Optimal Treatments for Photodynamic Therapy

Photodynamic therapy is a complex treatment for neoplastic diseases that uses the light-harvesting properties of a photosensitizer. The treatment depends on the amount of photosensitizer in the tissue and on the amount of light that is focused on the targeted area. We use a pharmacokinetic model to represent a photosensitizer\u27s movement through the anatomy and design treatments with a linear program. This technique allows us to investigate how a treatment\u27s success varies over time

Toxoplasma gondii profilin does not stimulate an innate immune response through bovine or human TLR5

Toxoplasma gondii is responsible for one of the most prevalent infections in people. T. gondii profilin (TgPr) is a protein integral to parasite movement and cellular invasion. Murine TLR has been described to bind TgPr. Furthermore, more recently, human TLR5 has been described to recognise recombinant TgPr, as well as bacterial flagellin. In addition to infections in humans, T. gondii infects farm animals, but little information is available about its innate recognition. We aimed to investigate whether, similarly to their human orthologue, bovine and porcine TLR5 could also be stimulated by TgPr by using a combination of reporter cell lines expressing full length TLR5 from each species as well as primary cells. Although human and bovine TLR5-transfected cells responded to flagellin, no response was detected upon stimulation with profilin. Furthermore, TgPr failed to elicit IL-6 secretion in human peripheral blood mononuclear cells and CD14þ monocytes. In contrast, exposure of RAW cells, known to express TLR11 to TgPr, slightly increased the IL-6 response. Our data cast doubts on the possibility that profilin is a specific ligand for human TLR5 and bovine TLR5. This leaves the immunogenic properties of this potential target antigen uncharacterised outside of the murine system

CMB Lensing Power Spectrum Biases from Galaxies and Clusters using High-angular Resolution Temperature Maps

The lensing power spectrum from cosmic microwave background (CMB) temperature maps will be measured with unprecedented precision with upcoming experiments, including upgrades to ACT and SPT. Achieving significant improvements in cosmological parameter constraints, such as percent level errors on sigma_8 and an uncertainty on the total neutrino mass of approximately 50 meV, requires percent level measurements of the CMB lensing power. This necessitates tight control of systematic biases. We study several types of biases to the temperature-based lensing reconstruction signal from foreground sources such as radio and infrared galaxies and the thermal Sunyaev-Zel'dovich effect from galaxy clusters. These foregrounds bias the CMB lensing signal due to their non-Gaussian nature. Using simulations as well as some analytical models we find that these sources can substantially impact the measured signal if left untreated. However, these biases can be brought to the percent level if one masks galaxies with fluxes at 150 GHz above 1 mJy and galaxy clusters with masses above M_vir = 10^14 M_sun. To achieve such percent level bias, we find that only modes up to a maximum multipole of l_max ~ 2500 should be included in the lensing reconstruction. We also discuss ways to minimize additional bias induced by such aggressive foreground masking by, for example, exploring a two-step masking and in-painting algorithm.Comment: 14 pages, 14 figures, to be submitted to Ap

The Impact of Halo Properties, Energy Feedback and Projection Effects on the Mass-SZ Flux Relation

We present a detailed analysis of the intrinsic scatter in the integrated SZ effect - cluster mass (Y-M) relation, using semi-analytic and simulated cluster samples. Specifically, we investigate the impact on the Y-M relation of energy feedback, variations in the host halo concentration and substructure populations, and projection effects due to unresolved clusters along the line of sight (the SZ background). Furthermore, we investigate at what radius (or overdensity) one should measure the integrated SZE and define cluster mass so as to achieve the tightest possible scaling. We find that the measure of Y with the least scatter is always obtained within a smaller radius than that at which the mass is defined; e.g. for M_{200} (M_{500}) the scatter is least for Y_{500} (Y_{1100}). The inclusion of energy feedback in the gas model significantly increases the intrinsic scatter in the Y-M relation due to larger variations in the gas mass fraction compared to models without feedback. We also find that variations in halo concentration for clusters of a given mass may partly explain why the integrated SZE provides a better mass proxy than the central decrement. Substructure is found to account for approximately 20% of the observed scatter in the Y-M relation. Above M_{200} = 2x10^{14} h^{-1} msun, the SZ background does not significantly effect cluster mass measurements; below this mass, variations in the background signal reduce the optimal angular radius within which one should measure Y to achieve the tightest scaling with M_{200}.Comment: 12 pages, 6 figures, to be submitted to Ap

