change temperature rise and drop, heating indicator equipment, overheating protection and buzzer warning function, single-chip microcomputer's burning port and anti-death circuit. The system is convenient to use, cost is comparatively low and control system in software can be further improved to expand its function without adding its hardware cost, which would enhance the cost performance of temperature controllers.

The digital control technique of single chip microcomputer is adopted in the design of DC voltage-stabilized power supply for a multifunctional, digitalized DC voltage-stabilized power supply with higher performance cost ratio. This power source uses the digital adjustment, the output precision is high. It also has short and over-current protection and alarm, which is suitable especially in each kind situation of the high accuracy request. This design intellectualization direct-current power supply uses the self-restraint keyboard entry. The single-chip microcomputer receives voltage value information of keyboard input, and caries on processing.

This study presents a subaperture stitching method to calibrate system errors of several ∼2 m large scale 3D profile measurement instruments (PMIs). The calibration process was carried out by measuring a Φ460 mm standard flat sample multiple times at different sites of the PMI with a length gauge; then the subaperture data were stitched together using a sequential or simultaneous stitching algorithm that minimizes the inconsistency (i.e., difference) of the discrete data in the overlapped areas. The system error can be used to compensate the measurement results of not only large flats, but also spheres and aspheres. The feasibility of the calibration was validated by measuring a Φ1070 mm aspheric mirror, which can raise the measurement accuracy of PMIs and provide more reliable 3D surface profiles for guiding grinding, lapping, and even initial polishing processes.