Linearized Krylov subspace Bregman iteration with nonnegativity constraint

Numerical Algorithms - Bregman-type iterative methods have received considerable attention in recent years due to their ease of implementation and the high quality of the computed solutions they...     

A general framework for ADMM acceleration

Numerical Algorithms - The Alternating Direction Multipliers Method (ADMM) is a very popular algorithm for computing the solution of convex constrained minimization problems. Such problems are...     

Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.     

Generalized cross validation for ℓp-ℓq minimization

Numerical Algorithms - Discrete ill-posed inverse problems arise in various areas of science and engineering. The presence of noise in the data often makes it difficult to compute an accurate...     

Iterated Tikhonov regularization with a general penalty term

Tikhonov regularization is one of the most popular approaches to solving linear discrete ill‐posed problems. The choice of the regularization matrix may significantly affect the quality of the computed solution. When the regularization matrix is the identity, iterated Tikhonov regularization can yield computed approximate solutions of higher quality than (standard) Tikhonov regularization. This paper provides an analysis of iterated Tikhonov regularization with a regularization matrix different from the identity. Computed examples illustrate the performance of this method.     

An N-capping asparagine–lysine–proline (NKP) motif contributes to a hybrid flexible/stable multifunctional peptide scaffold

Structural diversity drives multiple biological activities and mechanisms of action in linear peptides. Here we describe an unusual N-capping asparagine-lysine-proline (NKP) motif that confers a hybrid multifunctional scaffold to a computationally designed peptide (PaDBS1R7). PaDBS1R7 has a shorter α-helix segment than other computationally designed peptides of similar sequence but with key residue substitutions. Although this motif acts as an α-helix breaker in PaDBS1R7, the Asn5 presents exclusive N-capping effects, forming a belt to establish hydrogen bonds for an amphipathic α-helix stabilization. The combination of these different structural profiles was described as a coil/N-cap/α-helix scaffold, which was also observed in diverse computational peptide mutants. Biological studies revealed that all peptides displayed antibacterial activities. However, only PaDBS1R7 displayed anticancer properties, eradicated Pseudomonas aeruginosa biofilms, decreased bacterial counts by 100–1000-fold in vivo, reduced lipopolysaccharide-induced macrophages stress, and stimulated fibroblast migration for wound healing. This study extends our understanding of an N-capping NKP motif to engineering hybrid multifunctional peptide drug candidates with potent anti-infective and immunomodulatory properties.

An unusual N-capping asparagine-lysine-proline (5NKP7) motif yields a coil/N-cap/α-helix multifunctional scaffold in a computer-made peptide selective for anionic surfaces and with anticancer, antibacterial, antibiofilm, anti-infective (in vivo), and immunomodulatory potential.