Creating Virtual CD-ROM Collections

Over the past 20 years, more than 100,000 CD-ROM titles have been published including thousands of collections of government documents and data. CD-ROMs present preservation challenges at the bit level and in ensuring usability of the preserved artifact. We present techniques we have developed to archive and support user access to a collection of approximately 2,900 CD-ROMs published under the Federal Depository Library Program (FDLP) by the United States Government Printing Office (GPO). The project provides web-based access to CD-ROM contents using both migration and emulation and supports remote execution of the raw CD-ROM images. Our project incorporates off-the-shelf, primarily open-source software. The raw data and (METS) metadata are made available through AFS, a standard distributed file system, to encourage sharing among libraries

Migration Performance for Legacy Data Access

We present performance data relating to the use of migration in a system we are creating to provide web access to heterogeneous document collections in legacy formats. Our goal is to enable sustained access to collections such as these when faced with increasing obsolescence of the necessary supporting applications and operating systems. Our system allows searching and browsing of the original files within their original contexts utilizing binary images of the original media. The system uses static and dynamic file migration to enhance collection browsing, and emulation to support both the use of legacy programs to access data and long-term preservation of the migration software. While we provide an overview of the architectural issues in building such a system, the focus of this paper is an in-depth analysis of file migration using data gathered from testing our software on 1,885 CD-ROMs and DVDs. These media are among the thousands of collections of social and scientific data distributed by the United States Government Printing Office (GPO) on legacy media (CD-ROM, DVD, floppy disk) under the Federal Depository Library Program (FDLP) over the past 20 years

Assisted Emulation for Legacy Executables

Emulation is frequently discussed as a failsafe preservation strategy for born-digital documents that depend on contemporaneous software for access (Rothenberg, 2000). Yet little has been written about the contextual knowledge required to successfully use such software. The approach we advocate is to preserve necessary contextual information through scripts designed to control the legacy environment, and created during the preservation workflow. We describe software designed to minimize dependence on this knowledge by offering automated configuration and execution of emulated environments. We demonstrate that even simple scripts can reduce impediments to casual use of the digital objects being preserved. We describe tools to automate the remote use of preserved objects on local emulation environments.  This can help eliminate both a dependence on physical reference workstations at preservation institutions, and provide users accessing materials over the web with simplified, easy-to-use environments. Our implementation is applied to examples from an existing collection of over 4,000 virtual CD-ROM images containing thousands of custom binary executables

Born Broken: Fonts and Information Loss in Legacy Digital Documents

For millions of legacy documents, correct rendering depends upon resources such as fonts that are not generally embedded within the document structure. Yet there is a significant risk of information loss due to missing or incorrectly substituted fonts. Large document collections depend on thousands of unique fonts not available on a common desktop workstation, which typically has between 100 and 200 fonts. Silent substitution of fonts, performed by applications such as Microsoft Office, can yield poorly rendered documents. In this paper we use a collection of 230,000 Word documents to assess the difficulty of matching font requirements with a database of fonts. We describe the identifying information contained in common font formats, font requirements stored in Word documents, the API provided by Windows to support font requests by applications, the documented substitution algorithms used by Windows when requested fonts are not available, and the ways in which support software might be used to control font substitution in a preservation environment

Aspirin for the prevention of cognitive decline in the elderly: rationale and design of a neuro-vascular imaging study (ENVIS-ion)

<p>Abstract</p> <p>Background</p> <p>This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations.</p> <p>Methods/Design</p> <p>Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis.</p> <p>Discussion</p> <p>This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline.</p> <p>Trial Registration</p> <p>clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01038583">NCT01038583</a></p

From Bitstreams to Heritage: Putting Digital Forensics into Practice in Collecting Institutions

This paper examines the application of digital forensics methods to materials in collecting institutions – particularly libraries, archives and museums. It discusses motivations, challenges, and emerging strategies for the use of these technologies and workflows. It is a product of the BitCurator project. The BitCurator project began on October 1, 2011, through funding from the Andrew W. Mellon Foundation. BitCurator is an effort to build, test, and analyze systems and software for incorporating digital forensics methods into the workflows of a variety of collecting institutions. It is led by the School of Information and Library Science (SILS) at the University of North Carolina, Chapel Hill and the Maryland Institute for Technology in the Humanities (MITH) at the University of Maryland, and involves contributors from several other institutions. Two groups of external partners are contributing to this process: a Professional Expert Panel (PEP) of individuals who are at various levels of implementing digital forensics tools and methods in their collecting institution contexts, and a Development Advisory Group (DAG) of individuals who have significant experience with software development.2 This paper is a product of phase one of BitCurator (October 1, 2011 – September 30, 2013). The second phase of the project (October 1, 2013 – September 29, 2014) continues the development of the BitCurator environment, along with expanded professional engagement and community outreach activities

Dependence as a Unifying Construct in Defining Alzheimer's Disease Severity

This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression

A New Model for Raf Kinase Inhibitory Protein Induced Chemotherapeutic Resistance

Therapeutic resistance remains the most challenging aspect of treating cancer. Raf kinase inhibitory protein (RKIP) emerged as a molecule capable of sensitizing cancerous cells to radio- and chemotherapy. Moreover, this small evolutionary conserved molecule, endows significant resistance to cancer therapy when its expression is reduced or lost. RKIP has been shown to inhibit the Raf-MEK-ERK, NFκB, GRK and activate the GSK3β signaling pathways. Inhibition of Raf-MEK-ERK and NFκB remains the most prominent pathways implicated in the sensitization of cells to therapeutic drugs. Our purpose was to identify a possible link between RKIP-KEAP 1-NRF2 and drug resistance. To that end, RKIP-KEAP 1 association was tested in human colorectal cancer tissues using immunohistochemistry. RKIP miRNA silencing and its inducible overexpression were employed in HEK-293 immortalized cells, HT29 and HCT116 colon cancer cell lines to further investigate our aim. We show that RKIP enhanced Kelch-like ECH-associated protein1 (KEAP 1) stability in colorectal cancer tissues and HT29 CRC cell line. RKIP silencing in immortalized HEK-293 cells (termed HEK-499) correlated significantly with KEAP 1 protein degradation and subsequent NRF2 addiction in these cells. Moreover, RKIP depletion in HEK-499, compared to control cells, bestowed resistance to supra physiological levels of H2O2 and Cisplatin possibly by upregulating NF-E2-related nuclear factor 2 (NRF2) responsive genes. Similarly, we observed a direct correlation between the extent of apoptosis, after treatment with Adriamycin, and the expression levels of RKIP/KEAP 1 in HT29 but not in HCT116 CRC cells. Our data illuminate, for the first time, the NRF2-KEAP 1 pathway as a possible target for personalized therapeutic intervention in RKIP depleted cancers

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson