To see the other types of publications on this topic, follow the link: Hierarchical orthogonality.

Journal articles on the topic 'Hierarchical orthogonality'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 24 journal articles for your research on the topic 'Hierarchical orthogonality.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

He, Guiqing, Yincheng Huo, Mingyao He, Haixi Zhang, and Jianping Fan. "A Novel Orthogonality Loss for Deep Hierarchical Multi-Task Learning." IEEE Access 8 (2020): 67735–44. http://dx.doi.org/10.1109/access.2020.2985991.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Czajko, Jakub. "Operational Constraints on Dimension of Space Imply both Spacetime and Timespace." International Letters of Chemistry, Physics and Astronomy 36 (July 2014): 220–35. http://dx.doi.org/10.18052/www.scipress.com/ilcpa.36.220.

Full text
Abstract:
Since polynomials of higher than fourth degree, which is the algebraic counterpart of generic geometric dimension, are insolvable in general, then presumably no more than just four mutually orthogonal geometric dimensions can be placed within a single geometric space if it is expected to be fully operational. Hence a hierarchical notion of dimension is needed in order to ensure that at least virtual orthogonality is respected, which in turn implies presence of certain hierarchically organized multispatial structures. It is shown that the operational constraint on physical spaces implies of necessity presence of both: 4-dimensional (4D) spacetime and a certain 4D timespace.
APA, Harvard, Vancouver, ISO, and other styles
3

Wilson, S. "On the application of hierarchical orthogonality restrictions to spin-coupled wave functions." International Journal of Quantum Chemistry 74, no. 2 (1999): 135–44. http://dx.doi.org/10.1002/(sici)1097-461x(1999)74:2<135::aid-qua10>3.0.co;2-i.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Luo, Lei, Jie Xu, Cheng Deng, and Heng Huang. "Orthogonality-Promoting Dictionary Learning via Bayesian Inference." Proceedings of the AAAI Conference on Artificial Intelligence 33 (July 17, 2019): 4472–79. http://dx.doi.org/10.1609/aaai.v33i01.33014472.

Full text
Abstract:
Dictionary Learning (DL) plays a crucial role in numerous machine learning tasks. It targets at finding the dictionary over which the training set admits a maximally sparse representation. Most existing DL algorithms are based on solving an optimization problem, where the noise variance and sparsity level should be known as the prior knowledge. However, in practice applications, it is difficult to obtain these knowledge. Thus, non-parametric Bayesian DL has recently received much attention of researchers due to its adaptability and effectiveness. Although many hierarchical priors have been used to promote the sparsity of the representation in non-parametric Bayesian DL, the problem of redundancy for the dictionary is still overlooked, which greatly decreases the performance of sparse coding. To address this problem, this paper presents a novel robust dictionary learning framework via Bayesian inference. In particular, we employ the orthogonality-promoting regularization to mitigate correlations among dictionary atoms. Such a regularization, encouraging the dictionary atoms to be close to being orthogonal, can alleviate overfitting to training data and improve the discrimination of the model. Moreover, we impose Scale mixture of the Vector variate Gaussian (SMVG) distribution on the noise to capture its structure. A Regularized Expectation Maximization Algorithm is developed to estimate the posterior distribution of the representation and dictionary with orthogonality-promoting regularization. Numerical results show that our method can learn the dictionary with an accuracy better than existing methods, especially when the number of training signals is limited.
APA, Harvard, Vancouver, ISO, and other styles
5

Xin, Jianguo, and Wei Cai. "A Well-Conditioned Hierarchical Basis for Triangular H(curl)-Conforming Elements." Communications in Computational Physics 9, no. 3 (2011): 780–806. http://dx.doi.org/10.4208/cicp.220310.030610s.

Full text
Abstract:
AbstractWe construct a well-conditioned hierarchical basis for triangular H(curl)-conforming elements with selected orthogonality. The basis functions are grouped into edge and interior functions, and the later is further grouped into normal and bubble functions. In our construction, the trace of the edge shape functions are orthonormal on the associated edge. The interior normal functions, which are perpendicular to an edge, and the bubble functions are both orthonormal among themselves over the reference element. The construction is made possible with classic orthogonal polynomials, viz., Legendre and Jacobi polynomials. For both the mass matrix and the quasi-stiffness matrix, better conditioning of the new basis is shown by a comparison with the basis previously proposed by Ainsworth and Coyle [Comput. Methods. Appl. Mech. Engrg., 190 (2001), 6709-6733].
APA, Harvard, Vancouver, ISO, and other styles
6

Harbrecht, Helmut, and Reinhold Schneider. "A Note on Multilevel Based Error Estimation." Computational Methods in Applied Mathematics 16, no. 3 (2016): 447–58. http://dx.doi.org/10.1515/cmam-2016-0013.

