Topological Persistence for Relating Microstructure and Capillary Fluid Trapping in Sandstones

Results from a series of two‐phase fluid flow experiments in Leopard, Berea, and Bentheimer sandstones are presented. Fluid configurations are characterized using laboratory‐based and synchrotron based 3‐D X‐ray computed tomography. All flow experiments are conducted under capillary‐dominated conditions. We conduct geometry‐topology analysis via persistent homology and compare this to standard topological and watershed‐partition‐based pore‐network statistics. Metrics identified as predictors of nonwetting fluid trapping are calculated from the different analytical methods and are compared to levels of trapping measured during drainage‐imbibition cycles in the experiments. Metrics calculated from pore networks (i.e., pore body‐throat aspect ratio and coordination number) and topological analysis (Euler characteristic) do not correlate well with trapping in these samples. In contrast, a new metric derived from the persistent homology analysis, which incorporates counts of topological features as well as their length scale and spatial distribution, correlates very well (R2 = 0.97) to trapping for all systems. This correlation encompasses a wide range of porous media and initial fluid configurations, and also applies to data sets of different imaging and image processing protocols.We gratefully acknowledge funding from the member companies of the ANU/UNSW Digicore Research Consortium, as well as the Australian Research Council. Adrian Sheppard is supported by Discovery Project DP160104995, Vanessa Robins is supported by ARC Future Fellowship FT140100604, and Anna Herring is supported by ARC Discovery Early Career Fellowship DE180100082

An Interdisciplinary Analysis of a Corn-based Seed Saving Network

43 pagesThe practice of seed saving has the potential to play a critical role in enhancing the adaptive capacity of the U.S. agricultural system through the protection the crop genetic resource base. It is therefore of value to understand seed savers and the networks that connect them in order to assess their contributions to such a system. In this thesis I take an interdisciplinary approach at analyzing a network of corn (Zea mays) seed savers. Through interviews I explore the characteristics of and relationships among seed savers in the hopes of illuminating the strength of the network and its place in the larger agricultural system. Testing seeds for various seedborne fungal genes~ I explore the possibility of interaction between seed savers' practices and the biology of their seeds. This study serves as a foundation for future research in seed saving network analysis and the interactions of social behavior on seed microbial communities

Skeletonization and Partitioning of Digital Images Using Discrete Morse Theory

We show how discrete Morse theory provides a rigorous and unifying foundation for defining skeletons and partitions of grayscale digital images. We model a grayscale image as a cubical complex with a real-valued function defined on its vertices (the voxel values). This function is extended to a discrete gradient vector field using the algorithm presented in Robins, Wood, Sheppard TPAMI 33:1646 (2011). In the current paper we define basins (the building blocks of a partition) and segments of the skeleton using the stable and unstable sets associated with critical cells. The natural connection between Morse theory and homology allows us to prove the topological validity of these constructions; for example, that the skeleton is homotopic to the initial object. We simplify the basins and skeletons via Morse-theoretic cancellation of critical cells in the discrete gradient vector field using a strategy informed by persistent homology. Simple working Python code for our algorithms for efficient vector field traversal is included. Example data are taken from micro-CT images of porous materials, an application area where accurate topological models of pore connectivity are vital for fluid-flow modelling

DNA content analysis of colorectal cancer defines a distinct ‘microsatellite and chromosome stable’ group but does not predict response to radiotherapy

