Structural Insights into the Interaction of Heme with Protein Tyrosine Kinase JAK2**

Janus kinase 2 (JAK2) is the most important signal-transducing tyrosine kinase in erythropoietic precursor cells. Its malfunction drives several myeloproliferative disorders. Heme is a small metal-ion-carrying molecule that is incorporated into hemoglobin in erythroid precursor cells to transport oxygen. In addition, heme is a signaling molecule and regulator of various biochemical processes. Here, we show that heme exposure leads to hyperphosphorylation of JAK2 in a myeloid cancer cell line. Two peptides identified in JAK2 are heme-regulatory motifs and show low-micromolar affinities for heme. These peptides map to the kinase domain of JAK2, which is essential for downstream signaling. We suggest these motifs to be the interaction sites of heme with JAK2, which drive the heme-induced hyperphosphorylation. The results presented herein could facilitate the development of heme-related pharmacological tools to combat myeloproliferative disorders.     

Avoidance of Catastrophic Structural Failure as an Evolutionary Constraint: Biomechanics of the Acorn Weevil Rostrum

The acorn weevil (Curculio Linnaeus, 1758) rostrum (snout) exhibits remarkable flexibility and toughness derived from the microarchitecture of its exoskeleton. Modifications to the composite profile of the rostral cuticle that simultaneously enhance the flexibility and toughness of the distal portion of the snout are characterized. Using classical laminate plate theory, the effect of these modifications on the elastic behavior of the exoskeleton is estimated. It is shown that the tensile behavior of the rostrum across six Curculio species with high morphological variation correlates with changes in the relative layer thicknesses and orientation angles of layers in the exoskeleton. Accordingly, increased endocuticle thickness is strongly correlated with increased tensile strength. Rostrum stiffness is shown to be inversely correlated with work of fracture; thus allowing a highly curved rostrum to completely straighten without structural damage. Finally, exocuticle rich invaginations of the occipital sutures are identified both as a likely site of crack initiation in tensile failure and as a source of morphological constraint on the evolution of the rostrum in Curculio weevils. It is concluded that avoidance of catastrophic structural failure, as initiated in these sutures under tension, is the driving selective pressure in the evolution of the female Curculio rostrum.     

Modeling outcomes of soccer matches

We compare various extensions of the Bradley–Terry model and a hierarchical Poisson log-linear model in terms of their performance in predicting the outcome of soccer matches (win, draw, or loss). The parameters of the Bradley–Terry extensions are estimated by maximizing the log-likelihood, or an appropriately penalized version of it, while the posterior densities of the parameters of the hierarchical Poisson log-linear model are approximated using integrated nested Laplace approximations. The prediction performance of the various modeling approaches is assessed using a novel, context-specific framework for temporal validation that is found to deliver accurate estimates of the test error. The direct modeling of outcomes via the various Bradley–Terry extensions and the modeling of match scores using the hierarchical Poisson log-linear model demonstrate similar behavior in terms of predictive performance.

     

Recoverable Class Loaders for a Fast Restart of Java Applications

We present recoverable class loaders to enable a fast start-up and recovery of Java applications. This is achieved by snapshooting the static state of Java applications namely the class loaders and their associated class objects, which are then recovered during subsequent restarts. Recoverable class loaders are especially useful in the context of mobile applications and mobile services. First, they allow to speed up shutdown and restart of applications for power- and resource-management reasons on resource-restricted mobile devices. Second, services can be much faster rebooted to cure software faults such as memory leaks thereby improving the availability of services. We implemented recoverable class loaders inside the JamVM and the OSGi middleware Oscar. For both cases of use—Java application restart and service recovery—we provide experimental evaluations that show a substantially reduced start-up time from up to 96%.     

Structure of nanotubular titanium oxide templates prepared by electrochemical anodization in H2SO4/HF solutions

The electrochemical formation of nanotubular titanium oxide films was investigated in 1 M H₂SO₄ and 0.05-0.4 wt.% HF electrolytes. Depending on anodization condition, i.e. cell voltage, anodization time, HF concentration, TiO₂ porous films having different thickness (from 350 to 500 nm) and pore diameter (from 40 to 150 nm) were obtained. By varying the cell voltage from 10 V to 40 V it was possible to gradually change the crystal structure of titanium oxide from anatase to rutile. The effect of annealing temperature and duration on crystal structure was also considered.     

Experimental parametric investigation of platinum catalysts using hydrogen fuel

The aviation organization is creating awareness for the overall reduction of NOx emissions by up to 80% in the near future. This motivates to conduct research on the current state of art, catalytic stabilized combustion chamber using hydrogen. This was achieved by performing an experimental parametric investigation of Platinum catalysts in two phases. Firstly, the design of three diverse configurations of mixers and was investigated experimentally and numerically. The chosen mixer was implemented in the parametric study of five different Pt catalysts varying in geometric and material properties. This was executed at unpressurized and NOx emission solely due to the catalytic reaction was examined for varying thermal power and air/fuel ratios. Furthermore, temperatures were recorded. Additionally, CFD simulation was accomplished and compared with the measurement data. The overall least NOx achieved was 7.5  ppm at 5 kW for the metal catalyst. The result of this work proposed suitable catalyst for the development of a combined combustor configuration (including catalyst and combustion chamber) which will be intended for small aircraft engine applications.     

Identifying Structure–Property Relationships Through DREAM.3D Representative Volume Elements and DAMASK Crystal Plasticity Simulations: An Integrated Computational Materials Engineering Approach

Predicting, understanding, and controlling the mechanical behavior is the most important task when designing structural materials. Modern alloy systems—in which multiple deformation mechanisms, phases, and defects are introduced to overcome the inverse strength–ductility relationship—give raise to multiple possibilities for modifying the deformation behavior, rendering traditional, exclusively experimentally-based alloy development workflows inappropriate. For fast and efficient alloy design, it is therefore desirable to predict the mechanical performance of candidate alloys by simulation studies to replace time- and resource-consuming mechanical tests. Simulation tools suitable for this task need to correctly predict the mechanical behavior in dependence of alloy composition, microstructure, texture, phase fractions, and processing history. Here, an integrated computational materials engineering approach based on the open source software packages DREAM.3D and DAMASK (Düsseldorf Advanced Materials Simulation Kit) that enables such virtual material development is presented. More specific, our approach consists of the following three steps: (1) acquire statistical quantities that describe a microstructure, (2) build a representative volume element based on these quantities employing DREAM.3D, and (3) evaluate the representative volume using a predictive crystal plasticity material model provided by DAMASK. Exemplarily, these steps are here conducted for a high-manganese steel.