The Roman fort and fortlet at Castlehill on the Antonine Wall: the geophysical, LiDAR and early map evidence

No abstract available

High Tech Entrepreneurial Careers: A Model of Stages, Phases, and Ages

The meteoric rise, dramatic fall, and spectacular comeback associated with Steve Jobs’ career path is an evocative example of the risks and rewards associated with following a high-tech entrepreneurial career. While research on entrepreneurs has primarily focused on their characteristics, there is limited research on the career paths of entrepreneurs in either the careers or the entrepreneurship literature. The purpose of this paper is to propose a new model of entrepreneurial careers that better reflects the realities of pursuing a career in the high-tech computer industry. The proposed model considers the role that stages, phases, and ages play in the careers of hightech entrepreneurs

A Dictyostelium chalone uses G proteins to regulate proliferation

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in <it>Dictyostelium</it>. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation.</p> <p>Results</p> <p>We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of <it>galpha8^-</it>, <it>galpha9^-</it>and <it>gbeta^-</it>cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. <it>galpha8^-</it>cells show normal cell-surface binding of rAprA, whereas <it>galpha9^-</it>and <it>gbeta^-</it>cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [³H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [³H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like <it>aprA^-</it>cells, <it>galpha8^-</it>cells have reduced spore viability.</p> <p>Conclusion</p> <p>This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in <it>Dictyostelium</it>, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.</p

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

Duality covariant quantum field theory on noncommutative Minkowski space

We prove that a scalar quantum field theory defined on noncommutative Minkowski spacetime with noncommuting momentum coordinates is covariant with respect to the UV/IR duality which exchanges coordinates and momenta. The proof is based on suitable resonance expansions of charged noncommutative scalar fields in a background electric field, which yields an effective description of the field theory in terms of a coupled complex two-matrix model. The two independent matrix degrees of freedom ensure unitarity and manifest CT-invariance of the field theory. The formalism describes an analytic continuation of the renormalizable Grosse-Wulkenhaar models to Minkowski signature.Comment: 32 pages; v2: Typos corrected; v3: Further typos corrected - Final version to appear in JHE

Taste responsiveness, weight loss, and the ponderostat

Rats which lost weight due to exercise showed increased acceptance of good tasting food and increased rejection of bad tasting food. This indicates that energy deficit results in heightened taste responsiveness and suggests that obese human beings may be highly taste responsive because they chronically maintain their weight at a level below its set point.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33789/1/0000044.pd

Precision Studies of Duality in the 't Hooft Model

We address numerical aspects of local quark-hadron duality using the example of the exactly solvable 't Hooft model, two-dimensional QCD with N_c --> infinity. The primary focus of these studies is total semileptonic decay widths relevant for extracting |V_{cb}| and |V_{ub}|. We compare the exact channel-by-channel sum of exclusive modes to the corresponding rates obtained in the standard 1/m_Q expansion arising from the Operator Product Expansion. An impressive agreement sets in unexpectedly early, immediately after the threshold for the first hadronic excitation in the final state. Yet even at higher energy release it is possible to discern the seeds of duality-violating oscillations. We find the ``Small Velocity'' sum rules to be exceptionally well saturated already by the first excited state. We also obtain a convincing degree of duality in the differential distributions and in an analogue of R_{e^+e^-}(s). Finally, we discuss possible lessons for semileptonic decays of actual heavy quarks in QCD.Comment: 45 pages, 16 eps figures include

Hypohidrotic Ectodermal Dysplasia and Immunodeficiency with Coincident NEMO and EDA Mutations

Ectodermal dysplasias (ED) are uncommon genetic disorders resulting in abnormalities in ectodermally derived structures. Many ED-associated genes have been described, of which ectodysplasin-A (EDA) is one of the more common. The NF-κB essential modulator (NEMO encoded by the IKBKG gene) is unique in that mutations result in severe humoral and cellular immunologic defects in addition to ED. We describe three unrelated kindreds with defects in both EDA and IKBKG resulting from X-chromosome crossover. This demonstrates the importance of thorough immunologic consideration of patients with ED even when an EDA etiology is confirmed, and raises the possibility of a specific phenotype arising from coincident mutations in EDA and IKBKG

Shifting perspectives on coastal impacts and adaptation

The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a less hazardous coast.info:eu-repo/semantics/publishedVersio

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