The Sonic Hedgehog Pathway Stimulates Prostate Tumor Growth by Paracrine Signaling and Recaptures Embryonic Gene Expression in Tumor Myofibroblasts

The Hedgehog (Hh) pathway contributes to prostate cancer growth and progression. The presence of robust Shh expression in both normal prostate and localized cancer challenged us to explain the unique growth promoting effect in cancer. We show here that paracrine Hh signaling exerts a non-cell autonomous effect on xenograft tumor growth and that Hh pathway activation in myofibroblasts alone is sufficient to stimulate tumor growth. Nine genes regulated by Hh in the mesenchyme of the developing prostate were found to be regulated in the stroma of Hh over-expressing xenograft tumors. Correlation analysis of gene expression in matched specimens of benign and malignant human prostate tissue revealed a partial 5 gene fingerprint of Hh-regulated expression in stroma of all cancers and the complete 9 gene fingerprint in the subset of tumors exhibiting a reactive stroma. No expression fingerprint was observed in benign tissues. We conclude that changes in the prostate stroma due to association with cancer result in an altered transcriptional response to Hh that mimics the growth promoting actions of the fetal mesenchyme. Patients with an abundance of myofibroblasts in biopsy tissue may comprise a sub-group that will exhibit a particularly good response to anti-Hedgehog therapy

Regulation of Phosphatase Homologue of Tensin Protein Expression by Bone Morphogenetic Proteins in Prostate Epithelial Cells

Phosphatase homologue of tensin (PTEN) is the key endogenous inhibitor of phosphoinositide signaling and is the most commonly mutated gene in human prostate cancer. The bone morphogenetic proteins (BMPs) are secreted developmental signaling molecules known to promote differentiation in the prostate. BMP ligands have been shown to inhibit prostate cancer cell line proliferation and tumor growth and expression of BMPs, BMP ligands, receptors and signaling effectors are diminished in prostate cancer. A previous report in the colon led us to investigate the potential mechanistic relationship between PTEN and BMP signaling in prostate epithelial cells. We show here that BPM signaling positively regulates PTEN in normal and malignant prostate cells by increasing mRNA expression and stabilizing PTEN protein. Further, we show that BMP attenuates prostate cell growth at least in part through its effects on PTEN. BMP treatment did not further inhibit the growth of conditional PTEN over-expressing cells, and stable shRNA-PTEN transfectants were refractory to BMP-mediated growth inhibition. Loss-of-function of PTEN in prostate cancer cells may render them insensitive to the normal differentiating and growth-inhibitory effects of BMPs. These data are the first to identify a mechanistic linkage between BMP signaling and PTEN in normal prostate epithelial cells and to suggest coordinate dysregulation in prostate cancer

Development and Validation of the Single Item Trait Empathy Scale (SITES)

Empathy involves feeling compassion for others and imagining how they feel. In this article, we develop and validate the Single Item Trait Empathy Scale (SITES), which contains only one item that takes seconds to complete. In seven studies (N = 5724), the SITES was found to be both reliable and valid. It correlated in expected ways with a wide variety of intrapersonal outcomes. For example, it is negatively correlated with narcissism, depression, anxiety, and alexithymia. In contrast, it is positively correlated with other measures of empathy, self-esteem, subjective well-being, and agreeableness. The SITES also correlates with a wide variety of interpersonal outcomes, especially compassion for others and helping others. The SITES is recommended in situations when time or question quantity is constrained

Development and Validation of the Single Item Narcissism Scale (SINS)

Main Objectives: The narcissistic personality is characterized by grandiosity, entitlement, and low empathy. This paper describes the development and validation of the Single Item Narcissism Scale (SINS). Although the use of longer instruments is superior in most circumstances, we recommend the SINS in some circumstances (e.g. under serious time constraints, online studies). Methods: In 11 independent studies (total N = 2,250), we demonstrate the SINS\u27 psychometric properties. Results: The SINS is significantly correlated with longer narcissism scales, but uncorrelated with self-esteem. It also has high test-retest reliability. We validate the SINS in a variety of samples (e.g., undergraduates, nationally representative adults), intrapersonal correlates (e.g., positive affect, depression), and interpersonal correlates (e.g., aggression, relationship quality, prosocial behavior). The SINS taps into the more fragile and less desirable components of narcissism. Significance: The SINS can be a useful tool for researchers, especially when it is important to measure narcissism with constraints preventing the use of longer measures