Full text
Abstract:
AbstractBy employing the infinite multilevel representation of the residual, we derive computable bounds to estimate the distance of finite element approximations to the solution of the Poisson equation. If the finite element approximation is a Galerkin solution, the derived error estimator coincides with the standard element and edge based estimator. If Galerkin orthogonality is not satisfied, then the discrete residual additionally appears in terms of the BPX preconditioner. As a by-product of the present analysis, conditions are derived such that the hierarchical error estimation is reliable and efficient.
APA, Harvard, Vancouver, ISO, and other styles
7

Djordjevi?, Miroslav, and Branislav M. Notaro? "Higher-order hierarchical basis functions with improved orthogonality properties for moment-method modeling of metallic and dielectric microwave structures." Microwave and Optical Technology Letters 37, no. 2 (2003): 83–88. http://dx.doi.org/10.1002/mop.10831.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Luyts, Martial, Geert Molenberghs, Geert Verbeke, et al. "A Weibull-count approach for handling under- and overdispersed longitudinal/clustered data structures." Statistical Modelling 19, no. 5 (2018): 569–89. http://dx.doi.org/10.1177/1471082x18789992.

Full text
Abstract:
A Weibull-model-based approach is examined to handle under- and overdispersed discrete data in a hierarchical framework. This methodology was first introduced by Nakagawa and Osaki (1975, IEEE Transactions on Reliability, 24, 300–301), and later examined for under- and overdispersion by Klakattawi et al. (2018, Entropy, 20, 142) in the univariate case. Extensions to hierarchical approaches with under- and overdispersion were left unnoted, even though they can be obtained in a simple manner. This is of particular interest when analysing clustered/longitudinal data structures, where the underlying correlation structure is often more complex compared to cross-sectional studies. In this article, a random-effects extension of the Weibull-count model is proposed and applied to two motivating case studies, originating from the clinical and sociological research fields. A goodness-of-fit evaluation of the model is provided through a comparison of some well-known count models, that is, the negative binomial, Conway–Maxwell–Poisson and double Poisson models. Empirical results show that the proposed extension flexibly fits the data, more specifically, for heavy-tailed, zero-inflated, overdispersed and correlated count data. Discrete left-skewed time-to-event data structures are also flexibly modelled using the approach, with the ability to derive direct interpretations on the median scale, provided the complementary log–log link is used. Finally, a large simulated set of data is created to examine other characteristics such as computational ease and orthogonality properties of the model, with the conclusion that the approach behaves best for highly overdispersed cases.
APA, Harvard, Vancouver, ISO, and other styles
9

Yuan, Jianying, Qiong Wang, and Bailin Li. "A Flexile and High Precision Calibration Method for Binocular Structured Light Scanning System." Scientific World Journal 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/753932.

Full text
Abstract:
3D (three-dimensional) structured light scanning system is widely used in the field of reverse engineering, quality inspection, and so forth. Camera calibration is the key for scanning precision. Currently, 2D (two-dimensional) or 3D fine processed calibration reference object is usually applied for high calibration precision, which is difficult to operate and the cost is high. In this paper, a novel calibration method is proposed with a scale bar and some artificial coded targets placed randomly in the measuring volume. The principle of the proposed method is based on hierarchical self-calibration and bundle adjustment. We get initial intrinsic parameters from images. Initial extrinsic parameters in projective space are estimated with the method of factorization and then upgraded to Euclidean space with orthogonality of rotation matrix and rank 3 of the absolute quadric as constraint. Last, all camera parameters are refined through bundle adjustment. Real experiments show that the proposed method is robust, and has the same precision level as the result using delicate artificial reference object, but the hardware cost is very low compared with the current calibration method used in 3D structured light scanning system.
APA, Harvard, Vancouver, ISO, and other styles
10

Lo, James Ting-Ho. "A Low-Order Model of Biological Neural Networks." Neural Computation 23, no. 10 (2011): 2626–82. http://dx.doi.org/10.1162/neco_a_00166.