Colorectal cancers (CRC) are thought to have genetic instability in the form of either microsatellite instability (MSI) or chromosomal instability (CIN). Recently, tumours have been described without either MSI or CIN, that is, microsatellite and chromosome stable (MACS) CRCs. We investigated the (i) frequency of the MACS-CRCs and (ii) whether this genotype predicted responsiveness to neoadjuvant chemoradiotherapy. To examine the frequency of MACS-CRCs, DNA content (ploidy) was examined in 89 sporadic microsatellite-stable CRCs using flow cytometry. The tumours were also screened for mutations in KRAS/BRAF/TP53/PIK3CA by QMC-PCR. To examine the value of tumour ploidy in predicting response to chemoradiotherapy, DNA content was tested in a separate group of 62 rectal cancers treated with neoadjuvant chemoradiotherapy. Fifty-one of 89 CRCs (57%) were aneuploid and 38 (43%) were diploid. There was no significant association between mutations in TP53/KRAS/BRAF/PIK3CA and ploidy. Testing of association between mutations revealed only mutual exclusivity of KRAS/BRAF mutation (P < 0.001). Of the 62 rectal cancers treated with neoadjuvant chemoradiotherapy, 22 had responded (Mandard tumour regression grade 1/2) and 40 failed to respond (Grade 3–5). Twenty-five of 62 (40%) tumours were diploid, but there was no association between ploidy and response to therapy. We conclude that MACS-CRCs form a significant proportion of microsatellite-stable CRCs with a mutation profile overlapping that of CRCs with CIN. A diploid genotype does not, however, predict the responsiveness to radiotherapy

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

Heterogeneous microgeographic genetic structure of the common cockle (Cerastoderma edule) in the Northeast Atlantic Ocean: biogeographic barriers and environmental factors

Knowledge of genetic structure at the finest level is essential for the conservation of genetic resources. Despite no visible barriers limiting gene flow, significant genetic structure has been shown in marine species. The common cockle (Cerastoderma edule) is a bivalve of great commercial and ecological value inhabiting the Northeast Atlantic Ocean. Previous population genomics studies demonstrated significant structure both across the Northeast Atlantic, but also within small geographic areas, highlighting the need to investigate fine-scale structuring. Here, we analysed two geographic areas that could represent opposite models of structure for the species: (1) the SW British Isles region, highly fragmented due to biogeographic barriers, and (2) Galicia (NW Spain), a putative homogeneous region. A total of 9250 SNPs genotyped by 2b-RAD on 599 individuals from 22 natural beds were used for the analysis. The entire SNP dataset mostly confirmed previous observations related to genetic diversity and differentiation; however, neutral and divergent SNP outlier datasets enabled disentangling physical barriers from abiotic environmental factors structuring both regions. While Galicia showed a homogeneous structure, the SW British Isles region was split into four reliable genetic regions related to oceanographic features and abiotic factors, such as sea surface salinity and temperature. The information gathered supports specific management policies of cockle resources in SW British and Galician regions also considering their particular socio-economic characteristics; further, these new data will be added to those recently reported in the Northeast Atlantic to define sustainable management actions across the whole distribution range of the species

Identifying future models for delivering genetic services: a nominal group study in primary care

BACKGROUND: To enable primary care medical practitioners to generate a range of possible service delivery models for genetic counselling services and critically assess their suitability. METHODS: Modified nominal group technique using in primary care professional development workshops. RESULTS: 37 general practitioners in Wales, United Kingdom too part in the nominal group process. The practitioners who attended did not believe current systems were sufficient to meet anticipated demand for genetic services. A wide range of different service models was proposed, although no single option emerged as a clear preference. No argument was put forward for genetic assessment and counselling being central to family practice, neither was there a voice for the view that the family doctor should become skilled at advising patients about predictive genetic testing and be able to counsel patients about the wider implications of genetic testing for patients and their family members, even for areas such as common cancers. Nevertheless, all the preferred models put a high priority on providing the service in the community, and often co-located in primary care, by clinicians who had developed expertise. CONCLUSION: There is a need for a wider debate about how healthcare systems address individual concerns about genetic concerns and risk, especially given the increasing commercial marketing of genetic tests

PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis.

IL-23 is a potent stimulus for Th17 cells. These cells have a distinct developmental pathway from Th1 cells induced by IL-12 and are implicated in autoimmune and inflammatory disorders including multiple sclerosis (MS). TGF-β, IL-6, and IL-1, the transcriptional regulator RORγt (RORC) and IL-23 are implicated in Th17 development and maintenance. In human polyclonally activated T cells, IL-23 enhances IL-17 production. The aims of our study were: 1). To validate microarray results showing preferential expression of platelet activating factor receptor (PAF-R) on IL-23 stimulated T cells. 2). To determine whether PAF-R on activated T cells is functional, whether it is co-regulated with Th17-associated molecules, and whether it is implicated in Th17 function. 3). To determine PAF-R expression in MS. We show that PAF-R is expressed on activated T cells, and is inducible by IL-23 and IL-17, which in turn are induced by PAF binding to PAF-R. PAF-R is co-expressed with IL-17 and regulated similarly with Th17 markers IL-17A, IL-17F, IL-22 and RORC. PAF-R is upregulated on PBMC and T cells of MS patients, and levels correlate with IL-17 and with MS disability scores. Our results show that PAF-R on T cells is associated with the Th17 phenotype and function. Clinical Implications Targeting PAF-R may interfere with Th17 function and offer therapeutic intervention in Th17-associated conditions, including MS

The Stem Cell Marker CD133 Associates with Enhanced Colony Formation and Cell Motility in Colorectal Cancer

CD133 is a membrane molecule that has been, controversially, reported as a CSC marker in colorectal cancer (CRC). In this study, we sought to clarify the expression and role of CD133 in CRC. Initially the size of the CD133−expressing (CD133+) population in eight well-described CRC cell lines was measured by flow cytometry and was found to range from 0% to >95%. The cell line HT29 has a CD133+ population of >95% and was chosen for functional evaluation of CD133 after gene knockdown by RNA interference. A time course assay showed that CD133 inhibition had no significant effect on cell proliferation or apoptosis. However, CD133 knockdown did result in greater susceptibility to staurosporine-induced apoptosis (p = 0.01) and reduction in cell motility (p<0.04). Since gene knockdown may cause “off-target” effects, the cell line SW480 (which has a CD133+ population of 40%) was sorted into pure CD133+ and CD133− populations to allow functional comparison of isogenic populations separated only by CD133 expression. In concordance with the knockdown experiments, a time course assay showed no significant proliferative differences between the CD133+/CD133− populations. Also greater resistance to staurosporine-induced apoptosis (p = 0.008), greater cell motility (p = 0.03) and greater colony forming efficiency was seen in the CD133+ population than the CD133− population in both 2D and 3D culture (p<0.0001 and p<0.003 respectively). Finally, the plasticity of CD133 expression in tumour cells was tested. Quantitative PCR analysis showed there was transcriptional repression in the CD133− population of SW480. Prolonged culture of a pure CD133− population resulted in re-emergence of CD133+ cells. We conclude that CD133 expression in CRCs is associated with some features attributable to stemness and that there is plasticity of CD133 expression. Further studies are necessary to delineate the mechanistic basis of these features

Cell proliferation after ischemic infarction in gerbil brain

In order to study cell proliferation after ischemic infarction, a model of bilateral common carotid artery occlusion in the gerbil was developed. A comparison of survival rates after 15, 30, 45 and 60 min of occlusion revealed that 45 min was the maximum duration of ischemia after which most (72%) of the gerbils were alive at 1 week. The administration of pentobarbital (single dose, 30 mg/kg) post-operatively to badly seizing animals increased survival to 100%. Large, well-demarcated infarcts were present in posterior thalamus or midbrain in 62% of gerbils subjected to 45 min bilateral occlusion. In 60% of these animals the infarcts were unilateral; in 40% they were bilateral. To quantitate cell proliferation in the infarcts from 12 h to 25 days after ischemia, gerbils were injected with [3H]thymidine 4 h prior to sacrifice, and autoradiographs were prepared from sectioned brains. Proliferation took place from 2 to 7 days after occlusion, with a maximum of 24% labeled cells at 6 days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25494/1/0000035.pd