Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for elevated ICP can be identified. This may eventually lead to a blood test to diagnose intracranial hypertension

Secure synthesis and activation of protocol translation agents

Protocol heterogeneity is pervasive and is a major obstacle to effective integration of services in large systems. However, standardization is not a complete answer. Standardized protocols must be general to prevent a proliferation of standards, and can therefore become complex and inefficient. Specialized protocols can be simple and efficient, since they can ignore situations that are precluded by application characteristics. One solution is to maintain agents for translating between protocols. However, n protocol types would require agents, since an agent must exist for a source - destination pair. A better solution is to create agents as needed. This paper examines the issues in the creation and management of protocol translation agents. We focus on the design of Nestor, an environment for synthesizing and managing RPC protocol translation agents. We provide rationale for the translation mechanism and the synthesis environment, with specific emphasis on the security issues arising in Nestor. Nestor has been implemented and manages heterogeneous RPC agents generated using the Cicero protocol construction language and the URPC toolkit.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49229/2/ds7402.pd

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS

Non-Wiener solutions for the lms algorithm : A time domain approach

Cet article présente une analyse temporelle du comportement du poids de l'algorithme LMS quand le signal d'entrée est une sinusoide déterministe. La récursion matricielle linéaire variable en fonction du temps peut être résolue exactement en utilisant une décomposition en sous-espaces orthogonaux. Nous montrons que le comportement en régime transitoire et permanent et la stabilité de l'algorithme dépendent des valeurs propres de la matrice d'état pour la récursion induite invariante dans le temps. La réponse du signal utile à la sortie du filtre est décrite par une système lineaire invariant dans les temps. Ainsi cet article présente un autre dérivation des résultats donnés dans [1] and étend les résultats de [4] au cas d'un filtre adaptatif N-tap

Lightweight Thread Tunnelling in Network Applications

Active Network nodes are increasingly being used for nontrivial processing of data streams. These complex network applications typically benefit from protection between their components for faulttolerance or security. However, fine-grained memory protection introduces bottlenecks in communication among components. This paper describes memory protection in Expert, an OS for programmable network elements which re-examines thread tunnelling as a way of allowing these complex applications to be split over multiple protection domains. We argue that previous problems with tunnelling are symptoms of overly general designs, and we demonstrate a minimal domain-crossing primitive which nevertheless achieves the majority of benefits possible from tunnelling

Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study

Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neural systems and provides the opportunity for experimental tests of hypotheses regarding mechanisms underlying anorexia nervosa (AN). The present pilot study has investigated whether high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to a region of the right dorsolateral prefrontal cortex (DLPFC) might be associated with change in food selection among adult inpatients with AN. Ten women received one session of sham and one session of HF-rTMS targeting the right DLPFC while completing a computerized Food Choice Task. Compared to sham, HF-rTMS was associated with changes in food ratings and food choice: inpatients reported higher healthiness ratings of low- and high-fat foods and selected a significantly greater proportion of high-fat foods over a neutrally rated reference item while receiving HF-rTMS. Findings suggest that HF-rTMS to the right DLPFC was associated with a reduction of fat avoidance on a food choice task among inpatients with AN and provide additional support for the possibility that this region, and related neural circuits, may underlie restrictive food choice. Research using rTMS to experimentally test neural mechanisms is needed to elucidate the underpinnings of AN and supports the development of novel treatment targets

On designing a target-independent DSL for safe OS process-scheduling components

Abstract. Developing new process-scheduling components for multiple OSes is challenging because of the tight interdependence between an OS and its scheduler and because of the stringent safety requirements that OS code must satisfy. In this context, a domain-specific language (DSL), designed by a scheduling expert, can encapsulate scheduling expertise and thus facilitate scheduler programming and verification. Nevertheless, designing a DSL that is target-independent and provides safety guarantees requires expertise not only in scheduling but also in the structure of various OSes. To address these issues, we propose the introduction of an OS expert into the DSL design process and the use of a type system to enable the OS expert to express relevant OS properties. This paper instantiates our approach in the context of the Bossa processscheduling framework and describes how the types provided by an OS expert are used to ensure that Bossa scheduling components are safe.