Topological Signals of Singularities in Ricci Flow

We implement methods from computational homology to obtain a topological signal of singularity formation in a selection of geometries evolved numerically by Ricci flow. Our approach, based on persistent homology, produces precise, quantitative measures describing the behavior of an entire collection of data across a discrete sample of times. We analyze the topological signals of geometric criticality obtained numerically from the application of persistent homology to models manifesting singularities under Ricci flow. The results we obtain for these numerical models suggest that the topological signals distinguish global singularity formation (collapse to a round point) from local singularity formation (neckpinch). Finally, we discuss the interpretation and implication of these results and future applications.Comment: 24 pages, 14 figure

New concepts in breast cancer genomics and genetics

Massively parallel DNA and RNA sequencing approaches have generated data on thousands of breast cancer genomes. In this review, we consider progress largely from the perspective of new concepts and hypotheses raised so far. These include challenges to the multistep model of breast carcinogenesis and the discovery of new defects in DNA repair through sequence analysis. Issues for functional genomics include the development of strategies to differentiate between mutations that are likely to drive carcinogenesis and bystander background mutations, as well as the importance of mechanistic studies that examine the role of mutations in genes with roles in splicing, histone methylation, and long non-coding RNA function. The application of genome-annotated patient-derived breast cancer xenografts as a potentially more reliable preclinical model is also discussed. Finally, we address the challenge of extracting medical value from genomic data. A weakness of many datasets is inadequate clinical annotation, which hampers the establishment of links between the mutation spectra and the efficacy of drugs or disease phenotypes. Tools such as dGene and the DGIdb are being developed to identify possible druggable mutations, but these programs are a work in progress since extensive molecular pharmacology is required to develop successful ‘genome-forward’ clinical trials. Examples are emerging, however, including targeting HER2 in HER2 mutant breast cancer and mutant ESR1 in ESR1 endocrine refractory luminal-type breast cancer. Finally, the integration of DNA- and RNA-based sequencing studies with mass spectrometry-based peptide sequencing and an unbiased determination of post-translational modifications promises a more complete view of the biochemistry of breast cancer cells and points toward a new discovery horizon in our understanding of the pathophysiology of this complex disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0460-4) contains supplementary material, which is available to authorized users

Consistent Nest Site Selection by Turtles Across Habitats With Varying Levels of Human Disturbance

Human disturbance impacts the breeding behavior of many species, and it is particularly important to understand how these human-caused changes affect vulnerable taxa, such as turtles. Habitat alteration can change the amount and quality of suitable nesting habitat, while human presence during nesting may influence nesting behavior. Consequently, both habitat alteration and human presence can influence the microhabitat that females choose for nesting. In the summer of 2019, we located emydid turtle nests in east-central Alabama, USA, in areas with varying levels of human disturbance (high, intermediate, low). We aimed to determine whether turtles selected nest sites based on a range of microhabitat variables comparing maternally selected natural nests to randomly chosen artificial nests. We also compared nest site choice across areas with different levels of human disturbance. Natural nests had less variance in canopy openness and average daily mean and minimum temperature than artificial nests, but microhabitat variables were similar across differing levels of disturbance. Additionally, we experimentally quantified nest predation across a natural to human-disturbed gradient. Nest predation rates were higher in areas with low and intermediate levels of disturbance than in areas with high human disturbance. Overall, these results show that turtles are not adjusting their choices of nest microhabitat when faced with anthropogenic change, suggesting that preserving certain natural microhabitat features will be critical for populations in human-disturbed areas

Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening

Practising the Space Between: Embodying Belief as an Evangelical Anglican Student

This article explores the formation of British evangelical university students as believers. Drawing on ethnographic fieldwork conducted with a conservative evangelical Anglican congregation in London, I describe how students in this church come to embody a highly cognitive, word-based mode of belief through particular material practices. As they learn to identify themselves as believers, practices of reflexivity and accountability enable them to develop a sense of narrative coherence in their lives that allows them to negotiate tensions that arise from their participation in church and broader social structures. I demonstrate that propositional belief – in contexts where it becomes an identity marker – is bound up with relational practices of belief, such that distinctions between “belief in” and “belief that” are necessarily blurred in the lives of young evangelicals

High speed photometry of faint Cataclysmic Variables - VII. Targets selected from the Sloan Digital Sky Survey and the Catalina Real-time Transient Survey

We present high speed photometric observations of 20 faint cataclysmic variables, selected from the Sloan Digital Sky Survey and Catalina catalogues. Measurements are given of 15 new directly measured orbital periods, including four eclipsing dwarf novae (SDSS0904+03, CSS0826-00, CSS1404-10 and CSS1626-12), two new polars (CSS0810+00 and CSS1503-22) and two dwarf novae with superhumps in quiescence (CSS0322+02 and CSS0826-00). Whilst most of the dwarf novae presented here have periods below 2 h, SDSS0805+07 and SSS0617-36 have relatively long orbital periods of 5.489 and 3.440 h, respectively. The double humped orbital modulations observed in SSS0221-26, CSS0345-01, CSS1300+11 and CSS1443-17 are typical of low mass transfer rate dwarf novae. The white dwarf primary of SDSS0919+08 is confirmed to have non-radial oscillations and quasi-periodic oscillations were observed in the short-period dwarf nova CSS1028-08 during outburst. We further report the detection of a new nova-like variable (SDSS1519+06). The frequency distribution of orbital periods of CVs in the Catalina survey has a high peak near ~80 min orbital period, independently confirming that found by Gaensicke et al (2009) from SDSS sources. We also observe a marked correlation between the median in the orbital period distribution and the outburst class, in the sense that dwarf novae with a single observed outburst (over the 5-year baseline of the CRTS coverage) occur predominantly at shortest orbital period.Comment: 17 pages, 38 figures, accepted for publication in MNRA

A Characterization of the Shallow-Water Coral Reefs and Associated Habitats of Puerto Rico

We mapped bottom types and shelf zones of 1600 km2 or about one fourth of Puerto Rico’s insular shelf from the shoreline to the shelf edge. Overall map accuracy for these bottom types is estimated as 93.6% correct. Maps were produced through visual interpretation of benthic features using orthorectified aerial photographs within a Geographic Information System with customizable software. The maps are one component of an integrated mapping and monitoring program underway by NOAA and its partners in the US Coral Reef Task Force to assess all US reef ecosystems. Maps are currently being used to enhance coastal research and management activities in Puerto Rico such as fisheries assessments and designation of important fish habitats