Modeling Stem/Progenitor Cell-Induced Neovascularization and\ud Oxygenation around Solid Implants

Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nano-porous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells (BMPC) in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using non-invasive electron paramagnetic resonance (EPR) signal measurements. A consistently higher level of per-implant oxygenation was observed in the cell-treatment case as compared to the control over a 10-week period. In order to provide a mechanistic explanation of these experimental observations, we present in this paper a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a Foreign Body Reaction (FBR) while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem celltreated cases

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

Evidence for Accretion in the High-resolution X-ray Spectrum of the T Tauri Star System Hen 3-600

We present high-resolution X-ray spectra of the multiple T Tauri star system Hen 3-600, obtained with the High Energy Transmission Grating Spectrograph on the Chandra X-ray Observatory. Two binary components were detected in the zeroth-order image. Hen 3-600-A, which has a large mid-infrared excess, is a 2-3 times fainter in X-rays than Hen 3-600-B, due to a large flare on B. The dispersed X-ray spectra of the two primary components overlap spatially; spectral analysis was performed on the combined system. Analysis of the individual spectra was limited to regions where the contributions of A and B can be disentangled. This analysis results in two lines of evidence indicating that the X-ray emission from Hen 3-600 is derived from accretion processes: line ratios of O VII indicate that the characteristic density of its X-ray-emitting plasma is large; a significant component of low-temperature plasma is present and is stronger in component A. These results are consistent with results obtained from X-ray gratings spectroscopy of more rapidly accreting systems. All of the signatures of Hen 3-600 that are potential diagnostics of accretion activity -- X-ray emission, UV excess, H-alpha emission, and weak infrared excess -- suggest that its components represent a transition phase between rapidly accreting, classical T Tauri stars and non-accreting, weak-lined T Tauri stars.Comment: latex, 27 pages, 12 figures, 6 tables; accepted by Ap

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

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

Bouncing Neutrons and the Neutron Centrifuge

The recent observation of the quantum state of the neutron bouncing freely under gravity allows some novel experiments. A method of purifying the ground state is given, and possible applications to the measurement of the electric dipole moment of the neutron and the short distance behaviour of gravity are discussed.Comment: 7 pages, 7 figure

Understanding students’ motivation towards proactive career behaviours through goal-setting theory and the job demands–resources model

The graduate labour market is highly competitive but little is known about why students vary in their development of employability. This study contributes to the literature by applying goal-setting theory and the job demands–resources model to investigate how motivational processes influence students’ proactive career behaviours. We tested four hypotheses using structural equation modelling and moderation/mediation analysis using a nested model approach; 432 undergraduates from 21 UK universities participated in this cross-sectional study. The results showed that students higher in mastery approach had greater perceived employability mediated by two proactive career behaviours (skill development and network building). Students’ career goal commitment was associated with all four proactive career behaviours (career planning, skill development, career consultation and network building). Students’ academic and employment workloads did not negatively impact their proactive career behaviours. University tutors and career services should therefore encourage students to set challenging career goals that reflect mastery approach

Four-terminal resistance of an interacting quantum wire with weakly invasive contacts

We analyze the behavior of the four-terminal resistance, relative to the two-terminal resistance of an interacting quantum wire with an impurity, taking into account the invasiveness of the voltage probes. We consider a one-dimensional Luttinger model of spinless fermions for the wire. We treat the coupling to the voltage probes perturbatively, within the framework of non-equilibrium Green function techniques. Our investigation unveils the combined effect of impurities, electron-electron interactions and invasiveness of the probes on the possible occurrence of negative resistance.Comment: 10 pages, 7 figure

3D modelling of angiogenesis and vascular tumour growth

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute

Neutron charge radius and the Dirac equation

We consider the Dirac equation for a finite-size neutron in an external electric field. We explicitly incorporate Dirac-Pauli form factors into the Dirac equation. After a non-relativistic reduction, the Darwin-Foldy term is cancelled by a contribution from the Dirac form factor, so that the only coefficient of the external field charge density is $e/6 r^2_{En}$, i. e. the root mean square radius associated with the electric Sachs form factor . Our result is similar to a recent result of Isgur, and reconciles two apparently conflicting viewpoints about the use of the Dirac equation for the description of nucleons.Comment: 7 pages, no figures, to appear in Physical Review