Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study.

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

Critical role of electrons in the short lifetime of blue OLEDs.

Designing robust blue organic light-emitting diodes is a long-standing challenge in the display industry. The highly energetic states of blue emitters cause various degradation paths, leading to collective luminance drops in a competitive manner. However, a key mechanism of the operational degradation of organic light-emitting diodes has yet to be elucidated. Here, we show that electron-induced degradation reactions play a critical role in the short lifetime of blue organic light-emitting diodes. Our control experiments demonstrate that the operational lifetime of a whole device can only be explained when excitons and electrons exist together. We examine the atomistic mechanisms of the electron-induced degradation reactions by analyzing their energetic profiles using computational methods. Mass spectrometric analysis of aged devices further confirm the key mechanisms. These results provide new insight into rational design of robust blue organic light-emitting diodes.

Giant thermal rectification efficiency by geometrically enhanced asymmetric non-linear radiation.

Thermal rectification is an asymmetric heat transport phenomenon where thermal conductance changes depending on the temperature gradient direction. The experimentally reported efficiency of thermal rectification materials and devices, which are applicable for a wide range of temperatures, is relatively low. Here we report a giant thermal rectification efficiency of 218% by maximizing asymmetry in parameters of the Stefan-Boltzmann law for highly non-linear thermal radiation. The asymmetry in emissivity is realized by sputter-depositing manganese (ε = ∼0.38) on the top right half surface of a polyurethane specimen (ε = ∼0.98). The surface area of the polyurethane side is also dramatically increased (1302%) by 3D printing to realize asymmetry in geometry. There is an excellent agreement between the experimentally measured temperature profiles and finite element simulation results, demonstrating the reliability of the analysis. Machine learning analysis reveals that the surface area is a dominant factor for thermal rectification and suggests novel light-weight designs with high efficiencies. This work may find applications in energy efficient thermal rectification management of electronic devices and housings.

Enhancing Quality Control in Web-based Participatory Augmented Reality Business Card Information System Design.

The rapid development of information and communication technology has fostered a natural integration of technology and design. As a result, there is increasing interest in Augmented Reality (AR) business card systems that leverage digital media. This research aims to advance the design of an AR-based participatory business card information system in line with contemporary trends. Key aspects of this study include applying technology to acquire contextual information from paper business cards, transmitting it to a server, and delivering it to mobile devices; facilitating interactivity between users and content through a screen interface; providing multimedia business content (video, image, text, 3D elements) via image markers recognized by users on mobile devices, while also adapting the type and method of content delivery. The AR business card system designed in this research enhances traditional paper business cards by incorporating visual information and interactive elements and automatically generating buttons linked to phone numbers, location information, and homepages. This innovative approach enables users to interact and enriches their overall experience while adhering to strict quality control measures.

Transcriptional Responses of Stress-Related Genes in Pale Chub (Zacco platypus) Inhabiting Different Aquatic Environments: Application for Biomonitoring Aquatic Ecosystems.

Pale chub (Zacco platypus) is a dominant species in urban rivers and reservoirs, and it is used as an indicator to monitor the effects of environmental contaminants. Gene responses at the molecular level can reflect the health of fish challenged with environmental stressors. The objective of this study was to identify correlations between water quality factors and the expression of stress-related genes in Z. platypus from different lake environments (Singal and Juam Lakes). To do so, transcriptional responses of genes involving cellular homeostasis (heat-shock protein 70, HSP70; heat-shock protein 90, HSP90), metal detoxification (metallothionein, MT), and antioxidation (superoxide dismutase, SOD; catalase, CAT) were analyzed in the gill and liver tissues of Z. platypus. HSP70, HSP90, and MT genes were overall upregulated in Z. platypus from Singal Lake, which suffered from poorer water quality than Juam Lake. In addition, gene responses were significantly higher in Singal Lake outflow. Upregulation of HSP70, HSP90, and MT was significantly higher in Z. platypus gills than in the liver tissue. In addition, integrated biomarker response and heatmap analysis determined correlations between expression of biomarker genes or water quality factors and sampling sites of both lakes. These results suggest that stress-related genes used as multiple biomarkers may reflect spatial characteristics and water quality of different lake environments, and they can be used for biomonitoring and ecological risk assessment.

Mechanical Characterization and Analysis of Different-Type Polyimide Feedthroughs Based on Tensile Test and FEM Simulation for an Implantable Package.