Understanding Neural Pathways in Zebrafish through Deep Learning and High Resolution Electron Microscope Data

The tracing of neural pathways through large volumes of image data is an incredibly tedious and time-consuming process that significantly encumbers progress in neuroscience. We are exploring deep learning's potential to automate segmentation of high-resolution scanning electron microscope (SEM) image data to remove that barrier. We have started with neural pathway tracing through 5.1GB of whole-brain serial-section slices from larval zebrafish collected by the Center for Brain Science at Harvard University. This kind of manual image segmentation requires years of careful work to properly trace the neural pathways in an organism as small as a zebrafish larva (approximately 5mm in total body length). In automating this process, we would vastly improve productivity, leading to faster data analysis and breakthroughs in understanding the complexity of the brain. We will build upon prior attempts to employ deep learning for automatic image segmentation extending methods for unconventional deep learning data.Comment: 8 pages, 5 figures (1a to 5c), PEARC '18: Practice and Experience in Advanced Research Computing, July 22--26, 2018, Pittsburgh, PA, US

Soviet automated rendezvous and docking system overview

The Soviets have been performing automated rendezvous and docking for many years. This paper will present an overview and brief history of the Soviet AR&D system, based on the open literature and publicly available sources

Transparency, financial accounting information, and corporate governance

Audited financial statements along with supporting disclosures form the foundation of the firm-specific information set available to investors and regulators. In this article, the authors discuss economics-based research focused on the properties of accounting systems and the surrounding institutional environment important to effective governance of firms. They provide a framework for understanding the operation of accounting information in an economy, discuss a broad range of important research findings, present a conceptual framework for characterizing and measuring corporate transparency at the country level, and isolate a number of future research possibilities.Corporations - Accounting ; Stockholders ; Corporate governance

Soviet automated rendezvous and docking system overview

The Soviets have been performing automated rendezvous and docking for many years. It has been a reliable mode of resupply and reboost. During the course of the Soviet space program, the autodocking system has evolved. The earlier IGLA system was replaced with the current KURS system. Both systems are radar-based. The variation in strength between antennas is used for computing relative positions and attitudes. The active spacecraft has a transponder. From discussions with Soviet engineers, it seems the docking process can be controlled either from the ground or from the active (docking) spacecraft's onboard computer. The unmanned Progress resupply ships regularly dock with the current MIR Space Station. The Soyuz T spacecraft incorporated the IGLA system, and the later Soyuz TM and Progress M Series spacecraft incorporated the KURS. The MIR Complex has both systems installed. The rear port and the KVANT docking port have the IGLA system installed to support earlier Progress ships that use the IGLA. The first Soyuz TM docking occurred in May of 1986, while the first Progress M docked in September of 1989

Treasure-seeking Then and Now

Last August I attended the BYU conference on the Mark Hofmann documents where I had an opportunity to reflect on what the documents meant to me. After searching my thoughts and testing my feelings, I came to the conclusion that they meant very little. They did not mean much when they first came out, and their fall from historical authenticity had little effect on me later. That may sound like a strange confession from one who was writing on the early life of Joseph Smith at the very moment the Salamander and 1825 Joseph Smith letters came to light, with their presumably earthshaking revelations about Joseph Smith’s money-digging. Yet it is true

The Character of Joseph Smith

The title of this essay, The Character of Joseph Smith, may promise more than can ever be fulfilled. Joseph warned the Saints of the difficulty in trying to understand him. In the King Follett discourse given two months before his death, he told them, You don\u27t know me--you never will. Another version of the same speech says, You never knew my heart. No man knows my hist[ory]. He seems to say that what we want to know most--his heart and his history--are not to be found out. No matter how much we study him, we must be cautious about believing we have comprehended him. There is too much there, and much of it is far beyond the ordinary. As he continues, I don\u27t blame you for not believing my history had I not expected it [I] could not believe it myself