Full text
Abstract:
A biologically plausible low-order model (LOM) of biological neural networks is proposed. LOM is a recurrent hierarchical network of models of dendritic nodes and trees; spiking and nonspiking neurons; unsupervised, supervised covariance and accumulative learning mechanisms; feedback connections; and a scheme for maximal generalization. These component models are motivated and necessitated by making LOM learn and retrieve easily without differentiation, optimization, or iteration, and cluster, detect, and recognize multiple and hierarchical corrupted, distorted, and occluded temporal and spatial patterns. Four models of dendritic nodes are given that are all described as a hyperbolic polynomial that acts like an exclusive-OR logic gate when the model dendritic nodes input two binary digits. A model dendritic encoder that is a network of model dendritic nodes encodes its inputs such that the resultant codes have an orthogonality property. Such codes are stored in synapses by unsupervised covariance learning, supervised covariance learning, or unsupervised accumulative learning, depending on the type of postsynaptic neuron. A masking matrix for a dendritic tree, whose upper part comprises model dendritic encoders, enables maximal generalization on corrupted, distorted, and occluded data. It is a mathematical organization and idealization of dendritic trees with overlapped and nested input vectors. A model nonspiking neuron transmits inhibitory graded signals to modulate its neighboring model spiking neurons. Model spiking neurons evaluate the subjective probability distribution (SPD) of the labels of the inputs to model dendritic encoders and generate spike trains with such SPDs as firing rates. Feedback connections from the same or higher layers with different numbers of unit-delay devices reflect different signal traveling times, enabling LOM to fully utilize temporally and spatially associated information. Biological plausibility of the component models is discussed. Numerical examples are given to demonstrate how LOM operates in retrieving, generalizing, and unsupervised and supervised learning.
APA, Harvard, Vancouver, ISO, and other styles
11

Czajko, Jakub. "Operational Restrictions on Morphing of Quasi-Geometric 4D Physical Spaces." International Letters of Chemistry, Physics and Astronomy 41 (November 2014): 45–72. http://dx.doi.org/10.18052/www.scipress.com/ilcpa.41.45.

Full text
Abstract:
Since a hierarchical notion of dimension is needed to ensure that a virtual, indirect orthogonality of dimensions is maintained in higher-dimensional spatial structures, a generic function for furling and unfurling of the fourth dimension in four-dimensional (4D) spatial structures is proposed. The furling allows three extra dimensions (above the regular three) in a 6D algebraic structure to be represented as a single fourth dimension and thus effectively facilitates morphing of the 4D spacetime into its dual 4D timespace. The effect of the furling of the extra three dimensions resembles that of compactification proposed by Kaluza-Klein theory yet without curling of the furled dimension. The furling supports reexpansion of stringy space into yet another dimension and so enables mapping of radius R (of a closed string being squeezed beyond its minimal radius) into an inverse radius 1/R, which was attributed to string duality, but is shown as due to duality of the 4D spatial structures of spacetime and timespace. Mathematically, it may appear as if further squeezing of the minimal string morphs it into an expanding pointletlike energy bubble so that the stringy spacetime reexpands in a new direction/dimension located within the bubbly dual timespace. So vibrating string is a mirror image of an energy bubblet, both of which do represent the same stringlet. By analogy, particle cast in spacetime could appear mathematically as having a mirror image (or its superpartner) cast in the dual timespace.
APA, Harvard, Vancouver, ISO, and other styles
12

Yeari, Menahem, and Morris Goldsmith. "Hierarchical Navigation of Visual Attention." Experimental Psychology 62, no. 6 (2015): 353–70. http://dx.doi.org/10.1027/1618-3169/a000306.

