FiD: a software for ab initio structural identification of product ions from tandem mass spectrometric data

We present FiD (Fragment iDentificator), a software tool for the structural identification of product ions produced with tandem mass spectrometric measurement of low molecular weight organic compounds. Tandem mass spectrometry (MS/MS) has proven to be an indispensable tool in modern, cell-wide metabolomics and fluxomics studies. In such studies, the structural information of the MS(n) product ions is usually needed in the downstream analysis of the measurement data. The manual identification of the structures of MS(n) product ions is, however, a nontrivial task requiring expertise, and calls for computer assistance. Commercial software tools, such as Mass Frontier and ACD/MS Fragmenter, rely on fragmentation rule databases for the identification of MS(n) product ions. FiD, on the other hand, conducts a combinatorial search over all possible fragmentation paths and outputs a ranked list of alternative structures. This gives the user an advantage in situations where the MS/MS data of compounds with less well-known fragmentation mechanisms are processed. FiD software implements two fragmentation models, the single-step model that ignores intermediate fragmentation states and the multi-step model, which allows for complex fragmentation pathways. The software works for MS/MS data produced both in positive- and negative-ion modes. The software has an easy-to-use graphical interface with built-in visualization capabilities for structures of product ions and fragmentation pathways. In our experiments involving amino acids and sugar-phosphates, often found, e.g., in the central carbon metabolism of yeasts, FiD software correctly predicted the structures of product ions on average in 85% of the cases. The FiD software is free for academic use and is available for download from www.cs.helsinki.fi/group/sysfys/software/fragid. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Reduction of pyracylene by alkali metals: Mechanism and formation of aggregates

Five reaction stages have been identified in the reduction of pyracylene to its dianion. The same stages were also observed in the photochemical oxidation starting with the dianion. The formation of dimers of anions and of mixed valence aggregates is discussed.     

Electrostatic Interactions That Determine the Rate of Pseudorotation Processes in Oxyphosphorane Intermediates: Implications with Respect to the Roles of Metal Ions in the Enzymatic Cleavage of RNA

The enzymatic cleavage of RNA takes place via a cyclic pentacoordinate oxyphosphorane intermediate/transition state. We carried out ab initio investigations on the neutral cyclic oxyphosphorane, which exists as a stable intermediate. As a consequence of the conformational preferences of the pentacoordinate trigonal bipyramidal intermediates, the rotation of the P-OH bonds is strongly coupled with the reaction coordinate for the pseudorotation process. In addition, the neutral PF(4)OH species has a higher barrier to pseudorotation than the corresponding anionic species PF(4)O(-). These findings are related to the positive charge of the hydrogen atoms on the equatorial oxygens in the trigonal bipyramidal structures: the hydrogen atoms preferably adopt eclipsed positions relative to the axial ligands. Fixing the cationic species in these regions causes an increase in the barrier heights for pseudorotation processes and, thus, prevents isomerization by pseudorotation. Consequently, metal coordination in the double-metal ion mechanism for enzymatic cleavage of RNA should serve to exclusively stabilize the trigonal bipyramidal intermediate/transition state for the in-line attack and departure process.     

Potentiometric sensors for Ag+ based on poly(3-octylthiophene) (POT)

Potentiometric ion sensors were prepared from the conjugated polymer poly(3-octylthiopene) (POT). The influence of additional membrane components, including silver 7,8,9,10,11,12-hexabromocarborane (AgCB₁₁H₆Br₆) and potassium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (KTpFPB) as lipophilic salts, and [2.2.2]p,p,p-cyclophane as silver ionophore, was studied. The membrane components were dissolved in chloroform and membranes were prepared by solution casting on glassy carbon disk electrodes. For comparison, POT-based potentiometric sensors were also prepared by galvanostatic electrosynthesis of POT from the 3-octylthiophene monomer. All the POT-based ion sensors fabricated by solution casting show Nernstian or slightly sub-Nernstian response to Ag⁺, even those based only on POT without any additional membrane components. The potentiometric response of electrochemically polymerized POT depends on the film thickness and the doping anion incorporated in the conducting polymer during polymerization. It is of particular importance that chemically synthesized undoped POT (without any additives) shows a sensitive and selective potentiometric response to Ag⁺ ions although UV-vis results show that POT remains in its undoped form, i.e., POT is not oxidized by Ag⁺. This indicates that undoped POT can exhibit good sensitivity and selectivity to Ag⁺ also in the absence of metallic silver in the polymer film. In this case, the potentiometric response is related to interactions between Ag⁺ and the conjugated polymer backbone. Presented at the 4th Baltic Conference on Electrochemistry, Greifswald, 13–16, 2005     

