205 research outputs found
Exact, time-independent estimation of clone size distributions in normal and mutated cells
Biological tools such as genetic lineage tracing, three dimensional confocal microscopy and next generation DNA sequencing are providing new ways to quantify the distribution of clones of normal and mutated cells. Population-wide clone size distributions in vivo are complicated by multiple cell types, and overlapping birth and death processes. This has led to the increased need for mathematically informed models to understand their biological significance. Standard approaches usually require knowledge of clonal age. We show that modelling on clone size independent of time is an alternative method that offers certain analytical advantages; it can help parameterize these models, and obtain distributions for counts of mutated or proliferating cells, for example. When applied to a general birth-death process common in epithelial progenitors this takes the form of a gamblers ruin problem, the solution of which relates to counting Motzkin lattice paths. Applying this approach to mutational processes, an alternative, exact, formulation of the classic Luria Delbruck problem emerges. This approach can be extended beyond neutral models of mutant clonal evolution, and also describe some distributions relating to sub-clones within a tumour. The approaches above are generally applicable to any Markovian branching process where the dynamics of different "coloured" daughter branches are of interest
Formation of the black-hole binary M33 X-7 via mass-exchange in a tight massive system
M33 X-7 is among the most massive X-Ray binary stellar systems known, hosting
a rapidly spinning 15.65 Msun black hole orbiting an underluminous 70 Msun Main
Sequence companion in a slightly eccentric 3.45 day orbit. Although
post-main-sequence mass transfer explains the masses and tight orbit, it leaves
unexplained the observed X-Ray luminosity, star's underluminosity, black hole's
spin, and eccentricity. A common envelope phase, or rotational mixing, could
explain the orbit, but the former would lead to a merger and the latter to an
overluminous companion. A merger would also ensue if mass transfer to the black
hole were invoked for its spin-up. Here we report that, if M33 X-7 started as a
primary of 85-99 Msun and a secondary of 28-32 Msun, in a 2.8-3.1 day orbit,
its observed properties can be consistently explained. In this model, the Main
Sequence primary transferred part of its envelope to the secondary and lost the
rest in a wind; it ended its life as a ~16 Msun He star with a Fe-Ni core which
collapsed to a black hole (with or without an accompanying supernova). The
release of binding energy and, possibly, collapse asymmetries "kicked" the
nascent black hole into an eccentric orbit. Wind accretion explains the X-Ray
luminosity, while the black hole spin can be natal.Comment: Manuscript: 18 pages, 2 tables, 2 figure. Supplementary Information:
34 pages, 6 figures. Advance Online Publication (AOP) on
http://www.nature.com/nature on October 20, 2010. To Appear in Nature on
November 4, 201
Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement
Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source
Accreting Black Holes
This chapter provides a general overview of the theory and observations of
black holes in the Universe and on their interpretation. We briefly review the
black hole classes, accretion disk models, spectral state classification, the
AGN classification, and the leading techniques for measuring black hole spins.
We also introduce quasi-periodic oscillations, the shadow of black holes, and
the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and
Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer
Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin
note: substantial text overlap with arXiv:1711.1025
Telomerase activity in melanoma and non-melanoma skin cancer
Telomeres are specialized structures consisting of repeat arrays of TTAGGGn located at the ends of chromosomes. They are essential for chromosome stability and, in the majority of normal somatic cells, telomeres shorten with each cell division. Most immortalized cell lines and tumours reactivate telomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate telomerase activation in premalignant skin lesions and also in all forms of skin cancer. Telomerase activation in normal skin was a rare event, and among 16 samples of normal skin (one with a history of chronic sun exposure) 12.5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) benign proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease, 42% (11 out of 26) of samples exhibited telomerase activity. In the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase was activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. However, only 25% (3 out of 12) of squamous cell carcinomas (SCC) had telomerase activity. With the exception of one SCC sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not inhibited when mixed with the telomerase-negative SCC or CMM extracts, indicating that, overall, Taq polymerase and telomerase inhibitors were not responsible for the negative results. Mean telomere hybridizing restriction fragment (TRF) analysis was performed in a number of telomerase-positive and -negative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found
Genetic variation exists for telomeric array organization within and among the genomes of normal, immortalized, and transformed chicken systems
This study investigated telomeric array organization of diverse chicken genotypes utilizing in vivo and in vitro cells having phenotypes with different proliferation potencies. Our experimental objective was to characterize the extent and nature of array variation present to explore the hypothesis that mega-telomeres are a universal and fixed feature of chicken genotypes. Four different genotypes were studied including normal (UCD 001, USDA-ADOL Line 0), immortalized (DF-1), and transformed (DT40) cells. Both cytogenetic and molecular approaches were utilized to develop an integrated view of telomeric array organization. It was determined that significant variation exists within and among chicken genotypes for chromosome-specific telomeric array organization and total genomic-telomeric sequence content. Although there was variation for mega-telomere number and distribution, two mega-telomere loci were in common among chicken genetic lines (GGA 9 and GGA W). The DF-1 cell line was discovered to maintain a complex derivative karyotype involving chromosome fusions in the homozygous and heterozygous condition. Also, the DF-1 cell line was found to contain the greatest amount of telomeric sequence per genome (17%) as compared to UCD 001 (5%) and DT40 (1.2%). The chicken is an excellent model for studying unique and universal features of vertebrate telomere biology, and characterization of the telomere length variation among genotypes will be useful in the exploration of mechanisms controlling telomere length maintenance in different cell types having unique phenotypes
Foundations of Black Hole Accretion Disk Theory
This review covers the main aspects of black hole accretion disk theory. We
begin with the view that one of the main goals of the theory is to better
understand the nature of black holes themselves. In this light we discuss how
accretion disks might reveal some of the unique signatures of strong gravity:
the event horizon, the innermost stable circular orbit, and the ergosphere. We
then review, from a first-principles perspective, the physical processes at
play in accretion disks. This leads us to the four primary accretion disk
models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin)
disks, slim disks, and advection-dominated accretion flows (ADAFs). After
presenting the models we discuss issues of stability, oscillations, and jets.
Following our review of the analytic work, we take a parallel approach in
reviewing numerical studies of black hole accretion disks. We finish with a few
select applications that highlight particular astrophysical applications:
measurements of black hole mass and spin, black hole vs. neutron star accretion
disks, black hole accretion disk spectral states, and quasi-periodic
oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at
http://www.livingreviews.org/lrr-2013-
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