A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

Handgrip Strength and Phase Angle Predict Outcome After Bariatric Surgery

Background!#!The amount of postoperative weight loss after bariatric surgery varies interindividually. The quality of the pre- and postoperative body composition is an important predictor of success. The aim of this study was to investigate the role of preoperative handgrip strength and phase angle (PhA) as predictors of sustained postoperative weight loss in order to assess the influence of body composition on the postoperative outcome after bariatric surgery.!##!Method!#!In a prospective cohort study, bioelectrical impedance and follow-up data of 198 patients after laparoscopic sleeve gastrectomy (SG; n = 68) and Roux-en-Y gastric bypass (GB; n = 130) were analyzed for a period of 36 months postoperatively.!##!Results!#!The mean preoperative handgrip strength (31.48 kg, SD 9.97) correlates significantly with the postoperative body composition up to 24 months after surgery. Preoperative PhA, gender, size, and body weight influenced postoperative weight loss significantly. A significant correlation between preoperative PhA (mean 6.18°, SD 0.89°) and total weight loss (%TWL) was observed up to 3 months after SG (r = 0.31444, p = 0.0218) and up to 12 months after GB (r = 0.19184, p = 0.0467). The optimum cutoff for the prediction of a response of less than 50% excess weight loss was a preoperative PhA of 6.0°.!##!Conclusions!#!The preoperative handgrip strength confirmed its suitability for use as a predictor of postoperative body composition, whereas the preoperative PhA predicts postoperative weight loss after bariatric surgery. Further research is necessary to identify the role of these parameters for preconditioning

Co-overexpression of bacterial GroESL chaperonins partly overcomes non-productive folding and tetramer assembly of E. coli-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) carrying the prevalent disease-causing K304E mutation

The influence of co-overexpression of the bacterial chaperonins GroEL and GroES on solubility, tetramer formation and enzyme activity of three variants of heterologously-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) was analysed in order to investigate the molecular mechanism underlying MCAD deficiency by the prevalent K304E mutation. Depending on which of the three amino acids - lysine (wild-type), glutamic acid (K304E) or glutamine (K304Q) are present at position 304 of the mature polypeptide, three different patterns were observed in our asay system: (1) solubility, tetramer formation and yield of enzyme activity of wild-type MCAD is largely independent of GroESL co-overexpression; (ii) the larger part of the K304Q mutant is insoluble without and solubility is enhanced with GroESL co-overexpression; solubility correlates with the amount of tetramer detected and the enzyme activity measured as observed for the wild-type protein. (iii) Solubility of the K304E mutant is in a similar fashion GroESL responsive as the K304Q mutant, but the amount of tetramer observed and the enzyme activity measured do not correlate with the amount of soluble K304E MCAD protein detected in Western blotting. In a first attempt to estimate the specific activity, we show that tetrameric K304E and K30Q mutant MCAD display a specific activity in the range of the wild-type enzyme. Taken together, our results strongly suggest, that teh K304E mutation primarily impairs the rat of folding and subunit enzyme. Based on the data presented, we propose that lysine-304 is important for the folding pathway and that an exchange of this amino acid both to glutamine or glutamic acid levels to an increased tendency to misfold/aggregate. Futhermore, exchange of lysine-304 with amino acid with negative charge at position 304 (glutamic acid) but not with a neutral charge (glutamine) negatively affects conversion to active tetramers. A possible explanation for this latter effect - charge repulsion upon subunit docking - is discussed

Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme

We have used expression of human medium chain acyl-CoA dehydrogenase (MCAD) in Escherichia coli as a model system for dissecting the molecular effects of two mutations detected in patients with MCAD deficiency. We demonstrate that the R28C mutation predominantly affects polypeptide folding. The amounts of active R28C mutant enzyme produced could be modulated between undetectable to 100% of the wild-type control by manipulating the level of available chaperonins and the growth temperature. For the prevalent K304E mutation, however, the amounts of active mutant enzyme could be modulated only in a range from undetectable to approximately 50% of the wild-type, and the assembled mutant enzyme displayed a decreased thermal stability. Two artificially constructed mutants (K304Q and K304E/D346K) yielded clearly higher amounts of active MCAD enzyme than the K304E mutant but were also responsive to chaperonin co-overexpression and growth at low temperature. The thermal stability profile of the K304E/D346K double mutant was shifted to even lower temperatures than that of the K304E mutant, whereas that of the K304Q mutant was closely similar to the wild-type. Taken together, the results show that the K304E mutation affects (i) polypeptide folding due to elimination of the positively charged lysine and (ii) oligomer assembly and stability due to replacement of lysine 304 with the negatively charged glutamic acid