Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase

Actinoplanic acids A and B are macrocyclic polycarboxylic acids that are potent reversible inhibitors of farnesyl-protein transferase. Actinoplanic acids A and B were isolated from Actinoplanes sp. MA 7066 while actinoplanic acid B was isolated from both MA 7066 and Streptomyces sp. MA 7099. Actinoplanic acids A and B are competitive with respect to farnesyl diphosphate and are selective inhibitors of farnesyl-protein transferase because they do not inhibit geranylgeranyl-protein transferase type 1 or squalene synthase. MA 7066 is believed to be a novel species of actinomycetes while MA 7099 is believed to be a novel strain of Streptomyces violaceusniger on the basis of morphological, biochemical and chemotaxonomic characteristics as well as its production of actinoplanic acids.     

Parameter estimates for direct, maternal, and grandmaternal genetic effects for birth weight and weaning weight in Hereford cattle

Birth and weaning weights adjusted for age of dam from four lines of Hereford cattle were analyzed to determine the relationships among grandmaternal, maternal, and direct genetic effects. Three lines were selected for 1) weaning weight (WWL), 2) yearling weight (YWL), and 3) an index of yearling weight and muscle score (IXL). The fourth line was an unselected control line (CTL). Numbers of observations ranged from 1,699 (CTL) to 2,811 (WWL), and number of animals in the pedigree file ranged from 2,266 to 3,192. Two animal models were used to obtain estimates by REML using an average information method. Model 1 included random direct and maternal genetic, permanent maternal environmental, and residual environmental effects, and fixed sex x year effects. Model 2 additionally included random grandmaternal genetic and permanent grandmaternal environmental effects. For birth weight, Models 1 and 2 gave almost identical estimates for direct and maternal heritability, and for the fraction of variance that was due to maternal permanent environmental effects. Estimates for grandmaternal heritability could be obtained only for IXL (.03) and CTL (.01). For weaning weight, estimates for direct heritability were similar from both models. Estimates for maternal heritability from Model 1 were .18, .20, .13, and .20, and corresponding estimates from Model 2 were .34, .31, .13, and .34 for WWL, YWL, IXL, and CTL, respectively. For IXL, estimates for variances that were due to grandmaternal genetic and grandmaternal permanent environmental variances could not be obtained and were set to zero. Grandmaternal heritability estimates for WWL, YWL, and CTL were .05, .09, and .12. Estimates of correlations between direct and maternal genetic effects were -.13, -.44, -.11, and -.26 for WWL, YWL, IXL, and CTL. Estimates of correlations between direct and grandmaternal genetic effects were .21, .83, and .55, and those between maternal and grandmaternal genetic effects were -.99, -.84, and -.76 for WWL, YWL, and CTL, respectively. These results indicate that grandmaternal effects may be important for weaning weight and that maternal heritability may be underestimated if grandmaternal effects are not included in the model.     

Investigations of ductile damage during the process chains of toothed functional components manufactured by sheet-bulk metal forming

Sheet-bulk metal forming processes combine conventional sheet forming processes with bulk forming of sheet semi-finished parts. In these processes the sheets undergo complex forming histories. Due to in- and out-of-plane material flow and large accumulated plastic strains, the conventional failure prediction methods for sheet metal forming such as forming limit curve fall short. As a remedy, damage models can be applied to model damage evolution during those processes. In this study, damage evolution during the production of two different toothed components from DC04 steel is investigated. In both setups, a deep drawn cup is upset to form a circumferential gearing. However, the two final products have different dimensions and forming histories. Due to combined deep drawing and upsetting processes, the material flow on the cup walls is three-dimensional and non-proportional. In this study, the numerical and experimental investigations for those parts are presented and compared. Damage evolution in the process chains is simulated with a Lemaitre damage criterion. Microstructural analysis by scanning electron microscopy is performed in the regions with high mechanical loading. It is observed that the evolution of voids in terms of void volume fraction is strongly dependent on the deformation path. The comparison of simulation results with microstructural data shows that the void volume fraction decreases in the upsetting stage after an initial increase in the drawing stage. Moreover, the concurrent numerical and microstructural analysis provides evidence that the void volume fraction decreases during compression in sheet-bulk metal forming.     

