Geophysical Investigations of the North Scotia Ridge

This report describes results of marine geophysical surveys of the North Scotia Ridge (western South Atlantic) conducted by the Geoscience Division of the British Antarctic Survey (BAS). These investigations were initiated as part of a wider programme of research into Scotia Sea tectonic evolution and palaeo-circulation (BAS project B6153). The data which form the basis of this work were obtained on BAS scientific cruises between 1987 and 1993, and include bathymetric soundings, high-resolution sub-bottom profiles, multi-channel seismic reflection profiles, long-range side-scan sonographs and marine gravity measurements. F or clarity, interpretations have been arranged into three separate studies: (1) a long-range side-scan sonar survey of the southern Falkland Plateau, Falkland Trough and North Scotia Ridge between 40 and 58°W; (2) a multi-channel seismic reflection survey of the North Scotia Ridge near 46°W (Aurora Bank); and (3) a 3.5 kHz sub-bottom profile and bathymetry survey of the Falkland Trough east of 50oW. Essential background information describing the tectonic, sedimentary and oceanographic framework of the North Scotia Ridge region has been included, so that each study may be considered separately. Some of the work described in this thesis has been completed with the assistance of others, and these contributions have been acknowledged in the text. Published results are reproduced in Appendix A of this report

EC07-1780 Lady Beetles of Nebraska

Extension Circular 07-1780 discusses lady beetles of Nebraska

AZEuS: An Adaptive Zone Eulerian Scheme for Computational MHD

A new adaptive mesh refinement (AMR) version of the ZEUS-3D astrophysical magnetohydrodynamical (MHD) fluid code, AZEuS, is described. The AMR module in AZEuS has been completely adapted to the staggered mesh that characterises the ZEUS family of codes, on which scalar quantities are zone-centred and vector components are face-centred. In addition, for applications using static grids, it is necessary to use higher-order interpolations for prolongation to minimise the errors caused by waves crossing from a grid of one resolution to another. Finally, solutions to test problems in 1-, 2-, and 3-dimensions in both Cartesian and spherical coordinates are presented.Comment: 52 pages, 17 figures; Accepted for publication in ApJ

Safety and efficacy of an engineered hepatotropic AAV gene therapy for ornithine transcarbamylase deficiency in cynomolgus monkeys

X-linked inherited ornithine transcarbamylase deficiency (OTCD) is the most common disorder affecting the liver-based urea cycle, a pathway enabling detoxification of nitrogen waste and endogenous arginine biosynthesis. Patients develop acute hyperammonemia leading to neurological sequelae or death despite the best-accepted therapy based on ammonia scavengers and protein-restricted diet. Liver transplantation is curative but associated with procedure-related complications and lifelong immunosuppression. Adeno-associated viral (AAV) vectors have demonstrated safety and clinical benefits in a rapidly growing number of clinical trials for inherited metabolic liver diseases. Engineered AAV capsids have shown promising enhanced liver tropism. Here, we conducted a good-laboratory practice-compliant investigational new drug-enabling study to assess the safety of intravenous liver-tropic AAVLK03 gene transfer of a human codon-optimized OTC gene. Juvenile cynomolgus monkeys received vehicle and a low and high dose of vector (2 × 1012 and 2 × 1013 vector genome (vg)/kg, respectively) and were monitored for 26 weeks for in-life safety with sequential liver biopsies at 1 and 13 weeks post-vector administration. Upon completion of monitoring, animals were euthanized to study vector biodistribution, immune responses, and histopathology. The product was well tolerated with no adverse clinical events, predominant hepatic biodistribution, and sustained supra-physiological OTC overexpression. This study supports the clinical deployment of intravenous AAVLK03 for severe OTCD

Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing

Drug repurposing approaches have the potential advantage of facilitating rapid and cost-effective development of new therapies. Particularly, the repurposing of drugs with known safety profiles in children could bypass or streamline toxicity studies. We employed a phenotypic screening paradigm on a panel of well-characterized cell lines derived from pediatric solid tumors against a collection of ∼3,800 compounds spanning approved drugs and investigational agents. Specifically, we employed titration-based screening where compounds were tested at multiple concentrations for their effect on cell viability. Molecular and cellular target enrichment analysis indicated that numerous agents across different therapeutic categories and modes of action had an antiproliferative effect, notably antiparasitic/protozoal drugs with non-classic antineoplastic activity. Focusing on active compounds with dosing and safety information in children according to the Children's Pharmacy Collaborative database, we identified compounds with therapeutic potential through further validation using 3D tumor spheroid models. Moreover, we show that antiparasitic agents induce cell death via apoptosis induction. This study demonstrates that our screening platform enables the identification of chemical agents with cytotoxic activity in pediatric cancer cell lines of which many have known safety/toxicity profiles in children. These agents constitute attractive candidates for efficacy studies in pre-clinical models of pediatric solid tumors

Experts' Judgments of Management Journal Quality:An Identity Concerns Model

Many lists that purport to gauge the quality of journals in management and organization studies (MOS) are based on the judgments of experts in the field. This article develops an identity concerns model (ICM) that suggests that such judgments are likely to be shaped by the personal and social identities of evaluators. The model was tested in a study in which 168 editorial board members rated 44 MOS journals. In line with the ICM, respondents rated journal quality more highly to the extent that a given journal reflected their personal concerns (associated with having published more articles in that journal) and the concerns of a relevant ingroup (associated with membership of the journal’s editorial board or a particular disciplinary or geographical background). However, judges’ ratings of journals in which they had published were more favorable when those journals had a low-quality reputation, and their ratings of journals that reflected their geographical and disciplinary affiliations were more favorable when those journals had a high-quality reputation. The findings are thus consistent with the view that identity concerns come to the fore in journal ratings when there is either a need to protect against personal identity threat or a meaningful opportunity to promote social identity

Gravitational Lensing by Black Holes

We review the theoretical aspects of gravitational lensing by black holes, and discuss the perspectives for realistic observations. We will first treat lensing by spherically symmetric black holes, in which the formation of infinite sequences of higher order images emerges in the clearest way. We will then consider the effects of the spin of the black hole, with the formation of giant higher order caustics and multiple images. Finally, we will consider the perspectives for observations of black hole lensing, from the detection of secondary images of stellar sources and spots on the accretion disk to the interpretation of iron K-lines and direct imaging of the shadow of the black hole.Comment: Invited article for the GRG special issue on lensing (P. Jetzer, Y. Mellier and V. Perlick Eds.). 31 pages, 12 figure

Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886)

In 1886 Pierre Marie used the term “acromegaly” for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders