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Convergence Rates of GMM Estimators with Nonsmooth Moments under Misspecification
No full textThe asymptotic behavior of generalized method of moments (GMM) estimators depends critically on whether the underlying moment condition model is correctly specified. Hong and Li (2024) showed that GMM estimators with nonsmooth (nondirectionally differentiable) moment functions are at best n1/3 consistent under misspecification. Through simulations, we verify the decelerated convergence rate of GMM estimators in such cases. For the two-step GMM estimator with an estimated weight matrix, our results align with the theory. However, for the one-step GMM estimator with the identity weight matrix, the convergence rate remains n even under severe misspecification.N
Colorimetric detection of cancer biomarker by using porous Mn–N–C single-atom nanozyme with peroxidase-like activity
No full textGlutathione (GSH) is a critical antioxidant in biological systems involved in various cellular processes such as cell proliferation and apoptosis, and is considered as one of the cancer biomarkers. However, the conventional methods for detecting GSH levels often involve complex and time-consuming preparation and sophisticated equipment, posing challenges for rapid and straightforward analysis. Herein, we develop a colorimetric nanosensor using porous single-atom nanozymes (SAzymes), particularly those consisting of atomically dispersed metals on nitrogen-doped carbon supports (M-N-C), to monitor GSH quantitatively. The Mn–N–C SAzymes catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2), resulting in a measurable color change. The high porosity of the Mn–N–C SAzymes offers a large surface area accommodating a high density of accessible active sites for efficient catalysis. The addition of GSH in this system leads to a notable reduction in color intensity, offering an effective method for the quantitative measurement of GSH. The Mn–N–C SAzymes demonstrate high efficacy in the rapid colorimetric detection of GSH, with a low detection limit of 0.70 μM and a broad dynamic range of 0–40 μM. This method is further applied for a simple and rapid colorimetric analysis of the cancer biomarker in various biological samples, including tissues and serum. Demonstrating the potential for diagnostic applications, this approach offers a promising tool for clinical diagnostics, enabling reliable and convenient monitoring of GSH levels, which is crucial for assessing disease progression.N
Effect of electron beam irradiation on microbial inactivation, nutritional and quality properties of semi-moist pet foods
No full textThe objective of this study was to evaluate the effect of electron beam irradiation (E-beam) on semi-moist pet foods at different absorbed doses. The samples were exposed to e-beam at dose levels of 0, 2.5, 5, and 10 kGy. Then, their effect on microbiological, nutritional, and physicochemical properties was analyzed during 60 days of storage. A dose-dependent effect was observed in bacterial pathogens, especially, 10 kGy sterilized them without further growth throughout the storage period. The nutrient analysis confirmed that 10 kGy of e-beam irradiation did not significantly influence the nutritional components of semi-moist pet foods, ensuring they are nutritionally safe for pets. Irradiated samples showed less changes in quality over time, with lower microbial growth and stable attributes like water activity, pH, and redness (a∗). While samples treated with 10 kGy initially showed more lipid oxidation and protein degradation, these differences were not significant by day 60, suggesting that higher doses did not affect physicochemical properties during storage. In contrast, non-irradiated samples experienced microbial and physicochemical changes over the extended storage. Therefore, we conclude that e-beam irradiation up to 10 kGy can secure microbial safety in semi-moist pet foods, preserving their nutritional and quality attributes for pets consumption.N
Unraveling the dynamics of osteoblast differentiation in MC3T3-E1 cells: Transcriptomic insights into matrix mineralization and cell proliferation
No full textUnraveling the intricacies of osteoblast differentiation is crucial for advancing our comprehension of bone biology. This study investigated the complicated molecular events orchestrating osteoblast differentiation in MC3T3-E1 cells, a well-established in vitro culture model. Employing longitudinal RNA-sequencing analysis, we explored transcriptomic changes at the pivotal time points of 0, 1, 4, 7, 10, 14, and 21 days and categorized osteogenic differentiation into proliferation, matrix maturation, and mineralization stages. Notably, we observed a simultaneous increase in matrix mineralization and cell proliferation during the mineralization stage, accompanied by a positive correlation between proliferation-associated genes and those enriched in ossification. Additionally, we identified the presence of proliferating cells over the mineralizing matrix layers. These results could serve as a model for understanding the principles by which bone lining cells are formed on the calcified bone matrix and the mechanism by which new osteoblasts are recruited during the bone remodeling process.N
Identifying Factors Associated With Breastfeeding Length Among Filipino Migrant Women in South Korea
No full textBackground: Migrant women becoming mothers often face social, economic, and family challenges that can affect their dietary and breastfeeding practices. This study identified factors associated with breastfeeding length in migrant women. Methods: The study sample involved 504 migrant women from the Filipino Women's Diet and Health Study (FiLWHEL) in 2014-2016. Two-hundred-seventy women who had completed information on demographic characteristics, 24-h dietary recall, breastfeeding, parity, and health conditions were included in the analysis. Multivariable logistic and linear regression models were applied to identify significant factors associated with breastfeeding length cross-sectionally. Results: The median (interquartile range [IQR]) for age was 35 (30, 40) years, and the mean body mass index (BMI) was 23.8 kg/m(2); 62 women (23%) were breastfeeding for at least 1 year, with the median (IQR) length of 4 (1, 10) months per child. The median (IQR) of the total intake of fruits, vegetables, nuts, and legumes was 165.5 (76.9, 265.9) g/day. Women who consumed the highest tertile of fruits, vegetables, nuts, and legumes compared to those in the lowest tertile were more likely to breastfeed for at least 12 months (adjusted-OR [95% CI]: 2.24 [1.08-4.67]), primarily driven by vegetable consumption (adjusted-OR [95% CI]: 2.34 [1.11-4.93]). Additionally, women in the highest tertile of these food groups or earned an annual income of 20-40 M KRW (similar to 15-30 K USD) appeared to breastfeed longer compared to their counterparts (p < 0.05). Conclusions: This study suggests that dietary quality and income may impact breastfeeding duration for migrant women in South Korea.N
Rapid and sensitive protein complex alignment with Foldseek-Multimer
No full textAdvances in computational structure prediction will vastly augment the hundreds of thousands of currently available protein complex structures. Translating these into discoveries requires aligning them, which is computationally prohibitive. Foldseek-Multimer computes complex alignments from compatible chain-to-chain alignments, identified by efficiently clustering their superposition vectors. Foldseek-Multimer is 3-4 orders of magnitudes faster than the gold standard, while producing comparable alignments; this allows it to compare billions of complex pairs in 11 h. Foldseek-Multimer is open-source software available at GitHub via https://github.com/steineggerlab/foldseek/, https://search.foldseek.com/search/ and the BFMD database.Y
Inhibiting EZH2 complements steroid effects in Duchenne muscular dystrophy
No full textDuchenne muscular dystrophy (DMD) is a devastating X-linked disorder caused by dystrophin gene mutations. Despite recent advances in understanding the disease etiology and applying emerging treatment methodologies, glucocorticoid derivatives remain the only general therapeutic option that can slow disease development. However, the precise molecular mechanism of glucocorticoid action remains unclear, and there is still need for additional remedies to complement the treatment. Here, using single-nucleus RNA sequencing and spatial transcriptome analyses of human and mouse muscles, we investigated pathogenic features in patients with DMD and palliative effects of glucocorticoids. Our approach further illuminated the importance of proliferating satellite cells and revealed increased activity of a signal transduction pathway involving EZH2 in the patient cells. Subsequent administration of EZH2 inhibitors to Dmd mutant mice resulted in improved muscle phenotype through maintaining the immune-suppressing effect but overriding the muscle weakness and fibrogenic effects exerted by glucocorticoids. Our analysis reveals pathogenic mechanisms that can be readily targeted by extant therapeutic options for DMD.Y
Improving Image Quality of Chest Radiography with Artificial Intelligence-Supported Dual-Energy X-Ray Imaging System: An Observer Preference Study in Healthy Volunteers
