Sustainable change: long-term efforts toward developing a learning organization

Globalization and intensified competition require organizations to change and adapt to dynamic environments in order to stay competitive. This article describes a longitudinal action research study supporting the strategic change of a trading company. The strategic change was accompanied by planned changes in organizational structures and processes, management systems, emerging changes in leadership, and organization members’ attitudes and behaviors, and it was supported by management development activities. Longitudinal data over a 4-year period including participant observation and interviews reveal that a systemic approach, a learning and becoming perspective toward change, trust, an appropriate role perception, and the specific use of management instruments contribute to sustained change that resulted in performance improvements and a move toward a learning organization. We conclude with implications for strategic change and suggestions for further research in this area

Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2

Mammalian two-pore channels (TPCs) are activated by the low-abundance membrane lipid phosphatidyl-(3,5)-bisphosphate (PI(3,5)P2) present in the endo-lysosomal system. Malfunction of human TPC1 or TPC2 (hTPC) results in severe organellar storage diseases and membrane trafficking defects. Here, we compared the lipid-binding characteristics of hTPC2 and of the PI(3,5)P2-insensitive TPC1 from the model plant Arabidopsis thaliana. Combination of simulations with functional analysis of channel mutants revealed the presence of an hTPC2-specific lipid-binding pocket mutually formed by two channel regions exposed to the cytosolic side of the membrane. We showed that PI(3,5)P2is simultaneously stabilized by positively charged amino acids (K203, K204, and K207) in the linker between transmembrane helices S4 and S5 and by S322 in the cytosolic extension of S6. We suggest that PI(3,5)P2cross links two parts of the channel, enabling their coordinated movement during channel gating

Lipid Dynamics in Membranes Slowed Down by Transmembrane Proteins

Lipids and proteins, as essential components of biological cell membranes, exhibit a significant degree of freedom for different kinds of motions including lateral long-range mobility. Due to their interactions, they not only preserve the cellular membrane but also contribute to many important cellular functions as e.g., signal transport or molecular exchange of the cell with its surrounding. Many of these processes take place on a short time (up to some nanoseconds) and length scale (up to some nanometers) which is perfectly accessible by quasielastic neutron scattering (QENS) experiments and molecular dynamics (MD) simulations. In order to probe the influence of a peptide, a transmembrane sequence of the transferrin receptor (TFRC) protein, on the dynamics of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) large unilamellar vesicles (LUVs) on a nanosecond time scale, high-resolution QENS experiments and complementary MD simulations have been utilized. By using different scattering contrasts in the experiment (chain-deuterated lipids and protonated lipids, respectively), a model could be developed which allows to examine the lipid and peptide dynamics separately. The experimental results revealed a restricted lipid lateral mobility in the presence of the TFRC transmembrane peptides. Also the apparent self-diffusion coefficient of the lateral movement of the peptide molecules could be determined quantitatively for the probed short-time regime. The findings could be confirmed very precisely by MD simulations. Furthermore, the article presents an estimation for the radius of influence of the peptides on the lipid long-range dynamics which could be determined by consistently combining results from experiment and simulation

Coating of Ultra-Small Micro End Mills: Analysis of Performance and Suitability of Eight Different Hard-Coatings

Due to the constant need for better functionalized surfaces or smaller, function integrated components, precise and efficient manufacturing processes have to be established. Micro milling with micro end mills is one of the most promising processes for this task as it combines a high geometric flexibility in a wide range of machinable materials with low set-up costs. A downside of this process is the wear of the micro end mills. Due to size effects and the relatively low cutting speed, the cutting edge is especially subjected to massive abrasive wear. One possibility to minimize this wear is coating of micro end mills. This research paper describes the performance of eight different hard coatings for micro end mills with a diameter <40 µm and discusses some properties for the best performing coating type. With this research, it is therefore possible to boost the possibilities of micro milling for the manufacture of next generation products

Incidence and impact of subclinical epileptiform activity in Alzheimer's disease.

