Assessing systemic, developmental, and reproductive toxicity and estrogenicity of Korean red ginseng extract G1899 in juvenile Sprague-Dawley Rats.

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

Reproductive and developmental toxicity screening of bisphenol F by oral gavage in rats.

Bisphenol F (BPF, 4,4'-methylenediphenol) has recently been selected as an alternative to bisphenol A (BPA), which is used in the manufacturing of polycarbonates and epoxy resins. This study aimed to investigate the general, and reproductive/developmental effects of BPF. Therefore, BPF at dose levels of 0, 1, 5, 20, and 100 mg/kg/day was administered daily by oral gavage to Sprague-Dawley rats during the pre-mating, mating, gestation, and early lactation periods, and reproductive and developmental toxicities including general systemic toxicities were investigated. A decrease in body weight and food consumption was observed in the female rats treated with BPF at 20 and 100 mg/kg/day during the pre-mating and gestation periods. Additionally, gamma glutamyl transpeptidase levels were increased in the female rats administered 100 mg/kg/day. At 100 mg/kg/day, ovarian weight decreased and vaginal mucification increased according to a necropsy and histopathological examination, respectively. Moreover, the number of implantation sites and litter size decreased at 100 mg/kg/day. However, no significant BPF-related changes were observed in the male rats. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of BPF for general systemic and reproductive effects were 5 and 20 mg/kg/day, respectively.

Transcriptome-metabolome-wide association study (TMWAS) in rats revealed a potential carcinogenic effect of DEHP in thyroid associated with eicosanoids.

The incidence of thyroid cancer (TC) has increased considerably in the last few decades. Environmental factors, including plasticizers, are recognized as potential risks leading to thyroid cancer in humans. In this study, we used a transcriptome-metabolome-wide association study to find the unidentified carcinogenic mechanism of di-2-ethylhexyl phthalate (DEHP) in thyroid and biomarkers for non-invasive diagnosis. Rats were treated with different doses of DEHP (0, 0.3, 3, 30, 150 mg DEHP/kg bw/day) for 13 weeks. Then, the thyroids were processed for Ki67 staining and RNA-seq. Also, 17-h urine samples were collected for high-resolution metabolomics analysis. After a high dose of DEHP exposure, the terminal body weights and the thyroid and parathyroid glands weights were not altered. However, the liver weights and numbers of Ki67-positive cells were increased. Further, multivariate statistical analysis revealed that metabolic shifts were considerably altered above 30 mg DEHP/kg bw/day. In RNA-seq analysis, some cancer-related genes were altered, including 18 upregulated and 9 downregulated transcripts. These cancer transcripts and whole metabolome data were integrated to uncover thyroid cancer-related metabolic pathways, which revealed that cancer-related transcripts had a network structure linked to eicosanoids such as leukotriene D4 and prostaglandin. In brief, our study demonstrated that DEHP can induce thyroid hyperplasia through the eicosanoid-associated pathway, providing further insight into the mechanism of DEHP-associated thyroid cancer.

Bis-diamine administration during pregnancy induces developmental and reproductive toxicities in rats.

BACKGROUND: Bis-diamine was developed as amebicidal and male contraceptive agents; however, it is also reported to induce characteristic congenital heart defects especially in the cardiac conotruncal area of rats. Because of its characteristic congenital heart defects, bis-diamine-induced animal models can be used for studying congenital heart defects. However, comprehensive toxicological information regarding bis-diamine-induced congenital heart defects in this animal model is not available. METHODS: In this study, we investigated and characterized an animal model for bis-diamine-induced congenital heart defects. A single dose of 200-mg bis-diamine was administered by oral gavage to pregnant rats on gestation day 10, and then observed the representative toxicological endpoints for general systemic health of pregnant rats, embryo-fetal development, and parturition. RESULTS: Characteristic congenital heart defects and other birth defects similar to DiGeorge syndrome were observed in bis-diamine-administered pregnant rats. In addition, developmental and reproductive toxicity findings, including increased postimplantation loss, decreased fetal weight, increased perinatal death, and increased gestation period, were observed in bis-diamine-administered pregnant rats. In particular, these developmental and reproductive toxicities were observed without maternal toxicity findings. CONCLUSION: These results will be useful to use this animal model for further studies in congenital heart defects, cardiovascular defects, and understanding their mechanisms.

Prenatal developmental toxicity study of 2,4-dichlorobenzyl alcohol in rats.

