Quantitative Bioactivity Signatures of Dietary Supplements and Natural Products.

Dietary supplements and natural products are often marketed as safe and effective alternatives to conventional drugs, but their safety and efficacy are not well regulated. To address the lack of scientific data in these areas, we assembled a collection of Dietary Supplements and Natural Products (DSNP), as well as Traditional Chinese Medicinal (TCM) plant extracts. These collections were then profiled in a series of in vitro high-throughput screening assays, including a liver cytochrome p450 enzyme panel, CAR/PXR signaling pathways, and P-glycoprotein (P-gp) transporter assay activities. This pipeline facilitated the interrogation of natural product-drug interaction (NaPDI) through prominent metabolizing pathways. In addition, we compared the activity profiles of the DSNP/TCM substances with those of an approved drug collection (the NCATS Pharmaceutical Collection or NPC). Many of the approved drugs have well-annotated mechanisms of action (MOAs), while the MOAs for most of the DSNP and TCM samples remain unknown. Based on the premise that compounds with similar activity profiles tend to share similar targets or MOA, we clustered the library activity profiles to identify overlap with the NPC to predict the MOAs of the DSNP/TCM substances. Our results suggest that many of these substances may have significant bioactivity and potential toxicity, and they provide a starting point for further research on their clinical relevance.

Real-Time Scene Monitoring for Deaf-Blind People.

It is estimated that at least 15 million people worldwide live with severe deaf-blindness, with many more experiencing varying degrees of deaf-blindness. The existing options of assistance are mostly limited to walking canes, guide dogs and human care. We propose a wearable device which harnesses a multi-antenna mmWave radar transceiver and a haptic feedback array for real time detection of a person moving within a scene. We present our findings from a series of workshops with participants classed with multi-sensory impairments (MSI), to demonstrate the relative success of this approach and its potential for integration into existing assistance for the MSI of the future.

Global Substance Registration System: consistent scientific descriptions for substances related to health.

The US Food and Drug Administration (FDA) and the National Center for Advancing Translational Sciences (NCATS) have collaborated to publish rigorous scientific descriptions of substances relevant to regulated products. The FDA has adopted the global ISO 11238 data standard for the identification of substances in medicinal products and has populated a database to organize the agency's regulatory submissions and marketed products data. NCATS has worked with FDA to develop the Global Substance Registration System (GSRS) and produce a non-proprietary version of the database for public benefit. In 2019, more than half of all new drugs in clinical development were proteins, nucleic acid therapeutics, polymer products, structurally diverse natural products or cellular therapies. While multiple databases of small molecule chemical structures are available, this resource is unique in its application of regulatory standards for the identification of medicinal substances and its robust support for other substances in addition to small molecules. This public, manually curated dataset provides unique ingredient identifiers (UNIIs) and detailed descriptions for over 100 000 substances that are particularly relevant to medicine and translational research. The dataset can be accessed and queried at https://gsrs.ncats.nih.gov/app/substances.

New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection.

Complete automation of the macromolecular crystallography experiment has been achieved at SSRL through the combination of robust mechanized experimental hardware and a flexible control system with an intuitive user interface. These highly reliable systems have enabled crystallography experiments to be carried out from the researchers' home institutions and other remote locations while retaining complete control over even the most challenging systems. A breakthrough component of the system, the Stanford Auto-Mounter (SAM), has enabled the efficient mounting of cryocooled samples without human intervention. Taking advantage of this automation, researchers have successfully screened more than 200 000 samples to select the crystals with the best diffraction quality for data collection as well as to determine optimal crystallization and cryocooling conditions. These systems, which have been deployed on all SSRL macromolecular crystallography beamlines and several beamlines worldwide, are used by more than 80 research groups in remote locations, establishing a new paradigm for macromolecular crystallography experimentation.