LogP prediction performance with the SMD solvation model and the M06 density functional family for SAMPL6 blind prediction challenge molecules

This work presents a quantum mechanical model for predicting octanol-water partition coefficients of small protein-kinase inhibitor fragments as part of the SAMPL6 LogP Prediction Challenge. The model calculates solvation free energy differences using the M06-2X functional with SMD implicit solvation and the def2-SVP basis set. This model was identified as dqxk4 in the SAMPL6 Challenge and was the third highest performing model in the physical methods category with 0.49 log Root Mean Squared Error (RMSE) for predicting the 11 compounds in SAMPL6 blind prediction set. We also collaboratively investigated the use of empirical models to address model deficiencies for halogenated compounds at minimal additional computational cost. A mixed model consisting of the dqxk4 physical and hdpuj empirical models found improved performance at 0.34 log RMSE on the SAMPL6 dataset. This collaborative mixed model approach shows how empirical models can be leveraged to expediently improve performance in chemical spaces that are difficult for ab initio methods to simulate.     

Structural analysis of prion proteins by means of drift cell and traveling wave ion mobility mass spectrometry

The prion protein (PrP) is implicitly involved in the pathogenesis of transmissible spongiform encephalopathies (TSEs). The conversion of normal cellular PrP (PrP^C), a protein that is predominantly α-helical, to a β-sheet-rich isoform (PrP^Sc), which has a propensity to aggregate, is the key molecular event in prion diseases. During its short life span, PrP can experience two different pH environments; a mildly acidic environment, whilst cycling within the cell, and a neutral pH when it is glycosyl phosphatidylinositol (GPI)-anchored to the cell membrane. Ion mobility (IM) combined with mass spectrometry has been employed to differentiate between two conformational isoforms of recombinant Syrian hamster prion protein (SHaPrP). The recombinant proteins studied were α-helical SHaPrP(90-231) and β-sheet-rich SHaPrP(90-231) at pH 5.5 and pH 7.0. The recombinant proteins have the same nominal mass-to-charge ratio (m/z) but differ in their secondary and tertiary structures. A comparison of traveling-wave (T-Wave) ion mobility and drift cell ion mobility (DCIM) mass spectrometry estimated and absolute cross-sections showed an excellent agreement between the two techniques. The use of T-Wave ion mobility as a shape-selective separation technique enabled differentiation between the estimated cross-sections and arrival time distributions (ATDs) of α-helical SHaPrP(90-231) and β-sheet-rich SHaPrP(90-231) at pH 5.5. No differences in cross-section or ATD profiles were observed between the protein isoforms at pH 7.0. The findings have potential implications for a new ante-mortem screening assay, in bodily fluids, for prion misfolding diseases such as TSEs.     

A novel reference electrode for application in alkaline polymer electrolyte membrane fuel cells

An in-situ fuel cell reference electrode (RE) consisting of a Pd-coated Pt wire exhibits stable potentials in alkaline polymer electrolyte membrane fuel cells (APEMFC). Results indicate that the overpotential and impedance of the anode are higher than those of the cathode in the cells tested (even at low currents); this is contrary to that found in proton-exchange membrane fuel cells (PEMFC) and it shows that caution is required when translating prior understating of PEMFC to APEMFC. The working hypothesis is that there is flooding-derived mass transport loss at the anode (where water is electro-generated).     

Steady-state dc and impedance investigations of H2/O2 alkaline membrane fuel cells with commercial Pt/C, Ag/C, and Au/C cathodes

The performances of H(2)/O(2) metal-cation-free alkaline anion-exchange membrane (AAEM) fuel cells operated with commercially available Au/C and Ag/C cathodes are reported for the first time. Of major significance, the power density obtained with 4 mg cm(-2) Ag/C (60% mass) cathodes was comparable to that obtained with 0.5 mg cm(-2) Pt/C (20% mass) electrodes, whereas the performance when using the same Ag/C cathode in a Nafion-based acidic membrane electrode assembly (MEA) was poor. These initial studies demonstrate that the oxygen reduction electrokinetics are improved when operating Pt/C cathodes at high pH in AAEM-based fuel cells as compared with operation at low pH (in Nafion-based proton-exchange membrane fuel cells). The results of in situ alternating current impedance spectroscopy were core to the assignment of the source of the limited performances of the AAEM-based fuel cells as being the limited supply of water molecules to the cathode reaction sites. Minimizing the thickness of the AAEM improved the performances by facilitating back-transport of water molecules from the anode (where they are generated) to the cathode. The urgent need for development of electrode architectures that are specifically designed for use in AAEM-based fuel cells is highlighted.     

Formal synthesis of 6-deoxyerythronolide B

[reaction: see text] The enantioselective synthesis of the carbon skeleton of 6-deoxyerythronolide B has been achieved in 23 linear steps from propionaldehyde. The synthesis relies on an iterative approach employing an asymmetric acyl-thiazolidinethione propionate aldol reaction to establish eight of nine stereogenic centers. The remaining stereogenic center at C6 was set through a Myers alkylation employing a complex alkyl iodide.     

Random Subgraphs Of Finite Graphs: III. The Phase Transition For The n-Cube

We study random subgraphs of the n-cube {0,1}ⁿ, where nearest-neighbor edges are occupied with probability p. Let p_c(n) be the value of p for which the expected size of the component containing a fixed vertex attains the value λ2^n/3, where λ is a small positive constant. Let ε=n(p−p_c(n)). In two previous papers, we showed that the largest component inside a scaling window given by |ε|=Θ(2^−n/3) is of size Θ(2^2n/3), below this scaling window it is at most 2(log 2)nε⁻², and above this scaling window it is at most O(ε2ⁿ). In this paper, we prove that for the size of the largest component is at least Θ(ε2ⁿ), which is of the same order as the upper bound. The proof is based on a method that has come to be known as “sprinkling,” and relies heavily on the specific geometry of the n-cube.     

A new inductive approach to the lace expansion for self-avoiding walks

Summary. We introduce a new inductive approach to the lace expansion, and apply it to prove Gaussian behaviour for the weakly self-avoiding walk on ℤ ^d where loops of length m are penalised by a factor e ^{−β/m p} (0<β≪1) when: (1) d>4, p≥0; (2) d≤4, . In particular, we derive results first obtained by Brydges and Spencer (and revisited by other authors) for the case d>4, p=0. In addition, we prove a local central limit theorem, with the exception of the case d>4, p=0. Received: 29 October 1997 / In revised form: 15 January 1998     

High-field27Al mas NMR studies of the formation of metakaolinite by flash calcination of kaolinite

Flash calcination was used to dehydroxylate kaolinite and produced calcines kinetically frozen at various stages during metakaolinite formation. High speed magic-angle spinning²⁷Al NMR, in magnetic fields of 14.1 and 11.8 T, enabled new features to be observed in the metakaolinite spectrum. The dependence on magnetic field of simulated and experimental spectra is discussed, and the effects of a distribution of electric field gradients is examined. The evolution of the metakaolinite peaks is followed during dehydroxylation.