Development of a novel endolysin, PanLys.1, for the specific inhibition of

Objective The objective of this study was to develop a novel endolysin (PanLys.1) for the specific killing of the ruminal hyper-ammonia-producing bacterium Peptostreptococcus anaerobius (P. anaerobius). Methods Whole genome sequences of P. anaerobius strains and related bacteriophages were collected from the National Center for Biotechnology Information database, and the candidate gene for PanLys.1 was isolated based on amino acid sequences and conserved domain database (CDD) analysis. The gene was overexpressed using a pET system in Escherichia coli BL21 (DE3). The lytic activity of PanLys.1 was evaluated under various conditions (dosage, pH, temperature, NaCl, and metal ions) to determine the optimal lytic activity conditions. Finally, the killing activity of PanLys.1 against P. anaerobius was confirmed using an in vitro rumen fermentation system. Results CDD analysis showed that PanLys.1 has a modular design with a catalytic domain, amidase-2, at the N-terminal, and a cell wall binding domain, from the CW-7 superfamily, at the C-terminal. The lytic activity of PanLys.1 against P. anaerobius was the highest at pH 8.0 (p<0.05) and was maintained at 37°C to 45°C, and 0 to 250 mM NaCl. The activity of PanLys.1 significantly decreased (p<0.05) after Mn2+ or Zn2+ treatment. The relative abundance of P. anaerobius did not decrease after administration PanLys.1 under in vitro rumen conditions. Conclusion The application of PanLys.1 to modulate P. anaerobius in the rumen might not be feasible because its lytic activity was not observed in in vitro rumen system

Development of sensitizer peptide-fused endolysin Lys1S-L9P acting against multidrug-resistant gram-negative bacteria

The advent of multidrug-resistant (MDR) bacteria poses a major threat to public health, garnering attention to novel antibiotic replacements. Endolysin, a bacteriophage-derived cell wall-degrading enzyme, is a promising alternative to conventional antibiotics. However, it is challenging to control Gram-negative bacteria due to the presence of the outer membrane that shields the peptidoglycan layer from enzymatic degradation. To overcome this threshold, we constructed the fusion endolysin Lys1S-L9P by combining endolysin LysSPN1S with KL-L9P, a sensitizer peptide known to extend efficacy of antibiotics by perturbing the outer membrane of Gram-negative bacteria. In addition, we established a new endolysin purification procedure that increases solubility allowing a 4-fold increase in production yield of Lys1S-L9P. The sensitizer peptide-fused endolysin Lys1S-L9P exhibited high bactericidal effects against many MDR Gram-negative pathogens and was more effective in eradicating biofilms compared to LysSPN1S. Moreover, Lys1S-L9P showed potential for clinical use, maintaining stability at various storage temperatures without cytotoxicity against human cells. In the in vivo Galleria mellonella model, Lys1S-L9P demonstrated potent antibacterial activity against MDR Gram-negative bacteria without inducing any toxic activity. This study suggest that Lys1S-L9P could be a potential biocontrol agent to combat MDR Gram-negative bacteria

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder

Purpose Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. Methods A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. Results Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. Conclusions Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB

Iterative Channel Estimation for Wireless Communications

The main objective of this dissertation is to present the structural design, performance evaluation, and complexity reduction of iterative joint channel estimation and data detection receivers. One of the main technical challenges in advanced wireless communications stems from the characteristics of a wireless channel, e.g., time selectivity of a channel, mobility of users, and multipath propagation. Channel estimation is essential for achieving reliable information transmission for practical wireless communication applications. Numerous channel estimation structures have been developed for different underlying channels using pilot-symbol assisted modulation (PSAM) approaches. However, since pilot symbols carry no data information, the time and the power spent on pilot symbols degrades the efficiency and the throughput of the system. Therefore, it is necessary to minimize the pilot insertion ratio without degrading the error performance. This motivates our research on iterative joint channel estimation and data detection receivers with full- and reduced- or low-complexity. In this thesis, we first propose an iterative channel estimator (ICE), based on a maximum a posteriori (MAP) algorithm, for single-carrier systems with PSAM structures. In contrast to existing MAP channel estimators, the proposed channel estimator has a lower computational complexity, which increases linearly with the modulation alphabet size. The computational complexity is reduced by exploiting a survivor in an efficient manner, while achieving comparable error performance to a full complexity receiver. For orthogonal frequency division multiplexing (OFDM) systems, we also propose novel signal constellations to facilitate channel estimation without pilot symbol transmission, and analyze the bit error rate for the proposed constellations. We also develop a suitable joint channel estimation and data detector with full- and low-complexity for the proposed constellations. This low-complexity ICE achieves an error performance comparable to the ICE with full-complexity. Finally, for vertical Bell Laboratories layered space-time OFDM systems, we propose an ICE based on a PSAM structure for time-varying multipath fading channels. By exploiting the statistical properties of a wireless channel, we also develop a method to suppress intercarrier interference due to the channel time selectivity, and propose a low-complexity ICE that exploits a priori information in an efficient manner.Ph.D.Committee Chair: Gordon L. Stuber; Committee Co-Chair: Ye (Geoffrey) Li; Committee Member: Alfred D. Andrew; Committee Member: George F. Riley; Committee Member: John R. Barry; Committee Member: Mary A. Ingra

