Site-Directed Spin-Labeling Analysis of Reconstituted Mscl in the Closed State

The mechanosensitive channel from Escherichia coli (Eco-MscL) responds to membrane lateral tension by opening a large, water-filled pore that serves as an osmotic safety valve. In an attempt to understand the structural dynamics of MscL in the closed state and under physiological conditions, we have performed a systematic site-directed spin labeling study of this channel reconstituted in a membrane bilayer. Structural information was derived from an analysis of probe mobility, residue accessibility to O2 or NiEdda and overall intersubunit proximity. For the majority of the residues studied, mobility and accessibility data showed a remarkable agreement with the Mycobacterium tuberculosis crystal structure, clearly identifying residues facing the large water-filled vestibule at the extracellular face of the molecule, the narrowest point along the permeation pathway (residues 21–26 of Eco-MscL), and the lipid-exposed residues in the peripheral transmembrane segments (TM2). Overall, the present dataset demonstrates that the transmembrane regions of the MscL crystal structure (obtained in detergent and at low pH) are, in general, an accurate representation of its structure in a membrane bilayer under physiological conditions. However, significant differences between the EPR data and the crystal structure were found toward the COOH-terminal end of TM2

Far-Term Exploration of Advanced Single-Aisle Subsonic Transport Aircraft Concepts

Far-term single-aisle class aircraft concepts for potential entry-into-service of 2045 were investigated using an Interactive Reconfigurable Matrix of Alternatives (IRMA) approach. The configurations identified through this design space exploration were then distilled into three advanced aircraft concepts best characterizing the prominent features identified through the IRMA exploration. These three aircraft concepts were then configured and sized for a 150-passenger capacity and a 3,500 nautical mile design mission. Mission block fuel burn was estimated and compared to a far-term conventional configuration baseline concept and a 2005 l. These comparisons suggest considerable potential improvements in fuel efficiency from the investigated advanced concepts

Developmental Coordination Disorder: Disruption of the Cerebello-Cerebral Network evidenced by SPECT

Little is known about the neurobiological substrate of developmental coordination disorder (DCD), a neuro-developmental syndrome with significant, negative impact on the motor, cognitive and affective level throughout lifespan. This paper reports the clinical, neurocognitive and neuroradiological findings of a 19-year-old patient with typical DCD. As demonstrated by mild ataxia and a close semiological correspondence with the recently acknowledged ‘cerebellar cognitive affective syndrome’, clinical and neurocognitive investigations unambiguously indicated functional disruption of the cerebellum. Structural MRI of the brain confirmed cerebellar involvement revealing a slight anterior/superior asymmetry of vermal fissures consistent with rostral vermisdysplasia. Although this abnormality of vermal fissuration is generally considered an incidental neuroradiological finding without any clinical relevance, a potentially subtle impact on the developmental level has never been formally excluded. In addition to a generally decreased perfusion of the cerebellum, a quantified Tc-99m-ECD SPECT disclosed functional suppression of the anatomoclinically suspected supratentorial regions involved in the execution of planned actions, visuo-spatial processing and affective regulation. Based on these findings, it is hypothesised that the cerebellum is crucially implicated in the pathophysiologcial mechanisms of DCD, reflecting disruption of the cerebello-cerebral network involved in the execution of planned actions, visuo-spatial cognition and affective regulation

Performance analysis of kinetic Monte Carlo algorithms for synthesis of linear polymers

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Pushing forward the predictive power of kinetic Monte Carlo simulations for detailed (de)polymerization chemistries

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Monitoring the process mean when standards are unknown : a classic problem revisited

One of the most common applications in statistical process monitoring is the use of control charts to monitor a process mean. In practice, this is often done with a Shewhart X chart along with a Shewhart R (or an S) chart. Thus two charts are typically used together, as a scheme, each using the 3-sigma limits. Moreover, the process mean and standard deviation are often unknown and need to be estimated before monitoring can begin. We show that there are three major issues with this monitoring scheme described in most textbooks. The first issue is not accounting for the effects of parameter estimation, which is known to degrade chart performance. The second issue is the implicit assumption that the charting statistics are both normally distributed and, accordingly, using the 3-sigma limits. The third issue is multiple testing, since two charts are used, in this scheme, at the same time. We illustrate the deleterious effects of these issues on the in-control properties of the (X,R) charting scheme and present a method for finding the correct charting constants taking proper account of these issues. Tables of the new charting constants are provided for some commonly used nominal in-control average run-length (ICARL0) values and different sample sizes. This will aid in implementing the (X,R) charting scheme correctly in practice. Examples are given along with a summary and some conclusions.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-16382017-03-31hb2016Statistic

Cerebellar induced differential polyglot aphasia: a neurolinguistic and fMRI study

Research has shown that linguistic functions in the bilingual brain are subserved by similar neural circuits as in monolinguals, but with extra-activity associated with cognitive and attentional control. Although a role for the right cerebellum in multilingual language processing has recently been acknowledged, a potential role of the left cerebellum remains largely unexplored. This paper reports the clinical and fMRI findings in a strongly right-handed (late) multilingual patient who developed differential polyglot aphasia, ataxic dysarthria and a selective decrease in executive function due to an ischemic stroke in the left cerebellum. fMRI revealed that lexical-semantic retrieval in the unaffected L1 was predominantly associated with activations in the left cortical areas (left prefrontal area and left postcentral gyrus), while naming in two affected non-native languages recruited a significantly larger bilateral functional network, including the cerebellum. It is hypothesized that the left cerebellar insult resulted in decreased right prefrontal hemisphere functioning due to a loss of cerebellar impulses through the cerebello-cerebral pathways