No full textBackground/Objectives: To compare the image quality of chest radiography with a dual-energy X-ray imaging system using AI technology (DE-AI) to that of conventional chest radiography with a standard protocol. Methods: In this prospective study, 52 healthy volunteers underwent dual-energy chest radiography. Images were obtained using two exposures at 60 kVp and 120 kVp, separated by a 150 ms interval. Four images were generated for each participant: a conventional image, an enhanced standard image, a soft-tissue-selective image, and a bone-selective image. A machine learning model optimized the cancellation parameters for generating soft-tissue and bone-selective images. To enhance image quality, motion artifacts were minimized using Laplacian pyramid diffeomorphic registration, while a wavelet directional cycle-consistent adversarial network (WavCycleGAN) reduced image noise. Four radiologists independently evaluated the visibility of thirteen anatomical regions (eight soft-tissue regions and five bone regions) and the overall image with a five-point scale of preference. Pooled mean values were calculated for each anatomic region through meta-analysis using a random-effects model. Results: Radiologists preferred DE-AI images to conventional chest radiographs in various anatomic regions. The enhanced standard image showed superior quality in 9 of 13 anatomic regions. Preference for the soft-tissue-selective image was statistically significant for three of eight anatomic regions. Preference for the bone-selective image was statistically significant for four of five anatomic regions. Conclusions: Images produced by DE-AI provide better visualization of thoracic structures.Y
Evaluation of primary stability of implants in bovine bone defects models
No full textThis study assessed initial stability using Resonance Frequency Analysis (RFA) and Damping Capacity Analysis (DCA) devices in three different bone conditions: a control group without bone defects, a cortical bone defect model, and a cancellous bone defect model. Additionally, the correlation between Implant Stability Quotient (ISQ) and Implant Stability Test (IST) values was investigated. This in vitro study utilized a controlled experimental design with bovine rib specimens. Thirty implants were placed in specimens divided into three groups (n = 10): no defect (Group A), cortical bone defect (Group B), and cancellous bone defect (Group C). Implant stability was measured using RFA and DCA devices. ISQ and IST values in Group A were 84.83 ± 1.38 and 86.52 ± 1.73, respectively; in Group B, they were 64.20 ± 4.87 and 64.25 ± 5.26, respectively; and in Group C, they were 82.80 ± 5.74 and 86.47 ± 4.01, respectively. Statistical analyses were performed using Kruskal-Wallis test with Bonferroni test to compare differences among groups, and Spearmans correlation analysis was used to evaluate the relationship between ISQ and IST values. A significant reduction in ISQ(p < 0.001) and IST(p < 0.001) values was observed in the cortical bone defect group. In contrast, the cancellous bone defect group showed no significant difference from the control group (ISQ: p = 0.493, IST: p = 0.594). ISQ and IST values exhibited a significant positive correlation (r = 0.798, p < 0.001), and stability values varied significantly with measurement direction. This study confirmed that cortical bone defects significantly reduced primary stability, whereas cancellous bone defects had no significant impact when cortical bone was sufficient. Additionally, ISQ and IST values showed a strong positive correlation, indicating that both methods provide consistent assessments of implant stability.Y
A 65fsrms-Jitter and -272dB-FoMjitter,N10.1GHz Fractional-N Digital PLL with a Quantization-Error-Compensating BBPD and an Orthogonal-Polynomial LMS Calibration
No full textA digital PLL (DPLL) using a BBPD represents the optimal architecture for designing frequency synthesizers in a nanometer-scale CMOS technology because it minimizes reliance on analog circuits that require large headroom and numerous passive components. However, designing a fractional-N DPLL with low jitter, particularly at the sub-100fs level, is highly challenging due to the diverse quantization errors (Q-errors) that are inherent in digital circuits. To mitigate these Q-errors, various techniques have been proposed [1-5]. Recently, a common solution has involved using a digital-to-time converter (DTC) to eliminate the Q-error of the ΔΣM [6-13], which is the most dominant among various Qerrors. However, the DTC itself generates additional thermal noise that is proportional to the amount of delay [14], and this becomes another major source of in-band phase noise (PN). The DTC delay consists of a dynamic delay that is tunable to cancel the ΔΣM Q-error and a static delay that is inevitably generated when producing the dynamic delay. To cover a wider range of the ΔΣM Q-error, the DTC must be designed with a larger dynamic delay range, and this also increases the static delay. A straightforward approach to reducing the thermal noise of the DTC is to use more power, but this inevitably degrades the overall jitter-power FoM (FoMjitter) of the DPLL. This dilemma underscores the need for a new design to cancel the ΔΣM Q-error.N