Synergies Between Quantum Mechanics and Machine Learning in Reaction Prediction.

Machine learning (ML) and quantum mechanical (QM) methods can be used in two-way synergy to build chemical reaction expert systems. The proposed ML approach identifies electron sources and sinks among reactants and then ranks all source-sink pairs. This addresses a bottleneck of QM calculations by providing a prioritized list of mechanistic reaction steps.

Accurate and efficient target prediction using a potency-sensitive influence-relevance voter.

Background: A number of algorithms have been proposed to predict the biological targets of diverse molecules. Some are structure-based, but the most common are ligand-based and use chemical fingerprints and the notion of chemical similarity. These methods tend to be computationally faster than others, making them particularly attractive tools as the amount of available data grows.

Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry.

Squalene is a major component of skin and plant surface lipids and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized.

ReactionMap: an efficient atom-mapping algorithm for chemical reactions.

Large databases of chemical reactions provide new data-mining opportunities and challenges. Key challenges result from the imperfect quality of the data and the fact that many of these reactions are not properly balanced or atom-mapped. Here, we describe ReactionMap, an efficient atom-mapping algorithm.

HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.

Background: The purpose of this study was to identify mechanisms of innate resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib resistance.

Methods: Erlotinib sensitivity was determined by methyl thiazolyl-tetrazolium (MTT) assays.

COBRA: a computational brewing application for predicting the molecular composition of organic aerosols.

Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene.

Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model.

Background: We investigated the effects of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR), alone and in combination with paclitaxel in an orthotopic mouse model of human head and neck squamous cell carcinoma (HNSCC).

Methods: The in vitro effects of vandetanib (ZACTIMA) were assessed in 2 HNSCC cell lines on cell growth, apoptosis, receptor and downstream signaling molecule expression, and phosphorylation levels. We assessed in vivo effects of vandetanib and/or paclitaxel by measuring tumor cell apoptosis, endothelial cell apoptosis, microvessel density, tumor size, and animal survival.

The tyrosine kinase inhibitor, AZD2171, inhibits vascular endothelial growth factor receptor signaling and growth of anaplastic thyroid cancer in an orthotopic nude mouse model.

Purpose: Anaplastic thyroid cancer (ATC) is a locally aggressive type of thyroid tumor with high rate of distant metastases. With conventional treatment, the median survival ranges from 4 to 12 months; therefore, new treatment options are needed. AZD2171 is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptors (VEGFR) VEGFR-1, VEGFR-2, and VEGFR-3.

A semi-automatic method for peak and valley detection in free-breathing respiratory waveforms.

The existing commercial software often inadequately determines respiratory peaks for patients in respiration correlated computed tomography. A semi-automatic method was developed for peak and valley detection in free-breathing respiratory waveforms. First the waveform is separated into breath cycles by identifying intercepts of a moving average curve with the inspiration and expiration branches of the waveform.

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung.

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung.

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung.

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung.