On the conformational structure of a stiff homopolymer

In this paper we complete the study of the phase diagram and conformational states of a stiff homopolymer. It is known that folding of a sufficiently stiff chain results in formation of a torus. We find that the phase diagram obtained from the Gaussian variational treatment actually contains not one, but several distinct toroidal states distinguished by the winding number. Such states are separated by first order transition curves terminating in critical points at low values of the stiffness. These findings are further supported by off-lattice Monte Carlo simulation. Moreover, the simulation shows that the kinetics of folding of a stiff chain passes through various metastable states corresponding to hairpin conformations with abrupt U-turns.Comment: 9 pages, 16 PS figures. Journal of Chemical Physics, in pres

Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas

Platinum drug-resistance in ovarian cancers is a major factor contributing to chemotherapeutic resistance of recurrent disease. Members of the Bcl-2 family such as the anti-apoptotic protein Bcl-XL have been shown to play a role in this resistance. Consequently, concurrent inhibition of Bcl-XL in combination with standard chemotherapy may improve treatment outcomes for ovarian cancer patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-XL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo\ud experimental data, wherein tumor xenografts were established in mice and treated with ABT-737 and carboplatin on a fixed periodic schedule, alone or in combination, and tumor sizes recorded regularly. We show that the validated model can be used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the time of infusion of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin administered each week combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. We also investigate the potential of ABT-737 co-therapy with carboplatin to prevent or delay the onset of carboplatin-resistance under two scenarios. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, the model is used to identify drug delivery schedules that induce tumor remission with even low doses of combination therapy. When resistance is intrinsic, due to a pre-existing cohort of resistant cells, tumor remission is no longer feasible, but our model can be used to identify dosing strategies that extend disease-free survival periods. These results underscore the potential of our model to accelerate the development of novel therapeutics such as ABT-737, by predicting optimal treatment strategies when these drugs are given in combination with currently approved cancer medications

Inter-species variation in colour perception

Inter-species variation in colour perception poses a serious problem for the view that colours are mind-independent properties. Given that colour perception varies so drastically across species, which species perceives colours as they really are? In this paper, I argue that all do. Specifically, I argue that members of different species perceive properties that are determinates of different, mutually compatible, determinables. This is an instance of a general selectionist strategy for dealing with cases of perceptual variation. According to selectionist views, objects simultaneously instantiate a plurality of colours, all of them genuinely mind-independent, and subjects select from amongst this plurality which colours they perceive. I contrast selectionist views with relationalist views that deny the mind-independence of colour, and consider some general objections to this strategy

Initial/boundary-value problems of tumor growth within a host tissue

This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such as a priori nonnegativity, boundedness, and uniqueness of the solutions. Existence of the solutions is studied in the one-dimensional time-independent case.Comment: 30 pages, 5 figure

Mathematical analysis of a model for the growth of the bovine corpus luteum

The corpus luteum (CL) is an ovarian tissue that grows in the wound space created by follicular rupture. It produces the progesterone needed in the uterus to maintain pregnancy. Rapid growth of the CL and progesterone transport to the uterus require angiogenesis, the creation of new blood vessels from pre-existing ones, a process which is regulated by proteins that include fibroblast growth factor 2 (FGF2).\ud \ud In this paper we develop a system of time-dependent ordinary differential equations to model CL growth. The dependent variables represent FGF2, endothelial cells (ECs), luteal cells, and stromal cells (like pericytes), by assuming that the CL volume is a continuum of the three cell types. We assume that if the CL volume exceeds that of the ovulated follicle, then growth is inhibited. This threshold volume partitions the system dynamics into two regimes, so that the model may be classified as a Filippov (piecewise smooth) system.\ud \ud We show that normal CL growth requires an appropriate balance between the growth rates of luteal and stromal cells. We investigate how angiogenesis influences CL growth by considering how the system dynamics depend on the dimensionless EC proliferation rate, p5. We find that weak (low p5) or strong (high p5) angiogenesis leads to ‘pathological’ CL growth, since the loss of CL constituents compromises progesterone production or delivery. However, for intermediate values of p5, normal CL growth is predicted. The implications of these results for cow fertility are also discussed. For example, inadequate angiogenesis has been linked to infertility in dairy cows

ASYMMETRIC LEAVES1 reveals knox gene redundancy in Arabidopsis

The shoot apical meristem comprises undifferentiated stem cells and their derivatives, which include founder cells for lateral organs such as leaves. Meristem maintenance and lateral organ specification are regulated in part by negative interactions between the myb domain transcription factor ASYMMETRIC LEAVES1, which is expressed in lateral organ primordia, and homeobox transcription factors which are expressed in the shoot apical meristem (knox genes). The knox gene SHOOT MERISTEMLESS (STAT) negatively regulates ASYMMETRIC LEAVES1 (AS1) which, in turn, negatively, regulates other knox genes including KNAT1 and KNAT2, and positively regulates the novel gene LATERAL ORGAN BOUNDARIES (LOB). Genetic interactions with a second gene, ASYMMETRIC LEAVES2 (AS2), indicate it acts at the same position in this hierarchy as AS1. We have used a second-site suppressor screen to isolate mutations in KNAT1 and we show that KNAT1 is partially redundant with STM in regulating stem cell function. Mutations in KNAT2 show no such interaction. We discuss the regulation and evolution of redundancy among knox genes

Laser application to measure vertical sea temperature and turbidity, design phase

An experiment to test a new method was designed, using backscattered radiation from a laser beam to measure oceanographic parameters in a fraction of a second. Tyndall, Rayleigh, Brillouin, and Raman scattering all are utilized to evaluate the parameters. A beam from a continuous argon ion laser is used together with an interferometer and interference filters to gather the information. The results are checked by direct measurements. Future shipboard and airborne experiments are described

The Chromospheric Activity and Ages of M Dwarf Stars in Wide Binary Systems

We investigate the relationship between age and chromospheric activity for 139 M dwarf stars in wide binary systems with white dwarf companions. The age of each system is determined from the cooling age of its white dwarf component. The current limit for activity-age relations found for M dwarfs in open clusters is 4 Gyr. Our unique approach to finding ages for M stars allows for the exploration of this relationship at ages older than 4 Gyr. The general trend of stars remaining active for a longer time at later spectral type is confirmed. However, our larger sample and greater age range reveals additional complexity in assigning age based on activity alone. We find that M dwarfs in wide binaries older than 4 Gyr depart from the log-linear relation for clusters and are found to have activity at magnitudes, colors and masses which are brighter, bluer and more massive than predicted by the cluster relation. In addition to our activity-age results, we present the measured radial velocities and complete space motions for 161 white dwarf stars in wide binaries.Comment: 22 pages including 9 figures and 5 tables. Accepted for publication in The Astronomical Journa