A filter approach for feature selection in classification: application to automatic atrial fibrillation detection in electrocardiogram recordings.

Background: In high-dimensional data analysis, the complexity of predictive models can be reduced by selecting the most relevant features, which is crucial to reduce data noise and increase model accuracy and interpretability. Thus, in the field of clinical decision making, only the most relevant features from a set of medical descriptors should be considered when determining whether a patient is healthy or not. This statistical approach known as feature selection can be performed through regression or classification, in a supervised or unsupervised manner.

ANFO vapour detection with conducting polymer percolation network sensors and GC/MS.

Ammonium nitrate mixed with fuel oil (ANFO) is commonly used in improvised explosive devices (IEDs). The development of ANFO vapour sensors that are small, inexpensive, and easy to use will enable widespread IED detection in the context of security and humanitarian demining. Because of concealment and the low vapour pressures of most explosive materials, achieving sufficiently high sensitivity and low limits of detection are some of the main challenges of explosives vapour detection.

Heart rhythm characterization through induced physiological variables.

Atrial fibrillation remains a major cause of morbi-mortality, making mass screening desirable and leading industry to actively develop devices devoted to automatic AF detection. Because there is a tendency toward mobile devices, there is a need for an accurate, rapid method for studying short inter-beat interval time series for real-time automatic medical monitoring. We report a new methodology to efficiently select highly discriminative variables between physiological states, here a normal sinus rhythm or atrial fibrillation.

Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors.

Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF- and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70kDa dextran or albumin. A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo. In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model.

Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents.

The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents.

Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds.

V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin-4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor.

Synthesis and anti-HCV activity of 3',4'-oxetane nucleosides.

Hepatitis C virus afflicts approximately 180 million people worldwide and currently there are no direct acting antiviral agents available to treat this disease. Our first generation nucleoside HCV inhibitor, RG7128 has already established proof-of-concept in the clinic and is currently in phase IIb clinical trials. As part of our continuing efforts to discover novel anti-HCV agents, 3',4'-oxetane cytidine and adenosine nucleosides were prepared as inhibitors of HCV RNA replication.

Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1.

High-throughput screening against the human sirtuin SIRT1 led to the discovery of a series of indoles as potent inhibitors that are selective for SIRT1 over other deacetylases and NAD-processing enzymes. The most potent compounds described herein inhibit SIRT1 with IC50 values of 60-100 nM, representing a 500-fold improvement over previously reported SIRT inhibitors. Preparation of enantiomerically pure indole derivatives allowed for their characterization in vitro and in vivo.