The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies

SummaryTo understand the role of human epidermal growth factor receptor (hEGFR) kinase domain mutations in lung tumorigenesis and response to EGFR-targeted therapies, we generated bitransgenic mice with inducible expression in type II pneumocytes of two common hEGFR mutants seen in human lung cancer. Both bitransgenic lines developed lung adenocarcinoma after sustained hEGFR mutant expression, confirming their oncogenic potential. Maintenance of these lung tumors was dependent on continued expression of the EGFR mutants. Treatment with small molecule inhibitors (erlotinib or HKI-272) as well as prolonged treatment with a humanized anti-hEGFR antibody (cetuximab) led to dramatic tumor regression. These data suggest that persistent EGFR signaling is required for tumor maintenance in human lung adenocarcinomas expressing EGFR mutants

An experimental study of failure and softening in sand under three-dimensional stress condition

This paper describes an experimental study of failure and softening behaviour in dense Toyoura sand. A true triaxial apparatus equipped with three pairs of rigid loading platens is used to test sand sample under three-dimensional stress condition. The testing results demonstrate that the rigid boundary around the sand samples cannot prevent formation of shear localization. Shear localization are observed to emerge in the hardening or the softening regime in the loading depending on the magnitude of intermediate principal stress. Uniform deformation for the whole strain range is obtained only in triaxial compression tests. The peak stress state obtained from tests of sand samples of the same initial density can be described with good approximation by the Matsuoka-Nakai criterion

Weathering Process of In Situ Granite and Particle Breakage Characteristics of Compacted Weathered Granite

Quantificationally describing weathering process and characterizing particle breakage are important in predicting the behavior of coarse-grained soil (e.g., weathered granite). In order to comprehensively understand the mechanical properties of weathered granite and provide references for reasonable evaluation of the engineering properties of subgrade filling in mountains, a series of tests—X-ray diffraction, sieving, heavy compaction, large-scale triaxial, and field compaction tests—were carried out in this research. Based on the weathering process parameters (m and r) of in-situ granite samples at two typical sections of weathered granite mountains obtained by using previous grading equation, the mathematical model of weathering process with depth was proposed and the variation laws of weathering process with depth were described. The results show that, with an increase in burying depth of mountain profile (h) of weathered granite, the geological year’s parameter (m) decrease by power function, but the geometric progression constants (r) increase by power function. Some factors affecting the particle breakage properties of compacted weathered granite were evaluated by using relative breakage (Br). Especially, the effect of field compaction condition (such as thickness of loose paving layer and number of vibratory rolling passes) on particle breakage was analyzed creatively. Through laboratory and field tests, it was found that particle gradation, mineral composition, compaction effect, stress level, and number of rolling passes significantly affected the particle breakage characteristics of weathered granite. Furthermore, it is worthy of attention that the weathered granite in this paper showed obvious particle breakage characteristics under weak compaction effect and at low stress levels and over-compaction could result in a decrease in the degree of compaction of a certain thickness of loose paving layer filled with weathered granite. Findings in this research can provide a theoretical basis for evaluating the physical properties and mechanical behavior of weathered granite as subgrade fillings

Complete chloroplast genome of Castanopsis sclerophylla (Lindl.) Schott: Genome structure and comparative and phylogenetic analysis.

