Bmi1 regulates self-renewal and epithelial to mesenchymal transition in breast cancer cells through Nanog

Background: The Bmi1 polycomb ring finger oncogene, a transcriptional repressor belonging to the Polycomb group of proteins plays an important role in the regulation of stem cell self-renewal and is elevated in several cancers. In the current study, we have explored the role of Bmi1 in regulating the stemness and drug resistance of breast cancer cells. Methods: Using real time PCR and immunohistochemistry primary breast tissues were analyzed. Retro-and lentiviruses were utilized to overexpress and knockdown Bmi1, RT-PCR and Western blot was performed to evaluate mRNA and protein expression. Stemness properties were analyzed by flow cytometry and sphere-formation and tumor formation was determined by mouse xenograft experiments. Dual luciferase assay was employed to assess promoter activity and MTT assay was used to analyze drug response. Results: We found Bmi1 overexpression in 64% of grade III invasive ductal breast adenocarcinomas compared to normal breast tissues. Bmi1 overexpression in immortalized and transformed breast epithelial cells increased their sphere-forming efficiency, induced epithelial to mesenchymal transition ( EMT) with an increase in the expression of stemness-related genes. Knockdown of Bmi1 in tumorigenic breast cells induced epithelial morphology, reduced expression of stemness-related genes, decreased the IC50 values of doxorubicin and abrogated tumor-formation. Bmi1-high tumors showed elevated Nanog expression whereas the tumors with lower Bmi1 showed reduced Nanog levels. Overexpression of Bmi1 increased Nanog levels whereas knockdown of Bmi1 reduced its expression. Dual luciferase promoter-reporter assay revealed Bmi1 positively regulated the Nanog and NF kappa B promoter activity. RT-PCR analysis showed that Bmi1 overexpression activated the NF kappa B pathway whereas Bmi1 knockdown reduced the expression of NF kappa B target genes, suggesting that Bmi1 might regulate Nanog expression through the NF kappa B pathway. Conclusions: Our study showed that Bmi1 is overexpressed in several high-grade, invasive ductal breast adenocarcinomas, thus supporting its role as a prognostic marker. While Bmi1 overexpression increased self-renewal and promoted EMT, its knockdown reversed EMT, reduced stemness, and rendered cells drug sensitive, thus highlighting a crucial role for Bmi1 in regulating the stemness and drug response of breast cancer cells. Bmi1 may control self-renewal through the regulation of Nanog expression via the NF kappa B pathway.

Contributions to unsupervised and supervised learning with applications in digital image processing

311 p. : il.

Control of gene expression by modulated self-assembly

Numerous transcription factors self-assemble into different order oligomeric species in a way that is actively regulated by the cell. Until now, no general functional role has been identified for this widespread process. Here, we capture the effects of modulated self-assembly in gene expression with a novel quantitative framework. We show that this mechanism provides precision and flexibility, two seemingly antagonistic properties, to the sensing of diverse cellular signals by systems that share common elements present in transcription factors like p53, NF-kappa B, STATs, Oct and RXR. Applied to the nuclear hormone receptor RXR, this framework accurately reproduces a broad range of classical, previously unexplained, sets of gene expression data and corroborates the existence of a precise functional regime with flexible properties that can be controlled both at a genome-wide scale and at the individual promoter level.

Learning to perceive in the sensor motor approach: Piaget's theory of equilibration interpreted dynamically

Learning to perceive is faced with a classical paradox: if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the "laws" of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget's theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget's theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level.

Optical learning in a smart spatial light modulator

A synaptic plane rendered by an array of smart pixels was described regarding its application as a complementary component for neural network implementation. The smart spatial light modulator featured auto-modification abilities. Thus, an optical system incorporating this device can show self-reliant optical learning. Furthermore, the optical system design, in the area of its optical interconnection scheme, is highly flexible since the independent weight-plane pixels eliminated the difficulty between weight update calculation and weight representation.

