The risk linked to ionizing radiation: an alternative epidemiologic approach.

Radioprotection norms have been based on risk models that have evolved over time. These models show relationships between exposure and observed effects. There is a high level of uncertainty regarding lower doses. Recommendations have been based on the conservative hypothesis of a linear relationship without threshold value. This relationship is still debated, and the diverse observations do not allow any definitive conclusion. Available data are contradictory, and various interpretations can be made. Here we review an alternative approach for defining causation and reconciling apparently contradictory conclusions. This alternative epidemiologic approach is based on causal groups: Each component of a causal group is necessary but not sufficient for causality. Many groups may be involved in causality. Thus, ionizing radiation may be a component of one or several causal groups. This formalization reconciles heterogeneous observations but implies searching for the interactions between components, mostly between critical components of a causal profile, and, for instance, the reasons why specific human groups would not show any effect despite exposure, when an effect would be expected

Feasibility of quantum key distribution through dense wavelength division multiplexing network

In this paper, we study the feasibility of conducting quantum key distribution (QKD) together with classical communication through the same optical fiber by employing dense-wavelength-division-multiplexing (DWDM) technology at telecom wavelength. The impact of the classical channels to the quantum channel has been investigated for both QKD based on single photon detection and QKD based on homodyne detection. Our studies show that the latter can tolerate a much higher level of contamination from the classical channels than the former. This is because the local oscillator used in the homodyne detector acts as a "mode selector" which can suppress noise photons effectively. We have performed simulations based on both the decoy BB84 QKD protocol and the Gaussian modulated coherent state (GMCS) QKD protocol. While the former cannot tolerate even one classical channel (with a power of 0dBm), the latter can be multiplexed with 38 classical channels (0dBm power each channel) and still has a secure distance around 10km. Preliminary experiment has been conducted based on a 100MHz bandwidth homodyne detector.Comment: 18 pages, 5 figure

Selective Depletion of Eosinophils or Neutrophils in Mice Impacts the Efficiency of Apoptotic Cell Clearance in the Thymus

Developing thymocytes undergo a rigorous selection process to ensure that the mature T cell population expresses a T cell receptor (TCR) repertoire that can functionally interact with major histocompatibility complexes (MHC). Over 90% of thymocytes fail this selection process and die. A small number of macrophages within the thymus are responsible for clearing the large number of dying thymocytes that must be continuously cleared. We studied the capacity of thymic macrophages to clear apoptotic cells under acute circumstances. This was done by synchronously inducing cell death in the thymus and then monitoring the clearance of apoptotic thymocytes. Interestingly, acute cell death was shown to recruit large numbers of CD11b+ cells into the thymus. In the absence of a minor CSF-1 dependent population of macrophages, the recruitment of these CD11b+ cells into the thymus was greatly reduced and the clearance of apoptotic cells was disrupted. To assess a possible role for the CD11b+ cells in the clearance of apoptotic cells, we analyzed mice deficient for eosinophils and mice with defective trafficking of neutrophils. Failure to attract either eosinophils or neutrophils to the thymus resulted in the impaired clearance of apoptotic cells. These results suggested that there is crosstalk between cells of the innate immune system that is necessary for maximizing the efficiency of apoptotic cell removal

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential ‘Achilles’ heel’ of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases

Optics and Quantum Electronics

Contains table of contents for Section 2 and reports on twenty research projects.Charles S. Draper Laboratory Contract DL-H-404179Joint Services Electronics Program Contract DAALO3-89-C-0001National Sciences Foundation Grant EET 87-00474National Science Foundation Grant EET 88-15834U.S. Air Force - Office of Scientific Research Contract F49620-88-C-0089National Science Foundation Grant ECS 85-52701International Business Machines CorporationMassachusetts General Hospital Contract N00014-86K-0117National Institutes of Health Grant 2-RO1-GM35459U.S. Department of Energy Grant DE-FG02-89-ER14012Lawrence Livermore National Laboratory Subcontract B04870

Recursive Cluster Elimination Based Support Vector Machine for Disease State Prediction Using Resting State Functional and Effective Brain Connectivity

Brain state classification has been accomplished using features such as voxel intensities, derived from functional magnetic resonance imaging (fMRI) data, as inputs to efficient classifiers such as support vector machines (SVM) and is based on the spatial localization model of brain function. With the advent of the connectionist model of brain function, features from brain networks may provide increased discriminatory power for brain state classification.In this study, we introduce a novel framework where in both functional connectivity (FC) based on instantaneous temporal correlation and effective connectivity (EC) based on causal influence in brain networks are used as features in an SVM classifier. In order to derive those features, we adopt a novel approach recently introduced by us called correlation-purged Granger causality (CPGC) in order to obtain both FC and EC from fMRI data simultaneously without the instantaneous correlation contaminating Granger causality. In addition, statistical learning is accelerated and performance accuracy is enhanced by combining recursive cluster elimination (RCE) algorithm with the SVM classifier. We demonstrate the efficacy of the CPGC-based RCE-SVM approach using a specific instance of brain state classification exemplified by disease state prediction. Accordingly, we show that this approach is capable of predicting with 90.3% accuracy whether any given human subject was prenatally exposed to cocaine or not, even when no significant behavioral differences were found between exposed and healthy subjects.The framework adopted in this work is quite general in nature with prenatal cocaine exposure being only an illustrative example of the power of this approach. In any brain state classification approach using neuroimaging data, including the directional connectivity information may prove to be a performance enhancer. When brain state classification is used for disease state prediction, our approach may aid the clinicians in performing more accurate diagnosis of diseases in situations where in non-neuroimaging biomarkers may be unable to perform differential diagnosis with certainty

Identification, Isolation and Expansion of Myoendothelial Cells Involved in Leech Muscle Regeneration

Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells