scholarly journals Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium

2021 ◽  
Vol 22 (7) ◽  
pp. 3618
Author(s):  
Emmanuel N. Paul ◽  
Gregory W. Burns ◽  
Tyler J. Carpenter ◽  
Joshua A. Grey ◽  
Asgerally T. Fazleabas ◽  
...  

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.

2016 ◽  
Author(s):  
Yan Tan ◽  
Jernej Godec ◽  
Felix Wu ◽  
Pablo Tamayo ◽  
Jill P. Mesirov ◽  
...  

AbstractGene set enrichment analysis (GSEA) is a widely employed method for analyzing gene expression profiles. The approach uses annotated sets of genes, identifies those that are coordinately up‐ or down-regulated in a biological comparison of interest, and thereby elucidates underlying biological processes relevant to the comparison. As the number of gene sets available in various collections for enrichment analysis has grown, the resulting lists of significant differentially regulated gene sets may also become larger, leading to the need for additional downstream analysis of GSEA results. Here we present a method that allows the rapid identification of a small number of co-regulated groups of genes – “leading edge metagenes” (LEMs) - from high scoring sets in GSEA results. LEM are sub-signatures which are common to multiple gene sets and that “explain” their enrichment specific to the experimental dataset of interest. We show that LEMs contain more refined lists of context-dependent and biologically meaningful genes than the parental gene sets. LEM analysis of the human vaccine response using a large database of immune signatures identified core biological processes induced by five different vaccines in datasets from human peripheral blood mononuclear cells (PBMC). Further study of these biological processes over time following vaccination showed that at day 3 post-vaccination, vaccines derived from viruses or viral subunits exhibit patterns of biological processes that are distinct from protein conjugate vaccines; however, by day 7 these differences were less pronounced. This suggests that the immune response to diverse vaccines eventually converge to a common transcriptional response. LEM analysis can significantly reduce the dimensionality of enriched gene sets, improve the identification of core biological processes active in a comparison of interest, and simplify the biological interpretation of GSEA results.Author SummaryGenome-wide expression profiling is a widely used tool to identify biological mechanisms in a comparison of interest. One analytic method, Gene set enrichment analysis (GSEA) uses annotated sets of genes and identifies those that are coordinately up‐ or down-regulated in a biological comparison of interest. This approach capitalizes on the fact that alternations in biological processes often cause the coordinated change of a large number of genes. However, as the number of gene sets available in various collections for enrichment analysis has grown, the resulting lists of significant differentially regulated gene sets may also become larger, leading to the need for additional downstream analysis of GSEA results. Here we present a method that allows the identification of a small number of co-regulated groups of genes – “leading edge metagenes” (LEMs) – from high scoring sets in GSEA results. We show that LEMs contain more refined lists of context-dependent biologically meaningful genes than the parental gene sets and demonstrate the utility of this approach in analyzing the transcriptional response to vaccination. LEM analysis can significantly reduce the dimensionality of enriched gene sets, improve the identification of core biological processes active in a comparison of interest, and facilitate the biological interpretation of GSEA results.


2019 ◽  
Vol 63 (5) ◽  
pp. 50402-1-50402-9 ◽  
Author(s):  
Ing-Jr Ding ◽  
Chong-Min Ruan

Abstract The acoustic-based automatic speech recognition (ASR) technique has been a matured technique and widely seen to be used in numerous applications. However, acoustic-based ASR will not maintain a standard performance for the disabled group with an abnormal face, that is atypical eye or mouth geometrical characteristics. For governing this problem, this article develops a three-dimensional (3D) sensor lip image based pronunciation recognition system where the 3D sensor is efficiently used to acquire the action variations of the lip shapes of the pronunciation action from a speaker. In this work, two different types of 3D lip features for pronunciation recognition are presented, 3D-(x, y, z) coordinate lip feature and 3D geometry lip feature parameters. For the 3D-(x, y, z) coordinate lip feature design, 18 location points, each of which has 3D-sized coordinates, around the outer and inner lips are properly defined. In the design of 3D geometry lip features, eight types of features considering the geometrical space characteristics of the inner lip are developed. In addition, feature fusion to combine both 3D-(x, y, z) coordinate and 3D geometry lip features is further considered. The presented 3D sensor lip image based feature evaluated the performance and effectiveness using the principal component analysis based classification calculation approach. Experimental results on pronunciation recognition of two different datasets, Mandarin syllables and Mandarin phrases, demonstrate the competitive performance of the presented 3D sensor lip image based pronunciation recognition system.


