Glossary

21st century toxicology
Long-range strategic planning to update and improve testing procedures for potential stressors. The report by the U.S. National Research Council (NRC) ¹ envisions a shift away from traditional toxicity testing and towards a focused effort to explore and understand the signaling pathways perturbed by biologically active substances or their metabolites, that have the potential to cause adverse health effects in humans.
¹Testing NRCCoT and Agents AoE. Toxicity testing in the 21st century: A vision and a strategy. National Academy Press, 2007.

3R4F
Standard reference cigarette, used throughout the tobacco industry and academic laboratories as a consistent and uniform test item for inhalation toxicology research. It has been in use since 2006.

BEL
The Biological Expression Language (BEL) is a language for representing scientific findings in the life sciences in a computable form. BEL is designed to represent scientific findings by capturing causal and correlative relationships in context, where context can include information about the biological and experimental system in which the relationships were observed, the supporting publications cited and the curation process used.

Biological impact factor (BIF)
A holistic score that describes the systems-wide effect of all the processes captured in the underlying network models and their associated Network Perturbation Amplitude (NPA) scores.

Bronchioalveolar lavage fluid (BALF)
Fluid collected from the lumen of the lung (bronchioles and alveolar space) by a washing procedure with saline. It contains “free lung cells” and inflammatory mediators

Carboxyhaemoglobin
A stable complex of carbon monoxide and haemoglobin that forms in red blood cells upon contact with carbon monoxide. Large quantities of carbon monoxide hinders the ability of haemoglobin to deliver oxygen to the body.

Chronic obstructive pulmonary disease (COPD)
Progressive disease that makes it hard to breathe due to obstruction of the airways and destruction of the lung alveolar structure.

Emphysema
Lung condition in which alveolar walls are disrupted and large airspaces are formed that lack the elasticity needed for breathing.

Eosinophil
A normal type of white blood cell that is involved in inflammation. Eosinophils are produced in the bone marrow and migrate to tissues throughout the body.

Garuda Gadgets
Garuda is an open, community-driven, common platform that provides a framework to connect, discover and navigate through different applications, databases and services in biology and medicine.
The driving force of the platform are the Gadgets. Any software, analytics tool or service which implements the Garuda Protocol either through the available API SDKs or its own implementation and is able to communicate with the core becomes a Garuda Gadget. The Dashboard is the personal interface for users to Garuda and gadgets, from their computers. It provides one-stop access to explore the different gadgets users have installed, check their functions and get new gadgets.

Gross pathology
Relatively large manifestations of disease (ie, visible to the naked eye) in organs, tissues, and body cavities.

Harmful and potentially harmful constituents (HPHCs)
The FDA has determined that the phrase “harmful and potentially harmful constituents” (HPHCs) includes any chemical or chemical compound in a tobacco product or in tobacco smoke that i) is or potentially is inhaled, ingested, or absorbed into the body; and ii) causes or has the potential to cause direct or indirect harm to users or non-users of tobacco products.

Histomorphometry
Quantitative measure of histological changes.

Histopathology
Microscopic examination of tissue in order to study structural changes, including those associated with manifestations of disease.

Inflammation
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It involves immune cells, blood vessels, and molecular mediators to eliminate the cause of injury.

Isobaric-tag based quantification (iTRAQ)
An untargeted proteome quantification method, where each analyzed peptide sample is reacted with a different tag. During the pooled (multiplexed) analysis of up to 10 samples, these tags are released in the mass spectrometer for each peptide, and their intensities used for relative quantification.

Limit of quantification (LOQ)
The limit of quantification (LOQ) describes the smallest concentration of an analyte that can be reliably measured by an analytical procedure.

Lipidomics
Study of cellular lipids in biological systems leveraging Mass Spectrometry technologies. The Lipidome refers to the complete lipid profile within a cell.

Lymphocyte
Form of small white blood cell that is involved in inflammation and found especially in the lymphatic system.

Macrophage
A large white blood cell that mediates inflammation. Macrophages ingest foreign particles and infectious microorganisms and occur principally in connective tissue and the bloodstream.

Microarray
A technique used for analyzing the transcriptome which relies on the hybridization of a DNA sequence. Recognised as the gold standard for microarrays, the Affymetrix GeneChip system which monitors gene expression for thousands of transcripts (47,000 transcripts for a human chip) in a controlled process which offers high data reliability. The system also allows the inclusion of multiple probes to interrogate the same target sequence, providing statistical rigor for data interpretation.

Modified risk tobacco product (MRTP)
Term formally used by the US Food and Drug Administration to describe an alternative to cigarettes that is associated with less risk of disease.

Network perturbation amplitude (NPA)
A quantitative measure of the perturbation of biological networks scored with transcriptomic data. The NPA scoring method leverages high-throughput measurements and a priori literature-derived knowledge in the form of network models to characterize the activity change for a broad collection of biological processes at high-resolution. Applications of this framework include comparative assessment of the biological impact caused by environmental factors, toxic substances, or drug treatments.

Neutrophil
The primary type of white blood cell involved in inflammation.

Proteomics
The systematic approach to characterize all proteins in a given cell population. Mass Spectrometry (MS) is widely considered to be the central technology platform for toxicoproteomics. MS has brought many advantages to the advancement of toxicoproteomics including unsurpassed sensitivity and improved speed and the ability to produce High Throughput datasets. Due to the high accuracy of MS, peptides in the femtomolar to attomolar range can be detected in tissues and biological matrices with an accuracy level of less than 10 parts per million (ppm). This is greatly beneficial in comparative analysis where simultaneous comparisons between control and treated samples are key to increase our understanding of how stimuli affect the proteome.

Prototypic modified risk tobacco product (pMRTP)
See MRTP definition.

Reduced risk product (RRP)
Reduced-Risk Products (“RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continued smoking. We have a range of RRPs in various stages of development, scientific assessment and commercialization. Because our RRPs do not burn tobacco, they produce far lower quantities of harmful and potentially harmful compounds than found in cigarette smoke.

Reverse phase protein assay (RPA)
An antibody-based platform, in which protein lysates are spotted on a glass slide and incubated with a primary antibody followed by a secondary antibody that has a fluorescent tag. The interactions are detected using fluorescence reader.

SciPi
A SciPi is a specialized survey for scientists to weigh in with their opinion on important topics. Learn More at https://www.scipinion.com/.

Sham
Indicates that a test system has been exposed to fresh air instead of cigarette smoke, the data from which is used as a negative control.

Systems toxicology
Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization.

Tobacco Heating System (THS)
THS electrically heats tobacco without combustion to generate an aerosol that mainly contains water, glycerin, nicotine, and tobacco flavors. The electronically controlled heating technology is designed to avoid tobacco combustion, and in turn, reduce the formation of harmful and potentially harmful constituents (HPHCs).

Total particulate matter (TPM)
Total particulate matter is a specific term for the particle fraction trapped from an aerosol, especially from cigarette smoke. Cigarette smoke TPM contains most of the nicotine from a cigarette.

Transcriptomics
Also known as gene expression profiling, transcriptomics is used to study changes in gene expression taking into account the entire transcriptome, i.e., all RNAs in a cell population. Frequent methodologies utilize Gene-Chip and RNA-seq technologies.