Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Mixed mode data clustering: an approach based on tectrachoric correlations

In this paper we face the problem of clustering mixedmode data by assuming that the observed binary variables aregenerated from latent continuous variables. We perform a principalcomponents analysis on the matrix of tetrachoric correlations and wethen estimate the scores of each latent variable and construct adata matrix with continuous variables to be used in fully Guassianmixture models or in the k-means cluster analysis. The calculationof the expected a posteriori (EAP) estimates may proceed by simplyconsidering a limited number of quadrature points. Results on asimulation study and on a real data set are reported

Experimental Critical Current Patterns in Josephson Junction Ladders

We present an experimental and theoretical study of the magnetic field dependence of the critical current of Josephson junction ladders. At variance with the well-known case of a one-dimensional (1D) parallel array of Josephson junctions the magnetic field patterns display a single minimum even for very low values of the self-inductance parameter $\beta_{\rm L}$. Experiments performed changing both the geometrical value of the inductance and the critical current of the junctions show a good agreement with numerical simulations. We argue that the observed magnetic field patterns are due to a peculiar mapping between the isotropic Josephson ladder and the 1D parallel array with the self-inductance parameter $\beta_{\rm L}^{\rm eff}=\beta_{\rm L}+2$.Comment: 4 pages, 4 picture

Fibre Inflation: Observable Gravity Waves from IIB String Compactifications

We introduce a simple string model of inflation, in which the inflaton field can take trans-Planckian values while driving a period of slow-roll inflation. This leads naturally to a realisation of large field inflation, inasmuch as the inflationary epoch is well described by the single-field scalar potential $V = V_0 (3-4 e^{-\hat\varphi/\sqrt{3}})$. Remarkably, for a broad class of vacua all adjustable parameters enter only through the overall coefficient $V_0$, and in particular do not enter into the slow-roll parameters. Consequently these are determined purely by the number of \e-foldings, $N_e$, and so are not independent: $\varepsilon \simeq \frac32 \eta^2$. This implies similar relations among observables like the primordial scalar-to-tensor amplitude, $r$, and the scalar spectral tilt, $n_s$: $r \simeq 6(n_s - 1)^2$. $N_e$ is itself more model-dependent since it depends partly on the post-inflationary reheat history. In a simple reheating scenario a reheating temperature of $T_{rh}\simeq 10^{9}$ GeV gives $N_e\simeq 58$, corresponding to $n_s\simeq 0.970$ and $r\simeq 0.005$, within reach of future observations. The model is an example of a class that arises naturally in the context of type IIB string compactifications with large-volume moduli stabilisation, and takes advantage of the generic existence there of Kahler moduli whose dominant appearance in the scalar potential arises from string loop corrections to the Kahler potential. The inflaton field is a combination of Kahler moduli of a K3-fibered Calabi-Yau manifold. We believe there are likely to be a great number of models in this class -- `high-fibre models' -- in which the inflaton starts off far enough up the fibre to produce observably large primordial gravity waves.Comment: Extended calculations beyond the leading approximations, including numerical integrations of multi-field evolution; Display an example with $r = 0.01$; Simplify the discussion of large fields; Corrected minor errors and typos; Added references; 41 pages LaTeX, 25 figure

Measuring CMB Polarization with BOOMERANG

BOOMERANG is a balloon-borne telescope designed for long duration (LDB) flights around Antarctica. The second LDB Flight of BOOMERANG took place in January 2003. The primary goal of this flight was to measure the polarization of the CMB. The receiver uses polarization sensitive bolometers at 145 GHz. Polarizing grids provide polarization sensitivity at 245 and 345 GHz. We describe the BOOMERANG telescope noting changes made for 2003 LDB flight, and discuss some of the issues involved in the measurement of polarization with bolometers. Lastly, we report on the 2003 flight and provide an estimate of the expected results.Comment: 12 pages, 8 figures, To be published in the proceedings of "The Cosmic Microwave Background and its Polarization", New Astronomy Reviews, (eds. S. Hanany and K.A. Olive). Fixed typos, and reformatted citation

SPIDER: Probing the Early Universe with a Suborbital Polarimeter

We evaluate the ability of SPIDER, a balloon-borne polarimeter, to detect a divergence-free polarization pattern ("B-modes") in the Cosmic Microwave Background (CMB). In the inflationary scenario, the amplitude of this signal is proportional to that of the primordial scalar perturbations through the tensor-to-scalar ratio r. We show that the expected level of systematic error in the SPIDER instrument is significantly below the amplitude of an interesting cosmological signal with r=0.03. We present a scanning strategy that enables us to minimize uncertainty in the reconstruction of the Stokes parameters used to characterize the CMB, while accessing a relatively wide range of angular scales. Evaluating the amplitude of the polarized Galactic emission in the SPIDER field, we conclude that the polarized emission from interstellar dust is as bright or brighter than the cosmological signal at all SPIDER frequencies (90 GHz, 150 GHz, and 280 GHz), a situation similar to that found in the "Southern Hole." We show that two ~20-day flights of the SPIDER instrument can constrain the amplitude of the B-mode signal to r<0.03 (99% CL) even when foreground contamination is taken into account. In the absence of foregrounds, the same limit can be reached after one 20-day flight.Comment: 29 pages, 8 figures, 4 tables; v2: matches published version, flight schedule updated, two typos fixed in Table 2, references and minor clarifications added, results unchange

