Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Macrophage activation results in bone resorption

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.     

Numerical investigation of 3-D constraint effects on brittle fracture in SE(B) and C(T) specimens

Specimen size and geometry effects on cleavage fracture of ferritic steels tested in the ductile-to-brittle transition region remain an important technological impediment in industrial applications of fracture mechanics and in the on-going development of consensus fracture testing standards. This investigation employs 3-D nonllinear finite element analyses to conduct an extensive parametric evaluation of crack front stress triaxiality for deep notch SE(B) and C(T) specimens and shallow notch SE(B) specimens, with and without side grooves. Crack front conditions are characterized in terms of J-Q trajectories and the constraint model for cleavage fracture toughness proposed previously by Dodds and Anderson. An extension of the toughness scaling model suggested here combines a revised in-plane constraint correction with an explicit thickness correction derived from extreme value statistics. The 3-D analyses provide effective thicknesses for use in the statistical correction which reflect the interaction of material flow properties and specimen aspect ratios, a/W and W/B, on the varying levels of stress triaxiality over the crack front. The 3-D computational results imply that a significantly less strict size/deformation limit, relative to the limit indicated by previous plane-strain computations, is needed to maintain small-scale yielding conditions at fracture by a stress-controlled, cleavage mechanism in deep notch SE(B) and C(T) speciments. Moreover, the analyses indicate that side grooves (20 percent) should have essentially no net effect on measured toughness values of such specimens. Additional new results made available from the 3-D analyses also include revised -plastic factors for use in experimental studies to convert measured work quantities to thickness average and maximum (local) J-values over the crack front. To estimate CTOD values, new m-factors are included for use in the expression 131-1.     

Dynamic light scattering and ultrasonic investigations during the cure reaction of an epoxy resin

Brillouin scattering (BS), photon correlation spectroscopy (PCS), and ultrasonic (US) measurements were conducted to study the curing process of diglycidyl ether of bisphenol A with butane-1,4-diol at a curing temperature of 100°C. The experimental techniques probe the primary glass-rubber transition during the curing reaction. The primary relaxation time τ obtained from the BS and US velocity and absorption increases with curing time and hence the BS experiment measures τ at earlier stages of cure than the US experiment. The relaxation times at a different extent of reaction and for different measuring temperatures are consistent with BS, US, PCS, and DSC measurements and conform to a single reduced Vogel–Fulcher–Hesse–Tamann equation. Furthermore, the US experiments show evidence of secondary relaxations in the epoxy system.     

Comparison of concentrations and size distributions of fungal spores in buildings with and without mould problems

Concentrations and types of airborne fungal spores and their aerodynamic sizes were studied in nine buildings with mould problems and in matched reference buildings in order to characterize the exposure in buildings with mould problems. Samples were taken with Andersen six-stage impactors in the autumn and winter. In winter, total concentrations of fungal spores in buildings with mould problems were twice those in reference buildings, even though all concentrations were quite small. In the autumn, the differences were less obvious due to the masking effect of outdoor air fungi. Also, the compositions of fungal genera differed in buildings with mould problems from that in reference buildings. The difference was most significant in the size range 2.1-4.7 μm. The size distribution of fungal spores in dwellings with mould problems skewed towards larger particles than in reference dwellings. The observed differences in size distribution indicate differences in airborne behaviour of fungal spores and, consequently, in respiratory exposure.     

Sustainability in Web server systems

The exponential growth of Internet during the last decade leads us to make more efforts in the researching and developing of sustainable Web servers in order to decrease the global energy demand. In this paper, we cover, as a first step, a proper review of the literature related to the energy efficiency research in Web server systems to depict the state of the art to plan further contributions as more research in sustainable Web systems. We also propose and implement an energy metric that permits to establish a relation between the Quality of Service (QoS) obtained by the system and the power it consumes.     

Data and models for metonymy resolution

We describe the first shared task for figurative language resolution, which was organised within SemEval-2007 and focused on metonymy. The paper motivates the linguistic principles of data sampling and annotation and shows the task’s feasibility via human agreement. The five participating systems mainly used supervised approaches exploiting a variety of features, of which grammatical relations proved to be the most useful. We compare the systems’ performance to automatic baselines as well as to a manually simulated approach based on selectional restriction violations, showing some limitations of this more traditional approach to metonymy recognition. The main problem supervised systems encountered is data sparseness, since metonymies in general tend to occur more rarely than literal uses. Also, within metonymies, the reading distribution is skewed towards a few frequent metonymy types. Future task developments should focus on addressing this issue.