This paper presents the mechanical behaviors of different types of polyimide feedthroughs that are frequently used for implantable polymer encapsulation. Implantable packages of electronic devices often comprise circuits mounted on printed circuit boards (PCBs) encapsulated in a biocompatible polymer material, with input/output feedthroughs for electrical interconnections. The feedthroughs are regarded as essential elements of the reliability of the package since they create inevitable interfaces with the encapsulation materials. Flexible materials are frequently used for feedthroughs owing to their ease of manufacturing; thus, their mechanical properties are crucial as they directly interact with parts of the human body, such as the brain and neurons. For this purpose, tensile tests were performed to characterize the mechanical properties of flexible PCBs (FPCBs) and photosensitive polyimides (PSPIs). Commercial FPCBs and homemade PSPIs of two different thicknesses were subjected to tensile tests for mechanical characterization. The FPCBs showed typical stress-strain curves, while the PSPIs showed brittleness or strain hardening depending on the thickness. The material properties extracted from the tensile tests were used for explicit modeling using the finite element method (FEM) and simulations to assess mechanical behaviors, such as necking and strain hardening.

Role of the WNT/ß-catenin/ZKSCAN3 Pathway in Regulating Chromosomal Instability in Colon Cancer Cell lines and Tissues.

Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) acts as an oncogenic transcription factor in human malignant tumors, including colon and prostate cancer. However, most of the ZKSCAN3-induced carcinogenic mechanisms remain unknown. In this study, we identified ZKSCAN3 as a downstream effector of the oncogenic Wnt/ß-catenin signaling pathway, using RNA sequencing and ChIP analyses. Activation of the Wnt pathway by recombinant Wnt gene family proteins or the GSK inhibitor, CHIR 99021 upregulated ZKSCAN3 expression in a ß-catenin-dependent manner. Furthermore, ZKSCAN3 upregulation suppressed the expression of the mitotic spindle checkpoint protein, Mitotic Arrest Deficient 2 Like 2 (MAD2L2) by inhibiting its promoter activity and eventually inducing chromosomal instability in colon cancer cells. Conversely, deletion or knockdown of ZKSCAN3 increased MAD2L2 expression and delayed cell cycle progression. In addition, ZKSCAN3 upregulation by oncogenic WNT/ß-catenin signaling is an early event of the adenoma-carcinoma sequence in colon cancer development. Specifically, immunohistochemical studies (IHC) were performed using normal (NM), hyperplastic polyps (HPP), adenomas (AD), and adenocarcinomas (AC). Their IHC scores were considerably different (61.4 in NM; 88.4 in HPP; 189.6 in AD; 246.9 in AC). In conclusion, ZKSCAN3 could be responsible for WNT/ß-catenin-induced chromosomal instability in colon cancer cells through the suppression of MAD2L2 expression.

A Study on Biocompatible Polymer-Based Packaging of Neural Interface for Chronic Implantation.

This paper proposed and verified the use of polymer-based packaging to implement the chronic implantation of neural interfaces using a combination of a commercial thermal epoxy and a thin parylene film. The packaging's characteristics and the performance of the vulnerable interface between the thermal epoxy layer and polyimide layer, which is mainly used for neural electrodes and an FPCB, were evaluated through in vitro, in vivo, and acceleration experiments. The performance of neural interfaces-composed of the combination of the thermal epoxy and thin parylene film deposition as encapsulation packaging-was evaluated by using signal acquisition experiments based on artificial stimulation signal transmissions through in vitro and in vivo experiments. It has been found that, when commercial thermal epoxy normally cured at room temperature was cured at higher temperatures of 45 °C and 65 °C, not only is its lifetime increased with about twice the room-temperature-based curing conditions but also an interfacial adhesion is higher with more than twice the room-temperature-based curing conditions. In addition, through in vivo experiments using rats, it was confirmed that bodily fluids did not flow into the interface between the thermal epoxy and FPCB for up to 18 months, and it was verified that the rats maintained healthy conditions without occurring an immune response in the body to the thin parylene film deposition on the packaging's surface.

Highly Conductive Strong Healable Nanocomposites via Diels-Alder Reaction and Filler-Polymer Covalent Bifunctionalization.