Sore throat lozenges, which are over-the-counter drugs, contain 2,4-dichlorobenzyl alcohol (DCBA) as the primary ingredient. However, comprehensive data on the prenatal developmental toxicity of DCBA is limited. Therefore, this study was conducted to determine the effects of DCBA on pregnant rats and prenatal development. Sprague-Dawley rats were administered different doses of DCBA (0, 25, 100, 400, and 800 mg/kg/day) daily via an oral gavage from gestation day (GD) 6-19. Thereafter, all the live dams were sacrificed on GD 20, and caesarean sections were conducted. Live fetuses and their placenta were weighed and then examined for external, visceral, and skeletal malformations and variations. Based on the results obtained, dams at 800 mg/kg/day showed systemic toxicities, including a decrease in body weight and food consumption, and liver changes. Additionally, this treatment induced decreases in fetal and placental weights, as well as the increased incidence of retarded ossifications and full supernumery rib, and the decreased number of ossification centers. Therefore, based on these findings, the no-observed-adverse-effect level of DCBA was determined to be 400 mg/kg/day for dams and prenatal development.

Adverse postnatal developmental effects in offspring from humidifier disinfectant biocide inhaled pregnant rats.

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-P), one of the primary biocides used in humidifier disinfectants, caused a fatal pulmonary disease in Korea. Pregnant women were also exposed to PHMG-P, and subsequent studies showed that PHMG-P inhalation during pregnancy adversely affects their health and embryo-fetal development. However, the postnatal developmental effects after birth on prenatally PHMG-P-exposed offspring have not yet been investigated. Therefore, in this study, we aimed to examine the postnatal development of prenatally PHMG-P-exposed offspring. Pregnant rats (22 or 24 females per group) were exposed to PHMG-P during pregnancy in a whole-body inhalation chamber at the target concentrations of 0, 0.14, 1.60, and 3.20 mg/m3. After parturition, the prenatally exposed offspring were transferred to non-exposed surrogate mothers to minimize the secondary effects of severe maternal toxicities. Postnatal development of offspring was then examined with a modified extended one-generation reproductive toxicity study design. At 3.20 mg/m3 PHMG-P, increased perinatal death rates and decreased viability index (postnatal survival of offspring between birth and postnatal day 4) were observed. In addition, F1 offspring had lower body weight at birth that persisted throughout the study. PHMG-P-exposed pregnant rats also had severe systemic toxicities and increased gestation period. At 1.60 mg/m3 PHMG-P, a decreased viability index was also observed with systemic toxicities of PHMG-P-exposed pregnant rats. These results indicate that prenatal PHMG-P exposure adversely affects the offspring's future health and could be used for human risk assessment.

Vari-Focal Light Field Camera for Extended Depth of Field.

The light field camera provides a robust way to capture both spatial and angular information within a single shot. One of its important applications is in 3D depth sensing, which can extract depth information from the acquired scene. However, conventional light field cameras suffer from shallow depth of field (DoF). Here, a vari-focal light field camera (VF-LFC) with an extended DoF is newly proposed for mid-range 3D depth sensing applications. As a main lens of the system, a vari-focal lens with four different focal lengths is adopted to extend the DoF up to ~15 m. The focal length of the micro-lens array (MLA) is optimized by considering the DoF both in the image plane and in the object plane for each focal length. By dividing measurement regions with each focal length, depth estimation with high reliability is available within the entire DoF. The proposed VF-LFC is evaluated by the disparity data extracted from images with different distances. Moreover, the depth measurement in an outdoor environment demonstrates that our VF-LFC could be applied in various fields such as delivery robots, autonomous vehicles, and remote sensing drones.

Preclinical assessment of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells for neonatal hypoxic-ischaemic brain injury.

Hypoxic-ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin-preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells (th-hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th-hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th-hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague-Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th-hWJMSCs on the growth of newborn babies. Our results suggest that th-hWJMSCs are non-toxic and non-tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.

Serial blood sampling effects in rat embryo-fetal development studies for toxicokinetics.

