Consensus Rules in Variant Detection from Next-Generation Sequencing Data

A critical step in detecting variants from next-generation sequencing data is post hoc filtering of putative variants called or predicted by computational tools. Here, we highlight four critical parameters that could enhance the accuracy of called single nucleotide variants and insertions/deletions: quality and deepness, refinement and improvement of initial mapping, allele/strand balance, and examination of spurious genes. Use of these sequence features appropriately in variant filtering could greatly improve validation rates, thereby saving time and costs in next-generation sequencing projects

Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment

Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers

PURPOSE:We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. EXPERIMENTAL DESIGN:We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. RESULTS:152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5' partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected. CONCLUSION:The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Graphitized-rGO/Polyimide Aerogel as the Compressible Thermal Interface Material with Both High in-Plane and through-Plane Thermal Conductivities

Reduced graphene oxide (rGO) aerogels with a three-dimensional (3D) interconnected network provides continuous heat transport paths in multi-directions. However, the high porosity of rGO aerogels commonly leads to very low thermal conductivity (TC), and defects and grain boundaries of rGO sheets result in a high extent of phonon scattering, which is far from satisfying the requirement of thermal interface materials (TIMs). Here, a compressible graphitized-rGO/polyimide (g-rGO/PI) aerogel was prepared by the ice-template method and “molecular welding” strategy. The regular cellular structure and closely packed cell walls bring the g-rGO/PI aerogel high compressibility, which made the aerogel can maintain the continuous thermal transport paths well even in highly compacted status. The rGO sheets in the cell wall surface are welded up by g-PI during imidization and graphitization treatment, providing efficient channels for phonon transportation in the 3D network. The g-rGO/PI aerogel in a compressive strain of 95% has a high TC in the plane of 172.5 W m−1k−1 and a high TC through the plane of 58.1 W m−1k−1, which is superior to other carbon-based TIMs previously reported

Preparation and Hydrogen Storage Properties of Mg-Rich Mg-Ni Ultrafine Particles

In the present work, Mg-rich Mg-Ni ultrafine powders were prepared through an arc plasma method. The phase components, microstructure, and hydrogen storage properties of the powders were carefully investigated. It is found that Mg2Ni and MgNi2 could be obtained directly from the vapor state reactions between Mg and Ni, depending on the local vapor content in the reaction chamber. A nanostructured MgH2 + Mg2NiH4 hydrogen storage composite could be generated after hydrogenation of the Mg-Ni ultrafine powders. After dehydrogenation, MgH2 and Mg2NiH4 decomposed into nanograined Mg and Mg2Ni, respectively. Thermogravimetry/differential scanning calorimetry (TG/DSC) analyses showed that Mg2NiH4 phase may play a catalytic role in the dehydriding process of the hydrogenated Mg ultrafine particles

Dynamic Characteristics of Unsteady Aerodynamic Pressure on an Enclosed Housing for Sound Emission Alleviation Caused by a Passing High-Speed Train

Train speed is increasing due to the development of high-speed railway technology. However, high-speed trains generate more noise and discomfort for residents, enclosed housing for sound emission alleviation is needed to further reduce noise. Because these enclosed housings for sound emission alleviation restrain the air flow, strong and complicated aerodynamic pressures are generated inside the housing for sound emission alleviation when a train passes through at a high speed. This train-induced aerodynamic pressure, particularly its dynamic characteristics, is a key parameter in structural design. In the present study, the train-induced unsteady aerodynamic pressure in an enclosed housing for sound emission alleviation is simulated using the dynamic mesh method, and the dynamic characteristics of the aerodynamic pressure are investigated. The simulation results show that when the train is running in the enclosed housing for sound emission alleviation, the unsteady aerodynamic pressure is complicated and aperiodic, and after the train leaves the housing for sound emission alleviation, the aerodynamic pressure reverts to periodic decay curves. Two new terms, the duration of the extreme aerodynamic pressure and the pressure change rate, are proposed to evaluate the dynamic characteristics when the train passes through the barrier. The dominant frequency and decay rate are adopted to express the dynamic characteristics after the train exits. When the train runs in the enclosed housing for sound emission alleviation, the longest durations of the positive and negative extreme aerodynamic pressures are in the middle section, and the maximum change rate of aerodynamic pressure occurs at the entrance area. After the train exits the housing for sound emission alleviation, the pressure amplitude at the central region is always higher than those close to the entrance/exit. The dominant frequency of the aerodynamic pressure is identified and explained using wave propagation theory, the decay rate of the aerodynamic pressure at all sections is close

Review of applications and surface smoothing mechanisms of optical waveguide devices

Optical waveguide devices are widely used in many fields and have good development prospects. But surface roughness of waveguide device induces a passive effect on the light transmission loss and the Q value of ring cavity, which restricts the development and applications of optical waveguide devices. Currently, the common used surface and side wall smoothing methods for waveguide devices are the thermal oxidation method, laser beam method, and hydrogen annealing method, and the surface hydrogen annealing method has better smoothing effect. However, the mechanism of hydrogen annealing method is still not clear so far, thus the experimental parameters cannot be further optimized to obtain optimal experimental result. Based on the review of the contents mentioned above, the hydrogen annealing mechanism is primarily studied through the simulation analysis by Materials Studio, which provides theoretical foundation and guidance for smoothing of waveguide device by hydrogen annealing technology