Healable stretchable conductive nanocomposites have received considerable attention. However, there has been a trade-off between the filler-induced electrical conductivity (σ) and polymer-driven mechanical strength. Here significant enhancements in both σ and mechanical strength by designing reversible covalent bonding of the polymer matrix and filler-matrix covalent bifunctionalization are reported. A polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene grafted with maleic anhydride forms the strong reversible covalent bonding with furfuryl alcohol through the Diels-Alder reaction. Small (7.5 nm) and medium (117 nm) nanosatellite particles are generated by in situ etching of silver flakes, enabling electron tunneling-assisted percolation. The filler-polymer covalent bifunctionalization is achieved by 3-mercaptopropanoic acid. Altogether, this results in high σ (108 300 S m-1 ) and tensile strength (16.4 MPa), breaking the trade-off behavior. A nearly perfect (≈100%) healing efficiency is achieved in both σ and tensile strength. The conductive nanocomposite figure of merit (1.78 T Pa S m-1 ), defined by the product of σ and tensile strength, is orders of magnitude greater than the data in literature. The nanocomposite may find applications in healable strain sensors and electronic materials.

NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways.

Autophagy is an evolutionally conserved process that recycles aged or damaged intracellular components through a lysosome-dependent pathway. Although this multistep process is propagated in the cytoplasm by the orchestrated activity of the mTOR complex, phosphatidylinositol 3-kinase, and a set of autophagy-related proteins (ATGs), recent investigations have suggested that autophagy is tightly regulated by nuclear events. Thus, it is conceivable that the nucleolus, as a stress-sensing and -responding intranuclear organelle, plays a role in autophagy regulation, but much is unknown concerning the nucleolar controls in autophagy. In this report, we show a novel nucleolar-cytoplasmic axis that regulates the cytoplasmic autophagy process: nucleolar protein NOP53 regulates the autophagic flux through two divergent pathways, the ZKSCAN3-dependent and -independent pathways. In the ZKSCAN3-dependent pathway, NOP53 transcriptionally activates a master autophagy suppressor ZKSCAN3, thereby inhibiting MAP1LC3B/LC3B induction and autophagy propagation. In the ZKSCAN3-independent pathway, NOP53 physically interacts with histone H3 to dephosphorylate S10 of H3, which, in turn, transcriptionally downregulates the ATG7 and ATG12 expressions. Our results identify nucleolar protein NOP53 as an upstream regulator of the autophagy process.

Helminth Eggs Detected in Soil Samples of a Possible Toilet Structure Found at the Capital Area of Ancient Baekje Kingdom of Korea.

Although research conducted in East Asia has uncovered parasite eggs from ancient toilets or cesspits, data accumulated to date needs to be supplemented by more archaeoparasitological studies. We examined a total of 21 soil samples from a toilet-like structure at the Hwajisan site, a Baekje-period royal villa, in present-day Korea. At least 4 species of helminth eggs, i.e., Trichuris trichiura, Ascaris lumbricoides, Clonorchis sinensis, and Trichuris sp. (or Trichuris vulpis) were detected in 3 sediment samples of the structure that was likely a toilet used by Baekje nobles. The eggs of T. trichiura were found in all 3 samples (no. 1, 4, and 5); and A. lumbricoides eggs were detected in 2 samples (no. 4 and 5). C. sinensis and T. vulpis-like eggs were found in no. 5 sample. From the findings of this study, we can suppose that the soil-transmitted helminths were prevalent in ancient Korean people, including the nobles of Baekje Kingdom during the 5th to 7th century.

Microfluidic Airborne Metal Particle Sensor Using Oil Microcirculation for Real-Time and Continuous Monitoring of Metal Particle Emission.

Airborne metal particles (MPs; particle size > 10 µm) in workplaces result in a loss in production yield if not detected in time. The demand for compact and cost-efficient MP sensors to monitor airborne MP generation is increasing. However, contemporary instruments and laboratory-grade sensors exhibit certain limitations in real-time and on-site monitoring of airborne MPs. This paper presents a microfluidic MP detection chip to address these limitations. By combining the proposed system with microcirculation-based particle-to-liquid collection and a capacitive sensing method, the continuous detection of airborne MPs can be achieved. A few microfabrication processes were realized, resulting in a compact system, which can be easily replaced after contamination with a low-priced microfluidic chip. In our experiments, the frequency-dependent capacitive changes were characterized using MP (aluminum) samples (sizes ranging from 10 µm to 40 µm). Performance evaluation of the proposed system under test-bed conditions indicated that it is capable of real-time and continuous monitoring of airborne MPs (minimum size 10 µm) under an optimal frequency, with superior sensitivity and responsivity. Therefore, the proposed system can be used as an on-site MP sensor for unexpected airborne MP generation in precise manufacturing facilities where metal sources are used.

Morphology Transformation of Foldamer Assemblies Triggered by Single Oxygen Atom on Critical Residue Switch.

The synthesis of morphologically well-defined peptidic materials via self-assembly is challenging but demanding for biocompatible functional materials. Moreover, switching morphology from a given shape to other predictable forms by molecular modification of the identical building block is an even more complicated subject because the self-assembly of flexible peptides is prone to diverge upon subtle structural change. To accomplish controllable morphology transformation, systematic self-assembly studies are performed using congener short ß-peptide foldamers to find a minimal structural change that alters the self-assembled morphology. Introduction of oxygen-containing ß-amino acid (ATFC) for subtle electronic perturbation on hydrophobic foldamer induces a previously inaccessible solid-state conformational split to generate the most susceptible modification site for morphology transformation of the foldamer assemblies. The site-dependent morphological switching power of ATFC is further demonstrated by dual substitution experiments and proven by crystallographic analyses. Stepwise morphology transformation is shown by modifying an identical foldamer scaffold. This study will guide in designing peptidic molecules from scratch to create complex and biofunctional assemblies with nonspherical shapes.

Microfluidic ultrafine particle dosimeter using an electrical detection method with a machine-learning-aided algorithm for real-time monitoring of particle density and size distribution.

Growing concerns related to the adverse health effects of airborne ultrafine particles (UFPs; particles smaller than 300 nm) have highlighted the need for field-portable, cost-efficient, real-time UFP dosimeters to monitor individual exposure. These dosimeters must measure both the particle density and size distribution as these parameters are essential to the determination of where and how many UFPs will be deposited in human lungs. However, though various kinds of laboratory-grade instruments and hand-held monitors have been developed, they are expensive and only capable of measuring particle size distribution. A microfluidic UFP dosimeter is proposed in this study to address these limitations. The proposed sensor, based on an electrical detection method with a machine-learning-aided algorithm, can simultaneously measure the size distribution (number concentration, mean mobility diameter, geometric standard deviation) and particle density, and is compact owing to the microelectromechanical systems (MEMS) technology. In a comparison test using physically synthesised Ag and di-ethyl-hexyl sebacate (DEHS) aerosols, the mean measurement errors of the proposed sensor compared to the reference system were 6.1%, 4.5%, and 7.3% for number concentration, mean mobility diameter, and particle density, respectively. Moreover, when the machine-learning aided algorithm was operated, the geometric standard deviation could be deduced with a 7.6% difference. These results indicate that the proposed device can be successfully used as a field-portable UFP sensor to assess individual exposure, an on-site monitor for ambient air pollution, an analysis tool in toxicological studies of inhaled particles, for quality assurance of nanomaterials engineered via aerosol synthesis, etc.

Potential risk of exposure to heavy metals from co-processing of secondary wastes in the Republic of Korea.

The co-processing of secondary wastes during ordinary Portland cement (OPC) can result in high heavy metal concentrations in OPC products. However, earlier studies have not evaluated the concentrations of heavy metals (HMs) in OPC as a function of secondary input materials. Further, the health risk assessment (HRA) model has, thus far, has not been employed to assess the potential health risks associated with secondary raw materials and secondary fuels in OPC. Hence, to address these knowledge gaps, herein, monthly data for six HMs in the input materials and fuels from seven OPC manufacturers in the Republic of Korea were analyzed and modeled. Pb and Cu concentrations were found to be approximately 10-200 and 4-200 times higher than those of the other HMs, respectively. Furthermore, maximum Pb and Cu concentrations were 2-3 and 2-5 times higher than those reported in other countries, respectively. The quantity of input material had a significant influence on the observed patterns, and secondary raw materials, secondary additives, and secondary fuels were also determined to be important. Based on HRA assessment, although the risk levels were within permissible ranges, carcinogenic hazards attributable to Cr and Pb were not negligible. The results can aid in informed decision making and in implementing effective measures for managing risks associated with HMs in the OPC industry, thereby ameliorating threats to human health and environment.

Monitoring the Effective Density of Airborne Nanoparticles in Real Time Using a Microfluidic Nanoparticle Analysis Chip.

Determining the effective density of airborne nanoparticles (NPs; particles smaller than 100 nm in diameter) at a point of interest is essential for toxicology and environmental studies, but it currently requires complex analysis systems comprising several high-precision instruments as well as a specially trained operator. To address these limitations, a field-portable and cost-efficient microfluidic NP analysis device is presented, which provides quantitative information on the effective density and size distribution of NPs in real time. Unlike conventional analysis systems, the device can operate in a standalone mode because of the chip operating principle based on the electrostatic/inertial classification and electrical detection methods. Moreover, the device is both compact (16.0 × 10.9 × 8.6 cm3) and light (950 g) owing to the hardware strip down enabled by integrating the essential functions for effective density analysis on a single chip. Quantitative experiments performed to simulate real-life applications utilizing effective density (i.e., effective density-based morphology analysis on engineered NPs and multi-parametric NP monitoring in ambient air) demonstrate that the developed device can be used as an analysis tool in toxicological studies as an on-site sensor for the monitoring of individual NP exposure and environments, for quality monitoring of engineered NPs via aerosol synthesis, and other applications.

ACE-Molecule: An open-source real-space quantum chemistry package.

ACE-Molecule (advanced computational engine for molecules) is a real-space quantum chemistry package for both periodic and non-periodic systems. ACE-Molecule adopts a uniform real-space numerical grid supported by the Lagrange-sinc functions. ACE-Molecule provides density functional theory (DFT) as a basic feature. ACE-Molecule is specialized in efficient hybrid DFT and wave-function theory calculations based on Kohn-Sham orbitals obtained from a strictly localized exact exchange potential. It is open-source oriented calculations with a flexible and convenient development interface. Thus, ACE-Molecule can be improved by actively adopting new features from other open-source projects and offers a useful platform for potential developers and users. In this work, we introduce overall features, including theoretical backgrounds and numerical examples implemented in ACE-Molecule.

Ancient Echinostome Eggs Discovered in Archaeological Strata Specimens from a Baekje Capital Ruins of South Korea.

Echinostomiasis is prevalent in southeastern as well as northeastern Asian countries. This endemicity notwithstanding, no echinostome egg has as yet been reported by paleoparasitological studies conducted in Asian countries. Recently we analyzed geological-strata specimens retrieved from the ancient capital city of the Baekje Kingdom to uncover clues to the possible prevalence of echinostomiasis among contemporaneous populations of Korea. By means of archaeoparasitological technique, we found ancient Isthmiophora hortensis eggs in the specimens, thus revealing for the first time that ancient Korean people experienced isthmiophoriasis. Our report can be considered to have effectively broadened the spatial and temporal scope of research on echinostomiasis in human history.

Hydrotropism in the primary roots of maize.

Recent studies mainly in Arabidopsis have renewed interest and discussion in some of the key issues in hydrotropism of roots, such as the site of water sensing and the involvement of auxin. We examined hydrotropism in maize (Zea mays) primary roots. We determined the site of water sensing along the root using a nonintrusive method. Kinematic analysis was conducted to investigate spatial root elongation during hydrotropic response. Indole-3-acetic acid (IAA) and other hormones were quantified using LC-MS/MS. The transcriptome was analyzed using RNA sequencing. Main results: The very tip of the root is the most sensitive to the hydrostimulant. Hydrotropic bending involves coordinated adjustment of spatial cell elongation and cell flux. IAA redistribution occurred in maize roots, preceding hydrotropic bending. The redistribution is caused by a reduction of IAA content on the side facing a hydrostimulant, resulting in a higher IAA content on the dry side. Transcriptomic analysis of the elongation zone prior to bending identified IAA response and lignin synthesis/wall cross-linking as some of the key processes occurring during the early stages of hydrotropic response. We conclude that maize roots differ from Arabidopsis in the location of hydrostimulant sensing and the involvement of IAA redistribution.

Microfluidic condensation nanoparticle counter using water as the condensing liquid for assessing individual exposure to airborne nanoparticles.

We present a compact and inexpensive detection system that can accurately measure the number concentration of nanoparticles (NPs; particles smaller than 100 nm) in real-time for assessing individual exposure to airborne NPs in various environments. Our system is based on the condensation nucleation light scattering technique and uses water as the condensing liquid, which solves the self-contamination issues that affect most portable NP detection systems. Our system comprises two units: a microfluidic condensation chip for growing NPs into water droplets and a miniature optical detector for singly counting grown droplets. To effectively minimize the size and cost of our system, droplets are grown on a single chip according to the semiconductor manufacturing process. To use water as the condensing liquid, a super-hydrophilic wick (i.e., Cu micropillar array coated with CuO nanowires) is monolithically integrated into the chip. Simulations were performed to verify the method of generating supersaturated water vapor. Quantitative experiments using NaCl and Ag NPs revealed that our system grew NPs larger than 9.3 nm into 2.25 µm diameter water droplets and could count individual droplets over an extremely wide concentration range (0.021-105 N cm-3) with high accuracy. This outstanding performance allowed our system to resolve the daily pattern of the NP concentration along a metropolitan commuting street with strong agreement compared to the reference instrument. Because our system uses water, it can accurately monitor individual exposure to NPs in various kinds of environments, including multiuse facilities such as elementary schools and hospitals.