Dissecting Signaling Pathways That Govern Self-renewal of Rabbit Embryonic Stem Cells

The pluripotency and self-renewal of embryonic stem cells (ESC) are regulated by a variety of cytokines/growth factors with some species differences. We reported previously that rabbit ESC (rESC) are more similar to primate ESC than to mouse ESC. However,

Reinforcement learning with reference tracking control in continuous state spaces

The contribution described in this paper is an algorithm for learning nonlinear, reference tracking, control policies given no prior knowledge of the dynamical system and limited interaction with the system through the learning process. Concepts from the field of reinforcement learning, Bayesian statistics and classical control have been brought together in the formulation of this algorithm which can be viewed as a form of indirect self tuning regulator. On the task of reference tracking using a simulated inverted pendulum it was shown to yield generally improved performance on the best controller derived from the standard linear quadratic method using only 30 s of total interaction with the system. Finally, the algorithm was shown to work on the simulated double pendulum proving its ability to solve nontrivial control tasks. © 2011 IEEE.

Self-organization of spinal reflexes involving homonymous, antagonist and synergistic interactions

Recent results in spinal research are challenging the historical view that the spinal reflexes are mostly hardwired and fixed behaviours. In previous work we have shown that three of the simplest spinal reflexes could be self-organised in an agonist-antagonist pair of muscles. The simplicity of these reflexes is given from the fact that they entail at most one interneuron mediating the connectivity between afferent inputs and efferent outputs. These reflexes are: the Myotatic, the Reciprocal Inibition and the Reverse Myotatic reflexes. In this paper we apply our framework to a simulated 2D leg model actuated by six muscles (mono- and bi-articular). Our results show that the framework is successful in learning most of the spinal reflex circuitry as well as the corresponding behaviour in the more complicated muscle arrangement. © 2012 Springer-Verlag.

Learning legged locomotion

Legged locomotion of biological systems can be viewed as a self-organizing process of highly complex system-environment interactions. Walking behavior is, for example, generated from the interactions between many mechanical components (e.g., physical interactions between feet and ground, skeletons and muscle-tendon systems), and distributed informational processes (e.g., sensory information processing, sensory-motor control in central nervous system, and reflexes) [21]. An interesting aspect of legged locomotion study lies in the fact that there are multiple levels of self-organization processes (at the levels of mechanical dynamics, sensory-motor control, and learning). Previously, the self-organization of mechanical dynamics was nicely demonstrated by the so-called Passive Dynamic Walkers (PDWs; [18]). The PDW is a purely mechanical structure consisting of body, thigh, and shank limbs that are connected by passive joints. When placed on a shallow slope, it exhibits natural bipedal walking dynamics by converting potential to kinetic energy without any actuation. An important contribution of these case studies is that, if designed properly, mechanical dynamics can generate a relatively complex locomotion dynamics, on the one hand, and the mechanical dynamics induces self-stability against small disturbances without any explicit control of motors, on the other. The basic principle of the mechanical self-stability appears to be fairly general that there are several different physics models that exhibit similar characteristics in different kinds of behaviors (e.g., hopping, running, and swimming; [2, 4, 9, 16, 19]), and a number of robotic platforms have been developed based on them [1, 8, 13, 22]. © 2009 Springer London.

Learning object segmentation from video data

This memo describes the initial results of a project to create a self-supervised algorithm for learning object segmentation from video data. Developmental psychology and computational experience have demonstrated that the motion segmentation of objects is a simpler, more primitive process than the detection of object boundaries by static image cues. Therefore, motion information provides a plausible supervision signal for learning the static boundary detection task and for evaluating performance on a test set. A video camera and previously developed background subtraction algorithms can automatically produce a large database of motion-segmented images for minimal cost. The purpose of this work is to use the information in such a database to learn how to detect the object boundaries in novel images using static information, such as color, texture, and shape. This work was funded in part by the Office of Naval Research contract #N00014-00-1-0298, in part by the Singapore-MIT Alliance agreement of 11/6/98, and in part by a National Science Foundation Graduate Student Fellowship.

