Individualized prognosis in childhood immune thrombocytopenia

Children with immune thrombocytopenia (ITP) show a primary hemostasis defect due to reduced number of platelets (thrombocytopenia). This leads to bleeding. In children, ITP is often transient and self-limiting (transient ITP), but some children show persistent thrombocytopenia or even chronic ITP. Treatment with immune-modulating medication like intravenous immunoglobulins (IVIg) leads to early recovery from thrombocytopenia and prevents bleeding. Unfortunately, treatment is only effective in a part of the patients. This dissertation aims to better understand, explain, and predict spontaneous recovery and favorable treatment outcomes after IVIg in a specific child with ITP. To that end, molecular disease mechanisms are being evaluated and analyzed together with clinical data. The dissertation provides novel data working towards individualized care for children with ITP. This is relevant for communication with the child and caregivers over the expected prognosis, treatment decisions (IVIg), and indications for early additional diagnostic testing for other causes of thrombocytopenia (such as genetic tests). Landsteiner Foundation for Blood Transfusion Research (LSBR); Studienstiftung des Deutschen Volkes.LUMC / Geneeskund

Resonantly enhanced nonlinear optics in semiconductor quantum wells: An application to sensitive infrared detection

A novel class of coherent nonlinear optical phenomena, involving induced transparency in quantum wells, is considered in the context of a particular application to sensitive long-wavelength infrared detection. It is shown that the strongest decoherence mechanisms can be suppressed or mitigated, resulting in substantial enhancement of nonlinear optical effects in semiconductor quantum wells.Comment: 4 pages, 3 figures, replaced with revised versio

Creation and Growth of Components in a Random Hypergraph Process

Denote by an $\ell$-component a connected $b$-uniform hypergraph with $k$ edges and $k(b-1) - \ell$ vertices. We prove that the expected number of creations of $\ell$-component during a random hypergraph process tends to 1 as $\ell$ and $b$ tend to $\infty$ with the total number of vertices $n$ such that $\ell = o(\sqrt[3]{\frac{n}{b}})$. Under the same conditions, we also show that the expected number of vertices that ever belong to an $\ell$-component is approximately $12^{1/3} (b-1)^{1/3} \ell^{1/3} n^{2/3}$. As an immediate consequence, it follows that with high probability the largest $\ell$-component during the process is of size $O((b-1)^{1/3} \ell^{1/3} n^{2/3})$. Our results give insight about the size of giant components inside the phase transition of random hypergraphs.Comment: R\'{e}sum\'{e} \'{e}tend

CD8 T cell function and cross-reactivity explored by stepwise increased peptide-HLA versus TCR affinity.

Recruitment and activation of CD8 T cells occur through specific triggering of T cell receptor (TCR) by peptide-bound human leucocyte antigen (HLA) ligands. Within the generated trimeric TCR-peptide:HLA complex, the molecular binding affinities between peptide and HLA, and between TCR and peptide:HLA both impact T cell functional outcomes. However, how their individual and combined effects modulate immunogenicity and overall T cell responsiveness has not been investigated systematically. Here, we established two panels of human tumor peptide variants differing in their affinity to HLA. For precise characterization, we developed the "blue peptide assay", an upgraded cell-based approach to measure the peptide:HLA affinity. These peptide variants were then used to investigate the cross-reactivity of tumor antigen-specific CD8 T cell clonotypes derived from blood of cancer patients after vaccination with either the native or an affinity-optimized Melan-A/MART-1 epitope, or isolated from tumor infiltrated lymph nodes (TILNs). Vaccines containing the native tumor epitope generated T cells with better functionality, and superior cross-reactivity against potential low affinity escape epitopes, as compared to T cells induced by vaccines containing an HLA affinity-optimized epitope. Comparatively, Melan-A/MART-1-specific TILN cells displayed functional and cross-reactive profiles that were heterogeneous and clonotype-dependent. Finally, we took advantage of a collection of T cells expressing affinity-optimized NY-ESO-1-specific TCRs to interrogate the individual and combined impact of peptide:HLA and TCR-pHLA affinities on overall CD8 T cell responses. We found profound and distinct effects of both biophysical parameters, with additive contributions and absence of hierarchical dominance. Altogether, the biological impact of peptide:HLA and TCR-pHLA affinities on T cell responses was carefully dissected in two antigenic systems, frequently targeted in human cancer immunotherapy. Our technology and stepwise comparison open new insights into the rational design and selection of vaccine-associated tumor-specific epitopes and highlight the functional and cross-reactivity profiles that endow T cells with best tumor control capacity

Superconducting anisotropy and evidence for intrinsic pinning in single crystalline MgB2_2

We examine the superconducting anisotropy $\gamma_c = (m_c / m_{ab})^{1/2}$ of a metallic high-$T_c$ superconductor MgB$_2$ by measuring the magnetic torque of a single crystal. The anisotropy $\gamma_c$ does not depend sensitively on the applied magnetic field at 10 K. We obtain the anisotropy parameter $\gamma_c = 4.31 \pm 0.14$. The torque curve shows the sharp hysteresis peak when the field is applied parallel to the boron layers. This comes from the intrinsic pinning and is experimental evidence for the occurrence of superconductivity in the boron layers.Comment: REVTeX 4, To be published in Physical Review

Casimir Effect on the Worldline

We develop a method to compute the Casimir effect for arbitrary geometries. The method is based on the string-inspired worldline approach to quantum field theory and its numerical realization with Monte-Carlo techniques. Concentrating on Casimir forces between rigid bodies induced by a fluctuating scalar field, we test our method with the parallel-plate configuration. For the experimentally relevant sphere-plate configuration, we study curvature effects quantitatively and perform a comparison with the ``proximity force approximation'', which is the standard approximation technique. Sizable curvature effects are found for a distance-to-curvature-radius ratio of a/R >~ 0.02. Our method is embedded in renormalizable quantum field theory with a controlled treatment of the UV divergencies. As a technical by-product, we develop various efficient algorithms for generating closed-loop ensembles with Gaussian distribution.Comment: 27 pages, 10 figures, Sect. 2.1 more self-contained, improved data for Fig. 6, minor corrections, new Refs, version to be published in JHE

Guiding center picture of magnetoresistance oscillations in rectangular superlattices

We calculate the magneto-resistivities of a two-dimensional electron gas subjected to a lateral superlattice (LSL) of rectangular symmetry within the guiding-center picture, which approximates the classical electron motion as a rapid cyclotron motion around a slowly drifting guiding center. We explicitly evaluate the velocity auto-correlation function along the trajectories of the guiding centers, which are equipotentials of a magnetic-field dependent effective LSL potential. The existence of closed equipotentials may lead to a suppression of the commensurability oscillations, if the mean free path and the LSL modulation potential are large enough. We present numerical and analytical results for this suppression, which allow, in contrast to previous quantum arguments, a classical explanation of similar suppression effects observed experimentally on square-symmetric LSL. Furthermore, for rectangular LSLs of lower symmetry they lead us to predict a strongly anisotropic resistance tensor, with high- and low-resistance directions which can be interchanged by tuning the externally applied magnetic field.Comment: 12 pages, 9 figure

Axial vector form factor of nucleons in a light-cone diquark model

The nucleon axial vector form factor is investigated in a light-cone quark spectator diquark model, in which Melosh rotations are applied to both the quark and vector diquark. It is found that this model gives a very good description of available experimental data and the results have very little dependence on the parameters of the model. The relation between the nucleon axial constant and the anomalous magnetic moment of nucleons is also discussed.Comment: 8 pages, Revtex4, 1 figure, version to be published in Phys. Rev.

Single-photon Transistors Based on the Interaction of an Emitter and Surface Plasmons

A symmetrical approach is suggested (Chang DE et al. Nat Phys 3:807, 2007) to realize a single-photon transistor, where the presence (or absence) of a single incident photon in a ‘gate’ field is sufficient to allow (prevent) the propagation of a subsequent ‘signal’ photon along the nanowire, on condition that the ‘gate’ field is symmetrically incident from both sides of an emitter simultaneously. We present a scheme for single-photon transistors based on the strong emitter-surface-plasmon interaction. In this scheme, coherent absorption of an incoming ‘gate’ photon incident along a nanotip by an emitter located near the tip of the nanotip results in a state flip in the emitter, which controls the subsequent propagation of a ‘signal’ photon in a nanowire perpendicular to the axis of the nanotip