Serial blood sampling for toxicokinetics is generally conducted in regulatory embryo-fetal development (EFD) studies in rats. EFD studies are designed to detect the potential adverse effects of pharmaceuticals on pregnant females and their fetuses; this information is useful for understanding the relationships between systemic exposure levels and toxicity profiles. However, additional satellite pregnant females are needed for toxicokinetics because comprehensive information regarding the potential impact of serial blood sampling on pregnant females is scarce. Here, in this study, we investigated the potential impact of serial blood sampling in pregnant female rats using a typical EFD study design. Additionally, we investigated the additional endpoints (clinical pathology, organ weights, and histopathology) that were deemed likely to be sensitive to blood sampling. Results indicated that serial blood sampling in pregnant females induced physiological adaptive changes and did not affect the general endpoints in EFD studies. Nevertheless, inclusion of satellite groups in EFD studies may be a more prudent approach considering the physiological changes in pregnant females and potential off-target effects of candidate pharmaceuticals. These results provide background information on the impact of serial blood sampling in pregnant females and will be useful to design the regulatory EFD studies.

Genome-wide identification of GH3 genes in Brassica oleracea and identification of a promoter region for anther-specific expression of a GH3 gene.

BACKGROUND: The Gretchen Hagen 3 (GH3) genes encode acyl acid amido synthetases, many of which have been shown to modulate the amount of active plant hormones or their precursors. GH3 genes, especially Group III subgroup 6 GH3 genes, and their expression patterns in economically important B. oleracea var. oleracea have not been systematically identified. RESULTS: As a first step to understand regulation and molecular functions of Group III subgroup 6 GH3 genes, 34 GH3 genes including four subgroup 6 genes were identified in B. oleracea var. oleracea. Synteny found around subgroup 6 GH3 genes in B. oleracea var. oleracea and Arabidopsis thaliana indicated that these genes are evolutionarily related. Although expression of four subgroup 6 GH3 genes in B. oleracea var. oleracea is not induced by auxin, gibberellic acid, or jasmonic acid, the genes show different organ-dependent expression patterns. Among subgroup 6 GH3 genes in B. oleracea var. oleracea, only BoGH3.13-1 is expressed in anthers when microspores, polarized microspores, and bicellular pollens are present, similar to two out of four syntenic A. thaliana subgroup 6 GH3 genes. Detailed analyses of promoter activities further showed that BoGH3.13-1 is expressed in tapetal cells and pollens in anther, and also expressed in leaf primordia and floral abscission zones. CONCLUSIONS: Sixty-two base pairs (bp) region (- 340 ~ - 279 bp upstream from start codon) and about 450 bp region (- 1489 to - 1017 bp) in BoGH3.13-1 promoter are important for expressions in anther and expressions in leaf primordia and floral abscission zones, respectively. The identified anther-specific promoter region can be used to develop male sterile transgenic Brassica plants.

A humidifier disinfectant biocide, polyhexamethylene guanidine phosphate, inhalation exposure during pregnancy induced toxicities in rats.

Biocides are widely used for their effective antiseptic and disinfectant properties, including polyhexamethylene guanidine phosphate (PHMG-P), which is also used as a biocide as it selectively disrupts bacterial cell membrane. It is used to clean humidifiers commonly used in the dry winter season in South Korea, which exposes people to PHMG-P inhalation. However, comprehensive toxicological data on PHMG-P inhalation exposure, including in pregnant women, and the potential occurrence of lung disease is lacking. Therefore, in this study, we investigated PHMG-P inhalation exposure-induced toxicities in pregnant rats and prenatal development of their conceptus. Pregnant rats were exposed to PHMG-P via inhalation at target concentrations of 0, 0.14, 1.60, and 3.20 mg/m3 from implantation to nearly parturition (from gestation day 6-20) and then analyzed for relevant abnormalities. Results showed systemic toxicities in the pregnant rats including respiratory function abnormalities, decreased body weight gain, and decreased food consumption at ≥1.60 mg/m3. Prenatal development toxicities, including decreased fetal weight with ossification retardations of fetal bones, were observed at 3.20 mg/m3. These results will contribute to clarifying the PHMG-P inhalation exposure-induced toxicities during pregnancy and support its risk assessment in humans.

Safety assessment of cerium oxide nanoparticles: combined repeated-dose toxicity with reproductive/developmental toxicity screening and biodistribution in rats.

