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This thesis is an iconographic study of the four earliest and relatively complete tenth-century manuscripts of Beatus’ Commentary on the Apocalypse: New York, Pierpont Morgan Library MS M. 644 (the Morgan Beatus); Valladolid, Biblioteca de la Universidad de Valladolid MS 433 (the Valladolid Beatus); Girona, Museu de la Catedral de Girona MS 7(11) (the Girona Beatus) and La Seu d’Urgell, Museu Diocesá de La Seu d’Urgell MS 501 (the Urgell Beatus). As a part of the tenth-century revival of Beatus’ text that initially was penned in the eighth-century, these works were created in monastic centres during a period when conflict between the Christian kingdoms in the north and Islamic rulers in the south was at a peak, the manuscripts’ iconographic innovations reflect the social, political and religious circumstances of their patrons, creators and audiences. While these manuscripts offer the possibility of furthering scholastic understanding of Iberia prior to the year 1000 the majority of past scholarship has been devoted to defining dates, stemma and the physical characteristics of the works. Debates over descriptions of style, labels and influence have overshadowed discussions of iconographic significance, which have begun to emerge only in the last few decades. Therefore, this thesis provides iconographic analysis of five under-studied scenes, which include the Mappamundi, the Four Beasts and the Statue, Noah’s Ark, the Palm Tree and the Fox and the Cock. While these images are just five of up to 120 included in the illustrative programmes of these manuscripts, they are the only scenes that illustrate the text of Beatus’ Commentary, rather than the narrative of Revelation. This is significant because these extra-apocalyptic scenes were selected and created specifically because of the messages within the Commentary that they enhance; the ideas promoted through these images are not restricted by the narrative of Revelation and therefore reveal much about the political, religious and social situation in the northern Iberian Christian communities that created them. By discussing the visual elements of these five images in conjunction with iconographic traditions from other parts of western Europe, the Byzantine world, the Mediterranean and the Islamic world, this thesis will examine the Beatus illustrations and, on a larger scale, the production of these manuscripts, in relation to the historical struggles of the time. Informed by postcolonial theory, it will not only diverge from the standard ways of approaching these works, but also will bring new insight into the Christian perspective of Muslim occupation in medieval Iberia, suggesting that monastic communities were attempting to combat the Muslim threat by encouraging participation in and dispersal of the Christian faith in order to maintain Christian practices and beliefs on the Iberian Peninsula and furthermore to assert Christian dominance at the Judgment.

Shows how the tobacco mosaic virus can be used in conjunction with the common bean plant Phaseolus vulgaris to provide a discernable, experimental model that students can use to study induced resistance. (Contains 17 references.) (DDR)

Lifelong noninvasive rejection monitoring in heart transplant patients is a critical clinical need historically poorly met in adults and unavailable for children and infants. Cell-free DNA (cfDNA) donor-specific fraction (DF), a direct marker of selective donor organ injury, is a promising analytical target. Methodological differences in sample processing and DF determination profoundly affect quality and sensitivity of cfDNA analyses, requiring specialized optimization for low cfDNA levels typical of transplant patients. Using next-generation sequencing, we previously correlated elevated DF with acute cellular and antibody-mediated rejection (ACR and AMR) in pediatric and adult heart transplant patients. However, next-generation sequencing is limited by cost, TAT, and sensitivity, leading us to clinically validate a rapid, highly sensitive, quantitative genotyping test, myTAIHEART®, addressing these limitations. To assure pre-analytical quality and consider interrelated cfDNA measures, plasma preparation was optimized and total cfDNA (TCF) concentration, DNA fragmentation, and DF quantification were validated in parallel for integration into myTAIHEART reporting. Analytical validations employed individual and reconstructed mixtures of human blood-derived genomic DNA (gDNA), cfDNA, and gDNA sheared to apoptotic length. Precision, linearity, and limits of blank/detection/quantification were established for TCF concentration, DNA fragmentation ratio, and DF determinations. For DF, multiplexed high-fidelity amplification followed by quantitative genotyping of 94 SNP targets was applied to 1168 samples to evaluate donor options in staged simulations, demonstrating DF call equivalency with/without donor genotype. Clinical validation studies using 158 matched endomyocardial biopsy-plasma pairs from 76 pediatric and adult heart transplant recipients selected a DF cutoff (0.32%) producing 100% NPV for ≥2R ACR. This supports the assay's conservative intended use of stratifying low versus increased probability of ≥2R ACR. myTAIHEART is clinically validated for heart transplant recipients ≥2 months old and ≥8 days post-transplant, expanding opportunity for noninvasive transplant rejection assessment to infants and children and to all recipients >1 week post-transplant.

Purpose: Screening multiple genes for inherited cancer predisposition expands opportunities for cancer prevention; however, reports of variants of uncertain significance (VUS) may limit clinical usefulness. We used an expert-driven approach, exploiting all available information, to evaluate multigene panels for inherited cancer predisposition in a clinical series that included multiple cancer types and complex family histories. Methods: For 1,462 sequential patients referred for testing by BROCA or ColoSeq multigene panels, genomic DNA was sequenced and variants were interpreted by multiple experts using International Agency for Research on Cancer guidelines and incorporating evolutionary conservation, known and predicted variant consequences, and personal and family cancer history. Diagnostic yield was evaluated for various presenting conditions and family-history profiles. Results: Of 1,462 patients, 12% carried damaging mutations in established cancer genes. Diagnostic yield varied by clinical presentation. Actionable results were identified for 13% of breast and colorectal cancer patients and for 4% of cancer-free subjects, based on their family histories of cancer. Incidental findings explaining cancer in neither the patient nor the family were present in 1.7% of subjects. Less than 1% of patients carried VUS in BRCA1 or BRCA2 . For all genes combined, initial reports contained VUS for 10.5% of patients, which declined to 7.5% of patients after reclassification based on additional information. Conclusions: Individualized interpretation of gene panels is a complex medical activity. Interpretation by multiple experts in the context of personal and family histories maximizes actionable results and minimizes reports of VUS. Genet Med 18 10, 974–981.

Course-based Undergraduate Research Experiences (CUREs) provide an accessible, scalable platform for scientific discovery. Here, we present the WormFood CURE, which mines environmental bacterial isolates for bioactive secondary metabolites using Caenorhabditis elegans phenotype suppression as a functional readout. Utilizing the multivulva (Muv) phenotype, our pilot cohort interrogated 41 wild bacterial isolates for suppression of Ras/MAPK signaling. We identified one Bacillus safensis isolate BAC-08 and one Bacillus altitudinis isolate BAC-44 that significantly inhibited ectopic vulval precursor cell (VPC) induction in Muv strains when fed as a live food source. BAC-08 and BAC-44 also significantly affected wild-type nematode development and growth. Metabolic pathway reconstruction from annotated genome assemblies did not support nutritional deficiency as the potential mechanism; instead, we observed that methanol-soluble intracellular extracts from BAC-44 were sufficient to inhibit pseudovulvae growth. We concluded that the observed Muv suppression is likely driven by a secondary metabolite effect. Comparative genomic analysis further identified unique biosynthetic gene clusters (BGCs) present in both BAC-08 and BAC-44 isolates compared to the other isolated Bacillus species. Altogether, our study demonstrates that the WormFood CURE model successfully identifies novel bacterial-genetic interactions, providing a scalable platform for discovery of new natural microbial products that modulate conserved eukaryotic signaling pathways.