Digital Preservation Theory and Application: Transcontinental Persistent Archives Testbed Activity

The National Archives and Records Administration (NARA) and EU SHAMAN projects are working with multiple research institutions on tools and technologies that will supply a comprehensive, systematic, and dynamic means for preserving virtually any type of electronic record, free from dependence on any specific hardware or software. This paper describes the joint development work between the University of Liverpool and the San Diego Supercomputer Center (SDSC) at the University of California, San Diego on the NARA and SHAMAN prototypes. The aim is to provide technologies in support of the required generic data management infrastructure. We describe a Theory of Preservation that quantifies how communication can be accomplished when future technologies are different from those available at present. This includes not only different hardware and software, but also different standards for encoding information. We describe the concept of a “digital ontology” to characterize preservation processes; this is an advance on the current OAIS Reference Model of providing representation information about records. To realize a comprehensive Theory of Preservation, we describe the ongoing integration of distributed shared collection management technologies, digital library browsing, and presentation technologies for the NARA and SHAMAN Persistent Archive Testbeds

Development and characterization of positively selected brain-adapted SIV

HIV is found in the brains of most infected individuals but only 30% develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS

Estimating Bighorn Sheep (\u3ci\u3eOvis Canadensis\u3c/i\u3e) Abundance Using Noninvasive Sampling at a Mineral Lick within a National Park Wilderness Area

Conservation of species requires accurate population estimates. We used genetic markers from feces to determine bighorn sheep abundance for a herd that was hypothesized to be declining and in need of population status monitoring. We sampled from a small but accessible portion of the population\u27s range where animals natural congregate at a natural mineral lick to test whether we could accurately estimate population size by sampling from an area where animals concentrate. We used mark-recapture analysis to derive population estimates, and compared estimates from this smaller spatial sampling to estimates from sampling of the entire bighorn sheep range. We found that estimates were somewhat comparable; in 2009, the mineral lick sample and entire range sample differed by 20 individuals, and in 2010 they differed by only one individual. However, we captured 13 individuals in the entire range sample that were not captured at the mineral lick, and thus violated a model assumption that all individuals had an equal opportunity of being captured. This eliminated the possibility of inferring a total population estimate from just animals visiting the mineral lick, but because estimates were relatively similar, monitoring at the mineral lick can provide a useful index for management and conservation. We compared our results to a radio-collar study conducted in 2003-2004 and confirmed that the population remained stable since 2004. Our population estimates were 78 (CI 62-114) in 2009 and 95 (CI 77-131) in 2010. Between 7 and 11 sampling dates were needed to achieve a CV of 20% for population estimates, assuming a capture probability between 0.09 and 0.13. We relied on citizen science volunteers to maximize data collection and reduce costs; 71% of all fecal samples were collected by volunteers, compared to 29% collected by paid staff. We conclude that our technique provides a useful monitoring tool for managers. The technique could be tested and applied in similar populations where animals congregate with high fidelity at a mineral lick or other area

Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.

Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes. A coding single nucleotide polymorphism in the patient cell line allowed us to distinguish transcripts from the normal vs. mutant allele. Using digital droplet PCR (ddPCR), we determined that transcription from the mutant allele is upregulated at least 10-fold, and that sense transcription is independently regulated from each allele. Surprisingly, excision of the WT allele increased pathologic dipeptide repeat poly-GP expression from the mutant allele. Importantly, a single allele was sufficient to supply a normal amount of protein, suggesting that the C9orf72 gene is haplo-sufficient in induced motor neurons. Excision of the mutant repeat expansion reverted all pathology (RNA abnormalities, dipeptide repeat production, and TDP-43 pathology) and improved electrophysiological function, whereas silencing sense expression did not eliminate all dipeptide repeat proteins, presumably because of the antisense expression. These data increase our understanding of C9orf72 gene regulation and inform gene therapy approaches, including antisense oligonucleotides (ASOs) and CRISPR gene editing

Statins as antifungal agents

This poster paper describes the objectives, approach and use casesof the EC FP7 Integrated Project PERICLES. The project beganon 1st February 2013 and runs for four years. The aim is toresearch and prototype solutions for digital preservation incontinually evolving environments including changes in context,semantics and practices. The project addresses use cases focusingon digital art, media and science.Proceedings source: http://purl.pt/24107/1/iPres2013_PDF/iPres2013-Proceedings.pd

Protective Role for the Disulfide Isomerase PDIA3 in Methamphetamine Neurotoxicity

Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Methamphetamine treatment of mice also increased striatal PDIA3 expression. Treatment of primary striatal neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations