Induction of epithelial to mesenchymal transition in PMC42-LA human breast carcinoma cells by carcinoma-associated fibroblast secreted factors

Background
Breast carcinoma is accompanied by changes in the acellular and cellular components of the microenvironment, the latter typified by a switch from fibroblasts to myofibroblasts.


Methods
We utilised conditioned media cultures, Western blot analysis and immunocytochemistry to investigate the differential effects of normal mammary fibroblasts (NMFs) and mammary cancer-associated fibroblasts (CAFs) on the phenotype and behaviour of PMC42-LA breast cancer cells. NMFs were obtained from a mammary gland at reduction mammoplasty, and CAFs from a mammary carcinoma after resection.


Results
We found greater expression of myofibroblastic markers in CAFs than in NMFs. Medium from both CAFs and NMFs induced novel expression of α-smooth muscle actin and cytokeratin-14 in PMC42-LA organoids. However, although conditioned media from NMFs resulted in distribution of vimentin-positive cells to the periphery of PMC42-LA organoids, this was not seen with CAF-conditioned medium. Upregulation of vimentin was accompanied by a mis-localization of E-cadherin, suggesting a loss of adhesive function. This was confirmed by visualizing the change in active β-catenin, localized to the cell junctions in control cells/cells in NMF-conditioned medium, to inactive β-catenin, localized to nuclei and cytoplasm in cells in CAF-conditioned medium.


Conclusion
We found no significant difference between the influences of NMFs and CAFs on PMC42-LA cell proliferation, viability, or apoptosis; significantly, we demonstrated a role for CAFs, but not for NMFs, in increasing the migratory ability of PMC42-LA cells. By concentrating NMF-conditioned media, we demonstrated the presence of factor(s) that induce epithelial-mesenchymal transition in NMF-conditioned media that are present at higher levels in CAF-conditioned media. Our in vitro results are consistent with observations in vivo showing that alterations in stroma influence the phenotype and behaviour of surrounding cells and provide evidence for a role for CAFs in stimulating cancer progression via an epithelial-mesenchymal transition. These findings have implications for our understanding of the roles of signalling between epithelial and stromal cells in the development and progression of mammary carcinoma.

A novel monotonic fixed-point algorithm for l1-regularized least square vector and matrix problem

Least square problem with l₁ regularization has been proposed as a promising method for sparse signal reconstruction (e.g., basis pursuit de-noising and compressed sensing) and feature selection (e.g., the Lasso algorithm) in signal processing, statistics, and related fields. These problems can be cast as l₁-regularized least-square program (LSP). In this paper, we propose a novel monotonic fixed point method to solve large-scale l₁-regularized LSP. And we also prove the stability and convergence of the proposed method. Furthermore we generalize this method to least square matrix problem and apply it in nonnegative matrix factorization (NMF). The method is illustrated on sparse signal reconstruction, partner recognition and blind source separation problems, and the method tends to convergent faster and sparser than other l₁-regularized algorithms.

Blind Source Separation by Nonnegative Matrix Factorization with Minimum-Volume Constraint

Recently, nonnegative matrix factorization (NMF) attracts more and more attentions for the promising of wide applications. A problem that still remains is that, however, the factors resulted from it may not necessarily be realistically interpretable. Some constraints are usually added to the standard NMF to generate such interpretive results. In this paper, a minimum-volume constrained NMF is proposed and an efficient multiplicative update algorithm is developed based on the natural gradient optimization. The proposed method can be applied to the blind source separation (BSS) problem, a hot topic with many potential applications, especially if the sources are mutually dependent. Simulation results of BSS for images show the superiority of the proposed method.

Nonnegative Matrix Factorization Applied to Nonlinear Speech and Image Cryptosystems

Nonnegative matrix factorization (NMF) is widely used in signal separation and image compression. Motivated by its successful applications, we propose a new cryptosystem based on NMF, where the nonlinear mixing (NLM) model with a strong noise is introduced for encryption and NMF is used for decryption. The security of the cryptosystem relies on following two facts: 1) the constructed multivariable nonlinear function is not invertible; 2) the process of NMF is unilateral, if the inverse matrix of the constructed linear mixing matrix is not nonnegative. Comparing with Lin's method (2006) that is a theoretical scheme using one-time padding in the cryptosystem, our cipher can be used repeatedly for the practical request, i.e., multitme padding is used in our cryptosystem. Also, there is no restriction on statistical characteristics of the ciphers and the plaintexts. Thus, more signals can be processed (successfully encrypted and decrypted), no matter they are correlative, sparse, or Gaussian. Furthermore, instead of the number of zero-crossing-based method that is often unstable in encryption and decryption, an improved method based on the kurtosis of the signals is introduced to solve permutation ambiguities in waveform reconstruction. Simulations are given to illustrate security and availability of our cryptosystem.

Blind Spectral Unmixing Based on Sparse Nonnegative Matrix Factorization

Nonnegative matrix factorization (NMF) is a widely used method for blind spectral unmixing (SU), which aims at obtaining the endmembers and corresponding fractional abundances, knowing only the collected mixing spectral data. It is noted that the abundance may be sparse (i.e., the endmembers may be with sparse distributions) and sparse NMF tends to lead to a unique result, so it is intuitive and meaningful to constrain NMF with sparseness for solving SU. However, due to the abundance sum-to-one constraint in SU, the traditional sparseness measured by L0/L1-norm is not an effective constraint any more. A novel measure (termed as S-measure) of sparseness using higher order norms of the signal vector is proposed in this paper. It features the physical significance. By using the S-measure constraint (SMC), a gradient-based sparse NMF algorithm (termed as NMF-SMC) is proposed for solving the SU problem, where the learning rate is adaptively selected, and the endmembers and abundances are simultaneously estimated. In the proposed NMF-SMC, there is no pure index assumption and no need to know the exact sparseness degree of the abundance in prior. Yet, it does not require the preprocessing of dimension reduction in which some useful information may be lost. Experiments based on synthetic mixtures and real-world images collected by AVIRIS and HYDICE sensors are performed to evaluate the validity of the proposed method.

Online blind source separation using incremental nonnegative matrix factorization with volume constraint

Online blind source separation (BSS) is proposed to overcome the high computational cost problem, which limits the practical applications of traditional batch BSS algorithms. However, the existing online BSS methods are mainly used to separate independent or uncorrelated sources. Recently, nonnegative matrix factorization (NMF) shows great potential to separate the correlative sources, where some constraints are often imposed to overcome the non-uniqueness of the factorization. In this paper, an incremental NMF with volume constraint is derived and utilized for solving online BSS. The volume constraint to the mixing matrix enhances the identifiability of the sources, while the incremental learning mode reduces the computational cost. The proposed method takes advantage of the natural gradient based multiplication updating rule, and it performs especially well in the recovery of dependent sources. Simulations in BSS for dual-energy X-ray images, online encrypted speech signals, and high correlative face images show the validity of the proposed method.

Nonparametric discovery of learning patterns and autism subgroups from therapeutic data

Autism Spectrum Disorder (ASD) is growing at a staggering rate, but, little is known about the cause of this condition. Inferring learning patterns from therapeutic performance data, and subsequently clustering ASD children into subgroups, is important to understand this domain, and more importantly to inform evidence-based intervention. However, this data-driven task was difficult in the past due to insufficiency of data to perform reliable analysis. For the first time, using data from a recent application for early intervention in autism (TOBY Play pad), whose download count is now exceeding 4500, we present in this paper the automatic discovery of learning patterns across 32 skills in sensory, imitation and language. We use unsupervised learning methods for this task, but a notorious problem with existing methods is the correct specification of number of patterns in advance, which in our case is even more difficult due to complexity of the data. To this end, we appeal to recent Bayesian nonparametric methods, in particular the use of Bayesian Nonparametric Factor Analysis. This model uses Indian Buffet Process (IBP) as prior on a binary matrix of infinite columns to allocate groups of intervention skills to children. The optimal number of learning patterns as well as subgroup assignments are inferred automatically from data. Our experimental results follow an exploratory approach, present different newly discovered learning patterns. To provide quantitative results, we also report the clustering evaluation against K-means and Nonnegative matrix factorization (NMF). In addition to the novelty of this new problem, we were able to demonstrate the suitability of Bayesian nonparametric models over parametric rivals.

Spectral unmixing based on nonnegative matrix factorization with local smoothness constraint

Spectral unmixing (SU) is an emerging problem in the remote sensing image processing. Since both the endmember signatures and their abundances have nonnegative values, it is a natural choice to employ the attractive nonnegative matrix factorization (NMF) methods to solve this problem. Motivated by that the abundances are sparse, the NMF with local smoothness constraint (NMF-LSC) is proposed in this paper. In the proposed method, the smoothness constraint is utilized to impose the sparseness, instead of the traditional L1-norm which is restricted by the underlying column-sum-to-one requirement of the to the abundance matrix. Simulations show the advantages of our algorithm over the compared methods.

A fast non-smooth nonnegative matrix factorization for learning sparse representation

Nonnegative matrix factorization (NMF) is a hot topic in machine learning and data processing. Recently, a constrained version, non-smooth NMF (NsNMF), shows a great potential in learning meaningful sparse representation of the observed data. However, it suffers from a slow linear convergence rate, discouraging its applications to large-scale data representation. In this paper, a fast NsNMF (FNsNMF) algorithm is proposed to speed up NsNMF. In the proposed method, it first shows that the cost function of the derived sub-problem is convex and the corresponding gradient is Lipschitz continuous. Then, the optimization to this function is replaced by solving a proximal function, which is designed based on the Lipschitz constant and can be solved through utilizing a constructed fast convergent sequence. Due to the usage of the proximal function and its efficient optimization, our method can achieve a nonlinear convergence rate, much faster than NsNMF. Simulations in both computer generated data and the real-world data show the advantages of our algorithm over the compared methods.