Lyapunov constraints and global asymptotic stabilization

In this paper, we develop a method for stabilizing underactuated mechanical systems by imposing kinematic constraints (more precisely Lyapunov constraints). If these constraints can be implemented by actuators, i.e., if there exists a related constraint force exerted by the actuators, then the existence of a Lyapunov function for the system under consideration is guaranteed. We establish necessary and sufficient conditions for the existence and uniqueness of constraint forces. These conditions give rise to a system of PDEs whose solution is the required Lyapunov function. To illustrate our results, we solve these PDEs for certain underactuated mechanical systems of interest such as the inertia wheel-pendulum, the inverted pendulum on a cart system and the ball and beam system

The Jacobi-Maupertuis Principle in Variational Integrators

In this paper, we develop a hybrid variational integrator based on the Jacobi-Maupertuis Principle of Least Action. The Jacobi-Maupertuis principle states that for a mechanical system with total energy E and potential energy V(q), the curve traced out by the system on a constant energy surface minimizes the action given by ∫√[2(E-V(q))] ds where ds is the line element on the constant energy surface with respect to the kinetic energy of the system. The key feature is that the principle is a parametrization independent geodesic problem. We show that this principle can be combined with traditional variational integrators and can be used to efficiently handle high velocity regions where small time steps would otherwise be required. This is done by switching between the Hamilton principle and the Jacobi-Maupertuis principle depending upon the kinetic energy of the system. We demonstrate our technique for the Kepler problem and discuss some ongoing and future work in studying the energy and momentum behavior of the resulting integrator

Multiple target detection using Bayesian learning

n this paper, we study multiple target detection using Bayesian learning. The main aim of the paper is to present a computationally efficient way to compute the belief map update exactly and efficiently using results from the theory of symmetric polynomials. In order to illustrate the idea, we consider a simple search scenario with multiple search agents and an unknown but fixed number of stationary targets in a given region that is divided into cells. To estimate the number of targets, a belief map for number of targets is also propagated. The belief map is updated using Bayes' theorem and an optimal reassignment of vehicles based on the values of the current belief map is adopted. Exact computation of the belief map update is combinatorial in nature and often an approximation is needed. We show that the Bayesian update can be exactly computed in an efficient manner using Newton's identities and the detection history in each cell

Improving quality for maternal care - a case study from Kerala, India.

BACKGROUND: The implementation of maternal health guidelines remains unsatisfactory, even for simple, well established interventions. In settings where most births occur in health facilities, as is the case in Kerala, India, preventing maternal mortality is linked to quality of care improvements. CONTEXT: Evidence-informed quality standards (QS), including quality statements and measurable structure and process indicators, are one innovative way of tackling the guideline implementation gap. Having adopted a zero tolerance policy to maternal deaths, the Government of Kerala worked in partnership with the Kerala Federation of Obstetricians & Gynaecologists (KFOG) and NICE International to select the clinical topic, develop and initiate implementation of the first clinical QS for reducing maternal mortality in the state. Description of practice: The NICE QS development framework was adapted to the Kerala context, with local ownership being a key principle. Locally generated evidence identified post-partum haemorrhage as the leading cause of maternal death, and as the key priority for the QS. A multidisciplinary group (including policy-makers, gynaecologists and obstetricians, nurses and administrators) was established. Multi-stakeholder workshops convened by the group ensured that the statements, derived from global and local guidelines, and their corresponding indicators were relevant and acceptable to clinicians and policy-makers in Kerala. Furthermore, it helped identify practical methods for implementing the standards and monitoring outcomes. LESSONS LEARNED: An independent evaluation of the project highlighted the equal importance of a strong evidence-base and an inclusive development process. There is no one-size-fits-all process for QS development; a principle-based approach might be a better guide for countries to adapt global evidence to their local context

RNA sequencing of cancer reveals novel splicing alterations

Breast cancer transcriptome acquires a myriad of regulation changes, and splicing is critical for the cell to “tailor-make” specific functional transcripts. We systematically revealed splicing signatures of the three most common types of breast tumors using RNA sequencing: TNBC, non-TNBC and HER2-positive breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We validated the presence of novel hybrid isoforms of critical molecules like CDK4, LARP1, ADD3, and PHLPP2. Our study provides the first comprehensive portrait of transcriptional and splicing signatures specific to breast cancer sub-types, as well as previously unknown transcripts that prompt the need for complete annotation of tissue and disease specific transcriptome

Regulation of rDNA Transcription by Proto-Oncogene PELP1

Proline-, glutamic acid-, and leucine-rich protein (PELP1) is a novel nuclear receptor coregulator with a multitude of functions. PELP1 serves as a scaffolding protein that couples various signaling complexes with nuclear receptors and participates as a transcriptional coregulator. Recent data suggest that PELP1 expression is deregulated in hormonal cancers, and that PELP1 functions as a proto-oncogene; however, the mechanism by which PELP1 promotes oncogenesis remains elusive.Using pharmacological inhibitors, confocal microscopy and biochemical assays, we demonstrated that PELP1 is localized in the nucleolus and that PELP1 is associated with the active ribosomal RNA transcription. Cell synchronization studies showed that PELP1 nucleolar localization varies and the greatest amount of nucleolar localization was observed during S and G2 phases. Using pharmacological compounds and CDK site mutants of PELP1, we found that CDK's activity plays an important role on PELP1 nucleolar localization. Depletion of PELP1 by siRNA decreased the expression of pre-rRNA. Reporter gene assays using ribosomal DNA (pHrD) luc-reporter revealed that PELP1WT but not PELP1MT enhanced the expression of reporter. Deletion of nucleolar domains abolished PELP1-mediated activation of the pHrD reporter. ChIP analysis revealed that PELP1 is recruited to the promoter regions of rDNA and is needed for optimal transcription of ribosomal RNA.Collectively, our results suggest that proto-oncogene PELP1 plays a vital role in rDNA transcription. PELP1 modulation of rRNA transcription, a key step in ribosomal biogenesis may have implications in PELP1-mediated oncogenic functions

The ​oestrogen receptor alpha-regulated lncRNA ​NEAT1 is a critical modulator of prostate cancer

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription

Withania somnifera root extract (LongeFera™) confers beneficial effects on health and lifespan of the model worm Caenorhabditis elegans

Background: Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans. Methods: The extract’s effect on worm lifespan and fertility was observed microscopically. Worm motility was quantified through an automated worm tracker. The metabolic activity of the worms was captured using the Alamar Blue® assay. Differential gene expression in extract-treated worms was revealed through a whole transcriptome approach. Results: Extract-exposed gnotobiotic worms, in the absence of any bacterial food, registered longer lifespan, higher fertility, better motility, and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering the remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt-1, dpy-4, dpy-13, and col-17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy-13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through co-occurrence analysis to have their homologous counterpart in humans. Conclusions: Our results validate the suitability of W. somnifera extract as a nutraceutical for healthy aging