The effect of closed-loop feedback control on scalar mixing in a plane shear layer

The effect of feedback on mixing in a plane shear layer was studied using temperature as an analog to species concentration. Mixing was quantified using temperature measurements made by an array of cold-wire sensors. Upstream of the cold-wire sensors, a schlieren imager measured the cross-stream position of the temperature interface between the two streams before the primary vortical structures had formed. Surface heaters mounted on the flow partition were used as control actuators. Feeding the gained output from the interface position sensor back to the surface heaters closed the loop and created resonance and out-of-resonance conditions in the flow, both of which increased mixing. The feedback gains were adaptively modified in real time to maximize mixing at a given streamwise station. Finally, it was found that deliberately introducing streamwise vorticity, and then choosing feedback gains that strengthen these streamwise vortices, can greatly enhance mixing.     

Bioactive glycosides from the African medicinal plant Boerhavia erecta L.

Phytochemical studies of the previously unexplored stem of Boerhavia erecta from Burkina Faso, resulted in the isolation of an unreported glycoside 4, 2,3-dihydroxypropylbenzoate-3-O-β-[4″-methoxy] glucuronide as well as seven known glycosides (1–3, 5–8). The major isolate 5 and 8 indicated a significant inhibition against HIV integrase (IC₅₀ 10 and 22 μg/mL, respectively). The extracts and isolates were also tested for anti-malarial activity, but insignificant activity was observed.     

Polarizability of gyrotropic sphere

The polarizability of gyrotropic spheres is studied in this short article. Gyrotropic media are anisotropic in two respects: the symmetric part of the permittivity dyadic is uniaxial, and furthermore, there is also antisymmetric part in the permittivity. The polarizability is also dyadic with its components depending on the relations of the permittivity components of the material.     

Computing Voronoi skeletons of a 3-D polyhedron by space subdivision

We tackle the problem of computing the Voronoi diagram of a 3-D polyhedron whose faces are planar. The main difficulty with the computation is that the diagram's edges and vertices are of relatively high algebraic degrees. As a result, previous approaches to the problem have been non-robust, difficult to implement, or not provenly correct.

We introduce three new proximity skeletons related to the Voronoi diagram: (1) the Voronoi graph (VG), which contains the complete symbolic information of the Voronoi diagram without containing any geometry; (2) the approximate Voronoi graph (AVG), which deals with degenerate diagrams by collapsing sub-graphs of the VG into single nodes; and (3) the proximity structure diagram (PSD), which enhances the VG with a geometric approximation of Voronoi elements to any desired accuracy. The new skeletons are important for both theoretical and practical reasons. Many applications that extract the proximity information of the object from its Voronoi diagram can use the Voronoi graphs or the proximity structure diagram instead. In addition, the skeletons can be used as initial structures for a robust and efficient global or local computation of the Voronoi diagram.

We present a space subdivision algorithm to construct the new skeletons, having three main advantages. First, it solves at most uni-variate quartic polynomials. This stands in sharp contrast to previous approaches, which require the solution of a non-linear tri-variate system of equations. Second, the algorithm enables purely local computation of the skeletons in any limited region of interest. Third, the algorithm is simple to implement.     

The Dirichlet problem for the minimal hypersurface equation on arbitrary domains of a Riemannian manifold

We show that the Dirichlet problem for the minimal hypersurface equation defined on arbitrary C ² bounded domain Ω of an arbitrary complete Riemannian manifold M is solvable if the oscillation of the boundary data is bounded by a function \({\mathcal{C}}\) that is explicitely given and that depends only on the first and second derivatives of the boundary data as well as the second fundamental form of the boundary \({\partial\Omega}\) and the Ricci curvature of the ambient space M. This result extends Theorem 2 of Jenkins-Serrin (J Reine Angew Math 229:170–187,1968) about the solvability of the Dirichlet problem for the minimal hypersurface equation defined on bounded domains of the Euclidean space. We deduce that the Dirichlet problem for the minimal hypersurface equation is solvable for any continuous boundary data on a mean convex domain. We also show existence and uniqueness of the Dirichlet problem with boundary data at infinity—exterior Dirichlet problem—on Hadamard manifolds.