Cerium oxide nanoparticles (CeO2 NPs) are widely used in various commercial applications because of their characteristic properties. People can be easily exposed to CeO2 NPs in real life, but the safety assessment of CeO2 NPs has not been fully investigated. Therefore, in this study, we conducted a combined repeated-dose and reproductive/developmental toxicity screening study (OECD testing guideline 422) to investigate the potential hazards on human health, including reproductive/developmental functions, after repeated daily CeO2 NPs oral gavage administration to both males and females. In addition, tissues from parental animals and their pups were collected to analyze the internal accumulation of cerium. CeO2 NPs were orally administered to Sprague-Dawley rats at doses of 0, 100, 300 and 1000 mg/kg during their pre-mating, mating, gestation and early lactation periods. In the general systemic and reproductive/developmental examinations, no marked toxicities were observed in any in-life and terminal observation parameters in this study. In the biodistribution analysis, cerium was not detected in either parental or pup tissues (blood, liver, lungs and kidneys). Repeated oral exposure of CeO2 NPs did not induce marked toxicities affecting general systemic and reproductive/developmental functions up to the dose level of 1000 mg/kg and the CeO2 NPs were not systemically absorbed in parental animals or their pups. This result could be used in risk assessment for humans, and additional toxicity studies with CeO2 NPs will be necessary considering various physicochemical properties and exposure probabilities of these nanoparticles.

Effect of developmental exposure to bisphenol A on steroid hormone and vitamin D3 metabolism.

High exposure to bisphenol A (BPA) in children has been associated with the outcomes of several diseases, including those related to developmental problems. To elucidate the mechanism of BPA mediated developmental toxicity, plasma and urine from rats exposed to BPA was analyzed with high resolution metabolomics, beginning from post-natal day 9, for 91 days. Female and male rats were orally administered 5 different BPA doses to elucidate dose- and sex-specific BPA effects. Regarding dose-specific effects, multivariate statistical analysis showed that metabolic shifts were considerably altered between 5, 50 and 250 mg BPA/kg bw/day in treated rats. A nonmonotonicity and monotonicity between BPA dose and metabolic response were major trajectories, showing overall metabolic changes in plasma and urine, respectively. Metabolic perturbation in the steroid hormone biosynthesis pathway was significantly associated with dose- and sex-specific BPA effects. Intermediate metabolites in the rate-limiting step of steroid hormone biosynthesis down-regulated steroid hormones in the 250 mg treatment. Further, our study identified that BPA increased urinary excretion of vitamin D3 and decreased its concentration in blood, suggesting that perturbation of vitamin D3 metabolism may be mechanistically associated with neurodevelopmental disorders caused by BPA. Three metabolites showed a decrease in sex difference with high BPA dose because female rats were more affected than males, which can be related with early puberty onset in female. In brief, the results demonstrated that BPA induces dose- and sex-specific metabolic shifts and that perturbation of metabolism can explain developmental problems.

Reproductive and developmental toxicity screening of polyhexamethylene guanidine phosphate by oral gavage in rats.

Polyhexamethylene guanidine phosphate (PHMG-P) has effective antimicrobial activity against various microorganisms and has been widely used as a biocide in commercial products. However, its use as a humidifier disinfectant has provoked fatal idiopathic lung disease in South Korea, especially in pregnant or postpartum women and their young children. PHMG-P-related toxicological studies of reproduction and development in experimental animals have not been identified, and thus, we investigated the potential effects of early-stage oral exposure to PHMG-P by assessing its toxicological properties. PHMG-P was repeatedly administered by oral gavage at dose levels of 0, 13, 40 and 120 mg/kg to Sprague-Dawley rats during the pre-mating, mating, gestation and early lactation periods, and then general systemic and reproductive/developmental toxicities were investigated. At 120 mg/kg, PHMG-P-related toxicities including subdued behavior, thin appearance, decreased body weight, decreased food consumption and decreased F1 pup body weight were observed. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of PHMG-P for both general systemic effects and development are considered to be 40 mg/kg/day.

Titanium dioxide nanoparticles oral exposure to pregnant rats and its distribution.

BACKGROUND: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. RESULTS: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. CONCLUSION: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles.

Overexpression of Acyl-ACP Thioesterases, CpFatB4 and CpFatB5, Induce Distinct Gene Expression Reprogramming in Developing Seeds of Brassica napus.

We examined the substrate preference of Cuphea paucipetala acyl-ACP thioesterases, CpFatB4 and CpFatB5, and gene expression changes associated with the modification of lipid composition in the seed, using Brassica napus transgenic plants overexpressing CpFatB4 or CpFatB5 under the control of a seed-specific promoter. CpFatB4 seeds contained a higher level of total saturated fatty acid (FA) content, with 4.3 times increase in 16:0 palmitic acid, whereas CpFatB5 seeds showed approximately 3% accumulation of 10:0 and 12:0 medium-chain FAs, and a small increase in other saturated FAs, resulting in higher levels of total saturated FAs. RNA-Seq analysis using entire developing pods at 8, 25, and 45 days after flowering (DAF) showed up-regulation of genes for ß-ketoacyl-acyl carrier protein synthase I/II, stearoyl-ACP desaturase, oleate desaturase, and linoleate desaturase, which could increase unsaturated FAs and possibly compensate for the increase in 16:0 palmitic acid at 45 DAF in CpFatB4 transgenic plants. In CpFatB5 transgenic plants, many putative chloroplast- or mitochondria-encoded genes were identified as differentially expressed. Our results report comprehensive gene expression changes induced by alterations of seed FA composition and reveal potential targets for further genetic modifications.

Developmental and reproductive toxicity assessment in rats with KGC-HJ3, Korean Red Ginseng with Angelica gigas and Deer antlers.

BACKGROUND: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. METHODS: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. RESULTS AND CONCLUSION: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

Toxicological safety evaluation of freeze-dried Protaetia brevitarsis larva powder.

White-spotted flower chafer (Protaetia brevitarsis) is an edible insect and its larva was used as a traditional Asian medicine. It's a promising material as a novel food source because of its nutritional components. In this study, as part of the preclinical toxicity program, we evaluated the toxicity of freeze-dried P. brevitarsis larva powder to develop a novel food material. In a single-dose oral toxicity study in rats, there were no changes in mortality, clinical observations, and body weight in rats administered 5000 mg/kg P. brevitarsis larva powder. In a 13-week oral repeated dose toxicity study in rats, there were no adverse effects or changes in mortality, clinical observations, body weight, food consumption, ophthalmology, clinical pathology, necropsy, organ weight, and histopathology at doses of 300, 1000, and 3000 mg/kg/day. In identification of allergic reactions, P. brevitarsis larva powder induced no increases of serum immunoglobulin E and histamine concentrations over 13 weeks of oral administration in rats. In a genotoxicity assessment, P. brevitarsis larva powder didn't provoke bacterial reverse mutations, chromosomal aberrations, and micronucleated reticulocytes. Therefore, freeze-dried P. brevitarsis larva powder shows no evidence of toxic and mutagenic changes under the experimental conditions of the present in vitro and in vivo studies.

An accuracy improvement method for the topology measurement of an atomic force microscope using a 2D wavelet transform.

The topology image is constructed from the 2D matrix (XY directions) of heights Z captured from the force-feedback loop controller. For small height variations, nonlinear effects such as hysteresis or creep of the PZT-driven Z nano scanner can be neglected and its calibration is quite straightforward. For large height variations, the linear approximation of the PZT-driven Z nano scanner fail and nonlinear behaviors must be considered because this would cause inaccuracies in the measurement image. In order to avoid such inaccuracies, an additional strain gauge sensor is used to directly measure displacement of the PZT-driven Z nano scanner. However, this approach also has a disadvantage in its relatively low precision. In order to obtain high precision data with good linearity, we propose a method of overcoming the low precision problem of the strain gauge while its feature of good linearity is maintained. We expect that the topology image obtained from the strain gauge sensor showing significant noise at high frequencies. On the other hand, the topology image obtained from the controller output showing low noise at high frequencies. If the low and high frequency signals are separable from both topology images, the image can be constructed so that it is represented with high accuracy and low noise. In order to separate the low frequencies from high frequencies, a 2D Haar wavelet transform is used. Our proposed method use the 2D wavelet transform for obtaining good linearity from strain gauge sensor and good precision from controller output. The advantages of the proposed method are experimentally validated by using topology images.

Integral imaging system using an adaptive lens array.

We produced an adaptive lens array composed of multiple flat lens arrays arranged in a curved shape with an adjustable radius of curvature, in order to overcome the hardware problem of the conventional flat or curved lens array-based systems. The manufactured adaptive lens array is applied to an integral imaging system. The gap mismatch that occurs when using a curved lens array is resolved by computing the exact display mapping position of element images through each lens. The results of the experiment demonstrate that the adaptive lens array-based integral imaging system successfully generated elemental images according to the curvature transformation of the adaptive lens array, and they were reconstructed as 3D images.