Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data

Hyperactivated mTOR signaling in the developing brain has been implicated in multiple forms of pathology including tuberous sclerosis complex (TSC). To date, various phenotypic defects such as cortical lamination irregularity, subependymal nodule formation, dysmorphic astrocyte differentiation and dendritic malformation have been described for patients and animal models. However, downstream networks affected in the developing brain by hyperactivated mTOR signaling have yet to be characterized. Here, we present an integrated analysis of transcriptomes and proteomes generated from wild-type and Tsc1/Emx1-Cre forebrains. This led to comprehensive lists of genes and proteins whose expression levels were altered by hyperactivated mTOR signaling. Further incorporation of TSC patient data followed by functional enrichment and network analyses pointed to changes in molecular components and cellular processes associated with neuronal differentiation and morphogenesis as the key downstream events underlying developmental and morphological defects in TSC. Our results provide novel and fundamental molecular bases for understanding hyperactivated mTOR signaling-induced brain defects which can in turn facilitate identification of potential diagnostic markers and therapeutic targets for mTOR signaling-related neurological disorders. ? The Author(s) 2017.11Ysciescopu

Fast Neutron Detector for Fusion Reactor KSTAR Using Stilbene Scintillator

Various neutron diagnostic tools are used in fusion reactors to evaluate different aspects of plasma performance, such as fusion power, power density, ion temperature, fast ion energy, and their spatial distributions. The stilbene scintillator has been proposed for use as a neutron diagnostic system to measure the characteristics of neutrons from the Korea Superconducting Tokamak Advanced Research (KSTAR) fusion reactor. Specially designed electronics are necessary to measure fast neutron spectra with high radiation from a gamma-ray background. The signals from neutrons and gamma-rays are discriminated by the digital charge pulse shape discrimination (PSD) method, which uses total to partial charge ratio analysis. The signals are digitized by a flash analog-to-digital convertor (FADC). To evaluate the performance of the fabricated stilbene neutron diagnostic system, the efficiency of 10 mm soft-iron magnetic shielding and the detection efficiency of fast neutrons were tested experimentally using a 252Cf neutron source. In the results, the designed and fabricated stilbene neutron diagnostic system performed well in discriminating neutrons from gamma-rays under the high magnetic field conditions during KSTAR operation. Fast neutrons of 2.45 MeV were effectively measured and evaluated during the 2011 KSTAR campaign.Comment: 15 pages, 14 figures, conferenc

Spontaneous parity violation and minimal Higgs models

In this paper we present a model for the spontaneous breaking of parity with two Higgs doublets and two neutral Higgs singlets which are even and odd under D-parity. The condition $v_R >>v_L$ can be satisfied without introducing bidoublets and it is induced by the breaking of D-parity through the vacuum expectation value of the odd Higgs singlet. Examples of left-right symmetric and mirror fermions models in grand unified theories are presented.Comment: Revised version. Accepted in Eur. Phys. Journal

Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis

INTRODUCTION: Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and "stemness" characteristics, which resemble those of ESCs. We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. METHODS: A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-beige mice were injected with iPSCs and sacrificed to test for teratoma formation. RESULTS: After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. CONCLUSION: FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy

Light-cone QCD Sum Rules for the Λ\Lambda Baryon Electromagnetic Form Factors and its magnetic moment

We present the light-cone QCD sum rules up to twist 6 for the electromagnetic form factors of the $\Lambda$ baryon. To estimate the magnetic moment of the baryon, the magnetic form factor is fitted by the dipole formula. The numerical value of our estimation is $\mu_\Lambda=-(0.64\pm0.04)\mu_N$, which is in accordance with the experimental data and the existing theoretical results. We find that it is twist 4 but not the leading twist distribution amplitudes that dominate the results.Comment: 13 page, 7 figures, accepted for publication in Euro. Phys. J.

Smooth metric measure spaces, quasi-Einstein metrics, and tractors

We introduce the tractor formalism from conformal geometry to the study of smooth metric measure spaces. In particular, this gives rise to a correspondence between quasi-Einstein metrics and parallel sections of certain tractor bundles. We use this formulation to give a sharp upper bound on the dimension of the vector space of quasi-Einstein metrics, providing a different perspective on some recent results of He, Petersen and Wylie.Comment: 33 pages; final versio

New directions in earth system governance research

The Earth System Governance project is a global research alliance that explores novel, effective governance mechanisms to cope with the current transitions in the biogeochemical systems of the planet. A decade after its inception, this article offers an overview of the project's new research framework (which is built upon a review of existing earth system governance research), the goal of which is to continue to stimulate a pluralistic, vibrant and relevant research community. This framework is composed of contextual conditions (transformations, inequality, Anthropocene and diversity), which capture what is being observed empirically, and five sets of research lenses (architecture and agency, democracy and power, justice and allocation, anticipation and imagination, and adaptiveness and reflexivity). Ultimately the goal is to guide and inspire the systematic study of how societies prepare for accelerated climate change and wider earth system change, as well as policy responses

Production and Decay of Neutralinos in the Next-To-Minimal Supersymmetric Standard Model

Within the framework of the Next-To-Minimal Supersymmetric Standard Model (NMSSM) we study neutralino production $e^+e^- \longrightarrow \tilde{\chi}^0_i \tilde{\chi}^0_j$ ($i,j=1,\ldots ,5$) at center-of-mass energies between 100 and 600 GeV and the decays of the heavier neutralinos into the LSP plus a fermion pair, a photon or a Higgs boson. For representative gaugino/higgsino mixing scenarios, where the light neutralinos have significant singlet components, we find some striking differences between the NMSSM and the minimal supersymmetric model. Since in the NMSSM neutralino and Higgs sector are strongly correlated, the decay of the second lightest neutralino into a Higgs boson and the LSP often is kinematically possible and even dominant in a large parameter region of typical NMSSM scenarios. Also, the decay rates into final states with a photon may be enhanced.Comment: 36 pages, latex, 10 uuendcoded figures, complete ps file available at ftp://ftp.physik.uni-wuerzburg.de/pub/preprint/WUE-ITP-95-021.ps.g