Genealogical constructions of population models

Representations of population models in terms of countable systems of particles are constructed, in which each particle has a `type', typically recording both spatial position and genetic type, and a level. For finite intensity models, the levels are distributed on $[0,\lambda ]$, whereas in the infinite intensity limit $\lambda\rightarrow\infty$, at each time $t$, the joint distribution of types and levels is conditionally Poisson, with mean measure $\Xi (t)\times \ell$ where $\ell$ denotes Lebesgue measure and $\Xi (t)$ is a measure-valued population process. The time-evolution of the levels captures the genealogies of the particles in the population. Key forces of ecology and genetics can be captured within this common framework. Models covered incorporate both individual and event based births and deaths, one-for-one replacement, immigration, independent `thinning' and independent or exchangeable spatial motion and mutation of individuals. Since birth and death probabilities can depend on type, they also include natural selection. The primary goal of the paper is to present particle-with-level or lookdown constructions for each of these elements of a population model. Then the elements can be combined to specify the desired model. In particular, a non-trivial extension of the spatial $\Lambda$-Fleming-Viot process is constructed

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC subversion induces up-regulation of PKC II expression in B lymphocytes

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKCα leads to an up-regulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis

Constraining global properties of the Draco dwarf spheroidal galaxy

By fitting a flexible stellar anisotropy model to the observed surface brightness and line-of-sight velocity dispersion profiles of Draco we derive a sequence of cosmologically plausible two-component (stars + dark matter) models for this galaxy. The models are consistent with all the available observations and can have either cuspy Navarro-Frenk-White or flat-cored dark matter density profiles. The dark matter halos either formed relatively recently (at z~2...7) and are massive (up to ~5x10^9 M_Sun), or formed before the end of the reionization of the universe (z~7...11) and are less massive (down to ~7x10^7 M_Sun). Our results thus support either of the two popular solutions of the "missing satellites" problem of Lambda cold dark matter cosmology - that dwarf spheroidals are either very massive, or very old. We carry out high-resolution simulations of the tidal evolution of our two-component Draco models in the potential of the Milky Way. The results of our simulations suggest that the observable properties of Draco have not been appreciably affected by the Galactic tides after 10 Gyr of evolution. We rule out Draco being a "tidal dwarf" - a tidally disrupted dwarf galaxy. Almost radial Draco orbits (with the pericentric distance <15 kpc) are also ruled out by our analysis. The case of a harmonic dark matter core can be consistent with observations only for a very limited choice of Draco orbits (with the apocentric-to-pericentric distances ratio of <2.5).Comment: 18 pages, 14 figures; accepted by Ap

Surface Effects on the Dynamics of Liquid Crystalline Thin Films Confined in Nanoscale Cavities

The dynamics of 4-n-pentyl-4\u27-cyanobiphenyl (5CB) nematic liquid crystalline thin films have been studied in real time using step-scan Fourier transform infrared spectroscopy (FTIR). In these studies, the liquid crystal was confined in a nanocavity defined and bounded by an interdigitated gold electrode array. The gold microstructures were microfabricated on a zinc selenide (IR-transparent) window. The 5CB interactions with the ZnSe substrate result in surface-induced ordering of the ultrathin layers (on the order of 40 nm). As the films increase in thickness, the nanoscale organization induced by the surface layer becomes a less significant contributor to the overall bulk structure of the sample. Time-resolved FTIR studies have enabled the measurement of rate constants for the orientation and relaxation of the thin films under an applied electric field as a direct function of confinement dimensions. Cell thicknesses ranging from 40 to 300 nm were studied. The measured rate behaviors demonstrate the strong effects of the interactions occurring between the surfaces of the ZnSe crystals and the 5CB on the dynamics of the liquid crystalline assembly. Time-resolved studies reveal kinetically inhomogeneous line shapes for thicker films while ultrathin films maintain kinetically homogeneous peaks, suggesting the development of liquid crystalline domains or other inhomogeneities over this length scale in the transition from the surface layer to bulk

Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1 to S phase transition and identifies a conserved family of proteins

Regulation of cell cycle progression occurs in part through the targeted degradation of both activating and inhibitory subunits of the cyclin-dependent kinases. During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the destruction of these regulators. Here we describe evidence indicating that CDC53 also is involved in this process. Mutations in CDC53 cause a phenotype indistinguishable from those of cdc4 and cdc34 mutations, numerous genetic interactions are seen between these genes, and the encoded proteins are found physically associated in vivo. Cdc53p defines a large family of proteins found in yeasts, nematodes, and humans whose molecular functions are uncharacterized. These results suggest a role for this family of proteins in regulating cell cycle proliferation through protein degradation

Soil Nutrients and Vegetation Characteristics of a Dorset/Thule Site in the Canadian Arctic

We conducted a systematic study of soils and vegetation present at Arnaqquaksaat on Igloolik Island, Nunavut, a site occupied by Dorset and Thule people prior to 1823 and probably for over a thousand years. We compared this site to an area affected by ongoing mammal and bird activity and an area of relatively unfertilized polar semidesert. At these locations, we estimated percent cover of vegetation, identified vascular plant species, measured soil depth, and collected soil samples. The soil samples were analyzed for total nitrogen, sodium bicarbonate-extractable phosphorus, available potassium, available magnesium, and pH.Percent plant cover, abundance of plant species indicative of enrichment, and soil depth were greatest within the area of anthropogenic influence and decreased downslope to the sea. Total nitrogen level in the upslope area of anthropogenic influence (2.61% ±0.88) was similar to that in areas of bird and mammal activity (2.54% ±0.78); it was higher than the levels in the downslope area of human fertilization (0.65% ±0.82) and the unaltered polar semidesert area (0.28% ±0.38). Phosphorus levels in the influenced areas were 5 to 6 times those in the uninfluenced polar semidesert. The magnesium level was highest in the area of bird and mammal activity (766.8 mg/L ±53.35), whereas potassium levels were similar throughout the study area. The lowest pH was found in the upslope area of past human occupation, and pH differences among sites paralleled those observed for nitrogen.On a effectué une étude systématique des sols et de la végétation présents à Arnaqquaksaat dans l'île Igloolik au Nunavut, un site occupé par les peuples de Dorset et de Thulé avant 1823 et probablement durant plus de mille ans. On a comparé ce site à une zone affectée par l'activité continue de mammifères et d'oiseaux et à une zone de semi-désert polaire relativement non fertilisé. À ces endroits, on a évalué le pourcentage de couvert végétal, identifié les espèces de plantes vasculaires, mesuré la profondeur du sol et prélevé des échantillons de sol. On a analysé ces derniers pour en évaluer la teneur en azote total, phosphore extractible par le bicarbonate de soude, potassium disponible, magnésium disponible et le pH. On a trouvé que le pourcentage de couvert végétal, l'abondance d'espèces végétales révélatrice d'un enrichissement et la profondeur du sol étaient les plus importants à l'intérieur de la zone qui avait subi une influence anthropique et qu'ils décroissaient en descendant vers la mer. Le niveau d'azote total dans la zone supérieure de la pente, qui avait subi une influence anthropique (2,61 p. cent ± 0,88), était semblable à celui des zones où s'exerçait l'activité des oiseaux et des mammifères (2,54 p. cent ± 0,78); il était supérieur aux niveaux trouvés dans la partie inférieure qui avait connu une fertilisation humaine (0,65 p. cent ± 0,82) et dans la zone polaire semi-désertique non altérée (0,28 ± 0,38). Les niveaux de phosphore dans les zones ayant subi une influence étaient de 5 à 6 fois ceux des zones semi-désertiques polaires n'ayant pas subi d'influence. Le niveau de magnésium était le plus haut dans la zone où s'exerçait l'activité des oiseaux et des mammifères (766,8 mg/L ± 53,35), alors que les niveaux de potassium étaient semblables dans toute la zone d'étude. Le pH le plus bas se trouvait dans la zone supérieure de l'endroit ayant jadis été occupé par l'être humain, et les différences dans le pH parmi les sites s'alignaient sur celles observées pour l'azote