Vector meson production and nucleon resonance analysis in a coupled-channel approach for energies m_N < sqrt(s) < 2 GeV II: photon-induced results

We present a nucleon resonance analysis by simultaneously considering all pion- and photon-induced experimental data on the final states gamma N, pi N, 2 pi N, eta N, K Lambda, K Sigma, and omega N for energies from the nucleon mass up to sqrt(s) = 2 GeV. In this analysis we find strong evidence for the resonances P_{31}(1750), P_{13}(1900), P_{33}(1920), and D_{13}(1950). The omega N production mechanism is dominated by large P_{11}(1710) and P_{13}(1900) contributions. In this second part we present the results on the photoproduction reactions and the electromagnetic properties of the resonances. The inclusion of all important final states up to sqrt(s) = 2 GeV allows for estimates on the importance of the individual states for the GDH sum rule.Comment: 41 pages, 26 figures, discussion extended, typos corrected, references updated, to appear in Phys. Rev.

First Results from the Arcminute Cosmology Bolometer Array Receiver

We review the first science results from the Arcminute Cosmology Bolometer Array Receiver (ACBAR); a multifrequency millimeter-wave receiver optimized for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich (SZ) effect in clusters of galaxies. ACBAR was installed on the 2 m Viper telescope at the South Pole in January 2001 and the results presented here incorporate data through July 2002. We present the power spectrum of the CMB at 150 GHz over the range \ell = 150 - 3000 measured by ACBAR as well as estimates for the values of the cosmological parameters within the context of Lambda-CDM models. We find that the inclusion of Omega_Lambda greatly improves the fit to the power spectrum. We also observe a slight excess of small-scale anisotropy at 150 GHz; if interpreted as power from the SZ effect of unresolved clusters, the measured signal is consistent with CBI and BIMA within the context of the SZ power spectrum models tested.Comment: To be published in the proceedings of "The Cosmic Microwave Background and its Polarization", New Astronomy Reviews, (eds. S. Hanany and K.A. Olive). 10 pages, 2 figure

Taxonomic surrogacy in biodiversity assessments, and the meaning of Linnaean ranks

Copyright © 2006 The Natural History MuseumThe majority of biodiversity assessments use species as the base unit. Recently, a series of studies have suggested replacing numbers of species with higher ranked taxa (genera, families, etc.); a method known as taxonomic surrogacy that has an important potential to save time and resources in assesments of biological diversity. We examine the relationships between taxa and ranks, and suggest that species/higher taxon exchanges are founded on misconceptions about the properties of Linnaean classification. Rank allocations in current classifications constitute a heterogeneous mixture of various historical and contemporary views. Even if all taxa were monophyletic, those referred to the same rank would simply denote separate clades without further equivalence. We conclude that they are no more comparable than any other, non-nested taxa, such as, for example, the genus Rattus and the phylum Arthropoda, and that taxonomic surrogacy lacks justification. These problems are also illustrated with data of polychaetous annelid worms from a broad-scale study of benthic biodiversity and species distributions in the Irish Sea. A recent consensus phylogeny for polychaetes is used to provide three different family-level classifications of polychaetes. We use families as a surrogate for species, and present Shannon–Wiener diversity indices for the different sites and the three different classifications, showing how the diversity measures rely on subjective rank allocations.Y. Bertrand, F. Pleijel and G. W. Rous

The BOOMERanG experiment and the curvature of the Universe

We describe the BOOMERanG experiment and its main result, i.e. the measurement of the large scale curvature of the Universe. BOOMERanG is a balloon-borne microwave telescope with sensitive cryogenic detectors. BOOMERanG has measured the angular distribution of the Cosmic Microwave Background on $\sim 3$ of the sky, with a resolution of $\sim 10$ arcmin and a sensitivity of $\sim 20 \mu K$ per pixel. The resulting image is dominated by hot and cold spots with rms fluctuations $\sim 80 \mu K$ and typical size of $\sim 1^o$. The detailed angular power spectrum of the image features three peaks and two dips at $\ell = (213^{+10}_{-13}), (541^{+20}_{-32}), (845^{+12}_{-25})$ and $\ell = (416^{+22}_{-12}), (750^{+20}_{-750})$, respectively. Such very characteristic spectrum can be explained assuming that the detected structures are the result of acoustic oscillations in the primeval plasma. In this framework, the measured pattern constrains the density parameter $\Omega$ to be $0.85 < \Omega < 1.1$ (95% confidence interval). Other cosmological parameters, like the spectral index of initial density fluctuations, the density parameter for baryons, dark matter and dark energy, are detected or constrained by the BOOMERanG measurements and by other recent CMB anisotropy experiments. When combined with other cosmological observations, these results depict a new, consistent, cosmological scenario.Comment: Proc. of the Erice School on "Neutrinos in Astro, Particle and Nuclear Physics", 18.-26. September 2001, Amand Faessler, Jan Kuckei eds, "Progress in Particle and Nuclear Physics", vol. 4