2021 ◽  
Vol 13 (2) ◽  
pp. 270
Author(s):  
Adrian Doicu ◽  
Dmitry S. Efremenko ◽  
Thomas Trautmann

An algorithm for the retrieval of total column amount of trace gases in a multi-dimensional atmosphere is designed. The algorithm uses (i) certain differential radiance models with internal and external closures as inversion models, (ii) the iteratively regularized Gauss–Newton method as a regularization tool, and (iii) the spherical harmonics discrete ordinate method (SHDOM) as linearized radiative transfer model. For efficiency reasons, SHDOM is equipped with a spectral acceleration approach that combines the correlated k-distribution method with the principal component analysis. The algorithm is used to retrieve the total column amount of nitrogen for two- and three-dimensional cloudy scenes. Although for three-dimensional geometries, the computational time is high, the main concepts of the algorithm are correct and the retrieval results are accurate.


2019 ◽  
Vol 8 (10) ◽  
pp. 1580 ◽  
Author(s):  
Kyoung Min Moon ◽  
Kyueng-Whan Min ◽  
Mi-Hye Kim ◽  
Dong-Hoon Kim ◽  
Byoung Kwan Son ◽  
...  

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.


2021 ◽  
Vol 13 (2) ◽  
pp. 227-233
Author(s):  
Grażyna Pazera ◽  
Marta Młodawska ◽  
Jakub Młodawski ◽  
Kamila Klimowska

Objectives: Munich Functional Developmental Diagnosis (MFDD) is a scale for assessing the psychomotor development of children in the first months or years of life. The tool is based on standardized tables of physical development and is used to detect developmental deficits. It consists of eight axes on which the following skills are assessed: crawling, sitting, walking, grasping, perception, speaking, speech understanding, social skills. Methods: The study included 110 children in the first year of life examined with the MFDD by the same physician. The score obtained on a given axis was coded as a negative value (defined in months) below the child’s age-specific developmental level. Next, we examined the dimensionality of the scale and the intercorrelation of its axes using polychoric correlation and principal component analysis. Results: Correlation matrix analysis showed high correlation of MFDD axes 1–4, and MFDD 6–8. The PCA identified three principal components consisting of children’s development in the areas of large and small motor skills (axis 1–4), perception (axis 5), active speech, passive speech and social skills (axis 6–8). The three dimensions obtained together account for 80.27% of the total variance. Conclusions: MFDD is a three-dimensional scale that includes motor development, perception, and social skills and speech. There is potential space for reduction in the number of variables in the scale.


2008 ◽  
Vol 130 (3) ◽  
Author(s):  
Alvaro Gonzalez ◽  
Xabier Munduate

This work undertakes an aerodynamic analysis over the parked and the rotating NREL Phase VI wind turbine blade. The experimental sequences from NASA Ames wind tunnel selected for this study respond to the parked blade and the rotating configuration, both for the upwind, two-bladed wind turbine operating at nonyawed conditions. The objective is to bring some light into the nature of the flow field and especially the type of stall behavior observed when 2D aerofoil steady measurements are compared to the parked blade and the latter to the rotating one. From averaged pressure coefficients together with their standard deviation values, trailing and leading edge separated flow regions have been found, with the limitations of the repeatability of the flow encountered on the blade. Results for the parked blade show the progressive delay from tip to root of the trailing edge separation process, with respect to the 2D profile, and also reveal a local region of leading edge separated flow or bubble at the inner, 30% and 47% of the blade. For the rotating blade, results at inboard 30% and 47% stations show a dramatic suppression of the trailing edge separation, and the development of a leading edge separation structure connected with the extra lift.


2018 ◽  
Vol 314 (4) ◽  
pp. L617-L625 ◽  
Author(s):  
Arjun Mohan ◽  
Anagha Malur ◽  
Matthew McPeek ◽  
Barbara P. Barna ◽  
Lynn M. Schnapp ◽  
...  

