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.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Interpretation of the results of the CORA-33 dry core boiling water reactor test

All boiling water reactor (BWR) degraded core experiments performed prior to CORA-33 were conducted under ‘wet’ core degradation conditions, in which water remains within the core and continuous steaming feeds metal-steam oxidation reactions on the in-core metallic surfaces. However, one dominant set of accident scenarios would occur with reduced metal oxidation under ‘dry’ core degradation conditions and, prior to CORA-33, this set had been neglected experimentally. The CORA-33 experiment was designed specifically to address this dominant set of BWR ‘dry’ core severe accident scenarios and to resolve partially phenomenological uncertainties concerning the behavior of relocating metallic melts that drain into the lower regions of a ‘dry’ BWR core (the ex-reactor experiments at Sandia National Laboratories will further address these uncertainties). CORA-33 was conducted on 1 October 1992, in the CORA test facility at Karlsruhe. A review of the CORA-33 data indicates that the objectives were achieved; i.e. core degradation occurred at a core heat-up rate (characterized by the absence of any temperature escalation caused by oxidation) and a test section axial temperature profile (at incipient structural melting) that are prototypic of full-core nuclear power plant simulations under ‘dry’ core conditions. Simulations of the CORA-33 test at Oak Ridge National Laboratory (ORNL) have required the modification of existing control blade-canister materials interaction models to include the eutectic melting of the stainless steel-zircaloy interaction products and the heat of mixing of stainless steel and zircaloy. The timing and location of canister failure and melt intrusion into the fuel assembly appear to be adequately simulated by the ORNL models. This paper will present the results of the post-test analyses carried out at ORNL based on the experimental data and the post-test examination of the test bundle at Karlsruhe. The implications of these results with respect to degraded core modelling and the associated safety issues are also discussed.     

Fast Voronoi modeling

The common way to construct Voronoi tessellations is to compare the distances between given reference points using a given distance function. To generalize this distance-function concept we expand an existing approach which defines distance functions by their ``unit circles'. Our new approach allows modeling the ``unit circles' by a closed Spline curve. Changing the control polygon directly affects the tessellation's appearance. Typically generalized Voronoi diagrams are represented by Voronoi vertices and curves separating the individual tiles. To obtain interactive modeling we extended an existing hardware accelerated rendering approach computing a bitmap-representation using different colors for individual tiles. With our extension, we are able to use our Spline distance representations as input for a growing process. This growing process easily takes into account weighting approaches like multiplicative, additive, and even free functional weighting.     

Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen

Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult.     

On mesh-free valley surface extraction with application to low frequency sound simulation

Crease surfaces describe extremal structures of 3D scalar fields. We present a new region-growing-based approach to the meshless extraction of adaptive nonmanifold valley and ridge surfaces that overcomes limitations of previous approaches by decoupling point seeding and triangulation of the surface. Our method is capable of extracting valley surface skeletons as connected minimum structures. As our algorithm is inherently mesh-free and curvature adaptive, it is suitable for surface construction in fields with an arbitrary neighborhood structure. As an application for insightful visualization with valley surfaces, we choose a low frequency acoustics simulation. We use our valley surface construction approach to visualize the resulting complex-valued scalar pressure field for arbitrary frequencies to identify regions of sound cancellation. This provides an expressive visualization of the topology of wave node and antinode structures in simulated acoustics.     

Development of Cr and Al Pack Cementation Coatings on Co-Based γ/γ′ Superalloys

Metallurgical and Materials Transactions A - Co-based superalloys have been developed as candidate materials to replace Ni-based superalloys in hot sections of turbine engines, however, their...