SUPERVISING MICROWAVE TELECOMMUNICATION NETWORKS WITH THE REALEX EXPERT SYSTEM SHELL

To effectively supervise a telecommunication network, an intelligent supervisory system is proposed consisting of a traditional process monitoring. a fault diagnostic, a communication handler and a database manager subsystem. The whole system is based on a generic expert system shell designed to operate in industrial environment. The diagnostic subsystem contains a two-level inference engine to operate on structural information and traditional if-then rules. To ensure easy mapping of the supervisory system to any telecommunication network a configuration environment consisting of several compilers integrated into a multi-window editor was also developed. The system was implemented on two interconnected IBM PC-s running MS WINDOWS 3.0

Targeting miR-34a/Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth characterized by arrested lung alveolarization, which generates lungs that are incompetent for effective gas exchange. We report here deregulated expression of miR-34a in a hyperoxia-based mouse model of BPD, where miR-34a expression was markedly increased in platelet-derived growth factor receptor (PDGFR)α-expressing myofibroblasts, a cell type critical for proper lung alveolarization. Global deletion of miR-34a; and inducible, conditional deletion of miR-34a in PDGFRα+ cells afforded partial protection to the developing lung against hyperoxia-induced perturbations to lung architecture. Pdgfra mRNA was identified as the relevant miR-34a target, and using a target site blocker in vivo, the miR-34a/Pdgfra interaction was validated as a causal actor in arrested lung development. An antimiR directed against miR-34a partially restored PDGFRα+ myofibroblast abundance and improved lung alveolarization in newborn mice in an experimental BPD model. We present here the first identification of a pathology-relevant microRNA/mRNA target interaction in aberrant lung alveolarization and highlight the translational potential of targeting the miR-34a/Pdgfra interaction to manage arrested lung development associated with preterm birth

AMP-activated protein kinase deficiency reduces ozone-induced lung injury and oxidative stress in mice

<p>Abstract</p> <p>Background</p> <p>Acute ozone exposure causes lung oxidative stress and inflammation leading to lung injury. At least one mechanism underlying the lung toxicity of ozone involves excessive production of reactive oxygen and nitrogen intermediates such as peroxynitrite. In addition and beyond its major prooxidant properties, peroxynitrite may nitrate tyrosine residues altering phosphorylation of many protein kinases involved in cell signalling. It was recently proposed that peroxynitrite activates 5'-AMP-activated kinase (AMPK), which regulates metabolic pathways and the response to cell stress. AMPK activation as a consequence of ozone exposure has not been previously evaluated. First, we tested whether acute ozone exposure in mice would impair alveolar fluid clearance, increase lung tissue peroxynitrite production and activate AMPK. Second, we tested whether loss of AMP-activated protein kinase alpha1 subunit in mouse would prevent enhanced oxidative stress and lung injury induced by ozone exposure.</p> <p>Methods</p> <p>Control and AMPKα1 deficient mice were exposed to ozone at a concentration of 2.0 ppm for 3 h in glass cages. Evaluation was performed 24 h after ozone exposure. Alveolar fluid clearance (AFC) was evaluated using fluorescein isothiocyanate tagged albumin. Differential cell counts, total protein levels, cytokine concentrations, myeloperoxidase activity and markers of oxidative stress, i.e. malondialdehyde and peroxynitrite, were determined in bronchoalveolar lavage (BAL) and lung homogenates (LH). Levels of AMPK-Thr¹⁷²phosphorylation and basolateral membrane Na(+)-K(+)-ATPase abundance were determined by Western blot.</p> <p>Results</p> <p>In control mice, ozone exposure induced lung inflammation as evidence by increased leukocyte count, protein concentration in BAL and myeloperoxidase activity, pro-inflammatory cytokine levels in LH. Increases in peroxynitrite levels (3 vs 4.4 nM, p = 0.02) and malondialdehyde concentrations (110 vs 230 μmole/g wet tissue) were detected in LH obtained from ozone-exposed control mice. Ozone exposure consistently increased phosphorylated AMPK-Thr¹⁷²to total AMPK ratio by 80% in control mice. Ozone exposure causes increases in AFC and basolateral membrane Na(+)-K(+)-ATPase abundance in control mice which did not occur in AMPKα1 deficient mice.</p> <p>Conclusions</p> <p>Our results collectively suggest that AMPK activation participates in ozone-induced increases in AFC, inflammation and oxidative stress. Further studies are needed to understand how the AMPK pathway may provide a novel approach for the prevention of ozone-induced lung injury.</p

Similar dispersal patterns between two closely related birds with contrasting migration strategies

Studying dispersal is crucial to understand metapopulation and sink-source dynamics and invasion processes. The capability to disperse is especially important for species living in fragmented habitats like wetlands. We investigated the distribution of natal and breeding dispersal distances and philopatry in Spanish populations of two closely related reedbed-nesting birds, the Moustached Warbler Acrocephalus melanopogon and the Eurasian Reed Warbler Acrocephalus scirpaceus. These warblers are morphologically very similar, but differ in migration strategy and, in our study area, in population size. Our aims were to find the best model for dispersal distances and to assess the occurrence of intra- or interspecific differences in dispersal patterns. We used ringing data from the Spanish marking scheme and selected recaptures to avoid including migrating individuals. In both species, most individuals were philopatric but dispersing birds were able to cross large distances (up to more than 100 km), suggesting the capability to compensate for habitat fragmentation. We found the heavy-tailed Cauchy distribution to be the best conceptual description for our data, in all cases but natal dispersal of Moustached Warblers. Among Eurasian Reed Warblers, natal philopatry was lower than breeding philopatry. We found no significant interspecific differences. This does not confirm the hypothesis of higher dispersal ability in long distance migrants (like Eurasian Reed Warblers) than in resident/short distance migrant bird species (like Moustached Warblers). 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The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis

Background Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients’ safety and management. Objectives To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. Methods Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. Results The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. Conclusions MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients

Gas Exchange Disturbances Regulate Alveolar Fluid Clearance during Acute Lung Injury

Disruption of the alveolar–capillary barrier and accumulation of pulmonary edema, if not resolved, result in poor alveolar gas exchange leading to hypoxia and hypercapnia, which are hallmarks of acute lung injury and the acute respiratory distress syndrome (ARDS). Alveolar fluid clearance (AFC) is a major function of the alveolar epithelium and is mediated by the concerted action of apically-located Na+ channels [epithelial Na+ channel (ENaC)] and the basolateral Na,K-ATPase driving vectorial Na+ transport. Importantly, those patients with ARDS who cannot clear alveolar edema efficiently have worse outcomes. While hypoxia can be improved in most cases by O2 supplementation and mechanical ventilation, the use of lung protective ventilation settings can lead to further CO2 retention. Whether the increase in CO2 concentrations has deleterious or beneficial effects have been a topic of significant controversy. Of note, both low O2 and elevated CO2 levels are sensed by the alveolar epithelium and by distinct and specific molecular mechanisms impair the function of the Na,K-ATPase and ENaC thereby inhibiting AFC and leading to persistence of alveolar edema. This review discusses recent discoveries on the sensing and signaling events initiated by hypoxia and hypercapnia and the relevance of these results in identification of potential novel therapeutic targets in the treatment of ARDS