Modulator-Dependent RBPs Changes Alternative Splicing Outcomes in Kidney Cancer

Alternative splicing alterations can contribute to human disease. The ability of an RNA-binding protein to regulate alternative splicing outcomes can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we use a computational framework to investigate the roles of certain genes, termed modulators, on changing RBPs’ effect on splicing regulation. A total of 1,040,254 modulator-mediated RBP-splicing interactions were identified, including 137 RBPs, 4,309 splicing events and 2,905 modulator candidates from TCGA-KIRC RNA sequencing data. Modulators function categories were defined according to the correlation changes between RBPs expression and their targets splicing outcomes. QKI, as one of the RBPs influencing the most splicing events, attracted our attention in this study: 2,014 changing triplets were identified, including 1,101 modulators and 187 splicing events. Pathway enrichment analysis showed that QKI splicing targets were enriched in tight junction pathway, endocytosis and MAPK signaling pathways, all of which are highly associated with cancer development and progression. This is the first instance of a comprehensive study on how alternative splicing outcomes changes are associated with different expression level of certain proteins, even though they were regulated by the same RBP. Our work may provide a novel view on understanding alternative splicing mechanisms in kidney cancer

Cosmological diagrammatic rules

A simple set of diagrammatic rules is formulated for perturbative evaluation of ``in-in" correlators, as is needed in cosmology and other nonequilibrium problems. These rules are both intuitive, and efficient for calculational purposes.Comment: 7 pages, 3 figure

The JAK/STAT Pathway in Model Organisms Emerging Roles in Cell Movement

AbstractThe JAK/STAT pathway was originally identified in mammals. Studies of this pathway in the mouse have revealed that JAK/STAT signaling plays a central role during hematopoeisis and other developmental processes. The role of JAK/STAT signaling in blood appears to be conserved throughout evolution, as it is also required during fly hematopoeisis. Studies in Dictyostelium, Drosophila, and zebrafish have shown that the JAK/STAT pathway is also required in an unusually broad set of developmental decisions, including cell proliferation, cell fate determination, cell migration, planar polarity, convergent extension, and immunity. There is increasing evidence that the versatility of this pathway relies on its cooperation with other signal transduction pathways. In this review, we discuss the components of the JAK/STAT pathway in model organisms and what is known about its requirement in cellular and developmental processes. In particular, we emphasize recent insights into the role that this pathway plays in the control of cell movement

Control theoretically explainable application of autoencoder methods to fault detection in nonlinear dynamic systems

This paper is dedicated to control theoretically explainable application of autoencoders to optimal fault detection in nonlinear dynamic systems. Autoencoder-based learning is a standard method of machine learning technique and widely applied for fault (anomaly) detection and classification. In the context of representation learning, the so-called latent (hidden) variable plays an important role towards an optimal fault detection. In ideal case, the latent variable should be a minimal sufficient statistic. The existing autoencoder-based fault detection schemes are mainly application-oriented, and few efforts have been devoted to optimal autoencoder-based fault detection and explainable applications. The main objective of our work is to establish a framework for learning autoencoder-based optimal fault detection in nonlinear dynamic systems. To this aim, a process model form for dynamic systems is firstly introduced with the aid of control and system theory, which also leads to a clear system interpretation of the latent variable. The major efforts are devoted to the development of a control theoretical solution to the optimal fault detection problem, in which an analog concept to minimal sufficient statistic, the so-called lossless information compression, is introduced for dynamic systems and fault detection specifications. In particular, the existence conditions for such a latent variable are derived, based on which a loss function and further a learning algorithm are developed. This learning algorithm enables optimally training of autoencoders to achieve an optimal fault detection in nonlinear dynamic systems. A case study on three-tank system is given at the end of this paper to illustrate the capability of the proposed autoencoder-based fault detection and to explain the essential role of the latent variable in the proposed fault detection system

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM–TGF-β1 nexus plays in fetal-type scarless skin repair. © 2016 American Society for Investigative Patholog

Highly robust model of transcription regulator activity predicts breast cancer overall survival

Background: While several multigene signatures are available for predicting breast cancer prognosis, particularly in early stage disease, effective molecular indicators are needed, especially for triple-negative carcinomas, to improve treatments and predict diagnostic outcomes. The objective of this study was to identify transcriptional regulatory networks to better understand mechanisms giving rise to breast cancer development and to incorporate this information into a model for predicting clinical outcomes. Methods: Gene expression profiles from 1097 breast cancer patients were retrieved from The Cancer Genome Atlas (TCGA). Breast cancer-specific transcription regulatory information was identified by considering the binding site information from ENCODE and the top co-expressed targets in TCGA using a nonlinear approach. We then used this information to predict breast cancer patient survival outcome. Result: We built a multiple regulator-based prediction model for breast cancer. This model was validated in more than 5000 breast cancer patients from the Gene Expression Omnibus (GEO) databases. We demonstrated our regulator model was significantly associated with clinical stage and that cell cycle and DNA replication related pathways were significantly enriched in high regulator risk patients. Conclusion: Our findings demonstrate that transcriptional regulator activities can predict patient survival. This finding provides additional biological insights into the mechanisms of breast cancer progression

DBI Inflation in the Tip Region of a Warped Throat

Previous work on DBI inflation, which achieves inflation through the motion of a $D3$ brane as it moves through a warped throat compactification, has focused on the region far from the tip of the throat. Since reheating and other observable effects typically occur near the tip, a more detailed study of this region is required. To investigate these effects we consider a generalized warp throat where the warp factor becomes nearly constant near the tip. We find that it is possible to obtain 60 or more e-folds in the constant region, however large non-gaussianities are typically produced due to the small sound speed of fluctuations. For a particular well-studied throat, the Klebanov-Strassler solution, we find that inflation near the tip may be generic and it is difficult to satisfy current bounds on non-gaussianity, but other throat solutions may evade these difficulties.Comment: 26 pages, 1 figure. v1. references added, typos corrected v2. clarifications mad

Mechanisms of Family Impact on African American Adolescents\u27 HIV-Related Behavior

A longitudinal model that tested mediating pathways between protective family processes and HIV-related behavior was evaluated with 195 African American youth. Three waves of data were collected when the youth were 13, 15, and 19 years old. Evidence of mediation and temporal priority were assessed for 3 constructs: academic engagement, evaluations of prototypical risk-taking peers, and affiliations with risk-promoting peers. Structural equation modeling indicated that protective family processes assessed during early adolescence were associated with HIV-related behavior during emerging adulthood and that academic engagement, evaluations of prototypical risk-taking peers, and affiliations with risk-promoting peers accounted for this association. Evidence of a specific pathway emerged: protective family processes→academic engagement→negative evaluations of prototypical risk-taking peers→affiliations with risk-promoting peers→HIV-related behavior. Academic engagement also was a direct predictor of HIV-related risk behavior

Geometrical Tachyon Kinks and NS5 Branes

We further investigate the $NS$5 ring background using the tachyon map. Mapping the radion fields to the rolling tachyon helps to explain the motion of a probe $Dp$-brane in this background. It turns out that the radion field becomes tachyonic when the brane is confined to one dimensional motion inside the ring. We find explicit solutions for the geometrical tachyon field that describe stable kink solutions which are similar to those of the open string tachyon. Interestingly in the case of the geometric tachyon, the dynamics is controlled by a cosine potential. In addition, we couple a constant electric field to the probe-brane, but find that the only stable kink solutions occur when there is zero electric field or a critical field value. We also investigate the behaviour of Non-BPS branes in this background, and find that the end state of any probe brane is that of tachyonic matter 'trapped' around the interior of the ring. We conclude by considering compactification of the ring solution in one of the transverse directions.Comment: Latex, 24 pages, 1 eps fig; clarifying comments added to Section 2; typos correcte