Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis

Volume and Quantizations

The aim of this letter is to indicate the differences between the Rovelli-Smolin quantum volume operator and other quantum volume operators existing in the literature. The formulas for the operators are written in a unifying notation of the graph projective framework. It is clarified whose results apply to which operators and why.Comment: 8 page

Investigating the role of model-based reasoning while troubleshooting an electric circuit

We explore the overlap of two nationally-recognized learning outcomes for physics lab courses, namely, the ability to model experimental systems and the ability to troubleshoot a malfunctioning apparatus. Modeling and troubleshooting are both nonlinear, recursive processes that involve using models to inform revisions to an apparatus. To probe the overlap of modeling and troubleshooting, we collected audiovisual data from think-aloud activities in which eight pairs of students from two institutions attempted to diagnose and repair a malfunctioning electrical circuit. We characterize the cognitive tasks and model-based reasoning that students employed during this activity. In doing so, we demonstrate that troubleshooting engages students in the core scientific practice of modeling.Comment: 20 pages, 6 figures, 4 tables; Submitted to Physical Review PE

A project of universal computing platform - cluster of floating point DSP processors (Projekt uniwersalnej platformy obliczeniowej - klastra zmiennoprzecinkowych procesorów DSP)

In this paper, a project of DSP processors cluster is presented. This project is realized as an extension board for PC computers. A block diagram of the board is described. A DSP processor properties for cluster computation was described. The aim is to use a number of such boards for building a cluster of DSP clusters. Such architecture will be used for High Energy Physics Experiments results calculations with such data as CMS, ILC and E-XFEL

The Wilsonian Renormalization Group in Randall-Sundrum 1

We find renormalization group transformations for the compactified Randall-Sundrum scenario by integrating out an infinitesimal slice of ultraviolet degrees of freedom near the Planck brane. Under these transformations the coefficients of operators on the Planck brane experience RG evolution. The extra-dimensional radius also scales, flowing to zero in the IR. We find an attractive fixed point in the context of a bulk scalar field theory. Calculations are simplified in the low energy effective theory as we demonstrate with the computation of a loop diagram.Comment: 19 pages, typos adde

From Crystalline to Amorphous Germania Bilayer Films at the Atomic Scale: Preparation and Characterization

A new two-dimensional (2D) germanium dioxide film has been prepared. The film consists of interconnected germania tetrahedral units forming a bilayer structure, weakly coupled to the supporting Pt(111) metal-substrate. Density functional theory calculations predict a stable structure of 558-membered rings for germania films, while for silica films 6-membered rings are preferred. By varying the preparation conditions the degree of order in the germania films is tuned. Crystalline, intermediate ordered and purely amorphous film structures are resolved by analysing scanning tunnelling microscopy images

The Utility of Fusion Centres to Enhance Intelligence-Led Policing: An Exploration of End-Users

A developing literature on intelligence-led policing (ILP) and law enforcement fusion centres contends that intelligence and data-driven policing practices can be enhanced through improved intelligence dissemination from fusion centres. The literature has remained relatively silent on the extent to which law enforcement has connectivity with fusion centres, perceive fusion centre products to be useful, and further share intelligence products within their agency. The present study informs this knowledge gap using data gathered via an online survey of law enforcement subscribed to receive fusion centre products. Bivariate logistic regression models showed that rural agencies tend to be the most informed about the fusion centre of study while a disconnect was observed between the fusion centre with respect to frontline personnel and analysts; especially in urban police, health, and fire organizations. Implications for research and practice are discussed