Inference of random walk models to describe leukocyte migration

While the majority of cells in an organism are static and remain relatively immobile in their tissue, migrating cells occur commonly during developmental processes and are crucial for a functioning immune response. The mode of migration has been described in terms of various types of random walks. To understand the details of the migratory behaviour we rely on mathematical models and their calibration to experimental data. Here we propose an approximate Bayesian inference scheme to calibrate a class of random walk models characterized by a specific, parametric particle re-orientation mechanism to observed trajectory data. We elaborate the concept of transition matrices (TMs) to detect random walk patterns and determine a statistic to quantify these TM to make them applicable for inference schemes. We apply the developed pipeline to in vivo trajectory data of macrophages and neutrophils, extracted from zebrafish that had undergone tail transection. We find that macrophage and neutrophils exhibit very distinct biased persistent random walk patterns, where the strengths of the persistence and bias are spatio-temporally regulated. Furthermore, the movement of macrophages is far less persistent than that of neutrophils in response to wounding

Colour-electric spectral function at next-to-leading order

The spectral function related to the correlator of two colour-electric fields along a Polyakov loop determines the momentum diffusion coefficient of a heavy quark near rest with respect to a heat bath. We compute this spectral function at next-to-leading order, O(alpha_s^2), in the weak-coupling expansion. The high-frequency part of our result (omega >> T), which is shown to be temperature-independent, is accurately determined thanks to asymptotic freedom; the low-frequency part of our result (omega << T), in which Hard Thermal Loop resummation is needed in order to cure infrared divergences, agrees with a previously determined expression. Our result may help to calibrate the overall normalization of a lattice-extracted spectral function in a perturbative frequency domain T << omega << 1/a, paving the way for a non-perturbative estimate of the momentum diffusion coefficient at omega -> 0. We also evaluate the colour-electric Euclidean correlator, which could be directly compared with lattice simulations. As an aside we determine the Euclidean correlator in the lattice strong-coupling expansion, showing that through a limiting procedure it can in principle be defined also in the confined phase of pure Yang-Mills theory, even if a practical measurement could be very noisy there.Comment: 38 page

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Transport Through Andreev Bound States in a Graphene Quantum Dot

Andreev reflection-where an electron in a normal metal backscatters off a superconductor into a hole-forms the basis of low energy transport through superconducting junctions. Andreev reflection in confined regions gives rise to discrete Andreev bound states (ABS), which can carry a supercurrent and have recently been proposed as the basis of qubits [1-3]. Although signatures of Andreev reflection and bound states in conductance have been widely reported [4], it has been difficult to directly probe individual ABS. Here, we report transport measurements of sharp, gate-tunable ABS formed in a superconductor-quantum dot (QD)-normal system, which incorporates graphene. The QD exists in the graphene under the superconducting contact, due to a work-function mismatch [5, 6]. The ABS form when the discrete QD levels are proximity coupled to the superconducting contact. Due to the low density of states of graphene and the sensitivity of the QD levels to an applied gate voltage, the ABS spectra are narrow, can be tuned to zero energy via gate voltage, and show a striking pattern in transport measurements.Comment: 25 Pages, included SO

Spin polarization of carriers in InGaAs self-assembled quantum rings inserted in GaAs-AlGaAs resonant tunneling devices

In this work, we have investigated transport and polarization resolved photoluminescence (PL) of n-type GaAs-AlGaAs resonant tunneling diodes (RTDs) containing a layer of InGaAs self-assembled quantum rings (QRs) in the quantum well (QW). All measurements were performed under applied voltage, magnetic fields up to 15 T and using linearly polarized laser excitation. It was observed that the QRs’ PL intensity and the circular polarization degree (CPD) oscillate periodically with applied voltage under high magnetic fields at 2 K. Our results demonstrate an effective voltage control of the optical and spin properties of InGaAs QRs inserted into RTDs

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure