A cross-center smoothness prior for variational Bayesian brain tissue segmentation

Suppose one is faced with the challenge of tissue segmentation in MR images, without annotators at their center to provide labeled training data. One option is to go to another medical center for a trained classifier. Sadly, tissue classifiers do not generalize well across centers due to voxel intensity shifts caused by center-specific acquisition protocols. However, certain aspects of segmentations, such as spatial smoothness, remain relatively consistent and can be learned separately. Here we present a smoothness prior that is fit to segmentations produced at another medical center. This informative prior is presented to an unsupervised Bayesian model. The model clusters the voxel intensities, such that it produces segmentations that are similarly smooth to those of the other medical center. In addition, the unsupervised Bayesian model is extended to a semi-supervised variant, which needs no visual interpretation of clusters into tissues.Comment: 12 pages, 2 figures, 1 table. Accepted to the International Conference on Information Processing in Medical Imaging (2019

A New Statistical Image Analysis Approach and Its Application to Hippocampal Morphometry

In this work, we propose a novel and powerful image analysis framework for hippocampal morphometry in early mild cognitive impairment (EMCI), an early prodromal stage of Alzheimer’s disease (AD). We create a hippocampal surface atlas with subfield information, model each hippocampus using the SPHARM technique, and register it to the atlas to extract surface deformation signals. We propose a new alternative to standard random field theory (RFT) and permutation image analysis methods, Statistical Parametric Mapping (SPM) Distribution Analysis or SPM-DA, to perform statistical shape analysis and compare its performance with that of RFT methods on both simulated and real hippocampal surface data. The major strengths of our framework are twofold: (a) SPM-DA provides potentially more powerful algorithms than standard RFT methods for detecting weak signals, and (b) the framework embraces the important hippocampal subfield information for improved biological interpretation. We demonstrate the effectiveness of our method via an application to an AD cohort, where an SPM-DA method detects meaningful hippocampal shape differences in EMCI that are undetected by standard RFT methods

Observation of a One-Dimensional Spin-Orbit Gap in a Quantum Wire

Understanding the flow of spins in magnetic layered structures has enabled an increase in data storage density in hard drives over the past decade of more than two orders of magnitude1. Following this remarkable success, the field of 'spintronics' or spin-based electronics is moving beyond effects based on local spin polarisation and is turning its attention to spin-orbit interaction (SOI) effects, which hold promise for the production, detection and manipulation of spin currents, allowing coherent transmission of information within a device. While SOI-induced spin transport effects have been observed in two- and three-dimensional samples, these have been subtle and elusive, often detected only indirectly in electrical transport or else with more sophisticated techniques. Here we present the first observation of a predicted 'spin-orbit gap' in a one-dimensional sample, where counter-propagating spins, constituting a spin current, are accompanied by a clear signal in the easily-measured linear conductance of the system.Comment: 10 pages, 5 figures, supplementary informatio

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

A contemporaneous infrared flash from a long gamma-ray burst: an echo from the central engine

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes -- the activity of the central engine gives rise to the high-energy emission of the burst through internal shocking and the subsequent interaction of the flow with the external environment produces long-wavelength afterglow. While afterglow observations continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and was associated with emission from an external shock. Here we report the discovery of infrared (IR) emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a. Our robotic telescope acquired 21 images during the active phase of the burst, yielding the earliest multi-colour observations of any long-wavelength emission associated with a GRB. Analysis of an initial IR pulse suggests an origin consistent with internal shocks. This opens a new possibility to study the central engine of GRBs with ground-based observations at long wavelengths.Comment: Accepted to Nature on March 1, 2005. 9 pages, 4 figures, nature12.cls and nature1.cls files included. This paper is under press embargo until print publicatio

Peripheral T Cell Cytokine Responses for Diagnosis of Active Tuberculosis

BACKGROUND: A test for diagnosis of active Tuberculosis (TB) from peripheral blood could tremendously improve clinical management of patients. METHODS: Of 178 prospectively enrolled patients with possible TB, 60 patients were diagnosed with pulmonary and 27 patients with extrapulmonary TB. The frequencies of Mycobacterium tuberculosis (MTB) specific CD4(+) T cells and CD8(+) T cells producing cytokines were assessed using overnight stimulation with purified protein derivate (PPD) or early secretory antigenic target (ESAT)-6, respectively. RESULTS: Among patients with active TB, an increased type 1 cytokine profile consisting of mainly CD4(+) T cell derived interferon (IFN)-γ was detectable. Despite contributing to the cytokine profile as a whole, the independent diagnostic performance of one cytokine producing T cells as well as polyfunctional T cells was poor. IFN-γ/Interleukin(IL)-2 cytokine ratios discriminated best between active TB and other diseases. CONCLUSION: T cells producing one cytokine and polyfunctional T cells have a limited role in diagnosis of active TB. The significant shift from a "memory type" to an "effector type" cytokine profile may be useful for further development of a rapid immune-diagnostic tool for active TB

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited