Several Decades Of Investigation Research Articles

MRNA Vaccines and Therapeutics: Current Science and Implications for Future Development

The recent success of messenger RNA (mRNA) vaccines against SARS-CoV-2 has highlighted the value of mRNA technology to combat infectious diseases. Several decades of investigation on mRNA-based approaches hold promise for further application of mRNA in developing vaccines and therapeutics. The core components of mRNA-based vaccines are one or more mRNA sequences, which are synthesized by in vitro transcription and surrounded by a vehicle designed to stably deliver the mRNA across cell membranes. Currently, all approved SARS-CoV-2 mRNA vaccines use a lipid nanoparticle (LNP) as a delivery vehicle. Modifications in both the mRNA and LNP components can optimize mRNA stability, protein expression, and immunogenicity. The technology of mRNA-based vaccines enables a platform-based approach to development, as the same core components are used for each agent. This review discusses the key components of current mRNA-based vaccines and the advantages of the platform approach for vaccine development, mechanisms of mRNA vaccine-associated immune responses, and safety. Current challenges and future directions for mRNA technology are also described, including the expansion of the mRNA platform to develop novel therapeutics.

Chaperone function in antigen presentation by MHC class I molecules-tapasin in the PLC and TAPBPR beyond.

Peptide loading of MHC-I molecules plays a critical role in the T cell response to infections and tumors as well as to interactions with inhibitory receptors on natural killer (NK) cells. To facilitate and optimize peptide acquisition, vertebrates have evolved specialized chaperones to stabilize MHC-I molecules during their biosynthesis and to catalyze peptide exchange favoring high affinity or optimal peptides to permit transport to the cell surface where stable peptide/MHC-I (pMHC-I) complexes are displayed and are available for interaction with T cell receptors and any of a host of inhibitory and activating receptors. Although components of the endoplasmic reticulum (ER) resident peptide loading complex (PLC) were identified some 30 years ago, the detailed biophysical parameters that govern peptide selection, binding, and surface display have recently been understood better with advances in structural methods including X-ray crystallography, cryogenic electron microscopy (cryo-EM), and computational modeling. These approaches have provided refined mechanistic illustration of the molecular events involved in the folding of the MHC-I heavy chain, its coordinate glycosylation, assembly with its light chain, β2-microglobulin (β2m), its association with the PLC, and its binding of peptides. Our current view of this important cellular process as it relates to antigen presentation to CD8+ T cells is based on many different approaches: biochemical, genetic, structural, computational, cell biological, and immunological. In this review, taking advantage of recent X-ray and cryo-EM structural evidence and molecular dynamics simulations, examined in the context of past experiments, we attempt a dispassionate evaluation of the details of peptide loading in the MHC-I pathway. By critical evaluation of several decades of investigation, we outline aspects of the peptide loading process that are well-understood and indicate those that demand further detailed investigation. Further studies should contribute not only to basic understanding, but also to applications for immunization and therapy of tumors and infections.

New insights into anhydrobiosis using cellular dielectrophoresis-based characterization.

Late embryogenesis abundant (LEA) proteins are found in desiccation-tolerant species from all domains of life. Despite several decades of investigation, the molecular mechanisms by which LEA proteins confer desiccation tolerance are still unclear. In this study, dielectrophoresis (DEP) was used to determine the electrical properties of Drosophila melanogaster (Kc167) cells ectopically expressing LEA proteins from the anhydrobiotic brine shrimp, Artemia franciscana. Dielectrophoresis-based characterization data demonstrate that the expression of two different LEA proteins, AfrLEA3m and AfrLEA6, increases cytoplasmic conductivity of Kc167 cells to a similar extent above control values. The impact on cytoplasmic conductivity was surprising, given that the concentration of cytoplasmic ions is much higher than the concentrations of ectopically expressed proteins. The DEP data also supported previously reported data suggesting that AfrLEA3m can interact directly with membranes during water stress. This hypothesis was strengthened using scanning electron microscopy, where cells expressing AfrLEA3m were found to retain more circular morphology during desiccation, while control cells exhibited a larger variety of shapes in the desiccated state. These data demonstrate that DEP can be a powerful tool to investigate the role of LEA proteins in desiccation tolerance and may allow to characterize protein-membrane interactions in vivo, when direct observations are challenging.

