Time reversal method with stabilizing boundary conditions for Photoacoustic tomography

We study an inverse initial source problem that models photoacoustic tomo- graphy measurements with array detectors, and introduce a method that can be viewed as a modi fi cation of the so called back and forth nudging method. We show that the method converges at an exponential rate under a natural visibility condition, with data given only on a part of the boundary of the domain of wave propagation. In this paper we consider the case of noiseless measurements

A novel behavioral fish model of nociception for testing analgesics

Pain is a major symptom in many medical conditions, and often interferes significantly with a person's quality of life. Although a priority topic in medical research for many years, there are still few analgesic drugs approved for clinical use. One reason is the lack of appropriate animal models that faithfully represent relevant hallmarks associated with human pain. Here we propose zebrafish (Danio rerio) as a novel short-term behavioral model of nociception, and analyse its sensitivity and robustness. Firstly, we injected two different doses of acetic acid as the noxious stimulus. We studied individual locomotor responses of fish to a threshold level of nociception using two recording systems: a video tracking system and an electric biosensor (the MOBS system). We showed that an injection dose of 10% acetic acid resulted in a change in behavior that could be used to study nociception. Secondly, we validated our behavioral model by investigating the effect of the analgesic morphine. In time-course studies, first we looked at the dose-response relationship of morphine and then tested whether the effect of morphine could be modulated by naloxone, an opioid antagonist. Our results suggest that a change in behavioral responses of zebrafish to acetic acid is a reasonable model to test analgesics. The response scales with stimulus intensity, is attenuated by morphine, and the analgesic effect of morphine is blocked with naloxone. The change in behavior of zebrafish associated with the noxious stimulus can be monitored with an electric biosensor that measures changes in water impedance. © 2011 by the authors; licensee MDPI, Basel, Switzerland

The massless Dirac equation from the continuum mechanics and microlocal analysis perspectives

The thesis is concerned with the study of the massless Dirac equation. In the first part we study the massless Dirac equation in dimension 1+3 in the stationary setting, i.e. when the spinor field oscillates harmonically in time. We suggest a new geometric interpretation for this equation. We think of our 3-dimensional space as an elastic continuum and assume that material points can experience no displacements, only rotations. This framework is a special case of the Cosserat theory of elasticity. Rotations of material points are described mathematically by attaching to each geometric point an orthonormal basis which gives a field of orthonormal bases called the coframe. As the dynamical variables we choose the coframe and a density. We choose a particular potential energy which is conformally invariant and then incorporate time into our action by subtracting kinetic energy. We prove that in the stationary setting our model is equivalent to a pair of massless Dirac equations. In the second part we consider an elliptic self-adjoint first order pseudodifferential operator acting on columns of m complex-valued half-densities over a compact n-dimensional manifold. The eigenvalues of the principal symbol are assumed to be simple but no assumptions are made on their sign, so the operator is not necessarily semi-bounded. We study the spectral function and derive a two-term asymptotic formula. We then restrict our study to the case when m=2, n=3, the operator is differential and has trace-free principal symbol, and address the question: is our operator a massless Dirac operator? We prove that it is a massless Dirac operator if and only if, at every point, a) the subprincipal symbol is proportional to the identity matrix and b) the second asymptotic coefficient of the spectral function is zero

The Personal Genome Project-UK, an open access resource of human multi-omics data

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics

The local counting function of operators of Dirac and Laplace type

Let PP be a non-negative self-adjoint Laplace type operator acting on sections of a hermitian vector bundle over a closed Riemannian manifold. In this paper we review the close relations between various PP-related coefficients such as the mollified spectral counting coefficients, the heat trace coefficients, the resolvent trace coefficients, the residues of the spectral zeta function as well as certain Wodzicki residues. We then use the Wodzicki residue to obtain results about the local counting function of operators of Dirac and Laplace type. In particular, we express the second term of the mollified spectral counting function of Dirac type operators in terms of geometric quantities and characterize those Dirac type operators for which this coefficient vanishes

Leukocyte telomere length and mitochondrial DNA copy number association with colorectal cancer risk in an aging population

In this study, we evaluated the association of blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) with the risk of incident colorectal cancer (CRC). We studied and followed-up a cohort of Russian men and women (aged 45 – 69 years, n = 9360, 54% female) from the HAPIEE study for 15 years. Using the nested case-control design, we selected cases with incident CRC among those free from any baseline cancer (n = 146) and sex- and age-stratified controls among those free from baseline cancer and cardiovascular disease and alive at the end of the follow-up (n = 799). We employed multivariable-adjusted logistic regression to estimate the odds ratios (ORs) of CRC per 1 decile of LTL or mtDNA-CN. We observed an inverse association of LTL and mtDNA-CN baseline values with the 15-year risk of incident CRC. Carriers of shorter telomeres had an increased 15-year risk of incident CRC with adjusted OR 3.2 (95% CI: 2.56 – 3.87, P < 0.001) per 1 decile decrease in LTL, independent of baseline age, sex, smoking, body mass index, blood pressure, lipid levels, and education. Similarly, lower mtDNA-CN was associated with the higher risk of incident CRC with adjusted OR 1.7 (95% CI: 1.12 – 1.89, P < 0.001) per 1 decile decrease in mtDNA-CN, independent of the aforementioned factors. Using the modified values of LTL and mtDNA-CN adjusted for multiple factors and their interactions with a case–control status, the ORs of CRC were 2.53 and 1.52 per 1 decile decrease in adjusted baseline LTL and mtDNA-CN, respectively. In conclusion, LTL and mtDNA-CN were independent inverse predictors of the 15-year risk of CRC in the Russian cohort. These findings highlight the relevance for subsequent research to exploit the mechanisms through which LTL and mtDNA-CN may reflect human health