Full text
Abstract:
Abstract. This study explored the dynamics of attentional navigation between two hierarchically structured objects. Three experiments examined a Hierarchical Attentional Navigation (HAN) hypothesis, by which attentional navigation between two visual stimuli is constrained to follow the path linking the two stimuli in a hierarchical object-based representation. Presented with two adjacent compound-letter objects on each trial, participants successively identified the letter(s) at the specified hierarchical level (global or local) of the origin and destination object, respectively: local-local (Experiment 1), global-local (Experiment 2a), or local-global (Experiment 2b). The organizational complexity of the objects (2-level structure vs. 3-level structure) and their global size (large vs. small) were orthogonally manipulated. Results were generally consistent with the HAN hypothesis: overall response latency was positively related to the number of intervening levels of hierarchical object structure linking the two target levels. Hierarchical navigation was also suggested by the pattern of global size effects. The usefulness of the HAN framework for interpreting these and related findings in attention research is discussed.
APA, Harvard, Vancouver, ISO, and other styles
13

Šolín, Pavel, Tomáš Vejchodský, Martin Zítka, and Francisco Ávila. "Imposing orthogonality to hierarchic higher-order finite elements." Mathematics and Computers in Simulation 76, no. 1-3 (2007): 211–17. http://dx.doi.org/10.1016/j.matcom.2007.01.025.

Full text
APA, Harvard, Vancouver, ISO, and other styles
14

Zhang, Xiaoyan, Saifeng Zhang, Bohua Chen, et al. "Direct synthesis of large-scale hierarchical MoS2 films nanostructured with orthogonally oriented vertically and horizontally aligned layers." Nanoscale 8, no. 1 (2016): 431–39. http://dx.doi.org/10.1039/c5nr05938k.

Full text
Abstract:
Hierarchical MoS<sub>2</sub> nanofilms with orthogonally oriented vertical/horizontal layers are synthesized in an organic medium containing a small amount of water, and exhibit superior Q-switching behaviour in a fiber laser.
APA, Harvard, Vancouver, ISO, and other styles
15

Chang, Albert, Hsu-Ming Hsiao, Tsai-Hsiu Chen, Ming-Wen Chu, and Chia-Min Yang. "Hierarchical silicalite-1 octahedra comprising highly-branched orthogonally-stacked nanoplates as efficient catalysts for vapor-phase Beckmann rearrangement." Chemical Communications 52, no. 80 (2016): 11939–42. http://dx.doi.org/10.1039/c6cc05992a.

Full text
Abstract:
A structure-directing agent was designed to synthesize hierarchical silicalite-1 octahedra comprising highly-branched and orthogonally-stacked nanoplates that exhibited excellent and stable activity for Beckmann rearrangement of cyclic oximes and high lactam selectivity.
APA, Harvard, Vancouver, ISO, and other styles
16

Zhang, Xueyi, Dongxia Liu, Dandan Xu, et al. "Synthesis of Self-Pillared Zeolite Nanosheets by Repetitive Branching." Science 336, no. 6089 (2012): 1684–87. http://dx.doi.org/10.1126/science.1221111.

Full text
Abstract:
Hierarchical zeolites are a class of microporous catalysts and adsorbents that also contain mesopores, which allow for fast transport of bulky molecules and thereby enable improved performance in petrochemical and biomass processing. We used repetitive branching during one-step hydrothermal crystal growth to synthesize a new hierarchical zeolite made of orthogonally connected microporous nanosheets. The nanosheets are 2 nanometers thick and contain a network of 0.5-nanometer micropores. The house-of-cards arrangement of the nanosheets creates a permanent network of 2- to 7-nanometer mesopores, which, along with the high external surface area and reduced micropore diffusion length, account for higher reaction rates for bulky molecules relative to those of other mesoporous and conventional MFI zeolites.
APA, Harvard, Vancouver, ISO, and other styles
17

Chang, Albert, Tsung-Cheng Yang, Ming-Yi Chen, Hsu-Ming Hsiao, and Chia-Min Yang. "Hierarchical zeolites comprising orthogonally stacked bundles of zeolite nanosheets for catalytic and adsorption applications." Journal of Hazardous Materials 400 (December 2020): 123241. http://dx.doi.org/10.1016/j.jhazmat.2020.123241.

Full text
APA, Harvard, Vancouver, ISO, and other styles
18

Zhang, Xiaoyan, Saifeng Zhang, Bohua Chen, et al. "Correction: Direct synthesis of large-scale hierarchical MoS2films nanostructured with orthogonally oriented vertically and horizontally aligned layers." Nanoscale 8, no. 4 (2016): 2445. http://dx.doi.org/10.1039/c5nr90233a.

Full text
APA, Harvard, Vancouver, ISO, and other styles
19

Mehranfar, M., H. Arefi, and F. Alidoost. "A PROJECTION-BASED RECONSTRUCTION ALGORITHM FOR 3D MODELING OF BRIDGE STRUCTURES FROM DRONE-BASED POINT CLOUD." International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLVI-4/W1-2021 (September 3, 2021): 77–83. http://dx.doi.org/10.5194/isprs-archives-xlvi-4-w1-2021-77-2021.

