Incommensurate Antiferromagnetic Order in Weakly Frustrated Two-Dimensional van der Waals Insulator CrPSe3.

Although magnetic order is suppressed by a strong frustration, it appears in complex forms such as a cycloid or spin density wave in weakly frustrated systems. Herein, we report a weakly magnetically frustrated two-dimensional (2D) van der Waals material CrPSe3. Polycrystalline CrPSe3 was synthesized at an optimized temperature of 700 °C to avoid the formation of any secondary phases (e.g., Cr2Se3). The antiferromagnetic transition appeared at TN ≈ 127 K with a large Curie-Weiss temperature θCW ≈ -301 K via magnetic susceptibility measurements, indicating weak frustration in CrPSe3 with a frustration factor of f (|θCW|/TN) ≈ 2.4. Evidently, the formation of a long-range incommensurate antiferromagnetic order was revealed by neutron diffraction measurements at low temperatures (below 120 K). The monoclinic crystal structure of the C2/m symmetry is preserved over the studied temperature range down to 20 K, as confirmed by Raman spectroscopy measurements. Our findings on the incommensurate antiferromagnetic order in 2D magnetic materials, not previously observed in the MPX3 family, are expected to enrich the physics of magnetism at the 2D limit, thereby opening opportunities for their practical applications in spintronics and quantum devices.

Automatic detection of multilayer hexagonal boron nitride in optical images using deep learning-based computer vision.

Computer vision algorithms can quickly analyze numerous images and identify useful information with high accuracy. Recently, computer vision has been used to identify 2D materials in microscope images. 2D materials have important fundamental properties allowing for their use in many potential applications, including many in quantum information science and engineering. One such material is hexagonal boron nitride (hBN), an isomorph of graphene with a very indistinguishable layered structure. In order to use these materials for research and product development, the most effective method is mechanical exfoliation where single-layer 2D crystallites must be prepared through an exfoliation procedure and then identified using reflected light optical microscopy. Performing these searches manually is a time-consuming and tedious task. Deploying deep learning-based computer vision algorithms for 2D material search can automate the flake detection task with minimal need for human intervention. In this work, we have implemented a new deep learning pipeline to classify crystallites of hBN based on coarse thickness classifications in reflected-light optical micrographs. We have used DetectoRS as the object detector and trained it on 177 images containing hexagonal boron nitride (hBN) flakes of varying thickness. The trained model achieved a high detection accuracy for the rare category of thin flakes ([Formula: see text] atomic layers thick). Further analysis shows that our proposed pipeline could be generalized to various microscope settings and is robust against changes in color or substrate background.

Nanoscale Raman Characterization of a 2D Semiconductor Lateral Heterostructure Interface.

The nature of the interface in lateral heterostructures of 2D monolayer semiconductors including its composition, size, and heterogeneity critically impacts the functionalities it engenders on the 2D system for next-generation optoelectronics. Here, we use tip-enhanced Raman scattering (TERS) to characterize the interface in a single-layer MoS2/WS2 lateral heterostructure with a spatial resolution of 50 nm. Resonant and nonresonant TERS spectroscopies reveal that the interface is alloyed with a size that varies over an order of magnitude─from 50 to 600 nm─within a single crystallite. Nanoscale imaging of the continuous interfacial evolution of the resonant and nonresonant Raman spectra enables the deconvolution of defect activation, resonant enhancement, and material composition for several vibrational modes in single-layer MoS2, MoxW1-xS2, and WS2. The results demonstrate the capabilities of nanoscale TERS spectroscopy to elucidate macroscopic structure-property relationships in 2D materials and to characterize lateral interfaces of 2D systems on length scales that are imperative for devices.

Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish Embryos.

