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.     

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)     

COMPREHENSIVE STUDY OF THE GAS HOLD UP AND BUBBLE SIZE DISTRIBUTION IN HIGHLY VISCOUS LIQUIDS II. CMC SOLUTIONS

Following properties of short bubble columns employing CMC solutions (1.0, 1.4 and 2.0%) and perforated plates (0.5, 1.0 and 3.0 mm hole diameters) were determined: relative mean gas hold up, E_G, bubble size distribution, Sauter bubble diameter, d_s, and the specific geometrical bubble surface areas, a' and a' due to the “intermediate to large bubbles.” The a' values were compared with the corresponding volumetric mass transfer coefficients, k_La's and the mass transfer coefficients, k_L, were estimated. The properties of these systems were investigated as function of the superficial gas velocity, W_SG, CMC concentration and aerator type.     

Understanding users and their needs

Gaze-control enables people to control a computer by using eye-gaze to select items on screen. Gaze-control is a necessity for people who have lost all motor control of their body and only have control over eye movements. In addition, gaze-control can be the quickest and least tiring option for a far broader group of people with varying disabilities. This paper reports findings from gaze-control user trials involving users from both groups: people who are totally paralyzed, as well as people with a wide range of complex disabilities. The trials conducted involved four different centres supporting people with disabilities in three different European countries. Several gaze-control systems were trialled by a large number of users with varying needs and abilities. The perceived benefits of gaze-control are described, and recommendations for successful assessment and implementation of gaze-control are provided.     

Isoseparation curves: a mechanism for optimizing off-axis dose homogeneity of intact breast irradiation

The purpose of this paper is to determine whether using off-axis isoseparation curves to optimize the collimator rotation angle improves dose homogeneity. Eleven intact breast irradiation patients underwent computerized tomography (CT) treatment planning with 1 cm abutting slices. Central plane treatment planning, using 6 MV photons, tissue inhomogeneity corrections, and isocentric opposed tangent treatment fields, was performed. Collimators were rotated to match chest wall slope through the use of a beam's-eye-view setting. Patient separations were measured from the apex of the breast to the posterior field border on each axial CT slice. Sagittal-plane isoseparation curves were constructed from these measurements. Using these curves, the collimator rotation that minimized off-axis separation differences was determined. A comparison of off-axis dose inhomogeneity was performed for patients with a > or =10 degrees difference between this optimized collimator angle and the angle determined by chest wall slope. These comparative treatment plans differed only with respect to collimator angle rotation. The mean optimal collimator rotation angle differed significantly from the mean rotation angle which matched the chest wall slope (5.4 degrees vs. 11 degrees, respectively, P < 0.001). Four of the 11 patients had rotation angle differences of 10 degrees. In these patients, the optimization of collimator angle reduced the percentage of breast volume to "that" received > or =110% of the prescribed dose. For the patient with the largest breast size to the patient with the smallest breast size the decreases were, respectively, 5% (15% to 10%), 3% (24% to 21%), 1% (4% to 3%), and 1% (0.9% to 0%). The mean reduction in dose inhomogeneity was greatest in the inferior breast quadrants. At 6 cm and 4 cm off axis, the mean reductions in the percentages of the breast tissue to "that" received 110% of the prescribed dose were respectively 15.1% and 5.3 %. Optimizing the collimator angle through the use of isoseparation curves decreases dose inhomogeneity. The greatest improvements are in the inferior quadrants of the intact breast. The improved dose homogeneity may have clinical relevance in the treatment of patients with large breast sizes.     

Model Checking for a Class of Weighted Automata

A large number of different model checking approaches has been proposed during the last decade. The different approaches are applicable to different model types including untimed, timed, probabilistic and stochastic models. This paper presents a new framework for model checking techniques which includes some of the known approaches and enlarges the class of models to which model checking can be applied to the general class of weighted automata. The approach allows an easy adaption of model checking to models which have not been considered yet for this purpose. Examples for those new model types for which model checking can be applied are max/plus or min/plus automata which are well established models to describe different forms of dynamic systems and optimization problems. In this context, model checking can be used to verify temporal or quantitative properties of a system. The paper first presents briefly our class of weighted automata, as a very general model type. Then Valued Computational Tree Logic (CTL) is introduced as a natural extension of the well known branching time logic CTL. Afterwards, algorithms to check a weighted automaton with respect to a CTL) is introduced as a natural extension of the well known branching time logic CTL. Afterwards, algorithms to check a weighted automaton with respect to a CTL formula are presented. As a last result, bisimulation equivalence is extended to weighted automata and CTL$.