Qualitative and Quantitative Analysis of Timed SDL Specifications

. Timed SDL (TSDL) is a modified version of SDL designed for the examination of qualitative and quantitative system aspects within one model description. Because realistic communication protocols tend to be very large a program package was developed, which transforms a TSDL model into an internal representation of an equivalent Finite State Machine (FSM). This FSM representation can be efficiently analyzed by algorithms for qualitative and quantitative protocol analysis. In particular algorithms for partial state space exploration have shown to be very suitable. One of these algorithms is described in detail and is slightly improved. It is shown, that this kind of analysis leads to reasonable results, even for large models. 1 Introduction For the description and specification of communication protocols formal description techniques (FDTs) are widely used. Several FDTs have been standardized by the ISO or CCITT (see [7, 9, 10, 11]) among them SDL, which is the FDT we will focus on in t..

CCL2 disrupts the adherens junction: implications for neuroinflammation

Alterations to blood-brain barrier (BBB) adhesion molecules and junctional integrity during neuroinflammation can promote central nervous system (CNS) pathology. The chemokine CCL2 is elevated during CNS inflammation and is associated with endothelial dysfunction. The effects of CCL2 on endothelial adherens junctions (AJs) have not been defined. We demonstrate that CCL2 transiently induces Src-dependent disruption of human brain microvascular endothelial AJ. β-Catenin is phosphorylated and traffics from the AJ to PECAM-1 (platelet endothelial cell adhesion molecule-1), where it is sequestered at the membrane. PECAM-1 is also tyrosine-phosphorylated, an event associated with recruitment of the phosphatase SHP-2 (Src homology 2 domain-containing protein phosphatase) to PECAM-1, β-catenin release from PECAM-1, and reassociation of β-catenin with the AJ. Surface localization of PECAM-1 is increased in response to CCL2. This may enable the endothelium to sustain CCL2-induced alterations in AJ and facilitate recruitment of leukocytes into the CNS. Our novel findings provide a mechanism for CCL2-mediated disruption of endothelial junctions that may contribute to BBB dysfunction and increased leukocyte recruitment in neuroinflammatory diseases

Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats

Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43(low)CD11b+ and CCR2-CX3CR1+CD43(hi)CD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-alpha and IL-6, IL-1 beta (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development

Objective Assessment of Spectral Ripple Discrimination in Cochlear Implant Listeners Using Cortical Evoked Responses to an Oddball Paradigm

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R(2) = 0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users