Large Deviations for Random Trees

We consider large random trees under Gibbs distributions and prove a Large Deviation Principle (LDP) for the distribution of degrees of vertices of the tree. The LDP rate function is given explicitly. An immediate consequence is a Law of Large Numbers for the distribution of vertex degrees in a large random tree. Our motivation for this study comes from the analysis of RNA secondary structures.Comment: 10 page

Predicting substance use behavior among South African adolescents: The role of leisure experiences across time

Using seven waves of data, collected twice a year from the 8th through the 11th grades in a low-resource community in Cape Town, South Africa, we aimed to describe the developmental trends in three specific leisure experiences (leisure boredom, new leisure interests, and healthy leisure) and substance use (cigarettes, alcohol, and marijuana) behaviors and to investigate the ways in which changes in leisure experiences predict changes in substance use behaviors over time. Results indicated that adolescents’ substance use increased significantly across adolescence, but that leisure experiences remained fairly stable over time. We also found that adolescent leisure experiences predicted baseline substance use and that changes in leisure experiences predicted changes in substance use behaviors over time, with leisure boredom emerging as the most consistent and strongest predictor of alcohol, cigarette, and marijuana use. Implications for interventions that target time use and leisure experiences are discussed.Web of Scienc

Multiple novel caliciviruses identified from stoats (Mustela erminea) in the United Kingdom

The Caliciviridae family, comprising positive-sense RNA viruses, is characterised by its non-enveloped, small virions, broad host range, and notable tendency for host switching. These viruses are primarily associated with gastroenteric disease, though they can lead to haemorrhagic or respiratory infections. Our study employed a metagenomics analysis of faecal samples from stoats (Mustela erminea), identifying two novel calicivirus species, named stoat vesivirus and stoat valovirus. Stoat vesivirus was identified in three samples (ST008, ST006, ST004), exhibiting a genome wide nucleotide identity of approximately 92 %. The complete coding sequences of these samples were 8471 (ST004) and 8322 (ST006) nucleotides in length, respectively. Each comprised three open reading frames (ORF), closely resembling the Vesivirus mink calicivirus (China/2/2016), with 70–72 % similarity in ORF1, 61–62 % in ORF2 and 71 % in ORF3. Phylogenetic analysis robustly supported stoat vesivirus as belonging within the Vesivirus genus. The second calivicirus (stoat valovirus), detected solely in sample ST008, was 6527 nucleotides in length and with complete coding sequences present. It shared highest similarity with St-Valérien swine virus and marmot norovirus HT16, showing 39.5 and 38.8 % protein identity with ORF1 and 43.3 and 42.9 % for VP1. Stoat valovirus is borderline for meeting the ICTV criteria for a new genus, demonstrating 60 % divergence in ORF1 compared to the other valovirus’, however it clusters basally within the Valovirus genus, supporting leaving it included in this genus

Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study

Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs≥50 years) using chi-square tests and analysis of variance tests. Results: Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR=1.45, 95% CI=1.02 to 2.06, for Luminal B; OR=2.04, 95% CI=1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women. Conclusions: Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases

What Physical Processes Drive the Interstellar Medium in the Local Bubble?

Recent 3D high-resolution simulations of the interstellar medium in a star form- ing galaxy like the Milky Way show that supernova explosions are the main driver of the structure and evolution of the gas. Its physical state is largely controlled by turbulence due to the high Reynolds numbers of the average flows. For a constant supernova rate a dynam- ical equilibrium is established within 200 Myr of simulation as a consequence of the setup of a galactic fountain. The resulting interstellar medium reveals a typical density/pressure pattern, i.e. distribution of so-called gas phases, on scales of 500–700 pc, with interstellar bubbles being a common phenomenon just like the Local Bubble and the Loop I superbub- ble, which are assumed to be interacting. However, modeling the Local Bubble is special, because it is driven by a moving group, passing through its volume, as it is inferred from the analysis of Hipparcos data. A detailed analysis reveals that between 14 and 19 super- novae have exploded during the last 15 Myr. The age of the Local Bubble is derived from comparison with HI and UV absorption line data to be 14.5±0.7 Myr. We further predict the 0.4merging of the two bubbles in about 3 Myr from now, when the interaction shell starts to fragment. The Local Cloud and its companion HI clouds are the consequence of a dynamical instability in the interaction shell between the Local and the Loop I bubble

Discovery and development of the N-terminal procollagen type II (NPII) biomarker: a tool for measuring collagen type II synthesis

SummaryObjectiveProgression of joint damage in osteoarthritis (OA) is likely to result from an imbalance between cartilage degradation and synthesis processes. Markers reflecting these two components appear to be promising in predicting the rate of OA progression. Both N- and C-terminal propeptides of type II collagen reflect the rates of collagen type II synthesis. The ability to quantify the procollagen peptides in biological fluids would enable a better understanding of OA disease pathology and provide means for assessing the proof of mechanism of anabolic disease modifying OA drugs (DMOADs).MethodsA polyclonal antibody that recognizes the sequence GPKGQKGEPGDIKDI in the propeptide region of rat, dog, and human type II collagen was raised in chicken and peptide-affinity purified. The immunoaffinity liquid chromatography mass spectrometry (LC-MS/MS) was used to extensively characterize N-terminal procollagen type II (NPII) peptides found in biological fluids. The novel competition enzyme-linked immunosorbent assay (ELISA) assay was developed to quantitatively measure the NPII peptides.ResultsSeveral peptides ranging from 17 to 41 amino acids with various modifications including hydroxylations on proline and lysine residues, oxidation of lysines to allysines, and attachments of glucose and galactose moieties to hydroxylysines were identified in a simple system such as ex vivo cultures of human articular cartilage (HAC) explants as well as in more complex biological fluids such as human urine and plasma. A competitive ELISA assay has been developed and applied to urine, plasma, and synovial fluid matrices in human, rat and dog samples.ConclusionA novel NPII assay has been developed and applied to OA and normal human subjects to understand the changes in collagen type II synthesis related to the pathology of OA

Zinc supplement greatly improves the condition of parkin mutant Drosophila

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which oxidative stress is implicated as a major causative factor. Mutations in the gene encoding Parkin, a ubiquitin ligase, are responsible for a familial form of PD. In a Drosophila disease model lacking Parkin (park(25) null mutant), we tested the effect of zinc supplementation. Zinc is an essential trace metal and a component of many enzymes and transcriptional regulators. Unlike copper and iron, zinc is not redox-active and under most conditions serves as an antioxidant. We find that the condition of parkin mutants raised on zinc-supplemented food is greatly improved. At zinc concentrations where controls begin to show adverse effects as a result of the metal supplement, parkin mutants perform best, as manifested in a higher frequency of reaching adulthood, extended lifespan and improved motoric abilities