Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology

Loss of function mutations in granulin (GRN) are linked to two distinct neurological disorders, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). It is so far unknown how a complete loss of GRN in NCL and partial loss of GRN in FTLD can result in such distinct diseases. In zebrafish, there are two GRN homologues, Granulin A (Grna) and Granulin B (Grnb). We have generated stable Grna and Grnb loss of function zebrafish mutants by zinc finger nuclease mediated genome editing. Surprisingly, the grna and grnb single and double mutants display neither spinal motor neuron axonopathies nor a reduced number of myogenic progenitor cells as previously reported for Grna and Grnb knock down embryos. Additionally, grna-/-;grnb-/- double mutants have no obvious FTLD- and NCL-related biochemical and neuropathological phenotypes. Taken together, the Grna and Grnb single and double knock out zebrafish lack any obvious morphological, pathological and biochemical phenotypes. Loss of zebrafish Grna and Grnb might therefore either be fully compensated or only become symptomatic upon additional challenge

Overview of a new slicing method: Fixed Abrasive Slicing Technique (FAST)

The fixed abrasive slicing technique (FAST) was developed to slice silicon ingots more effectively. It was demonstrated that 25 wafers/cm can be sliced from 10 cm diameter and 19 wafers/cm from 15 cm diameter ingots. This was achieved with a combination of machine development and wire-blade development programs. Correlation was established between cutting effectiveness and high surface speeds. A high speed slicer was designed and fabricated for FAST slicing. Wirepack life of slicing three 10 cm diameter ingots was established. Electroforming techniques were developed to control widths and prolong life of wire-blades. Economic analysis indicates that the projected add-on price of FAST slicing is compatible with the DOE price allocation to meet the 1986 cost goals

Wire blade development for Fixed Abrasive Slicing Technique (FAST) slicing

A low cost, effective slicing method is essential to make ingot technology viable for photovoltaics in terrestrial applications. The fixed abrasive slicing technique (FAST) combines the advantages of the three commercially developed techniques. In its development stage FAST demonstrated cutting effectiveness of 10 cm and 15 cm diameter workpieces. Wire blade development is still the critical element for commercialization of FAST technology. Both impregnated and electroplated wire blades have been developed; techniques have been developed to fix diamonds only in the cutting edge of the wire. Electroplated wires show the most near term promise and this approach is emphasized. With plated wires it has been possible to control the size and shape of the electroplating, it is expected that this feature reduces kerf and prolongs the life of the wirepack

Quantum Cournot equilibrium for the Hotelling-Smithies model of product choice

This paper demonstrates the quantization of a spatial Cournot duopoly model with product choice, a two stage game focusing on non-cooperation in locations and quantities. With quantization, the players can access a continuous set of strategies, using continuous variable quantum mechanical approach. The presence of quantum entanglement in the initial state identifies a quantity equilibrium for every location pair choice with any transport cost. Also higher profit is obtained by the firms at Nash equilibrium. Adoption of quantum strategies rewards us by the existence of a larger quantum strategic space at equilibrium.Comment: 13 pages, 6 tables, 8 figure

Single Qubit Quantum Secret Sharing

We present a simple and practical protocol for the solution of a secure multiparty communication task, the secret sharing, and its experimental realization. In this protocol, a secret message is split among several parties in a way that its reconstruction require the collaboration of the participating parties. In the proposed scheme the parties solve the problem by a sequential communication of a single qubit. Moreover we show that our scheme is equivalent to the use of a multiparty entangled GHZ state but easier to realize and better scalable in practical applications.Comment: 5 pages, 2 figures, submitted December 29, 200

In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation

Support for graphicacy: a review of textbooks available to accounting students

This Teaching Note reports on the support available in textbooks for graphicacy that will help students understand the complexities of graphical displays. Graphical displays play a significant role in financial reporting, and studies have found evidence of measurement distortion and selection bias. To understand the complexities of graphical displays, students need a sound understanding of graphicacy and support from the textbooks available to them to develop that understanding. The Teaching Note reports on a survey that examined the textbooks available to students attending two Scottish universities. The support of critical graphicacy skills was examined in conjunction with textbook characteristics. The survey, which was not restricted to textbooks designated as required reading, examined the textbooks for content on data measurement and graphical displays. The findings highlight a lack of support for graphicacy in the textbooks selected. The study concludes that accounting educators need to scrutinize more closely the selection of textbooks and calls for more extensive research into textbooks as a pedagogic tool

Critical collapse and the primordial black hole initial mass function

It has normally been assumed that primordial black holes (PBHs) always form with mass approximately equal to the mass contained within the horizon at that time. Recent work studying the application of critical phenomena in gravitational collapse to PBH formation has shown that in fact, at a fixed time, PBHs with a range of masses are formed. When calculating the PBH initial mass function it is usually assumed that all PBHs form at the same horizon mass. It is not clear, however, that it is consistent to consider the spread in the mass of PBHs formed at a single horizon mass, whilst neglecting the range of horizon masses at which PBHs can form. We use the excursion set formalism to compute the PBH initial mass function, allowing for PBH formation at a range of horizon masses, for two forms of the density perturbation spectrum. First we examine power-law spectra with $n>1$, where PBHs form on small scales. We find that, in the limit where the number of PBHs formed is small enough to satisfy the observational constraints on their initial abundance, the mass function approaches that found by Niemeyer and Jedamzik under the assumption that all PBHs form at a single horizon mass. Second, we consider a flat perturbation spectrum with a spike at a scale corresponding to horizon mass $\sim 0.5 M_{\odot}$, and compare the resulting PBH mass function with that of the MACHOs (MAssive Compact Halo Objects) detected by microlensing observations. The predicted mass spectrum appears significantly wider than the steeply-falling spectrum found observationally.Comment: 8 pages RevTeX file with ten figures incorporated (uses RevTeX and epsf). Minor changes to dicussion onl