Spin Hall Conductivity and Anomalous Hall Conductivity in Full Heusler compounds

The spin Hall conductivity (SHC) and anomalous Hall conductivity (AHC) in more than 120 full Heusler compounds are calculated using density functional theory in a high-throughtput way. The electronic structures are mapped to the Wannier basis and the linear response theory is used to get the conductivity. Our results show that the mechanism under the SHC or AHC cannot be simply related to the valence electron numbers or atomic weights, is related to the very details of the electronic structure, which can only be obtained by calculations. A high throughput calculation is efficient to screen out the desired materials. According to our present results, Cu2CoSn, as well as Co2MnAl and Co2MnGa are candidates in spintronic materials regarding to their high SHC and AHC values, which can benefit the spin-torque-driven nanodevices

Particle shape effect on heat transfer performance in an oscillating heat pipe

The effect of alumina nanoparticles on the heat transfer performance of an oscillating heat pipe (OHP) was investigated experimentally. A binary mixture of ethylene glycol (EG) and deionized water (50/50 by volume) was used as the base fluid for the OHP. Four types of nanoparticles with shapes of platelet, blade, cylinder, and brick were studied, respectively. Experimental results show that the alumina nanoparticles added in the OHP significantly affect the heat transfer performance and it depends on the particle shape and volume fraction. When the OHP was charged with EG and cylinder-like alumina nanoparticles, the OHP can achieve the best heat transfer performance among four types of particles investigated herein. In addition, even though previous research found that these alumina nanofluids were not beneficial in laminar or turbulent flow mode, they can enhance the heat transfer performance of an OHP

Finite element analysis of laser shock peening of 2050-T8 aluminum alloy

AbstractLaser shock processing is a recently developed surface treatment designed to improve the mechanical properties and fatigue performance of materials, by inducing a deep compressive residual stress field. The purpose of this work is to investigate the residual stress distribution induced by laser shock processing in a 2050-T8 aeronautical aluminium alloy with both X-ray diffraction measurements and 3D finite element simulation. The method of X-ray diffraction is extensively used to characterize the crystallographic texture and the residual stress crystalline materials at different scales (macroscopic, mesoscopic and microscopic).Shock loading and materials’ dynamic response are experimentally analysed using Doppler velocimetry in order to use adequate data for the simulation. Then systematic experience versus simulation comparisons are addressed, considering first a single impact loading, and in a second step the laser shock processing treatment of an extended area, with a specific focus on impact overlap. Experimental and numerical results indicate a residual stress anisotropy, and a better surface stress homogeneity with an increase of impact overlap.A correct agreement is globally shown between experimental and simulated residual stress values, even if simulations provide us with local stress values whereas X-ray diffraction determinations give averaged residual stresses

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

Integrative analysis of gene and miRNA expression profiles with transcription factor–miRNA feed-forward loops identifies regulators in human cancers

We describe here a novel method for integrating gene and miRNA expression profiles in cancer using feed-forward loops (FFLs) consisting of transcription factors (TFs), miRNAs and their common target genes. The dChip-GemiNI (Gene and miRNA Network-based Integration) method statistically ranks computationally predicted FFLs by their explanatory power to account for differential gene and miRNA expression between two biological conditions such as normal and cancer. GemiNI integrates not only gene and miRNA expression data but also computationally derived information about TF–target gene and miRNA–mRNA interactions. Literature validation shows that the integrated modeling of expression data and FFLs better identifies cancer-related TFs and miRNAs compared to existing approaches. We have utilized GemiNI for analyzing six data sets of solid cancers (liver, kidney, prostate, lung and germ cell) and found that top-ranked FFLs account for ∼20% of transcriptome changes between normal and cancer. We have identified common FFL regulators across multiple cancer types, such as known FFLs consisting of MYC and miR-15/miR-17 families, and novel FFLs consisting of ARNT, CREB1 and their miRNA partners. The results and analysis web server are available at http://www.canevolve.org/dChip-GemiNi

HLungDB: an integrated database of human lung cancer research

The human lung cancer database (HLungDB) is a database with the integration of the lung cancer-related genes, proteins and miRNAs together with the corresponding clinical information. The main purpose of this platform is to establish a network of lung cancer-related molecules and to facilitate the mechanistic study of lung carcinogenesis. The entries describing the relationships between molecules and human lung cancer in the current release were extracted manually from literatures. Currently, we have collected 2585 genes and 212 miRNA with the experimental evidences involved in the different stages of lung carcinogenesis through text mining. Furthermore, we have incorporated the results from analysis of transcription factor-binding motifs, the promoters and the SNP sites for each gene. Since epigenetic alterations also play an important role in lung carcinogenesis, genes with epigenetic regulation were also included. We hope HLungDB will enrich our knowledge about lung cancer biology and eventually lead to the development of novel therapeutic strategies. HLungDB can be freely accessed at http://www.megabionet.org/bio/hlung

Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>P21^(WAF1/Cip1)binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer.</p> <p>Methods</p> <p>RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry.</p> <p>Results</p> <p>p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment.</p> <p>Conclusions</p> <p>Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.</p

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

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

Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells.</p> <p>Methods</p> <p>We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID₅₀assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods.</p> <p>Results</p> <p>Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice.</p> <p>Conclusions</p> <p>These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.</p