To advance our understanding of the pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)-based murine model that shows marked histological and inflammatory signal similarities to this disease. In this study, we compared the alveolar macrophage transcriptional signatures of our animal model with human sarcoidosis to identify overlapping molecular programs. Whole genome microarrays were used to assess gene expression of alveolar macrophages in six MWCNT-exposed and six control animals. The results were compared with the transcriptional profiles of alveolar immune cells in 15 sarcoidosis patients and 12 healthy humans. Rigorous statistical methods were used to identify differentially expressed genes. To better elucidate activated pathways, integrated network and gene set enrichment analysis (GSEA) was performed. We identified over 1,000 differentially expressed between control and MWCNT mice. Gene ontology functional analysis showed overrepresentation of processes primarily involved in immunity and inflammation in MCWNT mice. Applying GSEA to both mouse and human samples revealed upregulation of 92 gene sets in MWCNT mice and 142 gene sets in sarcoidosis patients. Commonly activated pathways in both MWCNT mice and sarcoidosis included adaptive immunity, T-cell signaling, IL-12/IL-17 signaling, and oxidative phosphorylation. Differences in gene set enrichment between MWCNT mice and sarcoidosis patients were also observed. We applied network analysis to differentially expressed genes common between the MWCNT model and sarcoidosis to identify key drivers of disease. In conclusion, an integrated network and transcriptomics approach revealed substantial functional similarities between a murine model and human sarcoidosis particularly with respect to activation of immune-specific pathways.


Author(s):  
Ranjan Saha ◽  
Jens Fridh ◽  
Torsten Fransson ◽  
Boris I. Mamaev ◽  
Mats Annerfeldt

An experimental study of the hub leading edge contouring using fillets is performed in an annular sector cascade to observe the influence of secondary flows and aerodynamic losses. The investigated vane is a three dimensional gas turbine guide vane (geometrically similar) with a mid-span aspect ratio of 0.46. The measurements are carried out on the leading edge fillet and baseline cases using pneumatic probes. Significant precautions have been taken to increase the accuracy of the measurements. The investigations are performed for a wide range of operating exit Mach numbers from 0.5 to 0.9 at a design inlet flow angle of 90°. Data presented include the loading, fields of total pressures, exit flow angles, radial flow angles, as well as profile and secondary losses. The vane has a small profile loss of approximately 2.5% and secondary loss of about 1.1%. Contour plots of vorticity distributions and velocity vectors indicate there is a small influence of the vortex-structure in endwall regions when the leading edge fillet is used. Compared to the baseline case the loss for the filleted case is lower up to 13% of span and higher from 13% to 20% of the span for a reference condition with Mach no. of 0.9. For the filleted case, there is a small increase of turning up to 15% of the span and then a small decrease up to 35% of the span. Hence, there are no significant influences on the losses and turning for the filleted case. Results lead to the conclusion that one cannot expect a noticeable effect of leading edge contouring on the aerodynamic efficiency for the investigated 1st stage vane of a modern gas turbine.


Author(s):  
A. Samson ◽  
S. Sarkar

The dynamics of separation bubble under the influence of continuous jets ejected near the semi-circular leading edge of a flat plate is presented. Two different streamwise injection angles 30° and 60° and velocity ratios 0.5 and 1 for Re = 25000 and 55000 (based on the leading-edge diameter) are considered here. The flow visualizations illustrating jet and separated layer interactions have been carried out with PIV. The objective of this study is to understand the mutual interactions of separation bubble and the injected jets. It is observed that flow separates at the blending point of semi-circular arc and flat plate. The separated shear layer is laminar up to 20% of separation length after which perturbations are amplified and grows in the second-half of the bubble leading to breakdown and reattachment. Blowing has significantly affected the bubble length and thus, turbulence generation. Instantaneous flow visualizations supports the unsteadiness and development of three-dimensional motions leading to formation of Kelvin-Helmholtz rolls and shedding of large-scale vortices due to jet and bubble interactions. In turn, it has been seen that both the spanwise and streamwise dilution of injected air is highly influenced by the separation bubble.


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