Finite Element Flow Simulations of the EUROLIFT DLR-F11 High Lift Configuration

This paper presents flow simulation results of the EUROLIFT DLR-F11 multi-element wing configuration, obtained with a highly scalable finite element solver, PHASTA. This work was accomplished as a part of the 2nd high lift prediction workshop. In-house meshes were constructed with increasing mesh density for analysis. A solution adaptive approach was used as an alternative and its effectiveness was studied by comparing its results with the ones obtained with other meshes. Comparisons between the numerical solution obtained with unsteady RANS turbulence model and available experimental results are provided for verification and discussion. Based on the observations, future direction for adaptive research and simulations with higher fidelity turbulence models is outlined.Comment: 52nd Aerospace Sciences Meetin

Grid-Adapted FUN3D Computations for the Second High Lift Prediction Workshop

Contributions of the unstructured Reynolds-averaged Navier-Stokes code FUN3D to the 2nd AIAA CFD High Lift Prediction Workshop are described, and detailed comparisons are made with experimental data. Using workshop-supplied grids, results for the clean wing configuration are compared with results from the structured code CFL3D Using the same turbulence model, both codes compare reasonably well in terms of total forces and moments, and the maximum lift is similarly over-predicted for both codes compared to experiment. By including more representative geometry features such as slat and flap brackets and slat pressure tube bundles, FUN3D captures the general effects of the Reynolds number variation, but under-predicts maximum lift on workshop-supplied grids in comparison with the experimental data, due to excessive separation. However, when output-based, off-body grid adaptation in FUN3D is employed, results improve considerably. In particular, when the geometry includes both brackets and the pressure tube bundles, grid adaptation results in a more accurate prediction of lift near stall in comparison with the wind-tunnel data. Furthermore, a rotation-corrected turbulence model shows improved pressure predictions on the outboard span when using adapted grids

Cancer risk in persons with HIV/AIDS in India: a review and future directions for research

Background India has a large and evolving HIV epidemic. Little is known about cancer risk in Indian persons with HIV/AIDS (PHA) but risk is thought to be low. Methods To describe the state of knowledge about cancer patterns in Indian PHA, we reviewed reports from the international and Indian literature. Results As elsewhere, non-Hodgkin lymphomas dominate the profile of recognized cancers, with immunoblastic/large cell diffuse lymphoma being the most common type. Hodgkin lymphoma is proportionally increased, perhaps because survival with AIDS is truncated by fatal infections. In contrast, Kaposi sarcoma is rare, in association with an apparently low prevalence of Kaposi sarcoma-associated herpesvirus. If confirmed, the reasons for the low prevalence need to be understood. Cervical, anal, vulva/vaginal and penile cancers all appear to be increased in PHA, based on limited data. The association may be confounded by sexual behaviors that transmit both HIV and human papillomavirus. Head and neck tumor incidence may also be increased, an important concern since these tumors are among the most common in India. Based on limited evidence, the increase is at buccal/palatal sites, which are associated with tobacco and betel nut chewing rather than human papillomavirus. Conclusion With improving care of HIV and better management of infections, especially tuberculosis, the longer survival of PHA in India will likely increase the importance of cancer as a clinical problem in India. With the population's geographic and social diversity, India presents unique research opportunities that can be embedded in programs targeting HIV/AIDS and other public health priorities

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response

BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours

BORIS (for brother of the regulator of imprinted sites), a paralogue of the transcription factor, CTCF, is a novel member of the cancer-testis antigen family. The aims of the present study were as follows: (1) to investigate BORIS expression in breast cells and tumours using immunohistochemical staining, western and real-time RT–PCR analyses and (2) assess potential correlation between BORIS levels in tumours with clinical/pathological parameters. BORIS was detected in all 18 inspected breast cell lines, but not in a primary normal breast cell culture. In 70.7% (41 of 58 cases) BORIS was observed in breast tumours. High levels of BORIS correlated with high levels of progesterone receptor (PR) and oestrogen receptor (ER). The link between BORIS and PR/ER was further confirmed by the ability of BORIS to activate the promoters of the PR and ER genes in the reporter assays. Detection of BORIS in a high proportion of breast cancer patients implies potential practical applications of BORIS as a molecular biomarker of breast cancer. This may be important for diagnosis of the condition and for the therapeutic use of BORIS. The ability of BORIS to activate promoters of the RP and ER genes points towards possible involvement of BORIS in the establishment, progression and maintenance of breast tumours

