A Cross-Entropy Approach to the Domination Problem and Its Variants.

The domination problem and three of its variants (total domination, 2-domination, and secure domination) are considered. These problems have various real-world applications, including error correction codes, ad hoc routing for wireless networks, and social network analysis, among others. However, each of them is NP-hard to solve to provable optimality, making fast heuristics for these problems desirable.

BRD4-mediated repression of p53 is a target for combination therapy in AML.

Acute myeloid leukemia (AML) is a typically lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, most AML retain wild-type TP53, encoding the pro-apoptotic tumor suppressor p53. MDM2 inhibitors (MDM2i), which activate wild-type p53, and BET inhibitors (BETi), targeting the BET-family co-activator BRD4, both show encouraging pre-clinical activity, but limited clinical activity as single agents.

Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia.

There is a desperate need for new and effective therapeutic approaches to acute myeloid leukemia (AML) in both children and adults. Epigenetic aberrations are common in adult AML, and many novel epigenetic compounds that may improve patient outcomes are in clinical development. Mutations in epigenetic regulators occur less frequently in AML in children than in adults.

The Evolution of quality by design (QbD) for biologics.

In recent years, regulators have recognized the need for more controls in drug manufacturing processes. Quality by design is a science- and risk-based approach to drug product development and several pilot programs are ongoing to evaluate enhanced drug development strategies. This article provides a commentary on a recent regulatory publication on the subject of design space verification.

Purification of tubulin from the fission yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe is an attractive source of tubulin for biochemical experiments as it contains few tubulin isoforms and is amenable to genetic manipulation. We describe the preparation of milligram quantities of highly purified native tubulin from S. pombe suitable for use in microtubule dynamics assays as well as structural and other biochemical studies.