Abstract
Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. ...The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion.
MGMT
promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries
MGMT
genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these
MGMT
rearrangements in glioma cells and demonstrated that the
MGMT
genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.
Prediction of remaining useful life (RUL) is greatly significant for improving the safety and reliability of manufacturing equipment. However, in real industry, it is difficult for RUL prediction ...models trained on a small sample of faults to obtain satisfactory accuracy. To overcome this drawback, this paper presents a long short-term memory (LSTM) neural network with transfer learning and ensemble learning and combines it with an unsupervised health indicator (HI) construction method for remaining-useful-life prediction. This study consists of the following parts: (1) utilizing the characteristics of deep belief networks and self-organizing map networks to translate raw sensor data to a synthetic HI that can effectively reflect system health; and (2) introducing transfer learning and ensemble learning to provide the required degradation mechanism for the RUL prediction model based on LSTM to improve the performance of the model. The performance of the proposed method is verified by two bearing datasets collected from experimental data, and the results show that the proposed method obtains better performance than comparable methods.
The demodulation algorithm based on 3 × 3 coupler in a fiber-optic hydrophone array has gained extensive attention in recent years. The traditional method uses a circulator to construct the normal ...path-match interferometry; however, the problem of increasing the asymmetry of the three-way signal to be demodulated is easily overlooked. To provide a solution, we report a pretreatment method for hydrophone array based on 3 × 3 coupler demodulation. We use cubic spline interpolation to perform nonlinear fitting to the reflected pulse train and calculate the peak-to-peak values of the single pulse to determine the light intensity compensation coefficient of the interference signal, so as to demodulate the corrected three-way interference signal. For experimental verification, ultra-weak fiber Bragg gratings (uwFBGs) with reflectivity of −50 dB are applied to construct a hydrophone array with 800 sensors, and a vibratory liquid column method is set up to generate a low-frequency hydroacoustic signal. Compared to the traditional demodulation algorithm based on a 3 × 3 coupler, the pretreatment method can improve the consistency of interference signals. The Lissajous figures show that cubic spline interpolation can improve the accuracy of monopulse peak seeking results by about 1 dB, and intensity compensation can further lead to a much lower noise density level for the interference pulse amplitude—specifically, more than 7 dB at 5~50 Hz—and the signal-to-noise ratio is improved by approximately 10 dB at 10 Hz. The distinct advantages of the proposed pretreatment method make it an excellent candidate for a hydrophone array system based on path-match interferometry.
In this paper, a dual-axis Fabry-Pérot (FP) accelerometer assembled on single optical fiber is proposed. The sensor is equipped with a special beam-splitting prism to split the light into two ...perpendicular directions (the X- and Y-axes); the prism surface coated with semi-permeable film and the reflective sheet on the corresponding Be-Cu vibration-sensitive spring form two sets of FP cavities of different sizes. When the Be-Cu spring with a proof mass (PM) is subjected to the vibration signal, the cavity length of the corresponding FP cavity is changed and the interference signal returns to the collimator through the original path of the prism. After bandpass filtering and demodulation, the two cavity lengths are obtained, and the acceleration measurement in dual-axis directions is completed. The resonant frequency of the proposed dual-axis fiber optic accelerometer is around 280 Hz. The results of the spectral measurements show 3.93 μm/g (g = 9.8 m/s
: gravity constant) and 4.19 μm/g for the applied acceleration along the X- and Y-axes, respectively, and the cross-axis sensitivity is below 5.1%. Within the angle range of 180°, the maximum error of measured acceleration is less than 3.77%. The proposed fiber optic dual-axis FP accelerometer has high sensitivity and strong immunity to electromagnetic interference. The size of the sensor mainly depends on the size of the prism, which is easy to reduce and mass produce. Moreover, this FP construction method has high flexibility and development potential.
Messenger RNA (mRNA) and long noncoding RNA (lncRNA) targets interact via competitive microRNA (miRNA) binding. However, the roles of cancer-specific lncRNAs in the competing endogenous RNA (ceRNA) ...networks of low-grade glioma (LGG) remain unclear. This study obtained RNA sequencing data for normal solid tissue and LGG primary tumour tissue from The Cancer Genome Atlas database. We used a computational method to analyse the relationships among the mRNAs, lncRNAs, and miRNAs in these samples. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to predict the biological processes (BPs) and pathways associated with these genes. Kaplan–Meier survival analysis was used to evaluate the association between the expression levels of specific mRNAs, lncRNAs, and miRNAs and overall survival. Finally, we created a ceRNA network describing the relationships among these mRNAs, lncRNAs, and miRNAs using Cytoscape 3.5.1. A total of 2555 differentially expressed (DE) mRNAs, 218 DElncRNAs, and 192 DEmiRNAs were identified using R. In addition, GO and KEGG pathway analysis of the mRNAs and lncRNAs in the ceRNA network identified 10 BPs, 10 cell components, 10 molecular functions, and 48 KEGG pathways as selectively enriched. A total of 55 lncRNAs, 50 miRNAs, and 10 mRNAs from this network were shown to be closely associated with overall survival in LGG. Finally, 59 miRNAs, 235 mRNAs, and 17 lncRNAs were used to develop a ceRNA network comprising 313 nodes and 1046 edges. This study helps expand our understanding of ceRNA networks and serves to clarify the underlying pathogenesis mechanism of LGG.
