916 research outputs found

    A Conviction of Texts Not Seen: Perceiving Exodus as the Generative Text of Hebrews

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    The Book of Hebrews has increasingly come to be regarded as a remarkable example of Jewish-Christian scriptural exegesis and biblical intertextuality. Scholars routinely apply terms associated with ancient Jewish exegesis to Hebrews, including midrash, gezerah shewa, qal wahomer, and synagogue homily. One problem, however, is that most analyses in which Christian views of scripture are operative tend to overlook key elements of Jewish concepts of scripture, particularly with regard to the significance of the Pentateuch. The Pentateuch, or Torah, forms the nucleus of the Scriptures from a Jewish perspective, the first and most important division of the Scriptures, different in nature and priority than the rest of the Hebrew Bible. Most ancient Jewish exegesis was Torah-centric, as is evident by the prominence of the Books of Moses in works like the Mekilta on Exodus, the oldest collections of rabbinic midrash, and even biblical texts and exegetical works like Jubilees among the Dead Sea Scrolls. Most studies of Hebrews, on the other hand, prioritize texts from the Psalms and Prophets in interpretation. Hebrews has often been characterized as a midrash on Ps 110 or as a series expositions on texts from the Prophets and Writings, for instance. Those approaches do not adequately account for the fundamental and generative role of the Pentateuch. If Hebrews is, indeed, an exegetical work like midrash or a form of synagogue homily, we would, instead, expect it to be based on a generative text (or texts) from the Pentateuch. This study proposes that the Sinai pericope of Exodus (Exod 19-40) serves as the primary generative text of Hebrews and that the many citations of the Prophets and Writings function exegetically in relation to Exodus. Hebrews\u27 message emerges from the juxtaposition of texts and themes of Exodus with texts from the Prophets and Writings. The Psalms, Proverbs, Isaiah, Jeremiah and Haggai are all used to explain and expound upon Pentateuchal paradigms such as the Sinai Covenant, Moses, Aaron\u27s priesthood, and the wilderness sanctuary, showing how Jesus and his ministry relate to what had been the reigning paradigms for centuries. This study examines five major exegetical sections of Hebrews to demonstrate how Hebrews uses texts from the Prophets and Writings in its exegesis of themes, passages and verses from Exodus 19-40 to legitimize and explain the person and ministry of Jesus in relation to the Law of Moses

    Surface materials of the Viking landing sites

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    Martian surface materials viewed by the two Viking landers (VL-1 and VL-2) range from fine-grained nearly cohesionless soils to rocks. Footpad 2 of VL-1, which landed at 2.30 m/s, penetrated 16.5 cm into very fine grained dunelike drift material; footpad 3 rests on a rocky soil which it penetrated ≈3.6 cm. Further penetration by footpad 2 may have been arrested by a hard substrate. Penetration by footpad 3 is less than would be expected for a typical lunar regolith. During landing, retroengine exhausts eroded the surface and propelled grains and rocks which produced craters on impact with the surface. Trenches excavated in drift material by the sampler have steep walls with up to 6 cm of relief. Incipient failure of the walls and failures at the end of the trenches are compatible with a cohesion near 10–10^2 N/m^2. Trenching in rocky soil excavated clods and possibly rocks. In two of five samples, commanded sampler extensions were not achieved, a situation indicating that buried rocks or local areas with large cohesions (≥10 kN/m^2) or both are present. Footpad 2 of VL-2, which landed at a velocity between 1.95 and 2.34 m/s, is partly on a rock, and footpad 3 appears to have struck one; penetration and leg strokes are small. Retroengine exhausts produced more erosion than occurred for VL-1 owing to increased thrust levels just before touchdown. Deformations of the soil by sampler extensions range from doming of the surface without visible fracturing to doming accompanied by fracturing and the production of angular clods. Although rocks larger than 3.0 cm are abundant at VL-1 and VL-2, repeated attempts to collect rocks 0.2–1.2 cm across imbedded in soil indicate that rocks in this size range are scarce. There is no evidence that the surface sampler of VL-2, while it was pushing and nudging rocks ≈25 cm across, spalled, chipped, or fractured the rocks. Preliminary analyses of surface sampler motor currents (≈25 N force resolution) during normal sampling are consistent with cohesionless frictional soils (ϕ ≈ 36°) or weakly cohesive frictionless soils (C < 2 kN/m^2). The soil of Mars has both cohesion and friction

    Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course

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    To characterize HIV-1 env compartmentalization between cerebrospinal fluid (CSF) and peripheral blood plasma over all stages of the HIV-1 disease course, and to determine the relationship between the extent of CSF HIV-1 env compartmentalization and clinical neurologic disease status

    Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

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    This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

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

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    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

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

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    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

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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

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

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    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

    HIV-1 superinfection results in broad polyclonal neutralizing antibodies

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    <div><p>HIV-1 vaccines designed to date have failed to elicit neutralizing antibodies (Nabs) that are capable of protecting against globally diverse HIV-1 subtypes. One relevant setting to study the development of a strong, cross-reactive Nab response is HIV-1 superinfection (SI), defined as sequential infections from different source partners. SI has previously been shown to lead to a broader and more potent Nab response when compared to single infection, but it is unclear whether SI also impacts epitope specificity and if the epitopes targeted after SI differ from those targeted after single infection. Here the post-SI Nab responses were examined from 21 Kenyan women collectively exposed to subtypes A, C, and D and superinfected after a median time of ~1.07 years following initial infection. Plasma samples chosen for analysis were collected at a median time point ~2.72 years post-SI. Because previous studies of singly infected populations with broad and potent Nab responses have shown that the majority of their neutralizing activity can be mapped to 4 main epitopes on the HIV-1 Envelope, we focused on these targets, which include the CD4-binding site, a V1/V2 glycan, the N332 supersite in V3, and the membrane proximal external region of gp41. Using standard epitope mapping techniques that were applied to the previous cohorts, the present study demonstrates that SI did not induce a dominant Nab response to any one of these epitopes in the 21 women. Computational sera delineation analyses also suggested that 20 of the 21 superinfected women’s Nab responses could not be ascribed a single specificity with high confidence. These data are consistent with a model in which SI with diverse subtypes promotes the development of a broad polyclonal Nab response, and thus would provide support for vaccine designs using multivalent HIV immunogens to elicit a diverse repertoire of Nabs.</p></div
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