An Introduction to Systems Biology for Mathematical Programmers

Many recent advances in biology, medicine and health care are due to computational efforts that rely on new mathematical results. These mathematical tools lie in discrete mathematics, statistics & probability, and optimization, and when combined with savvy computational tools and an understanding of cellular biology they are capable of remarkable results. One of the most significant areas of growth is in the field of systems biology, where we are using detailed biological information to construct models that describe larger entities. This chapter is designed to be an introduction to systems biology for individuals in Operations Research (OR) and mathematical programming who already know the supporting mathematics but are unaware of current research in this field

Theory of Dynamic Stripe Induced Superconductivity

Since the recently reported giant isotope effect on T* [1] could be consistently explained within an anharmonic spin-charge-phonon interaction model, we consider here the role played by stripe formation on the superconducting properties within the same model. This is a two-component scenario and we recast its basic elements into a BCS effective Hamiltonian. We find that the stripe formation is vital to high-Tc superconductivity since it provides the glue between the two components to enhance Tc to the unexpectedly large values observed experimentally.Comment: 7 pages, 2 figure

Predictions of the causal entropic principle for environmental conditions of the universe

The causal entropic principle has been proposed as a superior alternative to the anthropic principle for understanding the magnitude of the cosmological constant. In this approach, the probability to create observers is assumed to be proportional to the entropy production \Delta S in a maximal causally connected region -- the causal diamond. We improve on the original treatment by better quantifying the entropy production due to stars, using an analytic model for the star formation history which accurately accounts for changes in cosmological parameters. We calculate the dependence of \Delta S on the density contrast Q=\delta\rho/\rho, and find that our universe is much closer to the most probable value of Q than in the usual anthropic approach and that probabilities are relatively weakly dependent on this amplitude. In addition, we make first estimates of the dependence of \Delta S on the baryon fraction and overall matter abundance. Finally, we also explore the possibility that decays of dark matter, suggested by various observed gamma ray excesses, might produce a comparable amount of entropy to stars.Comment: RevTeX4, 13pp, 10 figures; v2. clarified introduction, added ref

The Relationship Between the Number of Shots and the Quality of Gamma Knife Radiosurgeries

Radiosurgery is a non-invasive alternative to brain surgery that uses a single focused application of high radiation to destroy intracerebral target tissues. A Gamma Knife delivers such treatments by using 201 cylindrically collimated cobalt-60 sources that are arranged in a hemispherical pattern and aimed to a common focal point. The accumulation of radiation at the focal point, called a \shot due to the spherical nature of the dose distribution, is used to ablate (or destroy) target tissue in the brain. If the target is small and spherical, it is easily treated by choosing one of four available collimators (4, 8, 14, or 18 mm). For large, irregular targets, multiple shots are typically required to treat the entire lesion, and the process of determining the optimal arrangement and number of shots is complex. In this research, fast simulated annealing and a novel objective function are used to investigate the relationship between the number of shots and the quality of the resulting treatment. Sets of 5, 10, 25, 50, and an unrestricted number of shots are studied for an arteriovenous malformation (AVM). As the shot limit increases the following improvements in plan quality are observed: the conformity of the prescription isodose line increases, the lesion dose becomes more homogeneous, and an increase use of smaller collimators to deposit dose. Large improvements in plan quality are realized by increasing the number of shots from 5 to 50, and to achieve a similar magnitude of improvement past 50 requires an increase over 1500 shots for the complex lesion investigated. This observation suggests that it is clinically valuable to improve the Gamma Knife\u27s delivery capabilities so that 50 shot treatments are possible