Correlation Networks from Flows. The Case of Forced and Time-Dependent Advection-Diffusion Dynamics

Complex network theory provides an elegant and powerful framework to statistically investigate different types of systems such as society, brain or the structure of local and long-range dynamical interrelationships in the climate system. Network links in climate networks typically imply information, mass or energy exchange. However, the specific connection between oceanic or atmospheric flows and the climate network’s structure is still unclear. We propose a theoretical approach for verifying relations between the correlation matrix and the climate network measures, generalizing previous studies and overcoming the restriction to stationary flows. Our methods are developed for correlations of a scalar quantity (temperature, for example) which satisfies an advection-diffusion dynamics in the presence of forcing and dissipation. Our approach reveals that correlation networks are not sensitive to steady sources and sinks and the profound impact of the signal decay rate on the network topology. We illustrate our results with calculations of degree and clustering for a meandering flow resembling a geophysical ocean jet.     

Two novel RAD21 mutations in patients with mild Cornelia de Lange syndrome-like presentation and report of the first familial case

Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by limb reduction defects, characteristic facial features and impaired cognitive development. Mutations in the NIPBL gene predominate; however, mutations in other cohesin complex genes have also been implicated, particularly in atypical and mild CdLS cases. Missense mutations and whole gene deletions in RAD21 have been identified in children with growth retardation, minor skeletal anomalies and facial features that overlap findings in individuals with CdLS. We report the first intragenic deletion and frameshift mutations identified in RAD21 in two patients presenting with atypical CdLS. One patient had an in-frame deletion of exon 13, while the second patient had a c.592_593dup frameshift mutation. The first patient presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features while, the second patient presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies, with the first patient being milder than the second. The in-frame deletion mutation was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems.     

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson''s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson''s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson''s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.     

Order patterns recurrence plots in the analysis of ERP data

Recurrence quantification analysis (RQA) is an established tool for data analysis in various behavioural sciences. In this article we present a refined notion of RQA based on order patterns. The use of order patterns is commonplace in time series analysis. Exploiting this concept in combination with recurrence plots (RP) and their quantification (RQA) allows for advances in contemporary EEG research, specifically in the analysis of event related potentials (ERP), as the method is known to be robust against non-stationary data. The use of order patterns recurrence plots (OPRPs) on EEG data recorded during a language processing experiment exemplifies the potentials of the method. We could show that the application of RQA to ERP data allows for a considerable reduction of the number of trials required in ERP research while still maintaining statistical validity.     

Altered folding, turnover, and polarized sorting act in concert to define a novel pathomechanism of congenital sucrase-isomaltase deficiency

Naturally occurring mutants of membrane and secretory proteins are often associated with the pathogenesis of human diseases. Here, we describe the molecular basis of a novel phenotype of congenital sucrase-isomaltase deficiency (CSID), a disaccharide malabsorption disorder of the human intestine in which several structural features and functional capacities of the brush-border enzyme complex sucrase-isomaltase (SI) are affected. The cDNA encoding SI from a patient with CSID reveals a mutation in the isomaltase subunit of SI that results in the substitution of a cysteine by an arginine at amino acid residue 635 (C635R). When this mutation is introduced into the wild type cDNA of SI a mutant enzyme, SI(C635R), is generated that shows a predominant localization in the endoplasmic reticulum. Nevertheless, a definite localization of SI(C635R) in the Golgi apparatus and at the cell surface could be also observed. Epitope mapping with conformation-specific mAbs protease sensitivity assays, and enzymatic activity measurements demonstrate an altered folding pattern of SI(C635R) that is responsible for a substantially increased turnover rate and an aberrant sorting profile. Thus, SI(C635R) becomes distributed also at the basolateral membrane in contrast to wild type SI. Concomitant with the altered sorting pattern, the partial detergent extractability of wild type SI shifts to a complete detergent solubility with Triton X-100. The mutation has therefore affected an epitope responsible for the apical targeting fidelity of SI. Altogether, the combined effects of the C635R mutation on the turnover rate, function, polarized sorting, and detergent solubility of SI constitute a unique and novel pathomechanism of CSID.