AMPPD Project Update

Academic libraries and archives are dealing with increasing numbers of digital audio and video (AV) files, acquired through both digitization of analog collections and acquisition of born-digital AV resources. While the emergence of low-cost storage options and maturity of streaming platforms has made it easier to store and deliver AV, these collections often lack metadata needed in order to make them discoverable and usable by researchers and other users. Since late 2018, the Indiana University Libraries have been working with partners at the University of Texas at Austin, New York Public Library, and digital consultant AVP to develop an open source software platform, known as AMP (Audiovisual Metadata Platform), that leverages automated machine learning-based tools together with human expertise to build workflows to create and augment metadata for AV resources to improve discovery, rights determination, and use. We will present an update on progress of the AMP project and its successes and challenges to date, including a demonstration of the AMP system and discussion of issues in system design, workflows, and the use of open source and commercial cloud-based machine learning tools. We will also discuss results to date of testing the AMP system using collections from the Cook Music Library and University Archives at IU and from the New York Public Library. This work is generously supported by a grant to IU from the Andrew W. Mellon Foundation

Audiovisual Metadata Platform Pilot Development (AMPPD), Final Project Report

This report documents the experience and findings of the Audiovisual Metadata Platform Pilot Development (AMPPD) project, which has worked to enable more efficient generation of metadata to support discovery and use of digitized and born-digital audio and moving image collections. The AMPPD project was carried out by partners Indiana University Libraries, AVP, University of Texas at Austin, and New York Public Library between 2018-2021

Impaired Autophagy Diurnal Rhythmicity in Rodent Diabetic Retinopathy

poster abstractPurpose: Retinal homeostasis is under both diurnal and circadian regulation. However, diurnal changes in retinal autophagy have not been hitherto explored. We sought to investigate the diurnal expression of autophagy proteins/genes in normal rodent retina to determine if this is impaired in diabetic retinopathy. Methods: Eyes from C57BL/6 mice and BBZ rats maintained under a 12h/12h; 6am/6pm light/dark cycle were enucleated every 2 or 3 hours over a 24 hour period. Eyes were also collected from C57BL/6 induced STZ for 2 or 9 month as type 1 and BBZDR/wor type 2 diabetic rats for 4 months. Immunohistochemistry, Western-blot and real-time PCR were performed for Atg7, Atg9, LC3 and Beclin. Retina vessel pathology and superoxide were assessed by enzyme digestion and a spectrofluorometer. Results: Autophagy proteins (Atgs) were abundantly expressed in neural retina and endothelia cells in both mice and rats with differential staining pattern across the retinas and demonstrated a distinctive diurnal rhythmicity. All Atgs showed localization to retinal blood vessels with Atg7 being the most highly expressed. Analysis of the immunostaining demonstrated distinctive diurnal rhythmicity of which Atg9 and LC3 shared a biphasic expression cycle with the highest level at 8:15 am and 8:15 pm. By contrast, Beclin revealed a 24-hour cycle with the highest level observed at midnight. Atg7 was also on a 24-hour cycle with peak expression at 8:15am, coinciding with the first peak expression of Atg9 and LC3. In diabetic animals, immunohistochemistry showed dramatic reduction in all four Atgs and this was further confirmed by Western Blot, especially a decrease in LC3II/LC3I ratio (a measure of autophagy flux). Furthermore, the distinctive diurnal rhythmicity of these autophagy proteins was significantly impaired and phase shifted in diabetic animals. Conclusions: Autophagy proteins show both spatial and diurnal-dependent expression in normal rodent retinas and this is severely impaired and phase shifted in both type 1 and type 2 diabetic animals. Decreased autophagy in diabetic animals may in part explain the increased generation of reactive oxygen species in diabetic retinopathy. Therefore, restoration of diurnal rhythmicity and facilitating autophagy pathway expression may provide new treatment strategies for diabetic retinopathy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Audio and Video at Scale: Indiana University’s Media Digitization and Preservation Initiative

Presented at the DLF Forum on Tuesday, October 27, 2014 at 3:45 p.m. at the Georgia Tech Hotel and Conference Center.Jon Dunn is the Interim Dean for Library Technologies at Indiana University Libraries.Juliet Hardesty is a Metadata Analyst at Indiana University Libraries.Runtime: 31:46 minutesIn 2013, Indiana University (IU) launched a five-year project, known as the Media Digitization and Preservation Initiative (MDPI: http://mdpi.iu.edu/), to digitize and preserve over 300,000 audio and video assets of value from across the university. Among academic institutions, IU has an unusually rich collection of rare and unique time-based media that document subjects of enduring value to the university, State of Indiana, and the world. Pieces range from wax cylinder sound recordings of Native American music to performances by notable graduates of its Jacobs School of Music to media from the collections of IU’s Kinsey Institute for Research in Sex, Gender, and Reproduction. The project is co-led by IU’s Vice President for Information Technology and Dean of University Libraries. IU is partnering with a commercial vendor, Memnon Archiving Services of Belgium, to set up a facility in Bloomington, Indiana to digitize these materials, in a workflow that will produce as much as 12 terabytes per day of digital data to be preserved beginning in summer 2014. MDPI was planned out of recognition by IU leadership that large portions of IU’s media holdings were becoming seriously endangered due to media degradation and/or format obsolescence. A 2008-2009 survey of holdings at IU Bloomington (http://www.indiana.edu/~medpres/documents/iub_media_preservation_survey_FINALwww.pdf) uncovered over 569,000 audiovisual items on 51 different physical formats held in collections of 80 different organizational units across the campus, with significant quantities of rare and unique items in danger of becoming inaccessible within 5-15 years due to degradation or obsolescence. In this presentation, we will outline the goals and history of MDPI, describe the workflows that we are establishing to feed content into the digitization process and manage content coming out of the process, and discuss planned strategies for preservation storage, access, and metadata

Scherzo: A FRBR-Based Music Discovery System

The Scherzo music discovery system is one deliverable from the Variations/FRBR (V/FRBR) project at Indiana University (Riley, 2010). The objective of the V/FRBR project is to provide a real-world test of the Functional Requirements for Bibliographic Records (FRBR) model (IFLA, 1998) in the domain of music. In addition to creating a schema and FRBRization algorithm to populate a repository with data drawn from MARC bibliographic records, one experiment in the utility of the FRBR model has been to create a discovery system based on the FRBRized data, to explore the value of exposing FRBR structuring in the discovery interface

PD-L1 and CD8+PD1+ lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy

Recent monoclonal antibody trials targeting the PD1/PD-L1 immune-checkpoint pathway have shown remarkable success in treating adult malignancies, with PD-L1-expressing tumors showing the most objective response. However, little is known as to whether pediatric cancers have also adopted this immune evasion mechanism. We evaluated 115 pediatric tumors (taken at diagnosis) for PD-L1 expression and the presence of CD8+ tumor-infiltrating lymphocytes (TILs). Tumors with >5% PD-L1 membrane staining were scored positive. The presence of CD8+ TILs expressing PD-1 was assessed using dual-labeling immunohistochemistry. Data were evaluated against clinical demographics. The proportion of PD-L1+ tumors was 86% for alveolar rhabdomyosarcoma (12/14), 72% for high-risk neuroblastoma (31/43), 57% for Ewing's sarcoma (8/14), 50% for embryonal rhabdomyosarcoma (8/16) and 47% for osteosarcoma (7/15). Increased proportions of CD8+ TILs significantly correlated with PD-1 expression. When grouped by cancer type, those with the highest proportion of PD-L1 positivity showed poorest survival. PD-L1+ patients with a particularly high frequency of CD8+ TILs (but not those with low numbers CD8+ TILs) had significantly better survival compared to PD-L1 negative patients. This study reveals the presence of an active PD-L1 pathway in a high proportion of pediatric cancers, as demonstrated by strong PD-L1 positivity and the presence of PD-1 expressing CD8+ TILs. In addition, patients with high proportions of CD8+ TILs showed better survival, suggesting that bolstering CD8+ T-cell responses through PD-1/PD-L1 blockade would be a viable treatment strategy, providing support for expediting these targeted immunotherapies in children