Changes in radiotherapy fractionation-breast cancer.

Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Four randomised trials testing fraction sizes in the range 2.7–3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.

Primary cilia as a novel horizon between neuron and environment.

The primary cilium, a hair-like sensory organelle found on most mammalian cells, has gained recent attention within the field of neuroscience. Although neural primary cilia have been known to play a role in embryonic central nervous system patterning, we are just beginning to appreciate their importance in the mature organism. After several decades of investigation and controversy, the neural primary cilium is emerging as an important regulator of neuroplasticity in the healthy adult central nervous system. Further, primary cilia have recently been implicated in disease states such as cancer and epilepsy. Intriguingly, while primary cilia are expressed throughout the central nervous system, their structure, receptors, and signaling pathways vary by anatomical region and neural cell type. These differences likely bear relevance to both their homeostatic and neuropathological functions, although much remains to be uncovered. In this review, we provide a brief historical overview of neural primary cilia and highlight several key advances in the field over the past few decades. We then set forth a proposed research agenda to fill in the gaps in our knowledge regarding how the primary cilium functions and malfunctions in nervous tissue, with the ultimate goal of targeting this sensory structure for neural repair following injury.

The Notion of Relevance in Information Science: Everybody knows what relevance is. But, what is it really?

Abstract Everybody knows what relevance is. It is a ya'know notion, concept, idea–no need to explain whatsoever. Searching for relevant information using information technology (IT) became a ubiquitous activity in contemporary information society. Relevant information means information that pertains to the matter or problem at hand—it is directly connected with effective communication. The purpose of this book is to trace the evolution and with it the history of thinking and research on relevance in information science and related fields from the human point of view. The objective is to synthesize what we have learned about relevance in several decades of investigation about the notion in information science. This book deals with how people deal with relevance—it does not cover how systems deal with relevance; it does not deal with algorithms. Spurred by advances in information retrieval (IR) and information systems of various kinds in handling of relevance, a number of basic questions are raised: But w...

Mergers and acquisitions: a review (part 2)

PurposeThis paper aims to review the relevant literature on mergers and acquisitions in an attempt to provide a comprehensive account of what we know about mergers and which parts of the puzzle are still incomplete.Design/methodology/approachThis literature review consists of three key sections. The first part of this paper summarises the literature on the cyclical nature of mergers referred to in the literature as merger waves. The second section reviews the causes and consequences of takeovers; it first reviews the causes, or drivers, of acquisitions, while focusing on the fact that acquisitions happen in waves and then reviews the consequences of takeovers, with a predominant focus on the impacts of mergers on the economic performance of acquirers. The third part of the review summarises the theories, as well as previous empirical studies, on determinants of announcement returns and post-acquisition performance of combined firms.FindingsMerger activity demonstrates a wavy pattern, i.e. mergers are clustered in industries through time. The causes suggested for this fluctuating pattern include industry- and economy-level shocks, mis-valuation and managerial herding. Market reaction to announcement of acquisitions is, on average, slightly negative for acquirer stocks and significantly positive for target stocks. The combined abnormal return is positive. These findings have been consistent over several decades of investigation. Prior research also identifies a number of factors that are related to performance of acquisitions. These factors are categorised and reviewed in five different groups: acquirer characteristics, target characteristics, bid characteristics, industry characteristics and macro-environment characteristics.Originality/valueThis review illustrates a number of issues. Prior research is heavily biased towards gains to acquirers and factors that affect these gains. It is also biased towards finding sources of value creation through mergers despite the fact that several theories suggest that mergers can be value-destroying. In fact, value destruction is often attributed to managers’ self-interest (agency problem) and mistakes (hubris). However, the mechanisms through which mergers destroy value are rarely addressed. Aside from that, the possibility of simultaneous creation and destruction of value in acquisitions is not often considered. Finally, after several decades of investigation, a key question is not completely answered yet: “What are the sources of value in mergers and acquisitions?”

Mergers and acquisitions: a review. Part 1

Purpose– This paper aims to review the relevant literature on mergers and acquisitions in an attempt to provide a comprehensive account of what we know about mergers and which parts of the puzzle are still incomplete.Design/methodology/approach– This literature review consists of three key sections. The first part of this paper summarises the literature on the cyclical nature of mergers referred to in the literature as merger waves. The second section reviews the causes and consequences of takeovers; it first reviews the causes, or drivers, of acquisitions, while focusing on the fact that acquisitions happen in waves and then reviews the consequences of takeovers, with a predominant focus on the impacts of mergers on the economic performance of acquirers. The third part of the review summarises the theories as well as previous empirical studies on determinants of announcement returns and post-acquisition performance of combined firms.Findings– Merger activity demonstrates a wavy pattern, i.e. mergers are clustered in industries through time. The causes suggested for this fluctuating pattern include industry and economy-level shocks, mis-valuation and managerial herding. Market reaction to announcement of acquisitions is, on average, slightly negative for acquirer stocks and significantly positive for target stocks. The combined abnormal return is positive. These findings have been consistent over several decades of investigation. The prior research also identifies a number of factors that are related to performance of acquisitions. These factors are categorised and reviewed in five different groups: acquirer characteristics, target characteristics, bid characteristics, industry characteristics and macro-environment characteristics.Originality/value– This review illustrates a number of issues. Prior research is heavily biased towards gains to acquirers and factors that affect these gains. It is also biased towards finding sources of value creation through mergers, despite the fact that several theories suggest that mergers can be value-destroying. In fact, value destruction is often attributed to managers’ self-interest (agency problem) and mistakes (hubris). However, the mechanisms through which mergers destroy value are rarely addressed. Aside from that, the possibility of simultaneous creation and destruction of value in acquisitions is not often considered. Finally, after several decades of investigation, a key question is not completely answered yet: “What are the sources of value in mergers and acquisitions?”

Abstract 164: A Field Synopsis of Gender Effects in Clinical Prediction Models for Cardiovascular Disease

Introduction: Gender differences in incidence, prognosis and treatment response have been observed across the spectrum of cardiovascular diseases (CVD). However, despite several decades of investigation, consistent findings regarding the magnitude and directionality of gender differences in CVD are elusive. We therefore conducted the first field synopsis of the role of gender on CVD conditions using a registry of clinical prediction models (CPMs). Methods: The Tufts PACE Center (CPM) Registry is based on a systematic review of cardiovascular CPMs published in English-language articles from 1/1990-5/2012. All included CPMs permit calculation of outcome probabilities from information provided in an equation, point score or nomogram. For the 15 most common unique index condition-outcome pair models, we calculated the proportion of models that included coefficients for the effect of gender on CVD incidence or prognosis, or presented gender-stratified models. The sample size, age distribution and proportion of females in the model development cohorts were summarized. Results: Out of 579 CPMs with CVD as either an index condition or outcome, 169 (29%) contained a coefficient for gender and 33 (6%) presented gender-stratified models. Gender was more frequently included as a covariate or stratification variable in models predicting incident CVD versus prognosis for patients with known CVD. Gender was included in 60/74 (81%) models predicting morbidity and/or mortality among a population sample, yet in only 9/53 (17%) of models predicting morbidity and/or mortality among patients with stroke, and 9/53 (17%) of models predicting mortality among patients with congestive heart failure. Gender was more likely to be included in CPMs developed from cohorts with larger sample sizes (150/299 cohorts with n≥2000 versus 54/277 cohorts with n<2000, p<0.001). For each 10% increase in the proportion of women in the model development cohort, there was a 22% increased odds of including gender in the CPM (OR = 1.22, 95% CI 1.08-1.39, p=0.002). Conclusions: Gender is an important prognostic factor in CVD, but is only included in about one third of published CPMs. Gender is much more frequently included as a predictor of incident CVD among the disease-free than of prognosis in those with established CVD.

Separation of transport lifetimes inSrTiO3-based two-dimensional electron liquids

Deviations from Landau Fermi liquid behavior are ubiquitous features of the normal state of unconventional superconductors. Despite several decades of investigation, the underlying mechanisms of these properties are still not completely understood. In this work, we show that two-dimensional electron liquids at SrTiO3/RTiO3 (R = Gd or Sm) interfaces reveal strikingly similar physics. Analysis of Hall and resistivity data show a clear separation of transport and Hall scattering rates, also known as "two-lifetime" behavior. This framework gives a remarkably simple and general description of the temperature dependence of the Hall coefficient. Distinct transport lifetimes accurately describe the transport phenomena irrespective of the nature of incipient magnetic ordering, the degree of disorder, confinement, or the emergence of non-Fermi liquid behavior. The Hall scattering rate diverges at a critical quantum well thickness, coinciding with a quantum phase transition. Collectively, these results introduce new constraints on the existing microscopic theories of lifetime separation and point to the need for unified understanding.

The 5-lipoxygenase pathway: oxidative and inflammatory contributions to the Alzheimer's disease phenotype.

Alzheimer’s disease (AD) is the most common, and, arguably, one of the most-well studied, neurodegenerative conditions. Several decades of investigation have revealed that amyloid-β and tau proteins are critical pathological players in this condition. Genetic analyses have revealed specific mutations in the cellular machinery that produces amyloid-β, but these mutations are found in only a small fraction of patients with the early-onset variant of AD. In addition to development of amyloid-β and tau pathology, oxidative damage and inflammation are consistently found in the brains of these patients. The 5-lipoxygenase protein enzyme (5LO) and its downstream leukotriene metabolites have long been known to be important modulators of oxidation and inflammation in other disease states. Recent in vivo evidence using murine knock-out models has implicated the 5LO pathway, which also requires the 5LO activating protein (FLAP), in the molecular pathology of AD, including the metabolism of amyloid-β and tau. In this manuscript, we will provide an overview of 5LO and FLAP, discussing their involvement in biochemical pathways relevant to AD pathogenesis. We will also discuss how the 5LO pathway contributes to the molecular and behavioral insults seen in AD and provide an assessment of how targeting these proteins could lead to therapeutics relevant not only for AD, but also other related neurodegenerative conditions.

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical–chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the low-osmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the iso-osmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.

Evidence that αC Region Is Origin of Low Modulus, High Extensibility, and Strain Stiffening in Fibrin Fibers

Fibrin fibers form the structural scaffold of blood clots and perform the mechanical task of stemming blood flow. Several decades of investigation of fibrin fiber networks using macroscopic techniques have revealed remarkable mechanical properties. More recently, the microscopic origins of fibrin's mechanics have been probed through direct measurements on single fibrin fibers and individual fibrinogen molecules. Using a nanomanipulation system, we investigated the mechanical properties of individual fibrin fibers. The fibers were stretched with the atomic force microscope, and stress-versus-strain data was collected for fibers formed with and without ligation by the activated transglutaminase factor XIII (FXIIIa). We observed that ligation with FXIIIa nearly doubled the stiffness of the fibers. The stress-versus-strain behavior indicates that fibrin fibers exhibit properties similar to other elastomeric biopolymers. We propose a mechanical model that fits our observed force extension data, is consistent with the results of the ligation data, and suggests that the large observed extensibility in fibrin fibers is mediated by the natively unfolded regions of the molecule. Although some models attribute fibrin's force-versus-extension behavior to unfolding of structured regions within the monomer, our analysis argues that these models are inconsistent with the measured extensibility and elastic modulus.

Ecological modeling of Yamal tundra ecosystems: Traditional nature use as a factor of instability

This paper represents the results of a comprehen� sive study on the consistent patterns of the functioning (dynamics) of the shrub and northern tundra ecosys� tems of the Yamal Peninsula that have been subjected to longterm anthropogenic impact connected with the traditional reindeer breeding and are now sub� jected to some new influences connected with the development of the oil and gas industry. The study is based on the integration of data accumulated during several decades of investigation of Yamal ecosystems in which we have participated. The main approach to solving this task was the use of system analysis, which implies the development of modeling (computer) models describing interactions between the key components of the northern and shrub tundra ecosystems of the Yamal Peninsula and verification and analysis of these models. Shwartz (1) considered that such a model can be developed only on the basis of actual data on the structure and dynam� ics of basic components ("blocks"), composing the "core" of tundra biocenoses and including plants, small mammals, reindeer (mainly domestic), preda� tory mammals (mainly Arctic foxes), and birds of pray. The abovementioned components are functionally related with one another; as a rule, these relations are complex (nonlinear), which complicates the predic� tion of the ecosystem dynamics (2). Tundra ecosys� tems of the Yamal Peninsula are considered to be a constellation of two overlapping subsystems, natural (biogeocenosis) and anthropogenic (anthropogeo� cenosis), which surrounds humans and "works" for them (3). A simplified diagram of such a system is shown in Fig. 1. In this paper, we describe only the results of our analysis of the influence of deer breeding (the main type of the traditional nature use in terrestrial Yamal ecosystems) on the vegetation; we did not take into account hunting, because it is less important for both economics of the aboriginal population and vegetation

Ice-age endurance: DNA evidence of a white spruce refugium in Alaska

Paleorecords offer key information for evaluating model simulations of species migration in response to forecast climatic change. However, their utility can be greatly compromised by the existence of glacial refugia that are undetectable in fossil records (cryptic refugia). Despite several decades of investigation, it remains controversial whether Beringia, the largely unglaciated area extending from northeastern Siberia to the Yukon Territory, harbored small populations of certain boreal tree species during the last glaciation. Here, we present genetic evidence for the existence of a glacial refuge in Alaska that helps to resolve this long-standing controversy. We sequenced chloroplast DNA (cpDNA) of white spruce (Picea glauca), a dominant boreal tree species, in 24 forest stands across northwestern North America. The majority of cpDNA haplotypes are unique, and haplotype diversity is relatively high in Alaska, arguing against the possibility that this species migrated into the region from areas south of the Laurentide Ice Sheet after the end of the last glaciation. Thus, white spruce apparently survived long glacial episodes under climatic extremes in a heterogeneous landscape matrix. These results suggest that estimated rates of tree migration from fossil records may be too high and that the ability of trees to track anthropogenic warming may be more limited than previously thought.

Chavicol formation in sweet basil (Ocimum basilicum): cleavage of an esterified C9 hydroxyl group with NAD(P)H-dependent reduction

Propenyl- and allyl-phenols, such as methylchavicol, p-anol and eugenol, have gained importance as flavoring agents and also as putative precursors in the biosynthesis of 9,9'-deoxygenated lignans, many of which have potential medicinal applications. In spite of several decades of investigation, however, the complete biosynthetic pathway to a propenyl/allylphenol had not yet been reported. We have subjected a Thai basil variety accumulating relatively large amounts of the simplest volatile allylphenol, methylchavicol, to in vivo administration of radiolabeled precursors and assays of protein preparations in vitro. Through these experiments, the biosynthesis of chavicol was shown to occur via the phenylpropanoid pathway to p-coumaryl alcohol. Various possibilities leading to deoxygenation of the latter were examined, including reduction of the side-chain double bond to form p-dihydrocoumaryl alcohol, followed by dehydration to afford chavicol, as well as formation of p-methoxycinnamyl alcohol, with further side-chain modification to afford methylchavicol. A third possibility studied was activation of the side-chain alcohol of p-coumaryl alcohol, e.g.via esterification, to form a more facile leaving group via reductive elimination. The latter was shown to be the case using p-coumaryl esters as potential substrates for a NAD(P)H-dependent reductase to afford chavicol, which is then O-methylated to afford methylchavicol.

Why Web GIS May Not Be Enough: A Case Study with the Virtual Research Vessel

During several decades of investigation, the East Pacific Rise seafloor-spreading center at 9°-10°N has been explored by marine geologists, geophysicists, chemists, and biologists, and has emerged as one of the best studied sections of the global midocean ridge. It is an example of a region for which there is now a great wealth of observational data, results, and data-driven theoretical studies. However, these have yet to be fully utilized, either by research scientists or educators. While the situation is improving, a large amount of data, results, and related theoretical models still exist either in an inert, noninteractive form (e.g., journal publications) or as unlinked and currently incompatible computer data or algorithms. Presented here is the prototype of a computational environment and toolset, called the Virtual Research Vessel, to improve the situation by providing marine scientists and educators with simultaneous access to data, maps, and numerical models. While infrastructure is desired and needed for ready access to data and the resulting maps via web GIS in order to link disparate data sets (data to data), it is argued that data must also be linked to models for better exploration of new relations between observables, refinement of numerical simulations, and the quantitative evaluation of scientific hypotheses. For widespread data access, web GIS is therefore only a preliminary step rather than a final solution, and the ongoing implementation of the Virtual Research Vessel (scheduled for final completion in 2004-2005) is a case study for the midocean ridge community to test the effectiveness of moving beyond the data-to-data mode towards data-to-models and data-to-interpretation.

DNA Target Motifs of Somatic Mutagenesis in Antibody Genes

During humoral immunity to T-cell-dependent antigens, responding B lymphocytes selectively mutate their antibody variable region genes at a high rate. This, together with the process of clonal selection, ultimately enhances the affinity and specificity of the antibody molecule and memory B cells that express it as a receptor. Despite several decades of investigation, the mutation mechanism has remained unresolved, largely due to the convoluted nature of experimental systems used to approach it. Somatic mutations preferentially occur within specific oligonudeotide motifs, and this targeting is consistent in all immunoglobulin genes of humans and mice that we have examined, suggesting that a conserved mechanism operates in both species. Our mutation targeting analyses implicate evolution of germline variable gene sequences to direct somatic mutations to specific codon positions in a manner that regulates the frequency of amino acid replacements to the benefit of the antibody product. Finally, our recent strand bias analyses support the idea that somatic mutation occurs preferentially, perhaps exclusively, at two bases on both strands of DNA. These and related observations from other laboratories support a mutation model that invokes at least two error-prone polymerases that have distinct template biases and requirements for elements of postreplicative mismatch repair.

The structure and evolution of angiosperm nuclear genomes

Despite several decades of investigation, the organization of angiosperm genomes remained largely unknown until very recently. Data describing the sequence composition of large segments of genomes, covering hundreds of kilobases of contiguous sequence, have only become available in the past two years. Recent results indicate commonalities in the characteristics of many plant genomes, including in the structure of chromosomal components like telomeres and centromeres, and in the order and content of genes. Major differences between angiosperms have been associated mainly with repetitive DNAs, both gene families and mobile elements. Intriguing new studies have begun to characterize the dynamic three-dimensional structures of chromosomes and chromatin, and the relationship between genome structure and co-ordinated gene function.

The sodium lauryl sulfate model: an overview.

Irritant contact dermatitis is a complex entity with several clinical forms (acute, cumulative, etc.) and multiple mechanisms. Sodium lauryl sulfate (SLS), the most widely utilized model for studying acute and cumulative irritation, has proved highly practical and informative for such studies. This article summarizes several decades of investigation, and provides details of dosing, application method (closed versus open), and biologic endpoints (visual grading, transepidermal water loss) that may be utilized in future studies.