Efficient Algorithms for Linear Summed Error Structural SVMs

Structural Support Vector Machines (SSVMs) have become a popular tool in machine learning for predicting structured objects like parse trees, Part-of-Speech (POS) label sequences and image segments. Various efficient algorithmic techniques have been proposed for training SSVMs for large datasets. The typical SSVM formulation contains a regularizer term and a composite loss term. The loss term is usually composed of the Linear Maximum Error (LME) associated with the training examples. Other alternatives for the loss term are yet to be explored for SSVMs. We formulate a new SSVM with Linear Summed Error (LSE) loss term and propose efficient algorithms to train the new SSVM formulation using primal cutting-plane method and sequential dual coordinate descent method. Numerical experiments on benchmark datasets demonstrate that the sequential dual coordinate descent method is faster than the cutting-plane method and reaches the steady-state generalization performance faster. It is thus a useful alternative for training SSVMs when linear summed error is used.

Stabilization and Structural Alteration of the G-Quadruplex DNA Made from the Human Telomeric Repeat Mediated by Troger's Base Based Novel Benzimidazole Derivatives

Ligand-induced stabilization of the G-quadruplex DNA structure derived from the single-stranded 3'-overhang of the telomeric DNA is an attractive strategy for the inhibition of the telomerase activity. The agents that can induce/stabilize a DNA sequence into a G-quadruplex structure are therefore potential anticancer drugs. Herein we present the first report of the interactions of two novel bisbenzimidazoles (TBBz1 and TBBz2) based on Troger's base skeleton with the G-quadruplex DNA (G4DNA). These Troger's base molecules stabilize the G4DNA derived from a human telomeric sequence. Evidence of their strong interaction with the G4DNA has been obtained from CD spectroscopy, thermal denaturation, and UV-vis titration studies. These ligands also possess significantly higher affinity toward the G4DNA over the duplex DNA. The above results obtained are in excellent agreement with the biological activity, measured in vitro using a modified TRAP assay. Furthermore, the ligands are selectively more cytotoxic toward the cancerous cells than the corresponding noncancerous cells. Computational studies suggested that the adaptive scaffold might allow these ligands to occupy not only the G-quartet planes but also the grooves of the G4DNA.