The expansion of mutant clones in tumorigenesis

The formation of a cancer is an evolutionary process. A somatic cell may acquire an (epi)-mutation that gives it a growth advantage relative to its neighbours. Progression to cancer occurs as cells in the resulting mutant clone acquire additional mutations, which may also confer a selective advantage. This thesis investigated the expansion of mutant clones both prior to, and during, tumour growth. First, the clonal expansion of a mutant lineage within a stem cell niche was considered. The behaviour of mutant germline stem cells in the Drosophila testis, a remarkably well-characterised niche, was investigated. A model was developed which identified stem cell phenotypes that were selectively advantageous in the niche. Crypt fission is thought to be the primary mechanism of clonal expansion in the gut. A model of crypt fission was developed, which was used to estimate the frequency of fission events in the normal human colon. Crypts were found to divide infrequently, and fission was predicted to decrease the likelihood that a mutant clone would be lost from the gut. Next, the expansion of mutant clones during the initial growth of colorectal adenomas was considered. Individual crypts were micro-dissected from small adenomas, and the mutation status of the APC and K-ras genes in each crypt was determined. Combining this information revealed how the adenoma had formed. It was found that K-ras mutations may have occurred earlier in tumorigenesis than had been previously established. Last, the effect of clonal expansion on the genetic heterogeneity in a cancer was examined. A model of microsatellite slippage during cancer growth was developed. The model showed that clonal expansion during cancer growth, coupled with a low rate of somatic mutation, can generate non-negligible amounts of genetic diversity. This suggested that there was little evidence for a low-level microsatellite mutator phenotype in colorectal cancers

An Investigation of Void Fraction in the Stratified/Annular Flow Regions in Smooth, Horizontal Tubes

Refrigerants R134a and R410A have been used for void fraction measurements in smooth horizontal tubes with diameters between 4mm and 7mm. Quality and mass flux were varied from 5% to 90% and 75 kglm2-s to 700 kglm2-s, respectively. Two test loops, one for condensing flows at 35C and the other for evaporating flows at 5C, were used in the investigation. Results show that near the transition from annular to stratified flow void fraction changed from viscousinertial dependence to gravitational-inertial dominated dependence. An important feature observed is the annular flow region's relative insensitivity to mass flux while the border region between annular and stratified flows is characterized by strong mass flux dependence.Air Conditioning and Refrigeration Project 7

Temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the compulsory eradication programme in Ireland

AbstractThe national BVD eradication programme in Ireland started on a voluntary basis in 2012, becoming compulsory in 2013. The programme relies on accurate identification and prompt removal of BVD+ calves. However, a minority of herd owners have chosen to retain BVD+ animals (defined as still being alive more than seven weeks after the date of the initial test), typically with a view to fattening them to obtain some salvage value. During each year of the programme, additional measures have been introduced and implemented to encourage prompt removal of BVD+ animals. The objective of this study was to describe temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the first three years of the compulsory eradication programme in Ireland.The study population included all BVD+ calves born in Ireland in 2013–2015. A parametric survival model was developed to model the time from the initial BVD test until the animal was slaughtered/died on farm or until 31 December 2015 (whichever was earlier). A total of 29,504 BVD+ animals, from 13,917 herds, were included in the study. The proportion of BVD+ animals that were removed from the herd within 7 weeks of the initial test date increased from 43.7% in 2013 to 70.3% in 2015. BVD+ animals born in 2015 had a much lower survival time (median=33days) compared to the 2013 birth cohort (median=62days), with a year on year reduction in survival of BVD+ calves. In the initial parametric survival models, all interactions with herd type were significant. Therefore, separate models were developed for beef and dairy herds. Overall the results of the survival models were similar, with birth year, BVD+ status, herd size, county of birth and birth month consistently identified as risk factors independent of herd type (beef or dairy) or the numbers of BVD+ animals (single or multiple) in the herd. In addition, the presence of a registered mobile telephone number was identified as a risk factor in all models except for dairy herds with a single BVD+, while the sex of the BVD+ calf was only identified as a risk factor in this model.Significant progress has been made in addressing the issue of retention of BVD+ calves, however, there is a need for further improvement. A number of risk factors associated with retention have been identified suggesting areas where future efforts can be addressed

Irreversible Quantum Baker Map

We propose a generalization of the model of classical baker map on the torus, in which the images of two parts of the phase space do overlap. This transformation is irreversible and cannot be quantized by means of a unitary Floquet operator. A corresponding quantum system is constructed as a completely positive map acting in the space of density matrices. We investigate spectral properties of this super-operator and their link with the increase of the entropy of initially pure states.Comment: 4 pages, 3 figures include