India’s contribution to mitigating the impacts of climate change through vegetation management

The changes in natural ecosystems provide opportunity to increase vegetation carbon sink capacity and thereby contribute to mitigation of climate change impacts. The Indian tropics and the large ecological variation within the country afford the advantage of diverse niches and offer opportunities to reveal the role of biotic factors at different levels of organization from populations to ecosystems. The last 4 decades of research and development in the Indian space science community has been primarily application driven in response to the government space programme for national development. The expenditure in R&D over next 5 year suggest that scientific research is higher on the country's agenda. The Indo-UK Terrestrial Carbon Group (IUTCG) comprising both Indian and UK scientists, funded jointly by the Department of Science and Technology, India and the Department of Business, Innovation and Skills organised a workshop to explore ways in which Earth observation data can be effectively utilised in mitigating the impacts of climate change through vegetation management. Effective integration of field observations, collected through various monitoring networks, and satellite sensor data has been proposed to provide country-wide monitoring

Combining modularity, conservation, and interactions of proteins significantly increases precision and coverage of protein function prediction

<p>Abstract</p> <p>Background</p> <p>While the number of newly sequenced genomes and genes is constantly increasing, elucidation of their function still is a laborious and time-consuming task. This has led to the development of a wide range of methods for predicting protein functions in silico. We report on a new method that predicts function based on a combination of information about protein interactions, orthology, and the conservation of protein networks in different species.</p> <p>Results</p> <p>We show that aggregation of these independent sources of evidence leads to a drastic increase in number and quality of predictions when compared to baselines and other methods reported in the literature. For instance, our method generates more than 12,000 novel protein functions for human with an estimated precision of ~76%, among which are 7,500 new functional annotations for 1,973 human proteins that previously had zero or only one function annotated. We also verified our predictions on a set of genes that play an important role in colorectal cancer (<it>MLH1</it>, <it>PMS2</it>, <it>EPHB4 </it>) and could confirm more than 73% of them based on evidence in the literature.</p> <p>Conclusions</p> <p>The combination of different methods into a single, comprehensive prediction method infers thousands of protein functions for every species included in the analysis at varying, yet always high levels of precision and very good coverage.</p

Integrated Analyses of Copy Number Variations and Gene Expression in Lung Adenocarcinoma

Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Identification of prognostic biomarkers for lung cancer using gene expression microarrays poses a major challenge in that very few overlapping genes have been reported among different studies. To address this issue, we have performed concurrent genome-wide analyses of copy number variation and gene expression to identify genes reproducibly associated with tumorigenesis and survival in non-smoking female lung adenocarcinoma. The genomic landscape of frequent copy number variable regions (CNVRs) in at least 30% of samples was revealed, and their aberration patterns were highly similar to several studies reported previously. Further statistical analysis for genes located in the CNVRs identified 475 genes differentially expressed between tumor and normal tissues (p<10−5). We demonstrated the reproducibility of these genes in another lung cancer study (p = 0.0034, Fisher's exact test), and showed the concordance between copy number variations and gene expression changes by elevated Pearson correlation coefficients. Pathway analysis revealed two major dysregulated functions in lung tumorigenesis: survival regulation via AKT signaling and cytoskeleton reorganization. Further validation of these enriched pathways using three independent cohorts demonstrated effective prediction of survival. In conclusion, by integrating gene expression profiles and copy number variations, we identified genes/pathways that may serve as prognostic biomarkers for lung tumorigenesis