Matanuska Valley Memoir

We acknowledge indebtedness to the historians and developers of Alaskana who preceded us and provided much of the information we have compiled into our account of the birth of a community. Many "old timers" from the Valley provided valuable insight into situations they had experienced. Mr. Roland Snodgrass, Mrs, June Murphy and Miss Dolores Pommier assisted in compilation and preparation of background data. Mr. James Hurley made available to us the ARRC unpublished files for compilation of certain data. Various public officials aided us in many ways as we worked· our way through recorded . history. Several old photos were contributed by Mr. Walter Teeland of Wasilla and Mr. Don L. Irwin of Palmer. Several persons in public and private life who know Alaskan conditions have reviewed the manuscript and suggested improvements, Special acknowledgement is due Don L. Irwin, Director of the Alaska Agricultural Experiment Station, His vision and foresight were largely responsible for the undertaking, His encouragement and advice bolstered our lagging spirits before the long task was completed. He has read each chapter critically and has assisted particularly with interpretation of materials since 1935,The Matanuska Valley was created through action of ice, water and wind. When the last glaciers retreated up the Susitna, the Knik and the Matanuska valleys, vegetation began cove ring the scars, Over several centuries a dense growth of trees and brush screened the land from Knik Arm to the mountain slopes of the Talkeetna range . Here and there a lake broke the uniform forest mantle. A salt marsh at the mouth of the Matanuska River kept the rank undergrowth from reaching tide water, A few low spots near the Little Susitna and other swampy areas supported a thick cover of moss or grass. The Valley, which really isn't a valley at all but a reworked foreland, rises from the Matanuska River in a series of benches ranging in width from a few hundred feet to more than a mile. Some areas are flat, others are rolling. Soil depth varies from eight feet in thickness for the region bordering the Matanuska River to a few inches in sections west of Wasilla. The soil mantle, of windblown loessial materials, is of relatively new geologic development, The Valley is bounded by the Chugach Mountains on the east, the Talkeetnas on the north, the Susitna Valley on the west and Knik Arm on the south. Winters are long but usually not unduly severe; summers cool and relatively moist, To this country came trappers, prospectors and traders in closing years of the nineteenth century. Hordes of insects, difficult trails, sparse population and great distance s from supply points discouraged many potential residents, Those who stayed were interested primarily in the Willow Creek gold field or the Matanuska coal deposits. Another generation, an uneasy international situation and social crises within the United States were required before the Matanuska Valley and the rest of Upper Cook Inlet were ripe for use. This history of the Valley is designed to trace the many human elements affecting the ebb and flow of agricultural development here. It brings into focus many problems that must be solved before new areas in Alaska can be settled satisfactorily

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The Enigma of Soil Animal Species Diversity Revisited: The Role of Small-Scale Heterogeneity

Peer reviewedPublisher PD

Model-Based Methods to Translate Adolescent Medicine Trials Network for HIV/AIDS Interventions Findings Into Policy Recommendations: Rationale and Protocol for a Modeling Core (ATN 161)

BACKGROUND: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway. OBJECTIVE: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective. METHODS: This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data-already collected by successfully completed National Institutes of Health-supported studies-to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions. RESULTS: This project was funded as of September 2017. CONCLUSIONS: The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States

Efficient Coding and Statistically Optimal Weighting of Covariance among Acoustic Attributes in Novel Sounds

To the extent that sensorineural systems are efficient, redundancy should be extracted to optimize transmission of information, but perceptual evidence for this has been limited. Stilp and colleagues recently reported efficient coding of robust correlation (r = .97) among complex acoustic attributes (attack/decay, spectral shape) in novel sounds. Discrimination of sounds orthogonal to the correlation was initially inferior but later comparable to that of sounds obeying the correlation. These effects were attenuated for less-correlated stimuli (r = .54) for reasons that are unclear. Here, statistical properties of correlation among acoustic attributes essential for perceptual organization are investigated. Overall, simple strength of the principal correlation is inadequate to predict listener performance. Initial superiority of discrimination for statistically consistent sound pairs was relatively insensitive to decreased physical acoustic/psychoacoustic range of evidence supporting the correlation, and to more frequent presentations of the same orthogonal test pairs. However, increased range supporting an orthogonal dimension has substantial effects upon perceptual organization. Connectionist simulations and Eigenvalues from closed-form calculations of principal components analysis (PCA) reveal that perceptual organization is near-optimally weighted to shared versus unshared covariance in experienced sound distributions. Implications of reduced perceptual dimensionality for speech perception and plausible neural substrates are discussed