Peter Windrem Oral History Interview

https://scholarlycommons.pacific.edu/raymond-college/1087/thumbnail.jp

Phyllis Morales Oral History Interview

https://scholarlycommons.pacific.edu/raymond-college/1082/thumbnail.jp

System for Secure Integration of Aviation Data

The Aviation Data Integration System (ADIS) of Ames Research Center has been established to promote analysis of aviation data by airlines and other interested users for purposes of enhancing the quality (especially safety) of flight operations. The ADIS is a system of computer hardware and software for collecting, integrating, and disseminating aviation data pertaining to flights and specified flight events that involve one or more airline(s). The ADIS is secure in the sense that care is taken to ensure the integrity of sources of collected data and to verify the authorizations of requesters to receive data. Most importantly, the ADIS removes a disincentive to collection and exchange of useful data by providing for automatic removal of information that could be used to identify specific flights and crewmembers. Such information, denoted sensitive information, includes flight data (here signifying data collected by sensors aboard an aircraft during flight), weather data for a specified route on a specified date, date and time, and any other information traceable to a specific flight. The removal of information that could be used to perform such tracing is called "deidentification." Airlines are often reluctant to keep flight data in identifiable form because of concerns about loss of anonymity. Hence, one of the things needed to promote retention and analysis of aviation data is an automated means of de-identification of archived flight data to enable integration of flight data with non-flight aviation data while preserving anonymity. Preferably, such an automated means would enable end users of the data to continue to use pre-existing data-analysis software to identify anomalies in flight data without identifying a specific anomalous flight. It would then also be possible to perform statistical analyses of integrated data. These needs are satisfied by the ADIS, which enables an end user to request aviation data associated with de-identified flight data. The ADIS includes client software integrated with other software running on flight-operations quality-assurance (FOQA) computers for purposes of analyzing data to study specified types of events or exceedences (departures of flight parameters from normal ranges). In addition to ADIS client software, ADIS includes server hardware and software that provide services to the ADIS clients via the Internet (see figure). The ADIS server receives and integrates flight and non-flight data pertaining to flights from multiple sources. The server accepts data updates from authorized sources only and responds to requests from authorized users only. In order to satisfy security requirements established by the airlines, (1) an ADIS client must not be accessible from the Internet by an unauthorized user and (2) non-flight data as airport terminal information system (ATIS) and weather data must be displayed without any identifying flight information. ADIS hardware and software architecture as well as encryption and data display scheme are designed to meet these requirements. When a user requests one or more selected aviation data characteristics associated with an event (e.g., a collision, near miss, equipment malfunction, or exceedence), the ADIS client augments the request with date and time information from encrypted files and submits the augmented request to the server. Once the user s authorization has been verified, the server returns the requested information in de-identified form

Human Glial Progenitor Cells Effectively Remyelinate the Demyelinated Adult Brain

Neonatally transplanted human glial progenitor cells (hGPCs) can myelinate the brains of myelin-deficient shiverer mice, rescuing their phenotype and survival. Yet, it has been unclear whether implanted hGPCs are similarly able to remyelinate the diffusely demyelinated adult CNS. We, therefore, ask if hGPCs could remyelinate both congenitally hypomyelinated adult shiverers and normal adult mice after cuprizone demyelination. In adult shiverers, hGPCs broadly disperse and differentiate as myelinating oligodendrocytes after subcortical injection, improving both host callosal conduction and ambulation. Implanted hGPCs similarly remyelinate denuded axons after cuprizone demyelination, whether delivered before or after demyelination. RNA sequencing (RNA-seq) of hGPCs back from cuprizone-demyelinated brains reveals their transcriptional activation of oligodendrocyte differentiation programs, while distinguishing them from hGPCs not previously exposed to demyelination. These data indicate the ability of transplanted hGPCs to disperse throughout the adult CNS, to broadly myelinate regions of dysmyelination, and also to be recruited as myelinogenic oligodendrocytes later in life, upon demyelination-associated demand

Human Glia Can Both Induce and Rescue Aspects of Disease Phenotype in Huntington Disease

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder

Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice

SummaryHuman astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.Video Abstrac

Organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia

Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory papillae: the fungiform, circumvallate, and foliate. The gustatory papillae are composed of an epithelium that covers a broad connective tissue core, with extensive innervation to taste bud and nongustatory epithelial locations. Although the temporal sequence of gustatory papilla development is known for several species, factors that regulate initiation, growth, and maintenance of the papillae are not understood. We tested the hypothesis that sensory innervation is required for the initial formation and early morphogenesis of fungiform papillae in a patterned array. An organ culture of the embryonic rat tongue was developed to provide an in vitro system for studying mechanisms involved in fungiform papilla morphogenesis in patterns on the anterior tongue. Tongues were dissected from embryos at 13 days of gestation (E13), a time when the tongue has not yet fully formed and gustatory papillae have not yet appeared, and at 14 days of gestation (E14), when the tongue is well formed and papillae make their initial morphological appearance. Dissected tongues were maintained at the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus 2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in culture, tongues were processed for scanning electron or light microscopy, or immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive morphogenesis and growth in vitro. Furthermore, fungiform papillae developed on these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the characteristic time for gustatory papilla formation in the intact embryo, results demonstrate that the cultured tongues retain important temporal information related to papilla development. In addition, fungiform papillae formed in the tongue cultures in the stereotypic pattern of rows. The papillae were large structures with epithelial and mesenchymal cell integrity, and an intact epithelial basement membrane was indicated with laminin immunoreactivity. The cultures demonstrate that gustatory papilla morphogenesis can progress in the absence of an intact sensory innervation. To exclude a potential developmental role for autonomic ganglion cells that are located in the posterior rat tongue, cultures consisting of only the anterior half of E14 tongues were established. Fungiform papilla development progressed in half tongues in a manner directly comparable to whole tongue cultures. Therefore, robust, reproducible development of fungiform papillae in patterns is supported in rat tongue cultures from E13 or E14, without inclusion of intact sensory or major, posterior tongue autonomic ganglia. This is direct evidence that papillae will form and develop further in vitro without sensory ganglion support. The data also provide the first detailed account of in vitro development of the entire embryonic tongue. J. Comp. Neurol. 377:324–340, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34447/1/2_ftp.pd