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.

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.

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.

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.

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.

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.

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.

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.

Growth hormone stimulation of glucose transport in isolated rat hepatocyte suspensions and primary cultures.

[14C]-3-O-Methyl-D-glucose transport in response to GH stimulation was measured in freshly prepared and cultured hepatocytes from hypophysectomized (hypox) adult female rats. Sugar transport in freshly isolated hepatocytes from hypox animals was stimulated by 10(-9) M human GH (hGH) and 10(-9) M rat GH (rGH) during 0-30 and 60-90 min of incubation, respectively. Monosaccharide transport in freshly isolated hepatocytes from normal female rats was unaffected by either hGH or rGH addition. Specific [125I]iodo-hGH binding to freshly isolated hepatocytes from hypox rats was detectable as early as 9 min of incubation and reached maximum binding levels by approximately 30-60 min. Specific [125I]iodo-rGH binding was not detectable until 30 min of incubation and reached a binding plateau after 60 min of incubation. Porcine insulin at 10(-9) and 10(-7) M was ineffective in stimulating sugar transport in either freshly isolated or cultured hepatocytes from hypox animals. Sugar transport in cultured hepatocytes was stimulated by 10(-7) M hGH ad 10(-7) rGH, with 30-60 and 60-90 min of incubation being the most frequent stimulatory intervals observed. Maximum specific [125I]iodo-hGH binding was observed at 60 min of incubation and decreased by 72% and 77% at 90 and 120 min, respectively. Specific [125I]iodo-rGH binding, however, was not detectable in cultured hepatocytes. Both hGH at 10(-9) M stimulated glucose oxidation to CO2 in freshly isolated hepatocytes from hypox animals. Stimulation was observed after 30 min of incubation with GH and indicated a regulatory function for GH in maintaining basal levels of glucose oxidation. The results presented here suggest a possible role for GH in glucose uptake and metabolism in the liver and indicate that differences may exist between the effects of hGH and rGH on glucose uptake.

Role of disulfide bonds in human growth hormone binding and dissociation in isolated rat hepatocytes and liver plasma membranes.

The role of disulfide bonds and sulfhydryl groups in rat hepatocytes and rat liver plasma membranes in the binding of human GH (hGH) has been studied. Since hGH binding involves uptake and irreversible binding, the effect of disulfide reducing agents [dithiothreitol (DTT) and 2-mercaptoethanol (ME)] and an alkylating agent [N-ethylmaleimide (NEM)] on the time course of binding and displacement of [125I]hGH was determined in the hepatocytes and membranes. The time course of binding and displacement of [125I]hGH was similar in membranes and cells, indicating that the irreversible nature of hGH binding is not dependent upon an intact cellular structure. Both 1% ME and 10 mM DTT prevented further binding of [125I]hGH when added at 60 min of the 300-min binding incubation for both hepatocytes and plasma membranes. The ME caused some initial dissociation of bound [125I]hGH, with subsequent binding to levels that were present when the ME was added. Only ME caused an increase in nonspecific binding with the plasma membranes. Both ME and DTT caused an increase in displacement of [125I]hGH in the presence of excess unlabeled hGH. The amount of [125I]hGH remaining bound in the presence of DTT and unlabeled hGH approached nonspecific levels by 240 min of incubation. NEM caused an increase in the total [125I]hGH bound, but this was apparently due to increased nonspecific binding in the presence of NEM. The effect of the reducers on binding was not secondary to an effect on hGH, since the disulfides of [125I]hGH were not reduced under the conditions of binding with either ME or DTT. The effect of the ME or DTT on binding could be reversed or prevented by subsequent or simultaneous addition of an oxidizer such as NAD or oxidized glutathione. The data indicate that disulfide bonds in the membranes are intimately involved in the maintenance of a receptor structure necessary for hGH binding. The disruption of the disulfides also results in increased dissociation and displacement of the bound [125I]hGH, indicating a possible role in the irreversible nature of hGH binding. This represents a partial delineation of the hGH binding process.

Comparison of costs of new atherectomy devices and balloon angioplasty for coronary artery disease.