ObjectiveSeizures are more frequent in patients with Alzheimer's disease (AD) and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in AD and its consequences are unknown. Motivated by results from animal studies, we hypothesized higher than expected rates of subclinical epileptiform activity in AD with deleterious effects on cognition.MethodsWe prospectively enrolled 33 patients (mean age, 62 years) who met criteria for AD, but had no history of seizures, and 19 age-matched, cognitively normal controls. Subclinical epileptiform activity was assessed, blinded to diagnosis, by overnight long-term video-electroencephalography (EEG) and a 1-hour resting magnetoencephalography exam with simultaneous EEG. Patients also had comprehensive clinical and cognitive evaluations, assessed longitudinally over an average period of 3.3 years.ResultsSubclinical epileptiform activity was detected in 42.4% of AD patients and 10.5% of controls (p = 0.02). At the time of monitoring, AD patients with epileptiform activity did not differ clinically from those without such activity. However, patients with subclinical epileptiform activity showed faster declines in global cognition, determined by the Mini-Mental State Examination (3.9 points/year in patients with epileptiform activity vs 1.6 points/year in patients without; p = 0.006), and in executive function (p = 0.01).InterpretationExtended monitoring detects subclinical epileptiform activity in a substantial proportion of patients with AD. Patients with this indicator of network hyperexcitability are at risk for accelerated cognitive decline and might benefit from antiepileptic therapies. These data call for more sensitive and comprehensive neurophysiological assessments in AD patient evaluations and impending clinical trials. Ann Neurol 2016;80:858-870

A Coiled-Coil Peptide Shaping Lipid Bilayers upon Fusion

A system based on two designed peptides, namely the cationic peptide K, (KIAALKE)(3), and its complementary anionic counterpart called peptide E, (EIAALEK)(3), has been used as a minimal model for membrane fusion, inspired by SNARE proteins. Although the fact that docking of separate vesicle populations via the formation of a dimeric E/K coiled-coil complex can be rationalized, the reasons for the peptides promoting fusion of vesicles cannot be fully explained. Therefore it is of significant interest to determine how the peptides aid in overcoming energetic barriers during lipid rearrangements leading to fusion. In this study, investigations of the peptides’ interactions with neutral PC/PE/cholesterol membranes by fluorescence spectroscopy show that tryptophan-labeled K∗ binds to the membrane (K(K∗) ∼6.2 10(3) M(−1)), whereas E∗ remains fully water-solvated. (15)N-NMR spectroscopy, depth-dependent fluorescence quenching, CD-spectroscopy experiments, and MD simulations indicate a helix orientation of K∗ parallel to the membrane surface. Solid-state (31)P-NMR of oriented lipid membranes was used to study the impact of peptide incorporation on lipid headgroup alignment. The membrane-immersed K∗ is found to locally alter the bilayer curvature, accompanied by a change of headgroup orientation relative to the membrane normal and of the lipid composition in the vicinity of the bound peptide. The NMR results were supported by molecular dynamics simulations, which showed that K reorganizes the membrane composition in its vicinity, induces positive membrane curvature, and enhances the lipid tail protrusion probability. These effects are known to be fusion relevant. The combined results support the hypothesis for a twofold role of K in the mechanism of membrane fusion: 1) to bring opposing membranes into close proximity via coiled-coil formation and 2) to destabilize both membranes thereby promoting fusion

Aesthetic appreciation of poetry correlates with ease of processing in event-related potentials

Rhetorical theory suggests that rhythmic and metrical features of language substantially contribute to persuading, moving, and pleasing an audience. A potential explanation of these effects is offered by “cognitive fluency theory,” which stipulates that recurring patterns (e.g., meter) enhance perceptual fluency and can lead to greater aesthetic appreciation. In this article, we explore these two assertions by investigating the effects of meter and rhyme in the reception of poetry by means of event-related brain potentials (ERPs). Participants listened to four versions of lyrical stanzas that varied in terms of meter and rhyme, and rated the stanzas for rhythmicity and aesthetic liking. The behavioral and ERP results were in accord with enhanced liking and rhythmicity ratings for metered and rhyming stanzas. The metered and rhyming stanzas elicited smaller N400/P600 ERP responses than their nonmetered, nonrhyming, or nonmetered and nonrhyming counterparts. In addition, the N400 and P600 effects for the lyrical stanzas correlated with aesthetic liking effects (metered–nonmetered), implying that modulation of the N400 and P600 has a direct bearing on the aesthetic appreciation of lyrical stanzas. We suggest that these effects are indicative of perceptual-fluency-enhanced aesthetic liking, as postulated by cognitive fluency theory