Optical chirality sensing ensembles : mechanistic studies and applications in synthetic methodology development

In the pharmaceutical industry, the development of molecular or chemical sensors for an analyte of interest and the determination of the enantiomeric purity of chiral molecules is essential. Chirality sensors were developed for analytes, such as alcohols, carboxylic acids, ketones, etc., which are valuable building blocks for the synthesis of complex pharmaceuticals. As such, the development of protocols for enantiomeric excess (ee) analysis of alcohols is of significant interest. Furthermore, high-throughput ee screening (HTS) has become crucial due to advances in the methods of combinatorial chemistry and parallel synthesis. Chapter 1 presents the overview of optical detection methods for ee analysis, as they are more suitable for HTS, compared to chromatographic techniques. The alcohols are important functional groups that are widely found in natural products such as terpenes, steroids and saccharides. Accordingly, the development of protocols involving multi-component dynamic assembly for ee analysis of alcohols has been extensively explored. Chapter 2 presents the ee screening method utilizing a reversible tetradentate ligand-based assembly that incorporates the chiral alcohols. The inclusion of alcohols into the ligand structure induces a twist which results in large Cotton effects in the circular dichroism spectra; indicative of the handedness of the alcohol. The objective of the work has been applying this chiral alcohol sensing assay for a true HTS in combination with the parallel synthesis of chiral homo-allylic alcohol. Chapter 3 reports on past studies performed to further gain kinetics and the mechanistic insight toward the multi-component assembly reaction. By elucidating the mechanism of the assembly reaction, we can further optimize the experimental conditions of the reaction in the development of a new assembly. Finally, Chapter 4 presents an effort toward the advancement of a novel sensor for α-chiral ketones. Chiral ketones produced by α-arylation of α,α-difluorocarbonyl compounds has been of interest in medicinal chemistry. This is not only contributed by carbonyl functionality, but by the importance of aromatic compounds containing a fluorine atom or a trifluoromethyl group on an aromatic ring. Improving the original chiral ketone assay to achieve HTS will substantially aid developments in synthetic methodology.Chemistr

Hierarchical burst model for complex bursty dynamics

Temporal inhomogeneities observed in various natural and social phenomena have often been characterized in terms of scaling behaviors in the autocorrelation function with a decaying exponent gamma, the interevent time distribution with a power-law exponent alpha, and the burst size distributions. Here the interevent time is defined as a time interval between two consecutive events in the event sequence, and the burst size denotes the number of events in a bursty train detected for a given time window. To understand such temporal scaling behaviors implying a hierarchical temporal structure, we devise a hierarchical burst model by assuming that each observed event might be a consequence of the multilevel causal or decision-making process. By studying our model analytically and numerically, we confirm the scaling relation alpha+gamma = 2, established for the uncorrelated interevent times, despite of the existence of correlations between interevent times. Such correlations between interevent times are supported by the stretched exponential burst size distributions, for which we provide an analytic argument. In addition, by imposing conditions for the ordering of events, we observe an additional feature of log-periodic behavior in the autocorrelation function. Our modeling approach for the hierarchical temporal structure can help us better understand the underlying mechanisms behind complex bursty dynamics showing temporal scaling behaviors.11Ysciescopu

The reemergence of long-term potentiation in aged Alzheimer's disease mouse model

Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons

Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives

Background The Encyclopedia of DNA Elements (ENCODE) project has advanced our knowledge of the functional elements in the genome and epigenome. The aim of this article was to provide the comprehension about current research trends from ENCODE project and establish the link between epigenetics and periodontal diseases based on epigenome studies and seek the future direction. Main body Global epigenome research projects have emphasized the importance of epigenetic research for understanding human health and disease, and current international consortia show an improved interest in the importance of oral health with systemic health. The epigenetic studies in dental field have been mainly conducted in periodontology and have focused on DNA methylation analysis. Advances in sequencing technology have broadened the target for epigenetic studies from specific genes to genome-wide analyses. Conclusions In line with global research trends, further extended and advanced epigenetic studies would provide crucial information for the realization of comprehensive dental medicine and expand the scope of ongoing large-scale research projects.This research was supported by Grants from MSIP/IITP (2017-0-00398) and Basic Science Research Program (2016R1A1A3A04004838/2020R1 C1C1005830) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning

Electrically Robust Single-Crystalline WTe2 Nanobelts for Nanoscale Electrical Interconnects

As the elements of integrated circuits are downsized to the nanoscale, the current Cu-based interconnects are facing limitations due to increased resistivity and decreased current-carrying capacity because of scaling. Here, the bottom-up synthesis of single-crystalline WTe2 nanobelts and low- and high-field electrical characterization of nanoscale interconnect test structures in various ambient conditions are reported. Unlike exfoliated flakes obtained by the top-down approach, the bottom-up growth mode of WTe2 nanobelts allows systemic characterization of the electrical properties of WTe2 single crystals as a function of channel dimensions. Using a 1D heat transport model and a power law, it is determined that the breakdown of WTe2 devices under vacuum and with AlOx capping layer follows an ideal pattern for Joule heating, far from edge scattering. High-field electrical measurements and self-heating modeling demonstrate that the WTe2 nanobelts have a breakdown current density approaching approximate to 100 MA cm(-2), remarkably higher than those of conventional metals and other transition-metal chalcogenides, and sustain the highest electrical power per channel length (approximate to 16.4 W cm(-1)) among the interconnect candidates. The results suggest superior robustness of WTe2 against high-bias sweep and its possible applicability in future nanoelectronics

Acute Diffuse Phlegmonous Esophagogastritis: A Case Report

Acute phlegmonous infection of the gastrointestinal tract is characterized by purulent inflammation of the submucosa and muscular layer with sparing of the mucosa. The authors report a rare case of acute diffuse phlegmonous esophagogastritis, which was well diagnosed based on the typical chest computed tomographic (CT) findings and was successfully treated. A 48-yr-old man presented with left chest pain and dyspnea for three days. Chest radiograph on admission showed mediastinal widening and bilateral pleural effusion. The patient became febrile and the amount of left pleural effusion is increased on follow-up chest radiograph. Left closed thoracostomy was performed with pus drainage. A CT diagnosis of acute phlegmonous esophagogastritis was suggested and a surgery was decided due to worsening of clinical condition of the patient and radiologic findings. Esophageal myotomies were performed and the submucosal layer was filled with thick, cheesy materials. The patient was successfully discharged with no postoperative complication

Next-Generation TLC: A Quantitative Platform for Parallel Spotting and Imaging

A high-throughput screening approach for simultaneous analysis and quantification of the percent conversion of up to 48 reactions has been developed using a thin-layer chromatography (TLC) imaging method. As a test-bed reaction, we monitored 48 thiol conjugate additions to a Meldrum's acid derivative (1) in parallel using TLC. The TLC elutions were imaged using a cell phone and a LEGO brick-constructed UV/vis light box. Further, a spotting device was constructed from LEGO bricks that allows simple transfer of the samples from a well-plate to the TLC plate. Using software that was developed to detect "blobs" and report their intensity, we were able to quantitatively determine the extent of completion of the 48 reactions with one analysis