Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase

Enzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC₅₀=0.29 μM). Surprisingly, the allosteric activation control point resides on the lysine residue K282 present in the catalytic site of PKL. These findings were confirmed by structural data, MS/MS experiments, and molecular modelling studies. Altogether, our study provides a molecular basis for the activation mechanism and establishes a framework for further development of human liver pyruvate kinase covalent activators.     

Mastitis and the shape of the lactation curve in Norwegian dairy cows

An investigation of the shape of the lactation curve and the mastitis incidence was conducted to identify whether management interventions of the lactation curve constitute a potential for reducing incidence of mastitis at herd level. Lactation curves were estimated to describe the variation of daily milk yield during the 305-d lactation period in Norwegian Red cows. Associations between mastitis incidence at herd level and lactation curve characteristics such as production level at onset of lactation, magnitude and time of peak milk yield, and increase and decrease of milk yield rates were studied. Data from 250,303 lactations occurring during 2005 and 2006 from 14,766 herds were obtained from the Norwegian Dairy Herd Recording System. Besides veterinary treatments, the records included information on monthly test-day milk yields. The shapes of the lactation curves at herd level were parameterized using a modified Wilmink model in two separate mixed model analyses. In the first analysis a subset of lactations with no records of veterinary treatments was used. Lactation curves from herds with high (>0·31 cases/305-d lactation) and low (<0·07 cases/305-d lactation) herd mastitis incidence rate were parameterized and compared for three separate strata of parity. The result showed that high herd mastitis incidence rate was associated with a low intercept (P<0·05), a steep slope before peak milk yield (P<0·01) and a rapid decline after peak milk yield (P<0·01). In the second analysis a subset of high-yielding lactations with veterinary treatments of mastitis only and lactations with no records of veterinary treatment were compared. This was done to investigate whether the findings at herd level were also reflected at cow level. These results showed that lactation curves from lactations with mastitis cases were associated with a steep slope before peak milk yield (P<0·05) in second and later parities and a rapid decline after peak milk yield (P<0·01) in all three parity groups.     

Saving time and memory in computational intelligence system with machine unification and task spooling

There are many knowledge-based data mining frameworks and it is common to think that new ones cannot come up with anything new. This article refutes such claims. We propose a sophisticated unification mechanism and two-tier machine cache system aimed at saving time and memory. No machine is run twice. Instead, machines are reused wherever they are repeatedly requested (regardless of request context). We also present an exceptional task spooler. Its unique design facilitates efficient automated management of large numbers of tasks with natural adjustment to available computational resources. Dedicated task scheduler cooperates with machine unification mechanism to save time and space. The solutions are possible thanks to very general and universal design of machine, configuration, machine context, unique machine life cycle, machine information exchange, configuration templates and other necessary concepts. Results gained by machines are stored in a uniform way, facilitating easy results exploration and collection by means of a special query system and versatile analysis with series transformations. No knowledge about internals of particular machines is necessary to extensively explore the results. The ideas presented here, have been implemented and verified inside Intemi framework for data mining and meta-learning tasks. They are general engine-level mechanisms that may be fruitful in all aspects of data analysis, all applications of knowledge-based data mining, computational intelligence, machine learning or neural networks methods.     

Simulation of ion-track ranges in uranium oxide

Direct comparisons between statistically sound simulations of ion-tracks and published experimental measurements of range densities of iodine implants in uranium dioxide have been made with implant energies in the range of 100–800 keV. Our simulations are conducted with REED-MD (Rare Event Enhanced Domain-following Molecular Dynamics) in order to account for the materials structure in both single crystalline and polycrystalline samples. We find excellent agreement between REED-MD results and experiments for polycrystalline target materials.     

Mechanical Stress on Lysozyme Crystals during Dynamic Cross‐Flow Filtration

The influence of mechanical stress on the crystal size distribution of lysozyme crystal slurries in a dynamic cross‐flow device is discussed. The reduction of crystal size may have an influence on mass and resistance of the fouling layer. A filter test device with a filter area of 130 cm² is used for thickening. After thickening, a model impurity, namely bovine serum albumin, is washed out of the suspension. A reduction of crystal size due to stirring and a reduced fouling layer with increasing stirrer speed is observed. Furthermore, a higher stirring speed increases the specific filtrate flux. In the presence of the impurity, more crystal aggregates than single isometric crystals are formed and, hence, the decrease of crystal size due to shear forces is more pronounced than without impurity.     

