T Cell Costimulatory and Coinhibitory Pathways in Vascular Inflammatory Diseases

A broad array of evidence indicates that T lymphocytes make significant contributions to vascular inflammation in the setting of atherosclerotic disease, hypertension, autoimmune vasculitis, and other disorders. Experimental data show that costimulatory and coinhibitory pathways involving molecules of the B7-CD28 and TNF–TNFR families regulate T cell responses that promote vascular disease. Antigen presenting cells (APCs) display both peptide–major histocompatibility complex antigen and costimulators or coinhibitors to T cells. Two major types of APCs, dendritic cells (DCs) and macrophages, are present in significant numbers in the walls of arteries affected by atherosclerosis and arteritis, and some DCs are present in normal arteries. Costimulatory and coinhibitory molecules expressed by these vascular APCs can contribute to the activation or inhibition of effector T cells within the arterial wall. Vascular DCs may also be involved in transport of antigens to secondary lymphoid organs, where they activate or tolerize naïve T cells, depending on the balance of costimulators and coinhibitors they express. Costimulatory blockade is already an approved therapeutic approach to treat autoimmune disease and prevent transplant rejection. Preclinical models suggest that costimulatory blockade may also be effective in treating vascular disease. Experiential data in mice show that DCs pulsed with the appropriate antigens and treated in a way that reduces costimulatory capacity can reduce atherosclerotic disease, presumably by inducing T cell tolerance. Progress in treating vascular disease by immune modulation will require a more complete understanding of the functions of different costimulatory and coinhibitory pathways and the different subsets of vascular APCs involved

Vulnerability of LTE to Hostile Interference

LTE is well on its way to becoming the primary cellular standard, due to its performance and low cost. Over the next decade we will become dependent on LTE, which is why we must ensure it is secure and available when we need it. Unfortunately, like any wireless technology, disruption through radio jamming is possible. This paper investigates the extent to which LTE is vulnerable to intentional jamming, by analyzing the components of the LTE downlink and uplink signals. The LTE physical layer consists of several physical channels and signals, most of which are vital to the operation of the link. By taking into account the density of these physical channels and signals with respect to the entire frame, as well as the modulation and coding schemes involved, we come up with a series of vulnerability metrics in the form of jammer to signal ratios. The ``weakest links'' of the LTE signals are then identified, and used to establish the overall vulnerability of LTE to hostile interference.Comment: 4 pages, see below for citation. M. Lichtman, J. Reed, M. Norton, T. Clancy, "Vulnerability of LTE to Hostile Interference'', IEEE Global Conference on Signal and Information Processing (GlobalSIP), Dec 201

Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been identified in immune cells such as monocytes, macrophages, basophils, lymphocytes, and dendritic cells and are believed to be enzymatically produced and released “on demand” in a similar fashion as the eicosanoids. It is now recognized that other phytocannabinoids such as cannabidiol (CBD) and cannabinol (CBN) can alter the functional activities of the immune system. This special edition of the Journal of Neuroimmune Pharmacology (JNIP) presents a collection of cutting edge original research and review articles on the medical implications of phytocannabinoids and the endocannabinoid system. The goal of this special edition is to provide an unbiased assessment of the state of research related to this topic from leading researchers in the field. The potential untoward effects as well as beneficial uses of marijuana, its phytocannabinoid composition, and synthesized cannabinoid analogs are discussed. In addition, the role of the endocannabinoid system and approaches to its manipulation to treat select human disease processes are addressed

Segment and track neurons in 3D by repulsive snake method

We present a snake (active contour) model based on repulsive force to segment neurons obtained from microscopy. Based on these segmentation results, we track the neurons in 3D image to look for its branch structure. These segmentation results allow user to study morphology of neurons to further investigate neuronal function and connectivity. This repulsive snake model can successfully segment two or multiple neurons that are close to each other by some alternating repulsive force generated from the neighboring objects. We apply our results on real data to demonstrate the performance of our method. © 2005 IEEE.published_or_final_versio

Accuracy of ICD-9-CM Codes by Hospital Characteristics and Stroke Severity: Paul Coverdell National Acute Stroke Program

Background—Epidemiological and health services research often use International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes to identify patients with clinical conditions in administrative databases. We determined whether there are systematic variations between stroke patient clinical diagnoses and ICD‐9‐CM codes, stratified by hospital characteristics and stroke severity. Methods and Results—We used the records of patients discharged from hospitals participating in the Paul Coverdell National Acute Stroke Program in 2013. Within this stroke‐enriched cohort, we compared agreement between the attending physician\u27s clinical diagnosis and principal ICD‐9‐CM code and determined whether disagreements varied by hospital characteristics (presence of a stroke unit, stroke team, number of hospital beds, and hospital location). For patients with a documented National Institutes of Health Stroke Scale score at admission, we assessed whether diagnostic agreement varied by stroke severity. Agreement was generally high (\u3e 89%); differences between the physician diagnosis and ICD‐9‐CM codes were primarily attributed to discordance between ischemic stroke and transient ischemic attack (TIA), and subarachnoid and intracerebral hemorrhage. Agreement was higher for patients in metropolitan hospitals with stroke units, stroke teams, and \u3e 200 beds (all P \u3c 0.001). Agreement was lowest (60.3%) for rural hospitals with ≤ 200 beds and without stroke units or teams. Agreement was also lower for milder (94.9%) versus more‐severe (96.4%) ischemic strokes (P \u3c 0.001). Conclusions—We identified disagreements in stroke/TIA coding by hospital characteristics and stroke severity, particularly for milder ischemic strokes. Such systematic variations in ICD‐9‐CM coding practices can affect stroke case identification in epidemiological studies and may have implications for hospital‐level quality metric

The transcription T-bet is required for optimal proinflammatory trafficking of CD4+ T cells

Background: The transcription factor T-bet is a critical regulator of Th1 effector function. Animals deficient in T-bet are protected from a variety of inflammatory diseases, including systemic lupus erythematosus and inflammatory arthritis. An essential function of Th1 cells is the ability to traffic appropriately to sites of inflammation, which is largely dependent on the expression of specific selectin ligands and chemokine receptors. We therefore hypothesised that T-bet would modulate lymphocyte trafficking in vitro and in vivo by direct regulation of both selectin binding and chemokine function. Methods: Balb/c mice deficient in, or transgenic for, T-bet had been generated previously. T-bet$^{-/-}$ × DO11.10 TCR and T-bet$^{-/-}$ × IFN$^{-/-}$ mice were generated by backcrossing for >10 generations. CD4$^+$ T cells were generated from primary lymph nodes from all these mice by positive selection and stimulation with appropriate antigen. Functional analysis used the following four methods: adoptive transfer into WT Balb/c mice, which were then injected with OVA, cells were harvested from the spleen, lymph node and peritoneum; selectin binding, interactions with immoblised P-selectin and E-selectin under conditions of laminar flow were examined in a parallel plate flow chamber; expression of selectin ligands, using flow cytometry, real-time PCR and 35S incorporation; and chemokine receptor expression and function, using flow cytometry, real-time PCR, transwell chemotaxis and endothelial binding under flow conditions. Results: Selective migration of T-bet$^{-/-}$ CD4$^+$ T cells in a Th1-dependent model of peritoneal inflammation was completely abrogated. Further investigation revealed that this effect was due to a 50% reduction in binding to P-selectin but not E-selectin under in vitro flow conditions and that this was as a result of impaired tyrosine sulfation of PSGL-1. In addition, mRNA and surface expression of CXCR3, but not CCR5, was reduced and this was associated with a reduction in both transwell chemotaxis and binding to endothelial cells. Retroviral transfer experiments of T-bet cDNA into T-bet$^{-/-}$ and T-bet$^{-/-}$ × IFN$^{-/-}$ cells demonstrated that these effects were independent of interferon. Conclusions: These data establish that T-bet imprints a specific migratory program onto developing CD4$^+$ cells via control of PSGL-1 sulfation (and thus P-selectin binding) and CXCR3 expression and function. Furthermore, as E-selectin and CCR5 binding are unimpaired, this reveals a level of control on trafficking of Th1 lymphocytes not recognised by previous paradigms