Training for professional librarians in Slovakia by distance-learning methods: an overview of the PROLIB and EDULIB projects

Tedd, L.A., Dahl, K., Francis, S.,Tet?evov?, M.& ?ihlavn?kov?, E.(2002).Training for professional librarians in Slovakia by distance-learning methods: an overview of the PROLIB and EDULIB projects. Library Hi Tech, 20(3), 340-351. Sponsorship: European Union and the Open Society Institute

Error-driven active learning in growing radial basis function networks for early robot learning

Q. Meng and M.H. Lee, 'Error-driven active learning in growing radial basis function networks for early robot learning', 2006 IEEE International Conference on Robotics and Automation (IEEE ICRA 2006), 2984-90, Orlando, Florida, USA.

Construction of Robot Intra-modal and Inter-modal Coordination Skills by Developmental Learning

Q. Meng and M. H. Lee, 'Construction of Robot Intra-modal and Inter-modal Coordination Skills by Developmental Learning', Journal of Intelligent and Robotic Systems, 48(1), pp 97-114, 2007.

Learning from triads: training undergraduates in counselling skills

Background: Research has shown that counselling skills training in undergraduate programmes is effective. However, there is potential that premature intimacy and disclosures during triad work may impact on relationships which must be maintained out-with the counselling component of the course. Little research has examined individual pedagogical practices within training. Aim: The aim of this research was to explore the experience of the practical skills training component of a counselling course for a cohort of undergraduate students, and the impact of this learning experience. The objective being an evaluation of the use of this approach for this group and of the impact of personal sharing within cohorts of undergraduates. Method: Semi-structured interviews focusing on the experience of skills training and self-disclosure during training were carried out on 12 undergraduates taking counselling skills modules as part of their BSc Psychology and Counselling degree. Thematic analysis was carried out on the interview transcripts. Results: As a result of engagement in skills training and acting as ‘clients’ for one another, individuals perceived the formation of a positive group identity with implicit ‘rules’, but also an impact of training on relationships within the group which relied on the ability to maintain boundaries and personal identities with peers, and this influenced the learning experience. The ability to manage their engagement on the programme was dependent on ongoing support and guidance from tutors. Discussion: While this pedagogical approach appears appropriate for facilitating learning and potentially provides a rich learning journey for undergraduate students, tutors must act proactively to ensure a safe learning environment.

Making Sadza with Deaf Zimbabwean Women: A Missiological Reorientation of Practical Theological Method toward Self-Theologizing Agency among Subaltern Communities

Missiological calls for self-theologizing among faith communities present the field of practical theology with a challenge to develop methodological approaches that address the complexities of cross-cultural, practical theological research. Although a variety of approaches can be considered critical correlative practical theology, existing methods are often built on assumptions that limit their use in subaltern contexts. This study seeks to address these concerns by analyzing existing theological methodologies with sustained attention to a community of Deaf Zimbabwean women struggling to develop their own agency in relation to child rearing practices. This dilemma serves as an entry point to an examination of the limitations of existing methodologies and a constructive, interdisciplinary theological exploration. The use of theological modeling methodology employs my experience of learning to cook sadza, a staple dish of Zimbabwe, as a guide for analyzing and reorienting practical theological methodology. The study explores a variety of theological approaches from practical theology, mission oriented theologians, theology among Deaf communities, and African women’s theology in relationship to the challenges presented by subaltern communities such as Deaf Zimbabwean women. Analysis reveals that although there is much to commend in these existing methodologies, questions about who does the critical correlation, whose interests are guiding the study, and consideration for the cross-cultural and power dynamics between researchers and faith communities remain problematic for developing self-theologizing agency. Rather than frame a comprehensive methodology, this study proposes three attitudes and guideposts to reorient practical theological researchers who wish to engender self-theologizing agency in subaltern communities. The creativity of enacted theology, the humility of using checks and balances in research methods, and the grace of finding strategies to build bridges of commonality and community offer ways to reorient practical theological methodologies toward the development of self-theologizing agency among subaltern people. This study concludes with discussion of how these guideposts can not only benefit particular work with a community of Deaf Zimbabwean women, but also provide research and theological reflection in other subaltern contexts.