Ion Channel Clustering at the Axon Initial Segment and Node of Ranvier Evolved Sequentially in Early Chordates

In many mammalian neurons, dense clusters of ion channels at the axonal initial segment and nodes of Ranvier underlie action potential generation and rapid conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7) potassium channels is based on linkage to the actin–spectrin cytoskeleton, which is mediated by the adaptor protein ankyrin-G. We identified key steps in the evolution of this axonal channel clustering. The anchor motif for sodium channel clustering evolved early in the chordate lineage before the divergence of the wormlike cephalochordate, amphioxus. Axons of the lamprey, a very primitive vertebrate, exhibited some invertebrate features (lack of myelin, use of giant diameter to hasten conduction), but possessed narrow initial segments bearing sodium channel clusters like in more recently evolved vertebrates. The KCNQ potassium channel anchor motif evolved after the divergence of lampreys from other vertebrates, in a common ancestor of shark and humans. Thus, clustering of voltage-gated sodium channels was a pivotal early innovation of the chordates. Sodium channel clusters at the axon initial segment serving the generation of action potentials evolved long before the node of Ranvier. KCNQ channels acquired anchors allowing their integration into pre-existing sodium channel complexes at about the same time that ancient vertebrates acquired myelin, saltatory conduction, and hinged jaws. The early chordate refinements in action potential mechanisms we have elucidated appear essential to the complex neural signaling, active behavior, and evolutionary success of vertebrates

Three-dimensional adaptive image compression concept for medical imaging : application to computed tomography angiography for peripheral arteries

Advances in computed tomography (CT) have resulted in a substantial increase in the size of datasets. We built a new concept of medical image compression that provides the best compromise between compression rate and image quality. The method is based on multiple contexts and regions-of-interest (ROI) defined according to the degree of clinical interest. High priority areas (primary ROIs) are assigned a lossless compression. Other areas (secondary ROIs and background) are compressed with moderate or heavy losses. The method is applied to a whole dataset of CT angiography (CTA) of the lower extremity vasculature. It is compared to standard lossy compression techniques in terms of quantitative and qualitative image quality. It is also compared to standard lossless compression techniques in terms of image size reduction and compression ratio. The proposed compression method met quantitative criteria for high-quality encoding. It obtained the highest qualitative image quality rating score, with a statistically significant difference compared to other methods. The average compressed image size was up to 61% lower compared to standard compression techniques, with a 9:1 compression ratio compared with original non-compressed images. Our new adaptive 3D compression method for CT images can save data storage space while preserving clinically relevant information

Production and reliability oriented SOFC cell and stack design

The paper presents an innovative development methodology for a production and reliability oriented SOFC cell and stack design aiming at improving the stacks robustness, manufacturability, efficiency and cost. Multi-physics models allowed a probabilistic approach to consider statistical variations in production, material and operating parameters for the optimization phase. A methodology for 3D description of spatial distribution of material properties based on a random field models was developed and validated by experiments. Homogenized material models on multiple levels of the SOFC stack were established. The probabilistic models were related to the experimentally obtained properties of base materials to establish a statistical relationship between the material properties and the most relevant load effects. Software algorithms for meta models that allow the detection of relationships between input and output parameters and to perform a sensitivity analysis were developed and implemented. The capabilities of the methodology is illustrated on two practical cases

A hybrid iterative method for common solutions of variational inequality problems and fixed point problems for single-valued and multi-valued mappings with applications

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Adherence to isoniazid preventive therapy in Indonesian children: A quantitative and qualitative investigation

<p>Abstract</p> <p>Background</p> <p>It is recommended that young child contacts of sputum smear positive tuberculosis cases receive isoniazid preventive therapy (IPT) but reported adherence is low and risk factors for poor adherence in children are largely unknown.</p> <p>Methods</p> <p>We prospectively determined rates of IPT adherence in children < 5 yrs in an Indonesian lung clinic. Possible risk factors for poor adherence, defined as ≤3 months prescription collection, were calculated using logistic regression. To further investigate adherence barriers in-depth interviews were conducted with caregivers of children with good and poor adherence.</p> <p>Results</p> <p>Eighty-two children eligible for IPT were included, 61 (74.4%) of which had poor adherence. High transport costs (OR 3.3, 95% CI 1.1-10.2) and medication costs (OR 20.0, 95% CI 2.7-414.5) were significantly associated with poor adherence in univariate analysis. Access, medication barriers, disease and health service experience and caregiver TB and IPT knowledge and beliefs were found to be important determinants of adherence in qualitative analysis.</p> <p>Conclusion</p> <p>Adherence to IPT in this setting in Indonesia is extremely low and may result from a combination of financial, knowledge, health service and medication related barriers. Successful reduction of childhood TB urgently requires evidence-based interventions that address poor adherence to IPT.</p

Prevalence of putative virulence factors and antimicrobial susceptibility of Enterococcus faecalis isolates from patients with dental Diseases

<p>Abstract</p> <p>Background</p> <p>This study investigated the prevalence of <it>Enterococcus faecalis</it>, its putative virulence factors and antimicrobial susceptibility in individuals with and without dental diseases. A total of 159 oral rinse specimens were collected from patients (n = 109) suffering from dental diseases and healthy controls (n = 50).</p> <p>Results</p> <p><it>E. faecalis </it>was detected using only culture in 8/109 (7.3%) of the patients with various types of dental diseases, whereas no <it>E. faecalis </it>was found in the healthy controls weather using both culture and PCR. Phenotype characterizations of the 8 <it>E. faecalis </it>isolates indicated that 25% of the isolates produced haemolysin and 37.5% produced gelatinase. Most important virulence genes; collagen binding protein (<it>ace</it>) and endocarditis antigen (<it>efaA</it>) were present in all 8 <it>E. faecalis </it>isolates, while haemolysin activator gene (<it>cylA</it>) was detected only in 25% of isolates, and all isolates were negative for <it>esp </it>gene. All <it>E. faecalis </it>isolates were 100% susceptible to ampicillin, chloramphenicol, ciprofloxacin, vancomycin, and teicoplanin, and to less extent to erythromycin (62.5%).</p> <p>Conclusion</p> <p>This study shows that all <it>E. faecalis </it>isolates were recovered only from patients with dental diseases especially necrotic pulps, and all isolates carried both collagen binding protein and endocarditis antigen genes and highly susceptible to frequently used antimicrobial drugs in Jordan.</p