Systematics of the North American Plums (Prunus subgenus Prunus section \u3cem\u3ePrunocerasus\u3c/em\u3e; Rosaceae)

The North American plums (Prunus subgenus Prunus section Prunocerasus; Rosaceae) are a closely related group with approximately 17 commonly recognized species and lesser taxa. They are infamous for their very poor development of reproductively isolating barriers and most are interfertile in many combinations. This interfertility blurs nearly all morphologically-based taxonomic boundaries. Even still, geographically related morphological variation exists and when intermediates are ignored several taxa may be seen as being reasonably different from one another with respect to both morphology and ecology. Additionally, the ranges of most of the North American plum taxa overlap with the ranges of several others. The only exception is P. subcordata, which is the only species in the section whose range is west of the Rocky Mountains. The aim of this dissertation research was to infer a phylogeny for the group in an attempt to understand their complicated evolutionary history. Emphasis was placed on using molecular tools (e.g., PCR and DNA sequencing) to tease apart their intricate relationships. The importance of this course of study includes but is not limited to: (1) better understanding a difficult group of taxa for academic reasons, (2) accumulating data to better understand these taxa so that conservation efforts can be better focused (e.g., P. geniculate is Federally Endangered), (3) better understanding the relationships among a group of plants with economic importance, (4) testing the limits of tools currently used in plant molecular systematics—the North American plums posit a problem at the boundary between molecular phylogenetics and population genetics, and (5) adding to a body of knowledge surrounding longstanding biogeographic questions of North America, namely the Atlantic and Gulf Coastal Plain disjunction to the Great Lakes region and the eastern North America-western North America disjunction. This research dissertation is the accumulation of information from four original research papers and a National Science Foundation Dissertation Improvement Grant. All papers have either been published, submitted, or will be submitted to the American Journal of Botany The results of this coarse of study showed that (1) predictable rate heterogeneity exists among noncoding cpDNA regions and several rarely used regions provide more mutations to phylogenetic investigations than the most commonly used regions (Part 3). (2) The North American plums are monophyletic (Part 4). (3) Most North American plum taxa are para- and polyphyletic with respect to their chloroplasts—more than one of the three primary chloro-haplotypes was observed in 12 of 17 of the North American plum taxa (Part 5). (4) Most North American plum taxa are not monophyletic with respect to their nuclear encoded s6pdh genes—three primary haplotypes are shared among most taxa (Part 6). Total evidence provided by this investigation strongly supports the hypothesis of the North American plums are a syngameon, or hybridizing species group

The Woody Plants of the Big South Fork National River and Recreation Area

The woody flora of the Big South Fork National River and Recreation Area was collected during two growing seasons from 1999 to 2000. The 123,000 acre study area lies on the Cumberland Plateau in Tennessee and Kentucky. Seven hundred and sixty accessions yielded 51 families, 100 genera, and 183 species. County records totaled 128. Magnolia fraseri was collected for the first time from the Cumberland Plateau in Tennessee. Fourteen Federal or State listed taxa were collected including Comptonia peregrina, which has only been collected two other times dating back to 1842. Voucher specimens were deposited in the herbarium of the University of Tennessee, Knoxville. Comparisons were drawn between the BSFNRRA and several other floras in the surrounding southern Appalachians. The BSFNRRA is also directly compared to the epitome of richness for the eastern USA, the Great Smoky Mountains National Park. These comparisons yielded unexpected results in that the BSFNRRA contains more woody families than does the GSMNP and is the richest among all of the natural areas of the Cumberland Plateau. An artificial key to the known and expected woody plants of the BSFNRRA was created and accompanies the great amount of data compiled in this study, all of which is available on the companion CD. With this work, I hope to elevate public awareness of this national land and help to secure its preservation for future biological entities

Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: A nine-year follow up of the UK Biobank cohort

Background: The association between loneliness and suicide is poorly understood. We investigated how living alone, loneliness and emotional support were related to suicide and self-harm in a longitudinal design. Methods: Between 2006 and 2010 UK Biobank recruited and assessed in detail over 0.5 million people in middle age. Data were linked to prospective hospital admission and mortality records. Adjusted Cox regression models were used to investigate relationships between living arrangements, loneliness and emotional support, and both suicide and self-harm as outcomes. Results: For men, both living alone (Hazard Ratio (HR) 2.16, 95%CI 1.51-3.09) and living with non-partners (HR 1.80, 95%CI 1.08-3.00) were associated with death by suicide, independently of loneliness, which had a modest relationship with suicide (HR 1.43, 95%CI 0.1.01-2.03). For women, there was no evidence that living arrangements, loneliness or emotional support were associated with death by suicide. Associations between living alone and self-harm were explained by health for women, and by health, loneliness and emotional support for men. In fully adjusted models, loneliness was associated with hospital admissions for self-harm in both women (HR 1.89, 95%CI 1.57-2.28) and men (HR 1.74, 95%CI 1.40-2.16). Limitations: Loneliness and emotional support were operationalized using single item measures. Conclusions: For men - but not for women - living alone or living with a non-partner increased the risk of suicide, a finding not explained by subjective loneliness. Overall, loneliness may be more important as a risk factor for self-harm than for suicide. Loneliness also appears to lessen the protective associations of cohabitation

Carotid intima-media thickness novel loci, sex-specific effects, and genetic correlations with obesity and glucometabolic traits in UK Biobank

Objective: Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements. Approach and Results: We used BOLT-LMM to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight VCAN as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease. Conclusions: These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression

Unlocking the genetic diversity and population structure of the newly introduced two-row spring European HerItage Barley collecTion (ExHIBiT)

In the last century, breeding programs have traditionally favoured yield-related traits, grown under high-input conditions, resulting in a loss of genetic diversity and an increased susceptibility to stresses in crops. Thus, exploiting understudied genetic resources, that potentially harbour tolerance genes, is vital for sustainable agriculture. Northern European barley germplasm has been relatively understudied despite its key role within the malting industry. The European Heritage Barley collection (ExHIBiT) was assembled to explore the genetic diversity in European barley focusing on Northern European accessions and further address environmental pressures. ExHIBiT consists of 363 spring-barley accessions, focusing on two-row type. The collection consists of landraces (~14%), old cultivars (~18%), elite cultivars (~67%) and accessions with unknown breeding history (~1%), with 70% of the collection from Northern Europe. The population structure of the ExHIBiT collection was subdivided into three main clusters primarily based on the accession's year of release using 26,585 informative SNPs based on 50k iSelect single nucleotide polymorphism (SNP) array data. Power analysis established a representative core collection of 230 genotypically and phenotypically diverse accessions. The effectiveness of this core collection for conducting statistical and association analysis was explored by undertaking genome-wide association studies (GWAS) using 24,876 SNPs for nine phenotypic traits, four of which were associated with SNPs. Genomic regions overlapping with previously characterised flowering genes (HvZTLb) were identified, demonstrating the utility of the ExHIBiT core collection for locating genetic regions that determine important traits. Overall, the ExHIBiT core collection represents the high level of untapped diversity within Northern European barley, providing a powerful resource for researchers and breeders to address future climate scenarios.</p

Unlocking the genetic diversity and population structure of the newly introduced two-row spring European HerItage Barley collecTion (ExHIBiT)

In the last century, breeding programs have traditionally favoured yield-related traits, grown under high-input conditions, resulting in a loss of genetic diversity and an increased susceptibility to stresses in crops. Thus, exploiting understudied genetic resources, that potentially harbour tolerance genes, is vital for sustainable agriculture. Northern European barley germplasm has been relatively understudied despite its key role within the malting industry. The European Heritage Barley collection (ExHIBiT) was assembled to explore the genetic diversity in European barley focusing on Northern European accessions and further address environmental pressures. ExHIBiT consists of 363 spring-barley accessions, focusing on two-row type. The collection consists of landraces (~14%), old cultivars (~18%), elite cultivars (~67%) and accessions with unknown breeding history (~1%), with 70% of the collection from Northern Europe. The population structure of the ExHIBiT collection was subdivided into three main clusters primarily based on the accession's year of release using 26,585 informative SNPs based on 50k iSelect single nucleotide polymorphism (SNP) array data. Power analysis established a representative core collection of 230 genotypically and phenotypically diverse accessions. The effectiveness of this core collection for conducting statistical and association analysis was explored by undertaking genome-wide association studies (GWAS) using 24,876 SNPs for nine phenotypic traits, four of which were associated with SNPs. Genomic regions overlapping with previously characterised flowering genes (HvZTLb) were identified, demonstrating the utility of the ExHIBiT core collection for locating genetic regions that determine important traits. Overall, the ExHIBiT core collection represents the high level of untapped diversity within Northern European barley, providing a powerful resource for researchers and breeders to address future climate scenarios.</p

Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide

Background: Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic. Methods: Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: ‘no suicidality’ controls (N = 83,557); ‘thoughts that life was not worth living’ (N = 21,063); ‘ever contemplated self-harm’ (N = 13,038); ‘act of deliberate self-harm in the past’ (N = 2498); and ‘previous suicide attempt’ (N = 2666). Outcomes: We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). Interpretation: These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level

Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer

INTRODUCTION: Multiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required. METHODS AND ANALYSIS: This study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer. ETHICS AND DISSEMINATION: Ethical approval was granted by the London-Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04792138

Digitization workflows for flat sheets and packets of plants, algae, and fungi

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141708/1/aps31500065.pd

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure