Dimer Formation Enhances Structural Differences between Amyloid β-Protein (1–40) and (1–42): An Explicit-Solvent Molecular Dynamics Study

Amyloid -protein (A) is central to the pathology of Alzheimer's disease. A 5% difference in the primary structure of the two predominant alloforms, A and A, results in distinct assembly pathways and toxicity properties. Discrete molecular dynamics (DMD) studies of A and A assembly resulted in alloform-specific oligomer size distributions consistent with experimental findings. Here, a large ensemble of DMD–derived A and A monomers and dimers was subjected to fully atomistic molecular dynamics (MD) simulations using the OPLS-AA force field combined with two water models, SPCE and TIP3P. The resulting all-atom conformations were slightly larger, less compact, had similar turn and lower -strand propensities than those predicted by DMD. Fully atomistic A and A monomers populated qualitatively similar free energy landscapes. In contrast, the free energy landscape of A dimers indicated a larger conformational variability in comparison to that of A dimers. A dimers were characterized by an increased flexibility in the N-terminal region D1-R5 and a larger solvent exposure of charged amino acids relative to A dimers. Of the three positively charged amino acids, R5 was the most and K16 the least involved in salt bridge formation. This result was independent of the water model, alloform, and assembly state. Overall, salt bridge propensities increased upon dimer formation. An exception was the salt bridge propensity of K28, which decreased upon formation of A dimers and was significantly lower than in A dimers. The potential relevance of the three positively charged amino acids in mediating the A oligomer toxicity is discussed in the light of available experimental data

Financial Pinch Analysis: Minimum opportunity cost targeting algorithm

To achieve the market competitiveness as well as sustainable products and processes, a firm invests in different environmental and conservation projects. Capital budgeting essentially entails the decision of funding a set of acceptable projects from a larger pool of available projects, subject to different funding constraints. This paper proposes a new algorithm, the minimum opportunity cost targeting algorithm (MOCTA), to address the capital budgeting problems for selecting environmental management projects. This algorithm is based on the principles of Pinch Analysis, a well-established resource conservation methodology and can be directly applied to partially acceptable projects which can be formulated as a linear programming problem. The proposed algorithm, in coordination with the branch and bound technique, can further be applied to solve mixed integer linear programming (MILP) formulation of the problem, where projects should either be completely accepted or completely rejected. A hypothetical example demonstrates the applicability of the methodology through a complex search tree. The proposed methodologies are demonstrated through a case study of selecting energy conservation projects in ;the Indian Paper and Pulp industry. (C) 2018 Elsevier Ltd. All rights reserved

Kawasaki Disease: A Case Report Every Otolaryngologist Should Know

Kawasaki disease is the acute febrile vasculitis of childhood, predominantly affecting medium sized arteries with predilection for coronary arteries. The diagnosis is mainly clinical, though investigations are helpful in early detection of complications. We report a case of Kawasaki disease in a 5 year old child who presented to our hospital with conjunctival congestion, lymphadenopathy and fever. When on treatment with antibiotics did not help resolve symptoms, particularly conjunctival congestion Kawasaki disease was suspected. She was treated with a single dose of intravenous immunoglobulin G, over a period of 12 h. She subsequently developed a systolic murmur with grade I mitral regurgitation not a known complication of Kawasaki disease. She responded to the treatment remarkably and promptly thus evading any fatal complication