•We discovered a thick layer of REE and yttrium-rich deep-sea mud in the Indian Ocean.•Chemical characteristics of the mud is similar to those in the Pacific Ocean.•Apatite makes a major contribution ...to the high rare-earth and yttrium concentrations.
Deep-sea sediments in parts of the Pacific Ocean were recently found to contain remarkably high concentrations of rare-earth elements and yttrium (REY) of possible economic significance. Here we report similar REY-rich mud in a core section from Deep Sea Drilling Project Site 213 in the eastern Indian Ocean. The sediments consist mainly of siliceous ooze, with subordinate zeolitic clay that contains relatively high REY concentrations. The maximum and average total REY (ΣREY) contents of this material are 1113 and 629ppm, respectively, which are comparable to those reported from the Pacific Ocean. The REY-rich mud at Site 213 shows enrichment in heavy rare-earth elements, negative Ce anomalies, and relatively low Fe2O3/ΣREY ratios, similar to those in the Pacific Ocean. In addition, the major-element composition of the Indian Ocean REY-rich mud indicates slight enrichment in lithogenic components, which probably reflects a contribution from southern African eolian dust. A volcaniclastic component from neighboring mid-ocean ridges or intraplate volcanoes is also apparent. Elemental compositions and X-ray diffraction patterns for bulk sediment, and microscopic observation and elemental mapping of a polished thin section, demonstrate the presence of phillipsite and biogenic apatite, such as fish debris, in the REY-rich mud. The strong correlation between total REY content and apatite abundance implies that apatite plays an important role as a host phase of REY in the present deep-sea sediment column. However, positive correlations between ΣREY and elements not present in apatite (e.g., Fe2O3, MnO, and TiO2) imply that the REY-rich mud is not formed by a simple mixture of REY-enriched apatite and other components.
Rosai–Dorfman disease (RDD) is a rare, benign, non-Langerhans cell histiocytic proliferative disease. RDD with central nervous system involvement is extremely rare. Surgical excision is generally ...regarded as the appropriate treatment of choice for this disease, especially when the lesion causes neurological compression. RDD can be accompanied by systemic symptoms, such as malaise, fever, weight change, leukocytosis, anemia, and hormonal disturbance, which may be challenging during general management. Little is known regarding peri-anesthesia management of this rare disease. We report a case of a patient in his 20s who had recurrent RDD and had general anesthesia with perioperative management. He was obese and hepatic insufficiency. This case report adds to the literature regarding the perioperative anesthetic management of RDD with central nervous system involvement.
Methylation of DNA, RNA or protein is a reversible modification. The proteins and genes that regulate this modification can be a candidate target for tumor therapy. However, the characteristics of ...methyltransferase related genes in glioma remain obscure. In this study, we systematically analyzed the relationship between methyltransferase-related genes expression profiles and outcomes in glioma patients based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas RNA sequencing datasets. Consensus clustering identified two robust groups with significantly different pathological features and prognosis. Then a methyltransferase-related risk signature was built by a Cox proportional hazards model with elastic net penalty. Moreover, the risk score is associated with patients' clinical and molecular features and can be used as an independent prognostic indicator for patients with glioma. Furthermore, genes associated with the high-risk group were involved in various aspects of the malignant progression of glioma via Gene Ontology analysis and Gene Set Enrichment Analysis. In summary, our study identified a methyltransferase-related risk signature for predicting the prognosis of gliomas.
Uncertain fractional differential equation (UFDE) is very suitable for describing the dynamic change in uncertain environments. In this paper, we consider the European option pricing problem by ...applying the Caputo-Hadamard UFDEs to simulate the dynamic change of stock price. First, an uncertain stock model with the mean-reverting process is studied, and the European option pricing formulas are given. Then, the effect of uncertain interference on the bond is considered, and the corresponding European option pricing formulas are presented. Finally, some numerical examples are given to illustrate the effectiveness of pricing formulas.
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