The in-hospital cost for 126 consecutive patients undergoing 1-vessel, single-lesion coronary atherectomy (atherectomy group) beginning January 1, 1991, was reviewed (65 directional, 44 rotational, and 17 extractional atherectomies), and compared with the cost for 126 consecutive patients matched by sex and age who underwent 1-vessel, single-lesion standard balloon coronary angioplasty (angioplasty group). The in-hospital cost for each patient was determined using charges divided by a correction factor for each hospital department involved. Six different cost fields were created. The overall cost/charge ratio was 0.72. Angiographic and clinical success was 91% and 90% in the angioplasty group and 93% and 90% in the atherectomy group, respectively. Patients who underwent angioplasty required 1.3 +/- 0.6 devices/procedure, as compared with those who underwent atherectomy (2.4 +/- 1 devices/procedure) (p < 0.0001). The mean cost of angioplasty was $7,301 +/- $4,637 and of atherectomy devices $9,345 +/- $8,856 (28% increase). The difference was principally related to an increase in cost of supplies: angioplasty $2,028 +/- $1,196 versus atherectomy $3,632 +/- $1,525 (79% increase). There were no significant differences in hospitalization cost, procedure-room cost, and pharmacy and laboratory costs. Thus, higher risk morphologic lesions can be approached with new atherectomy devices with clinical and complication rates similar to coronary angioplasty. However, these results were obtained at a 28% increase in cost.

Subcutaneous tissue cages for examination of slow release of materials from long-term implants.

A subcutaneous tissue cage implant system was examined for its utility in evaluating the subcutaneous response to slow release of potentially irritating materials from implanted devices. The degree of the inflammatory response was measured by the total number of polymorphonuclear leucocytes per microliter in the tissue exudate. Bolus injection of kappa carrageenan resulted in a 100-fold increase in polymorphonuclear leucocytes within 2 d with a return to basal levels within the next 3 d. Slow infusion of the same solution over 7 d also resulted in a statistically significant increase in polymorphonuclear leucocytes response 4 d following expected termination of infusion, which did not return to basal levels before study termination 3 d later. The peak response obtained from slow infusion of carrageenan did not differ significantly from that observed following bolus injection of the same solution.

Assessment of a model for measuring drug diffusion through implant-generated fibrous capsule membranes.

Fibrous tissue, which encapsulates subcutaneously implanted silastic, vinyl, polyurethane and Teflon discs in rats, has been isolated, characterized and tested for drug permeability in order to develop an in vitro model for determining the effect of this tissue on drug disposition from implant sites. With all materials, capsule tissue thickness and collagen content (approximately 59%) was consistent from 2 to 4 months after implantation. Silastic implants afforded the most consistent and usable tissue in terms of thickness and lack of vascularity, and these capsule membranes were used for determining the transport of three model compounds in an in vitro diffusion cell model. The rank ordering of permeability through these membranes was estrone (60.2 x 10(-6) cm s-1) > 3-O-methylglucose (18.7 x 10(-6) cm s-1) > dextran of molecular weight 70 000 (5.6 x 10(-6) cm s-1), which is consistent with expectations based on the molecular weights and partitioning behaviour of the model compounds. The results of these studies indicate that implant-generated encapsulating membranes can be successfully isolated and employed to study drug diffusion in an in vitro model, providing a direct assessment of the barrier properties of encapsulating membranes.

Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries.

Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly gamma, radiation. The combination of the data from the various studies increases the power to study associations between radiation and specific cancers. The combined analyses covered a total of 2,124,526 person-years (PY) at risk and 15,825 deaths, 3,976 of which were due to cancer. There was no evidence of an association between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)--the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates--was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI): -0.4, 0.3] and 2.18 per Sv (90% CI: 0.1, 5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to 0 mSv. These estimates, which did not differ significantly across cohorts or between men and women, are the most comprehensive and precise direct estimates of cancer risk associated with low-dose protracted exposures obtained to date. Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a range of possibilities, from a reduction of risk at low doses, to risks twice those on which current radiation protection recommendations are based.(ABSTRACT TRUNCATED AT 400 WORDS)

Phase-contrast microscopy of the primate retina.

The study of hematoxylin and eosin stained thick sections (15 microns) of the primate retina with the phase-contrast microscope provided a means for the selective demonstration of many cellular structures that could not be resolved with the same degree of detail which was possible when bright-field microscopy was used, or when phase-contrast microscopy was employed to examine unstained material. The H & E-stain greatly enhanced the phase-contrast image, so that cytoplasmic structure, fiber trajectories, and gross synaptic detail of the retina could be demonstrated to better advantage.

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.