Critical voxel learning with vision transformer and derivation of logical AV safety assessment scenarios.

Safety assessment is an active research subject for autonomous vehicles (AVs) that have emerged as a new mode of mobility. In particular, scenario-based safety assessments have garnered significant attention. AVs can be tested on how they safely avoid hypothetical situations leading to accidents. However, scenarios written by humans based on their expert knowledge and experience may only partially reflect real-world situations. Instead, we are keen on a different technique of extracting statistically significant and more detailed scenarios from sensor data captured during the critical moments when AVs become vulnerable to potential accidents. Specifically, we first render the three-dimensional space around an AV with fixed-sized voxels. Then, we modeled the aggregate kinetics of the objects in each voxel detected by 3D-LiDAR sensors mounted on real test AVs. The Vision Transformer we used to model the kinetics helped us quickly pinpoint critical voxels containing objects that threatened the AV's safety. We traced the trajectory of the critical voxels on a visual attention map to describe in detail how AVs become vulnerable to accidents according to the logical scenario format defined by the PEGASUS Project. We tested our novel method with 250 h of 3D-LiDAR recordings capturing critical moments. We devised an inference model that detected critical situations with an F1-score of 98.26%. For each type of scenario, our model consistently identified the critical objects and their tendency to influence AVs. Given the evaluation results, we can ensure that our data-driven approach yields an AV safety assessment scenario with high representativeness, coverage, expansion, and computational feasibility.

Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.

2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe) induce adverse cardiac effects in vitro and in vivo.

Two emerging psychoactive substances, 2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe), are being abused, leading to fatal and non-fatal intoxications. However, most of their adverse effects have been reported anecdotally. In the present study, cardiotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, rat electrocardiography (ECG), and human ether-a-go-go-related gene (hERG) assay. Expression levels of p21 (CDC42/RAC)-activated kinase 1 (PAK1), one of known biomarkers for cardiotoxicity, were also analyzed. Both 25D-NBOMe and 25C-NBOMe at 100 µM reduced cell viability in MTT assay. At 2.0 mg/kg and 0.75 mg/kg, they prolonged QT intervals in rat ECG. PAK1 was down-regulated by treatment with these two test compounds. Furthermore, potassium channels were inhibited by 25D-NBOMe treatment in hERG assay. Taken together, these results suggest that both 25D-NBOMe and 25C-NBOMe have potential cardiotoxicity, especially regarding cardiac rhythm. Further studies are needed to confirm the relationship between PAK1 down-regulation and cardiotoxicity.

Urinary arsenic species concentration in residents living near abandoned metal mines in South Korea.

BACKGROUND: Arsenic is a carcinogenic heavy metal that has a species-dependent health effects and abandoned metal mines are a source of significant arsenic exposure. Therefore, the aims of this study were to analyze urinary arsenic species and their concentration in residents living near abandoned metal mines and to monitor the environmental health effects of abandoned metal mines in Korea. METHODS: This study was performed in 2014 to assess urinary arsenic excretion patterns of residents living near abandoned metal mines in South Korea. Demographic data such as gender, age, mine working history, period of residency, dietary patterns, smoking and alcohol use, and type of potable water consumed were obtaining using a questionnaire. Informed consent was also obtained from all study subjects (n = 119). Urinary arsenic species were quantified using high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP/MS). RESULTS: The geometric mean of urinary arsenic (sum of dimethylarsinic acid, monomethylarsonic acid, As3+, and As5+) concentration was determined to be 131.98 µg/L (geometric mean; 95% CI, 116.72-149.23) while urinary inorganic arsenic (As3+ and As5+) concentration was 0.81 µg/L (95% CI, 0.53-1.23). 66.3% (n = 79) and 21.8% (n = 26) of these samples exceeded ATSDR reference values for urinary arsenic (>100 µg/L) and inorganic arsenic (>10 µg/L), respectively. Mean urinary arsenic concentrations (geometric mean, GM) were higher in women then in men, and increased with age. Of the five regions evaluated, while four regions had inorganic arsenic concentrations less than 0.40 µg/L, one region showed a significantly higher concentration (GM 15.48 µg/L; 95% CI, 7.51-31.91) which investigates further studies to identify etiological factors. CONCLUSION: We propose that the observed elevation in urinary arsenic concentration in residents living near abandoned metal mines may be due to environmental contamination from the abandoned metal mine. TRIAL REGISTRATION: Not Applicable (We do not have health care intervention on human participants).

