Conditioning bounds for traveltime tomography in layered media

This paper revisits the problem of recovering a smooth, isotropic, layered wave speed profile from surface traveltime information. While it is classic knowledge that the diving (refracted) rays classically determine the wave speed in a weakly well-posed fashion via the Abel transform, we show in this paper that traveltimes of reflected rays do not contain enough information to recover the medium in a well-posed manner, regardless of the discretization. The counterpart of the Abel transform in the case of reflected rays is a Fredholm kernel of the first kind which is shown to have singular values that decay at least root-exponentially. Kinematically equivalent media are characterized in terms of a sequence of matching moments. This severe conditioning issue comes on top of the well-known rearrangement ambiguity due to low velocity zones. Numerical experiments in an ideal scenario show that a waveform-based model inversion code fits data accurately while converging to the wrong wave speed profile

On the spectral properties of L_{+-} in three dimensions

This paper is part of the radial asymptotic stability analysis of the ground state soliton for either the cubic nonlinear Schrodinger or Klein-Gordon equations in three dimensions. We demonstrate by a rigorous method that the linearized scalar operators which arise in this setting, traditionally denoted by L_{+-}, satisfy the gap property, at least over the radial functions. This means that the interval (0,1] does not contain any eigenvalues of L_{+-} and that the threshold 1 is neither an eigenvalue nor a resonance. The gap property is required in order to prove scattering to the ground states for solutions starting on the center-stable manifold associated with these states. This paper therefore provides the final installment in the proof of this scattering property for the cubic Klein-Gordon and Schrodinger equations in the radial case, see the recent theory of Nakanishi and the third author, as well as the earlier work of the third author and Beceanu on NLS. The method developed here is quite general, and applicable to other spectral problems which arise in the theory of nonlinear equations

Global dynamics above the ground state for the nonlinear Klein-Gordon equation without a radial assumption

We extend our previous result on the focusing cubic Klein-Gordon equation in three dimensions to the non-radial case, giving a complete classification of global dynamics of all solutions with energy at most slightly above that of the ground state.Comment: 40 page

Spectral Analysis for Matrix Hamiltonian Operators

In this work, we study the spectral properties of matrix Hamiltonians generated by linearizing the nonlinear Schr\"odinger equation about soliton solutions. By a numerically assisted proof, we show that there are no embedded eigenvalues for the three dimensional cubic equation. Though we focus on a proof of the 3d cubic problem, this work presents a new algorithm for verifying certain spectral properties needed to study soliton stability. Source code for verification of our comptuations, and for further experimentation, are available at http://www.math.toronto.edu/simpson/files/spec_prop_code.tgz.Comment: 57 pages, 22 figures, typos fixe

A Centre-Stable Manifold for the Focussing Cubic NLS in R1+3R^{1+3}

Consider the focussing cubic nonlinear Schr\"odinger equation in $R^3$: $$i\psi_t+\Delta\psi = -|\psi|^2 \psi.$$ It admits special solutions of the form $e^{it\alpha}\phi$, where $\phi$ is a Schwartz function and a positive ($\phi>0$) solution of $$-\Delta \phi + \alpha\phi = \phi^3.$$ The space of all such solutions, together with those obtained from them by rescaling and applying phase and Galilean coordinate changes, called standing waves, is the eight-dimensional manifold that consists of functions of the form $e^{i(v \cdot + \Gamma)} \phi(\cdot - y, \alpha)$. We prove that any solution starting sufficiently close to a standing wave in the $\Sigma = W^{1, 2}(R^3) \cap |x|^{-1}L^2(R^3)$ norm and situated on a certain codimension-one local Lipschitz manifold exists globally in time and converges to a point on the manifold of standing waves. Furthermore, we show that \mc N is invariant under the Hamiltonian flow, locally in time, and is a centre-stable manifold in the sense of Bates, Jones. The proof is based on the modulation method introduced by Soffer and Weinstein for the $L^2$-subcritical case and adapted by Schlag to the $L^2$-supercritical case. An important part of the proof is the Keel-Tao endpoint Strichartz estimate in $R^3$ for the nonselfadjoint Schr\"odinger operator obtained by linearizing around a standing wave solution.Comment: 56 page

Disentangling the respective contribution of task selection and task execution in self-directed cognitive control development

peer reviewedTask selection and task execution are key constructs in cognitive control development. Yet, little is known about how separable they are and how each contributes to task switching performance. Here, 60 4- to 5-year olds, 60 7- to 8-year olds, and 60 10- to 11-year olds children completed the double registration procedure, which dissociates these two processes. Task selection yielded both mixing and switch costs, especially in younger children, and task execution mostly yielded switch costs at all ages, suggesting that task selection is costlier than task execution. Moreover, both task selection and execution varied with task self-directedness (i.e., to what extent the task is driven by external aids) demands. Whereas task selection and task execution are dissociated regarding performance costs, they nevertheless both contribute to self-directed control

High-resolution analysis of HLA class I alterations in colorectal cancer

BACKGROUND: Previous studies indicate that alterations in Human Leukocyte Antigen (HLA) class I expression are frequent in colorectal tumors. This would suggest serious limitations for immunotherapy-based strategies involving T-cell recognition. Distinct patterns of HLA surface expression might conceal different immune escape mechanisms employed by the tumors and are worth further study. METHOD: We applied four-color multiparameter flow cytometry (FCM), using a large panel of alloantigen-specific anti-HLA-A and -B monoclonal antibodies, to study membranous expression of individual HLA alleles in freshly isolated colorectal cancer cell suspensions from 21 patients. RESULTS: Alterations in HLA class I phenotype were observed in 8 (38%) of the 21 tumors and comprised loss of a single A or B alleles in 4 cases, and loss of all four A and B alleles in the other 4 cases. Seven of these 8 tumors were located on the right side of the colon, and those showing loss of both HLA-A and -B membranous expression were all of the MSI-H phenotype. CONCLUSION: FCM allows the discrimination of complex phenotypes related to the expression of HLA class I. The different patterns of HLA class I expression might underlie different tumor behavior and influence the success rate of immunotherapy

Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

<p>Abstract</p> <p>Background</p> <p>Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.</p> <p>Methods</p> <p>In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.</p> <p>Results</p> <p>In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.</p> <p>Conclusion</p> <p>An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00703651.</p

Low CD4+ T Cell Counts among African HIV-1 Infected Subjects with Group B KIR Haplotypes in the Absence of Specific Inhibitory KIR Ligands

Natural killer (NK) cells are regulated by interactions between polymorphic killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA). Genotypic combinations of KIR3DS1/L1 and HLA Bw4-80I were previously shown to influence HIV-1 disease progression, however other KIR genes have not been well studied. In this study, we analyzed the influence of all activating and inhibitory KIR, in association with the known HLA inhibitory KIR ligands, on markers of disease progression in a West African population of therapy-naïve HIV-1 infected subjects. We observed a significant association between carriage of a group B KIR haplotype and lower CD4+ T cell counts, with an additional effect for KIR3DS1 within the frame of this haplotype. In contrast, we found that individuals carrying genes for the inhibitory KIR ligands HLA-Bw4 as well as HLA-C1 showed significantly higher CD4+ T cell counts. These associations were independent from the viral load and from individual HIV-1 protective HLA alleles. Our data suggest that group B KIR haplotypes and lack of specific inhibitory KIR ligand genes, genotypes considered to favor NK cell activation, are predictive of HIV-1 disease progression