Development of bench-top photon-counting CT system and its application to calibration-based material decomposition

"Photon-counting CT", "Material decomposition", "Quantitative analysis"Ⅰ. Introduction 1 Ⅱ. Materials and methods 2 2.1 Development of bench-top PCD-CT system 2 2.2 Alignment 4 2.3 Data pre-processing for the calibration-based material decomposition 5 2.4 Image-based material decomposition(IMD) 7 2.5 Polynomial expansion-based material decomposition(PMD) 8 2.6 Least-squares-based material decomposition(LSMD) 9 2.7 Basis transform matrix 10 Ⅲ. Results 12 3.1 Basis transformation 12 3.2 Qualitative analysis(CT images) 14 3.3 Quantitative analysis 15 Ⅳ. Discussion and Conclusion 17 References 19 요약문 21MasterdCollectio

Effects of Red Ginseng Byproducts on Rumen Fermentation, Growth Performance, Blood Metabolites, and mRNA Expression of Heat Shock Proteins in Heat-Stressed Fattening Hanwoo Steers

The objective of this study was to evaluate the effects of dietary supplementation with red ginseng byproduct (RGB) on rumen fermentation, growth performance, blood metabolites, and mRNA expression of heat shock proteins (HSP) in fattening Hanwoo steers under heat stress. Two experimental total mixed rations (TMR) were prepared: (1) a TMR meeting the requirement of fattening beef having an average daily gain (ADG) 0.8 kg/day (CON) and (2) a TMR that included 2% RGB on a dry matter (DM) basis (GINSENG). In vitro rumen fermentation and in vivo growth experiments were conducted using two experimental diets. A total of 22 Hanwoo steers were distributed to two treatments (CON vs. GINSENG) in a completely randomized block design according to body weight (BW). The experiment was conducted during the summer season for five weeks. The final BW, ADG, DM intake, and feed conversion ratio did not differ between treatments in the growth trial. In the mRNA expression results, only HSP 90 showed an increasing tendency in the GINSENG group. The use of 2%DM RGB did not improve the growth performance or alleviate heat stress in fattening Hanwoo steers during the summer season

Prediction of Run-Off Road Crash Severity in South Korea&rsquo;s Highway through Tree Augmented Na&iuml;ve Bayes Learning

The run-off road crash (RORC) is a representative type of lethal crash. The severity of RORC has increased owing to a combination of factors, such as roadside geometry, traffic conditions, and weather/climatic conditions. In this study, a model for estimating the RORC severity was developed based on various factors, including fixed objects, roadway geometry, traffic conditions, and road traffic environment. To develop the model, the accident data of crashes with roadside fixed objects on highways, as well as information on fixed object-related variables and roadway geometry-related variables, were collected. To improve the model in terms of implementing a close reflection of the real world, a learning method with tree augmented na&iuml;ve Bayes (TAN), which takes into account the causal links between variables, was applied. The results of the analysis showed that the severity of crashes with roadside fixed objects increased sharply when the vertical slope was &ge;4%, the radius of the curve was &ge;250 m, the distance between the fixed object and the roadway was less than 3 m, or the density of fixed objects installation was greater than 2 for every 10 m. The proposed model allows for an analysis of sections with a high RORC severity on the roadways in operation and provides improvement measures to reduce the severity of RORC