Activities of daily living questionnaire from patients' perspectives in Parkinson's disease: a cross-sectional study.

BACKGROUND: The aim of this study was to develop an assessment tool for activities of daily living (ADL) from the perspective of patients with Parkinson's disease (PD) and examine the validity and reliability of the assessment. METHODS: A preliminary 45-item questionnaire was developed through intensive interviews with 54 patients with PD and administered to another group of 248 patients with PD. Based on clinical and statistical analyses, 20 ADL-items were selected. The final 20-item questionnaire was examined in the other group of 59 patients with PD. RESULTS: The new ADL questionnaire showed high internal consistency (Cronbach's α, 0.962-0.966) and acceptable test-retest reliability (0.632-0.984). Concurrent validity was shown as a significant positive correlation between the new ADL questionnaire and other ADL or clinical instruments. The Hoehn and Yahr stage showed the highest degree of correlation with the new ADL questionnaire, followed by the other ADL scales (Schwab and England ADL and the ADL subscore of the Unified Parkinson's Disease Rating Scale). Additionally, a regression analysis was conducted with the disease-specific quality of life questionnaire, and the new ADL questionnaire was the most powerful predictor of quality of life among the clinical instruments. CONCLUSIONS: The new ADL questionnaire is a valid tool for assessing ADL from the perspectives of patients with PD.

Development of biomarker positivity analysis system for cancer diagnosis based on clinical data.

In Korea, there were 224,000 new cases of cancer and 75,334 deaths caused by cancer in 2013, which was three times more than the number of death caused by heart disease, the second leading cause of death. This study proposes a biomarker positivity analysis system based on clinical data, for personalized diagnosis and therapy of cancer. Data of 78,912 cases were obtained from immunopathology and surgical pathology reports. Data on sex, age, organ, diagnosis, and biomarkers were entered into a database. To verify the reliability of the clinical data, an additional 50,450 cases from positivity-related research papers were added. The proposed biomarker positivity analysis system makes it possible to extract and combine information for searching. The positivity values are in graphical and tabular format for ease of use. With a link to the internal network of the hospital, real-time pathology reports are available. Twenty-five pathology specialists are chosen as subjects to further confirm the reliability of this system; primary assessment results demonstrate a satisfaction level of 4.7 out of 5 and a concordance rate of 79% with positive data under the same conditions as reported in the literature. In the present study, analysis methods and platforms using large volumes of clinical and literature data are developed for cancer prognoses. It is expected that these tools will benefit both healthcare professionals and non-professionals involved in cancer diagnosis and treatment.

Nonmotor symptoms more closely related to Parkinson's disease: comparison with normal elderly.

Nonmotor symptoms (NMSs) commonly occur in Parkinson's disease (PD). This study sought to explore the domains of NMSs that are more closely related to PD using nonmotor symptoms scale (NMSS), through a quantitative comparison of NMSs' prevalence and NMSS scores of PD patients with normal controls, and clinical implications. We performed a prospective case-control study on PD patients (n=131) and age- and gender-matched normal controls (n=129). We compared NMSs' prevalence and NMSS scores of the PD patients with those of normal controls, and obtained the ratio to identify the domains that were more closely related to PD than normal aging using the NMSS. NMSs are very common among normal elderly as well as PD patients. The domains with the highest ratio of NMSs' prevalence and NMSS scores between the patient and control groups were the miscellaneous, perceptual problems/hallucinations, and sexual function. These three domains were found to be most closely related to PD. NMSs with higher prevalence in PD patients do not always relate more to PD. As NMSs in PD can also commonly occur among the normal elderly, the NMS prevalence should be interpreted with extreme caution. To properly manage the NMSs in PD, it should be kept in mind that avoiding the overestimation of NMSs as part of PD is as important as their early recognition in PD.

Transformative two-dimensional layered nanocrystals.

Regioselective chemical reactions and structural transformations of two-dimensional (2D) layered transition-metal chalcogenide (TMC) nanocrystals are described. Upon exposure of 2D TiS(2) nanodiscs to a chemical stimulus, such as Cu ion, selective chemical reaction begins to occur at the peripheral edges. This edge reaction is followed by ion diffusion, which is facilitated by interlayer nanochannels and leads to the formation of a heteroepitaxial TiS(2)-Cu(2)S intermediate. These processes eventually result in the generation of a single-crystalline, double-convex toroidal Cu(2)S nanostructure. Such 2D regioselective chemical reactions also take place when other ionic reactants are used. The observations made and chemical principles uncovered in this effort indicate that a general approach exists for building various toroidal nanocrystals of substances such as Ag(2)S, MnS, and CdS.

Ultrathin zirconium disulfide nanodiscs.

We present a colloidal route for the synthesis of ultrathin ZrS(2) (UT-ZrS(2)) nanodiscs that are ~1.6 nm thick and consist of approximately two unit cells of S-Zr-S. The lateral size of the discs can be tuned to 20, 35, or 60 nm while their thickness is kept constant. Under the appropriate conditions, these individual discs can self-assemble into face-to-face-stacked structures containing multiple discs. Because the S-Zr-S layers within individual discs are held together by weak van der Waals interactions, each UT-ZrS(2) disc provides spaces that can serve as host sites for intercalation. When we tested UT-ZrS(2) discs as anodic materials for Li(+) intercalation, they showed excellent nanoscale size effects, enhancing the discharge capacity by 230% and greatly improving the stability in comparison with bulk ZrS(2). The nanoscale size effect was especially prominent for their performance in fast charging/discharging cycles, where an 88% average recovery of reversible capacity was observed for UT-ZrS(2) discs with a lateral diameter of 20 nm. The nanoscale thickness and lateral size of UT-ZrS(2) discs are critical for fast and reliable intercalation cycling because those dimensions both increase the surface area and provide open edges that enhance the diffusion kinetics for guest molecules.

Nanoscaling laws of magnetic nanoparticles and their applicabilities in biomedical sciences.

Magnetic nanoparticles, which exhibit a variety of unique magnetic phenomena that are drastically different from those of their bulk counterparts, are garnering significant interest since these properties can be advantageous for utilization in a variety of applications ranging from storage media for magnetic memory devices to probes and vectors in the biomedical sciences. In this Account, we discuss the nanoscaling laws of magnetic nanoparticles including metals, metal ferrites, and metal alloys, while focusing on their size, shape, and composition effects. Their fundamental magnetic properties such as blocking temperature (Tb), spin life time (tau), coercivity (Hc), and susceptibility (chi) are strongly influenced by the nanoscaling laws, and as a result, these scaling relationships can be leveraged to control magnetism from the ferromagnetic to the superparamagnetic regimes. At the same time, they can be used in order to tune magnetic values including Hc, chi, and remanence (Mr). For example, life time of magnetic spin is directly related to the magnetic anisotropy energy (KuV) and also the size and volume of nanoparticles. The blocking temperature (Tb) changes from room temperature to 10 K as the size of cobalt nanoparticles is reduced from 13 to 2 nm. Similarly, H c is highly susceptible to the anisotropy of nanoparticles, while saturation magnetization is directly related to the canting effects of the disordered surface magnetic spins and follows a linear relationship upon plotting of ms (1/3) vs r(-1). Therefore, the nanoscaling laws of magnetic nanoparticles are important not only for understanding the behavior of existing materials but also for developing novel nanomaterials with superior properties. Since magnetic nanoparticles can be easily conjugated with biologically important constituents such as DNA, peptides, and antibodies, it is possible to construct versatile nano-bio hybrid particles, which simultaneously possess magnetic and biological functions for biomedical diagnostics and therapeutics. As demonstrated in this Account, nanoscaling laws for magnetic components are found to be critical to the design of optimized magnetic characteristics of hybrid nanoparticles and their enhanced applicability in the biomedical sciences including their utilizations as contrast enhancement agents for magnetic resonance imaging (MRI), ferromagnetic components for nano-bio hybrid structures, and translational vectors for magnetophoretic sensing of biological species. In particular, systematic modulation of saturation magnetization of nanoparticle probes is important to maximize MR contrast effects and magnetic separation of biological targets.

Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging.

Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.

In situ one-pot synthesis of 1-dimensional transition metal oxide nanocrystals.

One-dimensional colloidal metal oxide nanocrystals are of great importance in materials chemistry, but reports on these materials are rare due to lack of well-defined synthetic protocols. In this paper, we present a general and highly effective one-pot synthetic protocol to produce 1-dimensional nanostructures of transition metal oxide (e.g., W(18)O(49), TiO(2), Mn(3)O(4), and V(2)O(5)) through thermally induced crystal growth processes from a mixture of metal chloride and surfactants.