BACKGROUND: Humans and environmental organisms are constantly exposed to complex mixtures of chemicals. Extending our knowledge about the combined effects of chemicals is thus essential for assessing the potential consequences of these exposures. In this context, comprehensive molecular readouts as retrieved by omics techniques are advancing our understanding of the diversity of effects upon chemical exposure. This is especially true for effects induced by chemical concentrations that do not instantaneously lead to mortality, as is commonly the case for environmental exposures. However, omics profiles induced by chemical exposures have rarely been systematically considered in mixture contexts. OBJECTIVES: In this study, we aimed to investigate the predictability of chemical mixture effects on the whole-transcriptome scale. METHODS: We predicted and measured the toxicogenomic effects of a synthetic mixture on zebrafish embryos. The mixture contained the compounds diuron, diclofenac, and naproxen. To predict concentration- and time-resolved whole-transcriptome responses to the mixture exposure, we adopted the mixture concept of concentration addition. Predictions were based on the transcriptome profiles obtained for the individual mixture components in a previous study. Finally, concentration- and time-resolved mixture exposures and subsequent toxicogenomic measurements were performed and the results were compared with the predictions. RESULTS: This comparison of the predictions with the observations showed that the concept of concentration addition provided reasonable estimates for the effects induced by the mixture exposure on the whole transcriptome. Although nonadditive effects were observed only occasionally, combined, that is, multicomponent-driven, effects were found for mixture components with anticipated similar, as well as dissimilar, modes of action. DISCUSSION: Overall, this study demonstrates that using a concentration- and time-resolved approach, the occurrence and size of combined effects of chemicals may be predicted at the whole-transcriptome scale. This allows improving effect assessment of mixture exposures on the molecular scale that might not only be of relevance in terms of risk assessment but also for pharmacological applications. https://doi.org/10.1289/EHP7773.

Genetic analysis of sow longevity and sow lifetime reproductive traits using censored data.

Sow longevity is a key component for efficient and profitable pig farming; however, approximately 50% of sows are removed annually from a breeding herd. There is no consensus in the scientific literature regarding a definition for sow longevity; however, it has been suggested that it can be measured using several methods such as stayability and economic indicators such as lifetime piglets produced. Sow longevity can be improved by genetic selection; however, it is rarely included in genetic evaluations. One reason is elongated time intervals required to collect complete lifetime data. The effect of genetic parameter estimation software in handling incomplete data (censoring) and possible early indicator traits were evaluated analysing a 30% censored data set (12 725 pedigreed Landrace × Large White sows that included approximately 30% censored data) with DMU6, THRGIBBS1F90 and GIBBS2CEN. Heritability estimates were low for all the traits evaluated. The results show that the binary stayability traits benefited from being analysed with a threshold model compared to analysing with a linear model. Sires were ranked very similarly regardless if the program handled censoring when all available data were included. Accumulated born alive and stayability were good indicators for lifetime born alive traits. Number of piglets born alive within each parity could be used as an early indicator trait for sow longevity.

Estimation of U.S. Yorkshire breed composition using genomic data.

The Yorkshire breed uses white coat color as a selection requirement to indicate breed purity. In this study, genomic information from chromosomal regions, as well as the whole genome, was applied to estimate breed composition of purebred Yorkshire animals. Genotypes for approximately 60,000 SNP from the Illumina PorcineSNP60 BeadChip (60K) were available for reference animals for which the genetic background was known, study animals that included Yorkshire sires (Tes_York, n = 889), and known crossbred animals that had Yorkshire heritage (Tes_U, n = 12). Haplotypes of SNP flanking the KIT (Dominant white locus) and MC1R (Melanocortin receptor 1) genes were developed for reference animals for the Duroc, Hampshire, Landrace, Yorkshire, and Pietrain breeds. For the KIT region, haplotypes observed in Yorkshire reference animals were also found in 84 and 7% of the haplotypes in Landrace and Pietrain reference animals, respectively. They were not found in Duroc or Hampshire reference animals. The sensitivity and specificity of haplotype analysis was 0.93 and 0.75, respectively. In addition, whole genome SNP information was used in regression analyses to further differentiate breed composition. Using 60K, 90% of regression coefficients for Yorkshire, indicating relative Yorkshire composition, ranged from 0.791 to 1.073 and 0.524 to 1.06 in Tes_York and Tes_U, respectively. Regression coefficients for 90% of Hampshire ranged from -0.029 to 0.052 and -0.005 to 0.379 in Tes_York and Tes_U, respectively. Animals in Tes_U were likely of Yorkshire and Hampshire breed origin. The sensitivity and specificity of regression analysis was 0.96 and 0.58, respectively. Combining haplotype and regression analyses, 810 Tes_York animals were accepted as purebred Yorkshire. Genomic information can be used as a tool to describe an animal's breed composition and reduce the need for progeny testing for white coat color verification.

Mayak worker dosimetry study: an overview.

The Mayak Production Association (MPA) was the first plutonium production plant in the former Soviet Union. Workers at the MPA were exposed to relatively large internal radiation intakes and external radiation exposures, particularly in the early years of plant operations. This paper describes the updated dosimetry database, "Doses-2005." Doses-2005 represents a significant improvement in the determination of absorbed organ dose from external radiation and plutonium intake for the original cohort of 18,831 Mayak workers. The methods of dose reconstruction of absorbed organ doses from external radiation uses: 1) archive records of measured dose and worker exposure history, 2) measured energy and directional response characteristics of historical Mayak film dosimeters, and 3) calculated dose conversion factors for Mayak Study-defined exposure scenarios using Monte Carlo techniques. The methods of dose reconstruction for plutonium intake uses two revised models developed from empirical data derived from bioassay and autopsy cases and/or updates from prevailing or emerging International Commission on Radiological Protection models. Other sources of potential significant exposure to workers such as medical diagnostic x-rays, ambient onsite external radiation, neutron radiation, intake of airborne effluent, and intake of nuclides other than plutonium were evaluated to determine their impact on the dose estimates.

Mayak film dosimeter response studies, part I: measurements.

The Mayak Worker Dosimetry study is a joint Russian/U.S. project to evaluate doses received by workers at the Mayak Production Association facilities from 1948-1972. A key investigation in this project is the characterization of responses of the three types of film dosimeters used to monitor workers during this time period. Experimental irradiations of the dosimeters were performed in the radiation calibration laboratories at the National Research Center for Environment and Health (GSF) in Munich, Germany. The irradiations used photon sources from x-ray beams with ten different energy distributions and with Co and Cs isotopic gamma sources. Irradiations were performed with the dosimeters on phantoms and free-in-air. The dosimeters and phantoms were also positioned at varying angles to the radiation beam. The result of the experiments was a thorough characterization of the dosimeter response as a function of photon energy and as a function of angle for energy and angular ranges that cover the conditions encountered in the Mayak workplaces. The characterization data were then available for use in developing correction factors, which could be applied to worker dosimeter readings to provide a more accurate assessment of worker dose and estimates of doses to organs.

Mayak film dosimeter response studies, part II: response models.

A study was performed of energy and angular responses of the film dosimeters that were used for worker monitoring at the Mayak Production Association (Mayak PA) in 1948-1992. The study used experimental data from tests with three types of individual film dosimeters, and the data were used to determine the dosimeters' energy and angular response characteristics in the range from 9 keV to Co energies, with the dosimeters exposed both free-in-air and on-phantom at horizontal and vertical rotation. Mathematical models of the dosimeters were developed to calculate the response characteristics of the dosimeters. The models of the film dosimeters were validated by comparing calculations to measurements. The models were then used as the basis for individual dose reconstruction in realistic photon spectra and worker exposure geometries at the Mayak PA workplaces. Reconstructed individual doses have been included in the Mayak worker database "Doses-2005" that is used for epidemiological studies of the Mayak workers' radiation exposures and subsequent health effects.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: study of errors in dosimetry.

To provide direct estimates of cancer risk after low-dose protracted exposure to ionizing radiation, a large-scale epidemiological study of nuclear industry workers was conducted in 15 countries. As part of this study, identification and quantification of errors in historical recorded doses was conducted based on a review of dosimetric practices and technologies in participating facilities. The main sources of errors on doses from "high-energy" photons (100-3000 keV) were identified as the response of dosimeters in workplace exposure conditions and historical calibration practices. Errors related to dosimetry technology and radiation fields were quantified to derive period- and facility-specific estimates of bias and uncertainties in recorded doses. This was based on (1) an evaluation of predominant workplace radiation from measurement studies and dosimetry expert assessment and (2) an estimation of the energy and geometry response of dosimeters used historically in study facilities. Coefficients were derived to convert recorded doses to H(p) (10) and organ dose, taking into account different aspects of the calibration procedures. A parametric, lognormal error structure model was developed to describe errors in doses as a function of facility and time period. Doses from other radiation types, particularly neutrons and radionuclide intake, could not be adequately reconstructed in the framework of the 15-Country Study. Workers with substantial doses from these radiation types were therefore identified and excluded from analyses. Doses from "lower-energy" photons (<100 keV) and from "higher-energy" photons (>3 MeV) were estimated to be small.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

External dose estimation for nuclear worker studies.

Epidemiological studies of nuclear workers are an important source of direct information on the health effects of exposure to radiation at low doses and low dose rates. These studies have the important advantage of doses that have been measured objectively through the use of personal dosimeters. However, to make valid comparisons of worker-based estimates with those obtained from data on A-bomb survivors or persons exposed for medical reasons, attention must be given to potential biases and uncertainties in dose estimates. This paper discusses sources of error in worker dose estimates and describes efforts that have been made to quantify these errors. Of particular importance is the extensive study of errors in dosimetry that was conducted as part of a large collaborative study of nuclear workers in 15 countries being coordinated by the International Agency for Research on Cancer. The study, which focused on workers whose dose was primarily from penetrating gamma radiation in the range 100 keV to 3 MeV, included (1) obtaining information on dosimetry practices and radiation characteristics through the use of questionnaires; (2) two detailed studies of exposure conditions, one of nuclear power plants and the other of mixed activity facilities; and (3) a study of dosimeter response characteristics that included laboratory testing of 10 dosimeter designs commonly used historically. Based on these efforts, facility- and calendar year-specific adjustment factors have been developed, which will allow risks to be expressed as functions of organ doses with reasonable confidence.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Regeneration and maintenance of bile canalicular networks in collagen-sandwiched hepatocytes.

The morphological and cytoskeletal reorganization of collagen-sandwiched rat hepatocytes during the de novo formation of complete canalicular networks was examined by phase, fluorescence and electron microscopy. During the initial stages of membrane repolarization, there was a marked accumulation of both microfilaments and microtubules at the sites of canalicular generation. Microtubule-disrupting agents (colchicine, nocodazole) inhibited the localization of actin filaments at cell margins and the initiation and branching of canalicular networks. After removal of microtubule-disrupting agents, microfilaments relocalized to the canalicular borders and microtubules nucleated along the margins of the bile canaliculi at sites distinct from the peri-canalicular actin networks. Microfilament-perturbing agents (cytochalasin D, phalloidin) did not affect the de novo initiation of bile canaliculi and only slightly impaired the development of canalicular lumina into networks. In established cultures with complete canalicular networks, subsequent treatment with microtubule-disrupting agents did not acutely affect the integrity of preformed canalicular networks. In contrast, treatment with microfilament-perturbing agents caused a marked dilation of most canaliculi. These results illustrate the differential role of the cytoskeleton in the regeneration and maintenance of bile canalicular networks by collagen-sandwiched hepatocytes. Moreover, this study shows the utility of this system as an in vitro model for examining the regulation of cell and membrane polarity.

In vitro and in vivo evaluation of effects of sodium caprate on enteral peptide absorption and on mucosal morphology.

Sodium salts of medium-chain fatty acids, sodium caprate (C10) in particular, have been used as absorption-enhancing agents to promote transmucosal drug absorption. In this study, we conducted both in vitro and in vivo experiments to investigate the effects of C10 on intestinal permeabilities and mucosal morphology. Mucosal addition of C10 (13-25 mM) reduced the transepithelial electric resistance (TEER) of cultured monolayers of the human intestinal cell line Caco-2 by 40-65% and, upon removal of C10, a marked tendency of TEER recovery was recorded. C10 added mucosally at 13-50 mM increased the transports of mannitol and polyethylene glycol (PEG) 900 across Caco-2 in a dose-dependent manner. In contrast, the transport of a model D-decapeptide was maximally enhanced with 20-25 mM C10. No noticeable morphological alteration of the Caco-2 monolayers was observed after a 1-h mucosal pretreatment with C10. Co-delivery with C10 (0.05-0.5 mmol/kg) into the rat terminal ileum increased the D-decapeptide bioavailability (BA) dose-dependently. With 0.5 mmol/kg C10 co-administered, D-decapeptide percent BA was elevated from 2 to 11%. Following a 1-h incubation with 0.5 mmol/kg C10 (in liquid or powder form) non-invasively delivered into the rectal lumen, no signs of histological change in the rectal mucosa were detected. These results demonstrate that C10 can promote intestinal absorption of a small peptide without causing detrimental alterations of the intestinal mucosa. C10 thus seems to be a good candidate as an enhancing agent for improving the oral BA of small therapeutic peptides.

Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin.

DS-1, a modified Quillaja saponin, has recently been shown to promote the absorption of insulin and aminoglycoside antibiotics via the ocular and nasal route. The purpose of this study is to investigate the effect of DS-1 on intestinal permeability, the mechanism of its action, and reversibility of the effect. The permeation-enhancing activity of DS-1 was evaluated in cultured monolayers of the Caco-2 intestinal epithelial cells by examining its effect on the transepithelial electric resistance (TEER) and on transport of mannitol and a model D-decapeptide. Mucosal addition of DS-1 promptly reduced the TEER of the Caco-2 monolayers, and a propensity of recovery of the TEER was observed upon its removal. DS-1 added at 0.01-0.1% (w/v) increased the transports of both mannitol and D-decapeptide in a dose-dependent manner; a relatively "flat" concentration-dependence was seen at 0.1-0.2%. Visualization studies conducted by confocal laser scanning microscopy (CLSM) seem to suggest that DS-1 enhances the Caco-2 permeability mainly via a transcellular route. Histological examination failed to reveal noticeable morphological alterations in the cell monolayers pretreated with DS-1. The integrity of the Caco-2 monolayers, as assessed by their permeability to mannitol, was found to be recoverable following the mucosal pretreatment of DS-1. These results suggest that DS-1 is an efficacious intestinal permeation-enhancing agent with low adverse effect on the epithelial viability and barrier function.

Molecular weight-dependent paracellular transport of fluorescent model compounds induced by palmitoylcarnitine chloride across the human intestinal epithelial cell line Caco-2.

Long-chain acylcarnitines, such as palmitoylcarnitine chloride (PCC), are endogenous compounds which have been shown to increase intestinal transport of small hydrophilic compounds (including some pharmaceutical agents) through the paracellular pathway. However, the size range of the compounds whose absorption can be improved by PCC has not been fully investigated. In the present study, we systematically examined the effect of PCC on the transport rate of a series of hydrophilic fluorescent model compounds of varying molecular weights (0.3-71.2 kD) across cultured monolayers of the human intestinal epithelial cells Caco-2. Mucosal addition of 100 or 200 microM PCC resulted in comparable time-dependent decreases in the transepithelial electric resistance (T1/2, approximately 15 min). PCC addition induced a striking increase in the transport of sodium fluorescein (Flu-Na; 0.3 kD) and a slight or moderate increase in transports of fluorescent compounds of 0.6-11 kD. The effect of PCC on transport of compounds with molecular weights of > or = 17 kD appeared to be negligible. Examination by confocal laser scanning microscopy clearly revealed dilated paracellular spaces in Caco-2 monolayers which had been mucosally pretreated with PCC, confirming that PCC increases intestinal permeability by opening a paracellular transport pathway. Our results suggest that PCC is particularly effective in enhancing intestinal absorption of small hydrophilic compound like Flu-Na and may also have limited use in promoting the transport of compounds of < or = 10 kD.

Adenovirus-mediated transduction of intestinal cells in vivo.

The intestinal tract has many features that make it an attractive target for therapeutic gene transfer. In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. After surgically accessing the intestine, an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was directly injected into various regions of the small and large intestine of rats and rabbits. Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. Expression of beta-Gal did not differ substantially when the virus was administered to the duodenum, ileum, or colon. When the vector was directly administered to segments of the distal ileum containing a Peyer's patch, transgene expression was approximately 10-fold higher than in segments lacking a Peyer's patch. In the Peyer's patches, a high level of expression was localized to epithelial cells, potentially M cells, overlying the lymphoid follicle domes. Transduction of these cells could have application in DNA-mediated oral vaccination. Administration of an adenoviral vector encoding a secreted alkaline phosphatase to the lumen resulted in expression and secretion of this gene product into the circulation. This finding demonstrates the potential of enterocytes to serve as heterotopic sites for the synthesis of heterologous gene products that would be secreted into the lumen of the intestinal tract or into the bloodstream.

Strategies for delivery of peptides utilizing absorption-enhancing agents.

The development of oral formulations for the effective delivery of peptides and proteins has been an elusive target. Although some success has been achieved (e.g., with cyclosporine), progress has been slow compared with what has been achieved with more traditional, organic drug molecules. Poor membrane permeability, enzymatic instability, and large molecular size are three factors that have remained major hurdles for peptide formulators. Absorption-enhancing agents that have been effective, at least in research environments, with smaller drug candidates, have also shown some limited efficacy in small animal models with certain peptides. In most cases, however, effective formulations have only achieved fairly low peptide absorption (< 10%) and have also resulted in significant alterations in the normal cellular morphology of the gastrointestinal tract, at least on a transient basis. Both literature and current data are reviewed in this report. Taken as a whole, the data suggest that the successful development of oral peptide formulations remains a significant challenge. Where successes are achieved, they will most likely be on a case-by-case basis and will reflect a balance between absorption-promoting efficacy of the formulation and the extent to which transient alteration of cell or tissue morphology occurs.