Full text
Abstract:
Abstract. This paper presents a projection-based method for 3D bridge modeling using dense point clouds generated from drone-based images. The proposed workflow consists of hierarchical steps including point cloud segmentation, modeling of individual elements, and merging of individual models to generate the final 3D model. First, a fuzzy clustering algorithm including the height values and geometrical-spectral features is employed to segment the input point cloud into the main bridge elements. In the next step, a 2D projection-based reconstruction technique is developed to generate a 2D model for each element. Next, the 3D models are reconstructed by extruding the 2D models orthogonally to the projection plane. Finally, the reconstruction process is completed by merging individual 3D models and forming an integrated 3D model of the bridge structure in a CAD format. The results demonstrate the effectiveness of the proposed method to generate 3D models automatically with a median error of about 0.025 m between the elements’ dimensions in the reference and reconstructed models for two different bridge datasets.
APA, Harvard, Vancouver, ISO, and other styles
20

Gould, Stephen Jay. "Gulliver's further travels: the necessity and difficulty of a hierarchical theory of selection." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 353, no. 1366 (1998): 307–14. http://dx.doi.org/10.1098/rstb.1998.0211.

Full text
Abstract:
For principled and substantially philosophical reasons, based largely on his reform of natural history by inverting the Paleyan notion of overarching and purposeful beneficence in the construction of organisms, Darwin built his theory of selection at the single causal level of individual bodies engaged in unconscious (and metaphorical) struggle for their own reproductive success. But the central logic of the theory allows selection to work effectively on entities at several levels of a genealogical hierarchy, provided that they embody a set of requisite features for defining evolutionary individuality. Genes, cell lineages, demes, species, and clades, as well as Darwin's favoured organisms, embody these requisite features in enough cases to form important levels of selection in the history of life. R. A. Fisher explicitly recognized the unassailable logic of species selection, but denied that this real process could be important in evolution because, compared with the production of new organisms within a species, the origin of new species is so rare, and the number of species within most clades so low. I review this and other classical arguments against higher–level selection, and conclude (in the first part of this paper) that they are invalid in practice for interdemic selection, and false in principle for species selection. Punctuated equilibrium defines the individuality of species and refutes Fisher's classical argument based on cycle time. In the second part of the paper, I argue that we have failed to appreciate the range and power of selection at levels above and below the organismic because we falsely extrapolate the defining properties of organisms to these other levels (which are characterized by quite different distinctive features), and then regard the other levels as impotent because their effective individuals differ so much from organisms. We would better appreciate the power and generality of hierarchical models of selection if we grasped two key principles: first, that levels can interact in all modes (positively, negatively, and orthogonally), and not only in the negative style (with a higher level suppressing an opposing force of selection from the lower level) that, for heuristic and operational reasons, has received almost exclusive attention in the existing literature; and second, that each hierarchical level differs from all others in substantial and interesting ways, both in the style and frequency of patterns in change and causal modes.
APA, Harvard, Vancouver, ISO, and other styles
21

Donen, Tsuyoshi, Shingo Otsubo, Ryo Nishide, Ian Piumarta, and Hideyuki Takada. "Network traffic reduction mechanism for collaborative Web activities." International Journal of Web Information Systems 13, no. 2 (2017): 106–13. http://dx.doi.org/10.1108/ijwis-12-2016-0075.

Full text
Abstract:
Purpose The purpose of this study is to reduce internet traffic when performing collaborative Web search. Mobile terminals are now in widespread use and people are increasingly using them for collaborative Web search to achieve a common goal. When performing such searches, the authors want to reduce internet traffic as much as possible, for example, to avoid bandwidth throttling that occurs when data usage exceeds a certain quota. Design/methodology/approach To reduce internet traffic, the authors use a proxy system based on the peer cache mechanism. The proxy shares Web content stored on mobile terminals participating in an ad hoc Bluetooth network, focusing on content that is accessed multiple times from different terminals. Evaluation of the proxy’s effectiveness was measured using experiments designed to replicate realistic usage scenarios. Findings Experimental results show that the proxy reduces internet traffic by approximately 20 per cent when four people collaboratively search the Web to find good restaurants for a social event. Originality/value Unlike previous work on co-operative Web proxies, the authors study a form of collaborative Web caching between mobile devices within an ad hoc Bluetooth network created specifically for the purpose of sharing cached content, acting orthogonally to (and independently of) traditional hierarchical Web caching.
APA, Harvard, Vancouver, ISO, and other styles
22

Plaska, Samuel W., Chia-Jen Liu, Jung Soo Lim, et al. "Targeted RNAseq of Formalin-Fixed Paraffin-Embedded Tissue to Differentiate Among Benign and Malignant Adrenal Cortical Tumors." Hormone and Metabolic Research 52, no. 08 (2020): 607–13. http://dx.doi.org/10.1055/a-1212-8803.

Full text
Abstract:
AbstractLack of routine fresh or frozen tissue is a barrier to widespread transcriptomic analysis of adrenal cortical tumors and an impediment to translational research in endocrinology and endocrine oncology. Our group has previously pioneered the use of targeted amplicon-based next-generation sequencing for archival formalin-fixed paraffin-embedded (FFPE) adrenal tissue specimens to characterize the spectrum of somatic mutations in various forms of primary aldosteronism. Herein, we developed and validated a novel 194-amplicon targeted next-generation RNA sequencing (RNAseq) assay for transcriptomic analysis of adrenal tumors using clinical-grade FFPE specimens. Targeted RNAseq-derived expression values for 27 adrenal cortical tumors, including aldosterone-producing adenomas (APA; n=8), cortisol-producing adenomas (CPA; n=11), and adrenal cortical carcinomas (ACC; n=8), highlighted known differentially-expressed genes (DEGs; i. e., CYP11B2, IGF2, etc.) and tumor type-specific transcriptional modules (i. e., high cell cycle/proliferation transcript expression in ACC, etc.), and a subset of DEGs was validated orthogonally using quantitative reverse transcription PCR (qRT-PCR). Finally, unsupervised hierarchical clustering using a subset of high-confidence DEGs revealed three discrete clusters representing APA, CPA, and ACC tumors with corresponding unique gene expression signatures, suggesting potential clinical utility for a transcriptomic-based approach to tumor classification. Overall, these data support the use of targeted amplicon-based RNAseq for comprehensive transcriptomic profiling of archival FFPE adrenal tumor material and indicate that this approach may facilitate important translational research opportunities for the study of these tumors.
APA, Harvard, Vancouver, ISO, and other styles
23

Onder, Ozlem, Rui Wu, Maria Wysocka, et al. "Epiproteomic Landscape and Histone Code of Cutaneous T-Cell Lymphoma/Sézary Syndrome." Blood 132, Supplement 1 (2018): 780. http://dx.doi.org/10.1182/blood-2018-99-115347.