Immunomodulatory monoclonal antibodies combined with peptide vaccination provide potent immunotherapy in an aggressive murine neuroblastoma model

PURPOSE: Neuroblastoma is one of the commonest extra-cranial tumors of childhood. The majority of patients present with metastatic disease for which outcome remains poor. Immunotherapy is an attractive therapeutic approach for this disease, and a number of neuroblastoma tumor antigens have been identified. Here we examine the therapeutic potential of combining immunomodulatory monoclonal antibodies (mAb) with peptide vaccination in murine neuroblastoma models. EXPERIMENTAL DESIGN: Neuroblastoma bearing mice were treated with mAb targeting 4-1BB, CD40 and CTLA-4 alone, or in combination with a peptide derived from the tumor antigen survivin (GWEDPPNDI). Survivin-specific immune response and therapeutic efficacy was assessed. RESULTS: In the Neuro2a model, treatment of established tumor with either anti-4-1BB, anti-CD40 or anti-CTLA-4 mAb results in tumor regression and long-term survival in 40-60% of mice. This is dependent on NK and CD8+ T cells and is associated with tumor CD8+ lymphocyte infiltrate. Successful therapy is achieved only if mAb is given to mice once tumors are established, suggesting dependence on sufficient tumor to provide antigen. In the more aggressive AgN2a and NXS2 models, single agent mAb therapy provides ineffective therapy. However if mAb (anti-CTLA-4) is given in conjunction with survivin peptide vaccination then 60% long term survival is achieved. This is associated with the generation of survivin-specific T cell immunity, which again is only demonstrated in the presence of tumor antigen. CONCLUSIONS: These data suggest the combination of antigen and co-stimulatory mAb may provide effective immunotherapy against neuroblastoma and may be of particular use in the minimal-residual disease setting

Indigenous Health: ACTION on Prevention - 50th Annual Australian Society for Medical Research National Scientific Conference (Conference report)

The 50th annual National Scientific Conference of the Australian Society for Medical Research was held in Cairns, Queensland, 13-16 November 2011. The theme, 'Indigenous Health: ACTION on Prevention' highlighted the direct action being undertaken by health and medical researchers, as well as allied health professionals, to improve long-term health outcomes for Indigenous Australians.</p

Immune characterization of pre-clinical murine models of neuroblastoma

Immunotherapy offers a potentially less toxic, more tumor-specific treatment for neuroblastoma than conventional cytotoxic therapies. Accurate and reproducible immune competent preclinical models are key to understanding mechanisms of action, interactions with other therapies and mechanisms of resistance to immunotherapy. Here we characterized the tumor and splenic microenvironment of two syngeneic subcutaneous (NXS2 and 9464D), and a spontaneous transgenic (TH-MYCN) murine model of neuroblastoma, comparing histological features and immune infiltrates to previously published data on human neuroblastoma. Histological sections of frozen tissues were stained by immunohistochemistry and immunofluorescence for immune cell markers and tumor architecture. Tissues were dissociated by enzymatic digestion, stained with panels of antibodies to detect and quantify cancer cells, along with lymphocytic and myeloid infiltration by flow cytometry. Finally, we tested TH-MYCN mice as a feasible model for immunotherapy, using prior treatment with cyclophosphamide to create a therapeutic window of minimal residual disease to favor host immune development. Immune infiltration differed significantly between all the models. TH-MYCN tumors were found to resemble immune infiltration in human tumors more closely than the subcutaneous models, alongside similar GD2 and MHC class I expression. Finally, TH-MYCN transgenic mice were administered cyclophosphamide alone or in combination with an anti-GD2 or anti-4-1BB monoclonal antibody, which resulted in increase in survival in both combination therapies. The TH-MYCN transgenic mouse is a promising in vivo model for testing immunotherapy compounds and combination therapy in a preclinical setting