Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

E. H. Dirksens Beiträge zu den Grundlagen der Analysis

Enno Heeren Dirksen (1788–1850) was one of several mathematicians originating from Eastern Frisia at the end of the eighteenth century to acquire prominence in neohumanist reformed Prussia. While striving—like so many of his contemporaries—for more rigour in the foundations of calculus, his work is significant due to his unusual emphasis on the semiotic aspects of the basic concepts. As a clear-sighted propagator of Cauchy's conceptual innovations in Germany, his achievements in improving sign expressions of such concepts enabled him to clarify hitherto not differentiated multiple limit processes—although less successfully in constructive concept formation itself. The contribution is based on the analysis of Dirksen's published texts and on the numerous texts which remained drafts for his projected voluminousOrganon der gesamten Analysis.

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Menso Folkerts zum 60. Geburtstag gewidmet     

Integrated Smart Sensor Calibration

In many applications electronic sensors are used toimprove performance and reliability of measurement systems. Suchsensors should provide a correct transfer from the physical signalto be measured to the electrical output signal. One importantstep to achieve this, is to calibrate each sensor by applyingdifferent reference input signals and adjusting the sensor transferaccordingly. Besides expensive reference equipment the calibrationprocess takes much time and attention per individual sensor,which means a considerable increase in sensor production costs.By including at the sensor or sensor interface chip a programmablecalibration facility the calibration of such smart sensors caneasily be automated and can be executed for a batch of sensorsat a time, thus minimizing the calibration time and costs. Thispaper presents a calibration method and options for integrationin the smart sensor concept, in hardware as well as in software.An advantage of the proposed method is that it does not needa large matrix of calibration data, which needs to be storedin a look-up table or converted into a correction formula, butinstead it uses a step-by-step approach to correct the sensortransfer at each calibration measurement until the error is sufficientlysmall.     

Anthropometric data for describing the kinematics of the human hand.

The major goal of this investigation was to collect statistically-based anthropometry describing the kinematics of the human hand and to model this anthropometry as a function of external hand measurements, so that it may be predicted noninvasively. Joint centres were anatomically estimated as the centre of curvature of the head of the bone proximal to the given joint. Joint centres determined using Reuleaux's method for PIP and DIP were within 1.4 mm of this anatomical estimate. Models using bone length as the independent variable explain more than 97% of the variability in the anatomically estimated joint centre position along the mid-line of the bone. Models for estimating the lengths of the kinematic segments using external hand length as the independent variable account for between 49 and 99% of the variability in segment length. Models for estimating the axial location of the finger MCP and thumb CMC joints with respect to the distal wrist crease using external hand length as the independent variable account for between 82 and 96% of the variability in these locations. Models for estimating the radio-ulnar location of the finger MCP and thumb CMC joints with respect to the long axis of the third metacarpal using external hand breadth as the independent variable account for between 30 and 74% of the variability in these locations.     

On becoming a supervisee: Preparation for learning in a supervisory relationship.

Proposes a more structured form of presupervisory preparation than generally exists in graduate training programs. Guidelines for incorporating such instruction are provided. Topics for discussion, including salient issues and perspectives in the supervision literature as well as research findings, are outlined. Potential pitfalls and strategies for trainees to deal with dissatisfactions are identified. The suggested curriculum for preparing the supervisee would cover the differences between a didactic and a therapeutic emphasis, stages of development within supervision, interpersonal relationships, and countertransference and parallel process. An overview of supervisory methods, especially with respect to the presentation of case material would also be valuable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain-computer communication: motivation, aim, and impact of exploring a virtual apartment.

The step away from a synchronized or cue-based brain-computer interface (BCI) and from laboratory conditions towards real world applications is very important and crucial in BCI research. This work shows that ten naive subjects can be trained in a synchronous paradigm within three sessions to navigate freely through a virtual apartment, whereby at every junction the subjects could decide by their own, how they wanted to explore the virtual environment (VE). This virtual apartment was designed similar to a real world application, with a goal-oriented task, a high mental workload, and a variable decision period for the subject. All subjects were able to perform long and stable motor imagery over a minimum time of 2 s. Using only three electroencephalogram (EEG) channels to analyze these imaginations, we were able to convert them into navigation commands. Additionally, it could be demonstrated that motivation is a very crucial factor in BCI research; motivated subjects perform much better than unmotivated ones.     

The Importance of Free Fatty Chain Length on the Lipid Organization in the Long Periodicity Phase

The skin’s barrier ability is an essential function for terrestrial survival, which is controlled by intercellular lipids within the stratum corneum (SC) layer. In this barrier, free fatty acids (FFAs) are an important lipid class. As seen in inflammatory skin diseases, when the lipid chain length is reduced, a reduction in the barrier’s performance is observed. In this study, we have investigated the contributing effects of various FFA chain lengths on the lamellar phase, lateral packing. The repeat distance of the lamellar phase increased with FFA chain length (C20–C28), while shorter FFAs (C16 to C18) had the opposite behaviour. While the lateral packing was affected, the orthorhombic to hexagonal to fluid phase transitions were not affected by the FFA chain length. Porcine SC lipid composition mimicking model was then used to investigate the proportional effect of shorter FFA C16, up to 50% content of the total FFA mixture. At this level, no difference in the overall lamellar phases and lateral packing was observed, while a significant increase in the water permeability was detected. Our results demonstrate a FFA C16 threshold that must be exceeded before the structure and barrier function of the long periodicity phase (LPP) is affected. These results are important to understand the lipid behaviour in this unique LPP structure as well as for the understanding, treatment, and development of inflammatory skin conditions.     

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.