The role of friction in the measurement of slipperiness, Part 1: friction mechanisms and definition of test conditions.

Friction has been widely used as a measure of slipperiness. However, controversies around friction measurements remain. The purposes of this paper are to summarize understanding about friction measurement related to slipperiness assessment of shoe and floor interface and to define test conditions based on biomechanical observations. In addition, friction mechanisms at shoe and floor interface on dry, liquid and solid contaminated, and on icy surfaces are discussed. It is concluded that static friction measurement, by the traditional use of a drag-type device, is only suitable for dry and clean surfaces, and dynamic and transition friction methods are needed to properly estimate the potential risk on contaminated surfaces. Furthermore, at least some of the conditions at the shoe/floor interface during actual slip accidents should be replicated as test conditions for friction measurements, such as sliding speed, contact pressure and normal force build-up rate.     

Reactive phenylbenzimidazole UV absorbers and their application to cellulose textiles

New types of reactive UV absorbers for applications to cellulose textiles have been prepared. These substances are condensation products of sulfobenzimidazolaniline, cyanuric chloride, and aminophenyl‐(2‐sulfethoxy)‐sulfone. They were applied to bleached, unbleached, as well as dyed cellulose textiles with the aim to increase the protection effect of these textiles against UV radiation. All the tested textiles showed a marked increase in the UV protection factor (UPF). The effects of the UV absorbers tested neither interfere with the function of fluorescent brighteners (FBs) nor affect the hue of the used dyestuffs. They exhibit synergistic effect in the protection effectiveness against UV radiation: the UV absorbers used together with dyestuffs and FBs have a higher UPF factor than is the sum of UPF contributions of the individual components. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Fracture resistance of a doped PZT ceramic for multilayer piezoelectric actuators: Effect of mechanical load and temperature

The fracture resistance behaviour of a doped lead zirconate titanate (PZT) ceramic after combined thermo-mechanical loading is investigated between room temperature (RT) and 400 °C, i.e. above the Curie temperature (T_C). The thermal- and stress-induced depolarisation effects due to domain switching have been assessed by the indentation method on bulk PZTs. This has been extended to multilayered actuators. Experimental findings show a depolarisation effect with the temperature, which is significantly enhanced when combined with mechanical loading. This partial or even full depolarisation of the PZT material below T_C leads to important anisotropy effects in the fracture resistance of the piezo-ceramic, which should be taking into account in the design of multilayer actuators where the direction of crack propagation (i.e. parallel or normal to electrodes) can affect the actuator functionality.     

Bücherschau

Ohne Zusammenfassung VDI     

Masc2, a gene from Ascobolus encoding a protein with a DNA-methyltransferase activity in vitro, is dispensable for in vivo methylation

We have shown previously that masc1, a gene encoding a putative C5-DNA-methyltransferase (MTase), was necessary for the de novo 'Methylation Induced Premeiotically' (MIP) process and sexual reproduction in Ascobolus, whereas it was dispensable for maintenance methylation. A second MTase gene from Ascobolus, masc2, encodes a protein, Masc2, which possesses the large amino-terminal part characteristic of eukaryotic maintenance MTases. In vitro assays have shown that Masc2 displays a methylation activity, suggesting that it might be the MTase responsible for maintenance methylation. To check its function in vivo, we engineered a disruption of the masc2 gene. The resulting mutant strains did not exhibit any particular phenotype during either vegetative growth or sexual reproduction. Neither the masc2 mutation nor the double masc1 masc2 mutation had any detectable effect upon the maintenance of the pre-existing methylation of single gene copies previously subjected to MIP, natural retroelement-like repeats and tandemly repeated rDNA. The masc2 mutation did not alter either MIP or the other de novo methylation process that operates in vegetatives cells. Nor did it impair the meiotic process of methylation transfer. These results suggest that at least a third MTase gene responsible for maintenance and vegetative de novo methylation is present in Ascobolus.