Castanopsis sclerophylla (Lindl.) Schott is an important species of evergreen broad-leaved tree in subtropical areas and has high ecological and economic value. However, there are few studies on its chloroplast genome. In this study, the complete chloroplast genome sequence of C. sclerophylla was determined using the Illumina HiSeq 2500 platform. The complete chloroplast genome of C. sclerophylla is 160,497 bp long, including a pair of inverted repeat (IR) regions (25,675 bp) separated by a large single-copy (LSC) region of 90,255 bp and a small single-copy (SSC) region of 18,892 bp. The overall GC content of the chloroplast genome is 36.82%. A total of 131 genes were found; of these, 111 genes are unique and annotated, including 79 protein-coding genes, 27 transfer RNA genes (tRNAs), and four ribosomal RNA genes (rRNAs). Twenty-one genes were found to be duplicated in the IR regions. Comparative analysis indicated that IR contraction might be the reason for the smaller chloroplast genome of C. sclerophylla compared to three congeneric species. Sequence analysis indicated that the LSC and SSC regions are more divergent than IR regions within Castanopsis; furthermore, greater divergence was found in noncoding regions than in coding regions. The maximum likelihood phylogenetic analysis showed that four species of the genus Castanopsis form a monophyletic clade and that C. sclerophylla is closely related to Castanopsis hainanensis with strong bootstrap values. These results not only provide a basic understanding of Castanopsis chloroplast genomes, but also illuminate Castanopsis species evolution within the Fagaceae family. Furthermore, these findings will be valuable for future studies of genetic diversity and enhance our understanding of the phylogenetic evolution of Castanopsis

3D Numerical Analysis of Synergetic Interaction between High-Rise Building Basement and CFG Piles Foundation

A strong bearing capacity and the satisfaction of strict settlement requirements are necessary for high-rise buildings. A single-raft foundation cannot meet certain settlement requirements, in which case CFG (cement/fly ash/gravel, an emerging and sustainable construction material) piles can be used in the foundation to set up a cushion between the top of the pile and the raft slab, where the piles act as settlement reducers. The rafts of disconnected piles (DPs) exhibit complex synergetic interactions involving the raft, cushion, pile, and soil under the load of the superstructure. Multiple piles in particular lead to an increase in the number of degrees of freedom of the problem, resulting in difficulty in solving it. However, when the number of piles is very large and the structure is complex—for example, many buildings are placed on the same raft with basement structures—even if the embedded pile element is used during numerical calculations, either the method remains prone to non-convergence or the time needed for numerical calculations is too long. It is, thus, difficult to satisfy the requirement of an efficient scheme of evaluation in practice. To solve this problem, a method that uses a simulation of the integral equivalent of the CFG pile reinforcement zone is proposed in this paper. In the CFG pile reinforcement zone, the effect of the pile is reflected in the enhancement of parameters of the soil in the strengthened zone, and the reinforcement zone (including the soil and the pile) is regarded as an anisotropic elastoplastic material. As the structure of the pile is no longer needed in the model, its elimination significantly reduces the complexity of the model and improves its calculation efficiency. An example of a numerical calculation is provided to verify the viability and accuracy of the integral equivalent simulation method in comparison with the embedded pile element simulation method. Finally, the proposed method is applied to the three-dimensional numerical analysis of a scheme for the treatment of foundations of high- and low-rise buildings with basements, and its effectiveness is further verified through comparison with theoretical results

Can Hyperpolarized Helium MRI add to radiation planning and follow‐up in lung cancer?†

Locally advanced non‐small‐cell lung cancer (NSCLC) is a common disease with a low overall survival even with aggressive treatments. Standard imaging (CT and PET/CT) provide no information about normal lung function. We therefore, sought to pilot HeMRI in patients with non‐small‐cell lung cancer before and after definitive radiotherapy (RT). Five patients with NSCLC receiving RT were enrolled on a prospective IRB approved study. Patients underwent CT, FDG‐PET and HeMRI before and (within 10 days) following RT. All images (CT, FDG‐PET and HeMRI) were co‐registered. The CT and PET GTVs were contoured, as well as the ventilation defects on HeMRI caused by the tumor. Patients also underwent pulmonary function tests (PFTs). Correlations between the images and PFTs were evaluated by linear regression. CT and FDG‐PET tumor volumes were highly correlated (r2=0.91 before treatment and 0.99 following RT). There was less correlation between HeMRI and CT or PET (r2=0.67 (CT) and 0.38 (PET)) prior to treatment and 0.27 following RT). However, HeMRI volumes correlated very well with FEV1, both prior to and following RT. (r2=0.89 and 0.83, respectively). 3Helium MRI scanning is feasible in NSCLC before and after treatment. HeMRI provides important functional information in addition to CT and CT/PET scanning. PACS number: 87.55.D