Screening a peptidyl database for potential ligands to proteins with side-chain flexibility

OBJECTIVE: Microdialysis and 31P-NMR spectroscopy were used to test opposing hypotheses that ischemic preconditioning inhibits adenine nucleotide degradation and purine efflux, or that preconditioning activates cardiovascular adenosine formation to provide enhanced cardioprotection. METHODS: 31P-NMR spectra and matching interstitial fluid (ISF) or venous effluent samples were obtained from Langendorff perfused rat hearts. Control hearts (n = 9) underwent 30 min of global normothermic ischemia and 30 min reperfusion. Preconditioned hearts (n = 6) were subjected to a 5 min ischemic episode and 10 min reflow prior to 30 min ischemia and 30 min reperfusion. Effects of repetitive ischemia-reperfusion (3 x 5 min ischemic episodes) on adenosine levels and energy metabolism were also assessed (n = 8). RESULTS: Preconditioning improved post-ischemic recovery of heart rate x left ventricular developed pressure (71 +/- 5 vs 43 +/- 8%, P < 0.05) and end-diastolic pressure (14 +/- 3 vs 29 +/- 4 mmHg, P < 0.05) compared with control hearts, respectively. Preconditioning did not alter intracellular ATP, phosphocreatine (PCr), inorganic phosphate (Pi), H+ or free Mg2+ during global ischemia, but improved recoveries of PCr, Pi, and delta GATP on reperfusion. ISF adenosine increased more than 20-fold during 30 min ischemia. The 5 min preconditioning episode increased ISF adenosine 3-fold, and reduced ISF adenosine and inosine during subsequent prolonged ischemia by up to 75%. Venous purine levels during reperfusion were also reduced by preconditioning. Accumulation of adenosine in ISF and venous effluent during repetitive ischemia was progressively reduced despite comparable changes in substrate for adenosine formation via 5'-nucleotidase, (5'-AMP), and in allosteric modulators of this enzyme (Mg2+, H+, Pi, ADP, ATP). CONCLUSIONS: (i) Ischemic preconditioning reduces interstitial and vascular adenosine levels during ischemia-reperfusion, (ii) reduced ISF adenosine during ischemia is not due to reduced ischemic depletion of adenine nucleotides in preconditioned rat hearts, (iii) preconditioning may inhibit adenosine formation via 5'-nucleotidase in ischemic rat hearts, and (iv) improved functional recovery with preconditioning is unrelated to metabolic/bioenergetic changes during the ischemic insult, but may be related to improved post-ischemic recovery of [Pi] and delta GATP in this model.     

Hybrid genetic algorithms for constrained placement problems

When solving real-world problems, often the main task is to find a proper representation for the candidate solutions. Strings of elementary data types with standard genetic operators may tend to create infeasible individuals during the search because of the discrete and often constrained search space. This article introduces a generally applicable representation for 2D combinatorial placement and packing problems. Empirical results are presented for two constrained placement problems, the facility layout problem and the generation of VLSI macro-cell layouts. For multiobjective optimization problems, common approaches often deal with the different objectives in different phases and thus are unable to efficiently solve the global problem. Due to a tree structured genotype representation and hybrid, problem-specific operators, the proposed approach is able to deal with different constraints and objectives in one optimization step     

Sternpolymere als funktionale Bausteine für neuartige Nanofiltrationsmembranen

Interest in thin‐film membranes with properties specially tailored to the respective separation process is growing. In order to obtain such membranes with high permselectivity and fouling resistance, established membrane systems are combined with new building blocks. Star polymers are a class of promising building blocks. In this study, star polymers with anion exchange groups of variable molecular weight and low polydispersity were synthesized by atom transfer radical polymerization. The anion exchange groups were tertiary amino and quaternary ammonium groups. The resulting star polymers were integrated into polyamide thin‐film composite membranes using interfacial polymerization.