1,515 research outputs found
Downregulation of miR-199b-5p is associated with chemoresistance via Jagged1 mediated notch signaling in human ovarian cancer cells
This journal suppl. entitled: 22nd Biennial Congress of the European Association for Cancer Research - proceedings of EACR 22BACKGROUND: Ovarian cancer is one of the most deadly gynaecological malignancies worldwide. Adjuvant chemotherapy combined with other treatments is the current management of the advanced ovarian cancers. However, the acquisition of resistance to initially responsive tumors limits the successful curative rate. The underlying molecular mechanism remains largely unknown. Here, we report that the downregulation of miR-199b-5p leading to elevated JAG1-mediated NOTCH signal...postprin
Study of four-dimensional DOA and polarisation estimation with crossed-dipole and tripole arrays
Electromagnetic (EM) vector sensor arrays can track both the polarisation and direction of arrival (DOA) of the impinging signals. For linear crossed-dipole arrays, as shown by our analysis, due to inherent limitation of the structure, it can only track one DOA parameter and two polarisation parameters. For full four-dimensional (4-D, 2 DOA and 2 polarization parameters) estimation, we could extend the linear crossed-dipole array to the planar case. In this paper, instead of extending the array geometry, we replace the crossed-dipoles by tripoles and construct a linear tripole array. It is proved that such a structure can estimate the 2-D DOA and 2-D polarisation information effectively in general and a dimension-reduction based MUSIC algorithm is developed so that the 4-D estimation problem can be simplified into two separate 2-D estimation problems, significantly reducing the computational complexity of the solution. The Cramr-Rao Bound (CRB) is also derived as a reference for algorithm performance. A brief comparison between the planar crossed-dipole array and the linear tripole array is performed at last, showing that although the planar structure has a better performance, it is achieved at the cost of increased physical size
A threshold dislocation dynamics method
The Merriman-Bence-Osher threshold dynamics method is an efficient algorithm
to simulate the motion by mean curvature. It has the advantages of being easy
to implement and with high efficiency. In this paper, we propose a threshold
dynamics method for dislocation dynamics in a slip plane, in which the spatial
operator is essentially an anisotropic fractional Laplacian. We show that this
threshold dislocation dynamics method is able to give { two correct leading
orders} in dislocation velocity, including both the local
curvature force and the nonlocal force due to the long-range stress
field generated by the dislocations as well as the force due to the applied
stress, where is the dislocation core size, { if the time step is
set to be . This generalizes the available result of
threshold dynamics with the corresponding fractional Laplacian, which is on the
leading order local curvature velocity under the isotropic
kernel.} We also propose a numerical method based on spatial variable
stretching to correct the mobility and to rescale the velocity for efficient
and accurate simulations, which can be applied generally to any threshold
dynamics method. We validate the proposed threshold dislocation dynamics method
by numerical simulations of various motions and interaction of dislocations.Comment: 35 pages, 13 figure
Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets.
BackgroundLiposarcoma, the most common soft tissue tumor, is understudied cancer, and limited progress has been made in the treatment of metastatic disease. The Achilles heel of cancer often is their kinases that are excellent therapeutic targets. However, very limited knowledge exists of therapeutic critical kinase targets in liposarcoma that could be potentially used in disease management.MethodsLarge RNAi and small-molecule tyrosine kinase inhibitor screens were performed against the proliferative capacity of liposarcoma cell lines of different subtypes. Each small molecule inhibitor was either FDA approved or in a clinical trial.ResultsScreening assays identified several previously unrecognized targets including PTK2 and KIT in liposarcoma. We also observed that ponatinib, multi-targeted tyrosine kinase inhibitor, was the most effective drug with anti-growth effects against all cell lines. In vitro assays showed that ponatinib inhibited the clonogenic proliferation of liposarcoma, and this anti-growth effect was associated with apoptosis and cell cycle arrest at the G0/G1 phase as well as a decrease in the KIT signaling pathway. In addition, ponatinib inhibited in vivo growth of liposarcoma in a xenograft model.ConclusionsTwo large-scale kinase screenings identified novel liposarcoma targets and a FDA-approved inhibitor, ponatinib with clear anti-liposarcoma activity highlighting its potential therapy for treatment of this deadly tumor
Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 -9 ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR < 10 -3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection.published_or_final_versio
Risk of cervical cancer is not increased in Chinese carrying homozygous arginine at codon 72 of p53
Homozygous arginine at codon 72 (HA72) of p53 was found in 22% of normal cervices and 30.0% of cervical cancers and no significant difference was detected between normal and cervical cancer with or without HPV 16/18. There was no correlation between HA72 and risk of cervical cancer in Chinese.link_to_subscribed_fulltex
Sersiclets - A Matched Filter Extension of Shapelets for Weak Lensing Studies
The precision study of dark matter using weak lensing by large scale
structure is strongly constrained by the accuracy with which one can measure
galaxy shapes. Several methods have been devised but none have demonstrated the
ability to reach the level of precision required by future weak lensing
surveys. In this Letter we explore new avenues to the existing Shapelets
approach, combining a priori knowledge of the galaxy profile with the power of
orthogonal basis function decomposition. This Letter discusses the new issues
raised by this matched filter approach and proposes promising alternatives to
shape measurement techniques. In particular it appears that the use of a
matched filter (e.g. Sersic profile) restricted to elliptical radial fitting
functions resolves several well known Shapelet issues.Comment: 6 pages, 6 figures. MNRAS Accepte
Application of Rigorous Interface Boundary Conditions in Mesoscale Plasticity Simulations
The interactions between dislocations and interface/grain boundaries,
including dislocation absorption, transmission, and reflection, have garnered
significant attention from the research community for their impact on the
mechanical properties of materials. However, the traditional approaches used to
simulate grain boundaries lack physical fidelity and are often incompatible
across different simulation methods. We review a new mesoscale interface
boundary condition based on Burgers vector conservation and kinetic dislocation
reaction processes. The main focus of the paper is to demonstrate how to unify
this boundary condition with different plasticity simulation approaches such as
the crystal plasticity finite element, continuum dislocation dynamics, and
discrete dislocation dynamics methods. To validate our interface boundary
condition, we implemented simulations using both the crystal plasticity finite
element method and a two-dimensional continuum dislocation dynamics model. Our
results show that our compact and physically realistic interface boundary
condition can be easily integrated into multiscale simulation methods and yield
novel results consistent with experimental observations.Comment: 19 pages and 7 figure
Health and nutrition of Orang Asli (Che Wong) at Krau Wildlife Reserve, Pahang – a descriptive study
This study was conducted to determine the nutritional status of Orang Asli (Che Wong) men,
women and children. Through purposive sampling, 29 households consisting of 29 men, 28 women,
and 20 children (10 female and 10 male) were chosen. Demographic and socioeconomic information
were collected using structured questionnaire. Men and women were measured for height, weight,
blood pressure and waist circumference while weight and height was measured for children.
Mean age for men, women and children were 39.89±17.09 years, 33.7±16.08 years, and 3.25±1.33
years respectively. Only 6.9% of men and 14.3% of women completed 3 years of primary school
education. The average household income was RM 261.56±254.40. Mean Body Mass Index (BMI) for
men was 21.83±3.40 (underweight: 13.8%, normal: 72.4%, overweight: 10.3%, and obese: 3.3%).
Mean Body Mass Index (BMI) for women was 28.6±4.05 (underweight: 23.3%, normal weight:
46.3%, and overweight: 26.7%). The mean circumference for men was 74.43±6.09cm and for women,
it was 73.92±6.80 cm. However, caution should be exercised when interpreting the BMI results
when none of them had waist circumference more than 102 cm (men) and 88 cm (women). About
10.3% of the men and 10.7% of women had blood pressure of more than 130/85 mmHg. The
prevalence of underweight, stunting and wasting of children was 45%, 35% and 30% respectively.
Food frequency questionnaire (FFQ) consisting of seven food groups (cereals, meats, fish, fruits,
vegetables, dairy products and drinks) was used to determine the dietary diversity score. The
minimum score was 0 and the maximum score was 37. Mean total score for men was 9.46±3.70
(maximum score of 18) and for women, it was 9.48 ± 4.63 (maximum score of 21). Food patterns for
both male and female were similar whereby fruits and milk groups were the least consumed. In
conclusion, further research should be conducted in the Che Wong community to determine the
association between food intake and nutritional status of Orang Asli
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