H-ATLAS/GAMA and HeViCS - dusty early-type galaxies in different environments

NKA acknowledges the support of the Science and Technology Facilities Council. LD, RJI and SJM acknowledge support from the European Research Council Advanced Grant COSMICISM. IDL gratefully acknowledges the support of the Flemish Fund for Scientific Research (FWO-Vlaanderen). KR acknowledges support from the European Research Council Starting Grant SEDmorph (P.I. V. Wild). Date of acceptance: 22/05/2015The Herschel Space Observatory has had a tremendous impact on the study of extragalactic dust. Specifically, early-type galaxies (ETG) have been the focus of several studies. In this paper, we combine results from two Herschel studies -a Virgo cluster study Herschel Virgo Cluster Survey (HeViCS) and a broader, low-redshift Herschel-Astrophysical Terahertz Large Area Survey (H-ATLAS)/Galaxy and Mass Assembly (GAMA) study -and contrast the dust and associated properties for similar mass galaxies. This comparison is motivated by differences in results exhibited between multiple Herschel studies of ETG. A comparison between consistent modified blackbody derived dust mass is carried out, revealing strong differences between the two samples in both dust mass and dust-to-stellar mass ratio. In particular, the HeViCS sample lacks massive ETG with as high a specific dust content as found in H-ATLAS. This is most likely connected with the difference in environment for the two samples. We calculate nearest neighbour environment densities in a consistent way, showing that H-ATLAS ETG occupy sparser regions of the local Universe, whereas HeViCS ETG occupy dense regions. This is also true for ETG that are not Herschel-detected but are in the Virgo and GAMA parent samples. Spectral energy distributions are fit to the panchromatic data. From these, we find that in H-ATLAS the specific star formation rate anticorrelates with stellar mass and reaches values as high as in our Galaxy. On the other hand HeViCS ETG appear to have little star formation. Based on the trends found here, H-ATLAS ETG are thought to have more extended star formation histories and a younger stellar population than HeViCS ETG.Publisher PDFPeer reviewe

Integrating discrete- and continuous-time metric temporal logics through sampling

Abstract. Real-time systems usually encompass parts that are best described by a continuous-time model, such as physical processes under control, together with other components that are more naturally formalized by a discrete-time model, such as digital computing modules. Describing such systems in a unified framework based on metric temporal logic requires to integrate formulas which are interpreted over discrete and continuous time. In this paper, we tackle this problem with reference to the metric temporal logic TRIO, that admits both a discrete-time and a continuous-time semantics. We identify sufficient conditions under which TRIO formulas have a consistent truth value when moving from continuous-time to discrete-time interpretations, or vice versa. These conditions basically involve the restriction to a proper subset of the TRIO language and a requirement on the finite variability over time of the basic items in the specification formulas. We demonstrate the approach with an example of specification and verification

Chaos in a double driven dissipative nonlinear oscillator

We propose an anharmonic oscillator driven by two periodic forces of different frequencies as a new time-dependent model for investigating quantum dissipative chaos. Our analysis is done in the frame of statistical ensemble of quantum trajectories in quantum state diffusion approach. Quantum dynamical manifestation of chaotic behavior, including the emergence of chaos, properties of strange attractors, and quantum entanglement are studied by numerical simulation of ensemble averaged Wigner function and von Neumann entropy.Comment: 9 pages, 18 figure

Complementarity of Galactic radio and collider data in constraining WIMP dark matter models

In this work we confront dark matter models to constraints that may be derived from radio synchrotron radiation from the Galaxy, taking into account the astrophysical uncertainties and we compare these to bounds set by accelerator and complementary indirect dark matter searches. Specifically we apply our analysis to three popular particle physics models. First, a generic effective operator approach, in which case we set bounds on the corresponding mass scale, and then, two specific UV completions, the Z' and Higgs portals. We show that for many candidates, the radio synchrotron limits are competitive with the other searches, and could even give the strongest constraints (as of today) with some reasonable assumptions regarding the astrophysical uncertainties.Comment: 22 pages, 12 figure

Extreme Ultra-Violet Spectroscopy of the Lower Solar Atmosphere During Solar Flares

The extreme ultraviolet portion of the solar spectrum contains a wealth of diagnostic tools for probing the lower solar atmosphere in response to an injection of energy, particularly during the impulsive phase of solar flares. These include temperature and density sensitive line ratios, Doppler shifted emission lines and nonthermal broadening, abundance measurements, differential emission measure profiles, and continuum temperatures and energetics, among others. In this paper I shall review some of the advances made in recent years using these techniques, focusing primarily on studies that have utilized data from Hinode/EIS and SDO/EVE, while also providing some historical background and a summary of future spectroscopic instrumentation.Comment: 34 pages, 8 figures. Submitted to Solar Physics as part of the Topical Issue on Solar and Stellar Flare