Evaluation of dynamic modulus measurement for C/C-SiC composites at different temperatures

The determination of elastic properties at application temperature is fundamental for the design of fibre reinforced ceramic composite components. An attractive method to characterize the flexural modulus at room and high temperature under specific atmosphere is the nondestructive Resonant Frequency Damping Analysis (RFDA). The objective of this paper was to evaluate and validate the modulus measurement via RFDA for orthotropic C/C-SiC composites at the application temperature. At room temperature flexural moduli of C/C-SiC with 0/90° reinforcement were measured under quasi-static 4-point bending loads and compared with dynamic moduli measured via RFDA longitudinally to fibre direction. The dynamic modulus of C/C-SiC was then measured via RFDA up to 1250°C under flowing inert gas and showed an increase with temperature which fitted with literature values. The measured fundamental frequencies were finally compared to those resulting from numerical modal analyses. Dynamic and quasi-static flexural moduli are comparable and the numerical analyses proved that bending modes are correctly modeled by means of dynamic modulus measured via RFDA. The nondestructive RFDA as well as the numerical modeling approach are suitable for evaluation of C/C-SiC and may be transferred to other fibre reinforced ceramic composite materials.     

Dynamic behavior of nanometer-scale amorphous intergranular film in silicon nitride by in situ high-resolution transmission electron microscopy

We report about the dynamic behavior of a nanometer-scale amorphous intergranular film (IGF) in a Si₃N₄ ceramic by an in situ heating experiment in a high-resolution transmission electron microscopy (HRTEM). During the experiment the IGF gradually vanishes at 820 °C accompanied by the formation of crystal planes within the IGF. The IGF reappears after cooling back to room temperature. The results cannot be explained within the framework of a force balance model. We argue that the dynamic behavior of the IGF in our experiment originates from the open system observed.     

A graphics simulator for a robotic arm

A graphics robot simulator designed for an IBM PC/XT/AT or PS/2 personal computer is presented. The simulator is a terminate-and-stay resident (TSR) program that runs in the background and intercepts commands that would normally go to the robot controller through the COM1 serial communication device. With the use of the simulator, students can develop and test robot control programs offline without a physical robot present, using the language of their choice. The status of the simulated robot is available through a 3-D graphics display and a one-line text window, each of which can be activated from the keyboard or from within a user program. Data files are used to specify the robot to be simulated and the environment or workcell within which it is to operate. Currently supported robots include the Rhino XR-3 educational robot and the Adept One and Inteledex 660 industrial robots. The workcell features an overhead camera and objects that can be sensed by the camera and manipulated by the robot.<>     

Microstructure of the HMX‐Based PBX KS32 after Mechanical Loading

Non‐destructive X‐ray diffraction techniques were applied in order to monitor the influence of mechanical and shock‐loading on the microstructure of the plastic‐bonded high explosive KS32. The investigations uncovered damage to embedded coarse HMX crystals and to the binder system HTPB‐IPDI. Damage to the crystals occurred already during the kneading process in terms of deformation twinning. On higher loading between 400 MPa (static) and 480 MPa (dynamic) also crystal fracture was observed. The change in the binder structure was found after both static and dynamic loading, but not in the cured, differently kneaded samples. Moreover, the change in binder structure after dynamic loading was verified by dynamic mechanical analysis, and interpreted as a partial damage of the binder rubber shell around the explosive particles. The results are compared to literature data from imaging techniques.     

Interspecific Comparison of Constitutive Ash Phloem Phenolic Chemistry Reveals Compounds Unique to Manchurian Ash, a Species Resistant to Emerald Ash Borer

The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer indigenous to Asia and is responsible for widespread ash (Fraxinus spp.) mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies among Fraxinus spp., which is a result of their co-evolutionary history with the pest. We characterized constitutive phenolic profiles and lignin levels in the phloem of green, white, black, blue, European, and Manchurian ash. Phloem was sampled twice during the growing season, coinciding with phenology of early and late instar EAB. We identified 66 metabolites that displayed a pattern of variation, which corresponded strongly with phylogeny. Previously identified lignans and lignan derivatives were confirmed to be unique to Manchurian ash, and may contribute to its high level of resistance to EAB. Other compounds that had been considered unique to Manchurian ash, including hydroxycoumarins and the phenylethanoids calceolarioside A and B, were detected in closely related, but susceptible species, and thus are unlikely to contribute to EAB resistance of Manchurian ash. The distinct phenolic profile of blue ash may contribute to its relatively high resistance to EAB.     

Mechanistic Insights into Cyclic Peptide Generation by DnaE Split-Inteins through Quantitative and Structural Investigation

Inteins carry out protein-splicing reactions, which are used in protein chemistry, protein engineering and biotechnological applications. Rearrangement of the order of the domains in split-inteins results in head-to-tail cyclisation of the target sequence, which can be used for genetic encoding and expression of libraries of cyclic peptides (CPs). The efficiency of the splicing reaction depends on the target sequence. Here we used mass spectrometry to assess in vivo cyclic peptide formation from different hexameric target sequences by the DnaE split-inteins from Synechocystis sp. and Nostoc punctiforme, revealing a strong impact of the target sequence and of the intein on the intracellular peptide concentration. Furthermore, we determined the crystal structures of their pre-splicing complexes, which allowed us to identify F-block Asp17 as crucial for the DnaE-mediated splicing reaction.