Full text
Abstract:
Abstract Background: The genetic basis and the genome-wide abnormalities underlying most forms of cancer are being comprehensively annotated in many human malignancies. However, the contribution of epigenetic aberrations, particularly the post-translational modifications (PTM) of histone tails has not been investigated. This is largely due to lack of approaches to comprehensively interrogate the status of the numerous PTMs that define histone marks which control gene expression and complex biologic processes such as cancer. Sézary Syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) characterized by poor outcomes and complex genetic alterations frequently targeting epigenetic regulators and chromatin remodelers. CTCLs represent the first FDA-approved disease for treatment using histone deacetylase inhibitors (HDACi) such as romidepsin, but the direct consequences of this treatment on histone PTMs remain unknown. Here we define the histone PTM signatures of CTCL/SS by using a novel unbiased strategy leveraging tandem mass spectrometry (MS/MS)-based quantitative proteomics to study the comprehensive combinatorial histone PTM code in a cohort of primary SS samples, and 4 CTCL/SS cell lines in comparison with normal reactive CD4+ T-lymphocytes from healthy individuals. Methods: CD4+ T-cells were isolated using CD4 immunomagnetic beads from PBMC's of healthy volunteers (n=8) or patients with diagnosed SS (n=20). CD4+ cells were frozen and subsequently analyzed in batches. The CTCL/SS-derived cell lines (HH and MJ, HuT78 and H9) were also analyzed each with three biological replicates. Histones were acid extracted from isolated nuclei. Total bulk histones were propionylated and trypsinized prior to MS analysis. Nano-scale liquid chromatography followed by -tandem mass spectrometry (nano LC-MS/MS) data acquisition was performed in an Orbitrap FusionTM TribridTM MS in technical triplicates for each sample with a data-independent acquisition (DIA)-method using a 50 m/z quadrupole-isolation windows that steps across the 200-1500 m/z ranges. Data analysis was performed using EpiProfile for single and combinatorial histone PTM analysis and quantification. Orthogonal validation for selected modifications was performed using western blotting and single-cell mass cytometry by time of flight (CyTOF) analysis. Results: Our quantitative epiproteomic strategy interrogated the relative ratios of a total of 228 histone PTM combinations, and 20 histone variants in a well-characterized cohort of SS patient samples, four CTCL cell lines and a cohort of normal primary CD4+ T-lymphocytes isolated from healthy individuals. With this approach, we were able to identify and quantify 23 unique histone peptides on histone H4, 105 on histone H3, 80 on histone H2A, 12 on histone H2B and 28 on histone H1 across every sample. Pearson correlation and principal component analysis of overall histone PTMs profiles across all samples provided accurate discrimination. We found a distinct pattern of histone PTMs in both SS patient samples and CTCL cell lines that were strikingly different from CD4+ T-cells obtained from healthy individuals. Notably, differences between cell lines and primary patient samples are more marked than those within individual SS primary patient samples, implying that cell lines may poorly recapitulate some aspects of in vivo biology. Unsupervised hierarchical clustering of the primary patient samples, cell lines and the normal CD4+ T-cells performed based on abundances of the identified histone PTMs revealed disease-specific ubiquitous marks as well as disease-specific unique marks for SS. Among the analyzed histone PTMs, H3K27ac, H3.3K27ac, H4K8ac, H4K20ac, H3K4me3, H3K18me1, H3K79me3 and H4K20me3 were distinct between healthy and CTCL CD4+ T-cells. Selected differential marks such as H4K20me3 were orthogonally corroborated by Western blotting and CyTOF mass cytometry analysis. Conclusions: For the first time, we have defined the histone code of CTCL/SS using global mass spectrometry based quantitative proteomics with high specificity and sensitivity. The results of our MS-based epiproteomic profiling revealed disease-specific histone PTM signatures and opportunities to exploit tractable changes induced by HDACi treatment as clinically actionable molecular biomarkers and therapeutic targets. Disclosures No relevant conflicts of interest to declare.
APA, Harvard, Vancouver, ISO, and other styles
24

Chen, Li, Xinglong Liu, Siyuan Zhang, Hong Yi, Yongmei Lu, and Pan Yao. "Efficacy-specific herbal group detection from traditional Chinese medicine prescriptions via hierarchical attentive neural network model." BMC Medical Informatics and Decision Making 21, no. 1 (2021). http://dx.doi.org/10.1186/s12911-021-01411-2.

Full text
Abstract:
Abstract Background Mining massive prescriptions in Traditional Chinese Medicine (TCM) accumulated in the lengthy period of several thousand years to discover essential herbal groups for distinct efficacies is of significance for TCM modernization, thus starting to draw attentions recently. However, most existing methods for the task treat herbs with different surface forms orthogonally and determine efficacy-specific herbal groups based on the raw frequencies an herbal group occur in a collection of prescriptions. Such methods entirely overlook the fact that prescriptions in TCM are formed empirically by different people at different historical stages, and thus full of herbs with different surface forms expressing the same material, or even noisy and redundant herbs. Methods We propose a two-stage approach for efficacy-specific herbal group detection from prescriptions in TCM. For the first stage we devise a hierarchical attentive neural network model to capture essential herbs in a prescription for its efficacy, where herbs are encoded with dense real-valued vectors learned automatically to identify their differences on the semantical level. For the second stage, frequent patterns are mined to discover essential herbal groups for an efficacy from distilled prescriptions obtained in the first stage. Results We verify the effectiveness of our proposed approach from two aspects, the first one is the ability of the hierarchical attentive neural network model to distill a prescription, and the second one is the accuracy in discovering efficacy-specific herbal groups. Conclusion The experimental results demonstrate that the hierarchical attentive neural network model is capable to capture herbs in a prescription essential to its efficacy, and the distilled prescriptions significantly could improve the performance of efficacy-specific herbal group detection.
APA, Harvard, Vancouver, ISO, and other styles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography