Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior in Mice

The advent and recent advances of single-cell RNA sequencing (scRNA-seq) have yielded transformative insights into our understanding of cellular diversity in the central nervous system (CNS) with unprecedented detail. However, due to current experimental and computational limitations on defining transcriptomic cell types (T-types) and the multiple phenotypic features of cell types in the CNS, an integrative and multimodal approach should be required for the comprehensive classification of cell types. To this end, performing multimodal analysis of scRNA-seq in hypothalamus would be very beneficial in that hypothalamus, controlling homeostatic and innate survival behaviors which known to be highly conserved across a wide range of species and encoded in hard-wired brain circuits, is likely to display the more straightforward relationship between transcriptomic identity, axonal projections, and behavioral activation, respectively. In my dissertation, I have been focused on the cell type characterizations of a hypothalamic node controlling innate social behavior in mice, the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). VMHvl only contains ~4,000 neurons per hemisphere in mice but due to its behavioral, anatomical, and molecular heterogeneity, which T-types in VMHvl are related to connectivity and behavioral function is largely unknown. In Chapter II, I described my main thesis work to perform scRNA-seq in VMHvl using two independent platforms: SMART-seq2 (~4,500 neurons sequenced) and 10x (~78,000 neurons sequenced). Specifically, 17 joint VMHvl T-types including several sexually dimorphic clusters were identified by canonical correlation analysis (CCA) in Seurat, and the majority of them were validated by multiplexed single-molecule FISH (seqFISH). Correspondence between transcriptomic identity, and axonal projections or behavioral activation, respectively, was also investigated. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity. In Chapter III, I will discuss about future directions for a deeper and better understanding of VMHvl cell types. Briefly, my previous data from whole-cell patch clamp recording in VMHvl slices suggested that there were at least 4 distinct electrophysiological cell types (E-types). Additionally, two distinct neuromodulatory effects on VMHvl were observed (persistently activated by vasopressin/oxytocin vs. silenced by nitric oxide) by monitoring populational activities using two-photon Ca2+ imaging in slices. Based on the results from the first part and combined with advanced molecular techniques (e.g. Patch-seq and CRISPR-Cas9), we can further dissect out the cellular diversity in VMHvl and their functional implications.</p

Robust optimization utilizing the second-order design sensitivity information

This paper presents an effective methodology for robust optimization of electromagnetic devices. To achieve the goal, the method improves the robustness of the minimum of the objective function chosen as a design solution by minimizing the second-order sensitivity information, called a gradient index (GI) and defined by a function of gradients of performance functions with respect to uncertain variables. The constraint feasibility is also enhanced by adding a GI corresponding to the constraint value. The distinctive feature of the method is that it requires neither statistical information on design variables nor calculation of the performance reliability during the robust optimization process. The validity of the proposed method is tested with the TEAM Workshop Problem 2

Long-Term Ultrasonography Follow-Up of Thyroid Colloid Cysts at the Health Center: A Single-Center Study

Objective. No previous study has employed long-term follow-up ultrasonography (US) examinations for evaluating thyroid colloid cysts (TCCs) in the general population. This study aimed to assess the interval changes of TCCs at the health center by evaluating long-term US follow-up examinations. Methods. For evaluation of the thyroid gland at our health center from 2006 to 2010, 3692 individuals underwent 4 or more thyroid US examinations at an interval of 1 year or 2 years. We assessed the interval changes of TCCs ≥ 5 mm on US follow-up examinations. Results. Of the 3692 subjects, only 115 (3.1%) showed TCCs ≥ 5 mm on one or more thyroid US examinations. The interval changes in TCCs, as shown by the thyroid US examinations performed during the study period, were classified as follows: no interval change (n=60), gradual increase (n=37), gradual decrease (n=6), positive fluctuation (n=10), negative fluctuation (n=0), and disappearance (n=2). No subject reported any relevant symptom pertaining to TCCs. Conclusions. Overall, follow-up US examinations showed various interval changes in TCCs, but a majority of TCCs showed no interval change or a gradual increase in size

Deformation Characteristics of Hydraulic-Filled Choesionless Soils in Korea

In this study, deformation characteristics of hydraulic-tilled cohesionless soils in Korea were investigated using resonant column tests. Seven representative hydraulic-tilled soil samples, which mostly classified as SM, SP or SP-SM, were collected along the coastal area in Korea, and the deformational characteristics at small to medium strains (10-4 % ~ 0.1 %) were investigated. The predicting equation of small-strain shear modulus, Gmax was suggested using Hardin model. At strains above elastic threshold, the variations of shear modulus (G) and damping ratio (D) with strain amplitude were investigated at various densities and confining pressures. The normalized modulus reduction curve (G/Gmax- log γ) was almost independent of density for a given soil but it was affected by confining pressure. The G/Gmax- log γ curve of hydraulic filled soils moves to the right as confining pressure increases. The representative modulus reduction curves of hydraulic-tilled soils in Korea were determined for 5 confining pressure levels using Ramberg-Osgood model and the proposed curve was composed and compared with the well-known modulus reduction curves. The variations in damping ratio with strain amplitude were also determined and the representative damping curves were proposed for 5 confining pressure levels. The proposed modulus reduction and damping ratio curves would be used as a valuable database for the site response analysis during earthquake

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Cryogenic machining uses liquid nitrogen (LN2) as a coolant. This machining process can reduce the cutting temperature and increase tool life. Titanium alloys have been widely used in the aerospace and automobile industries because of their high strength-to-weight ratio. However, they are difficult to machine because of their poor thermal properties, which reduce tool life. In this study, we applied cryogenic machining to titanium alloys. Orthogonal cutting experiments were performed at a low cutting speed (1.2 - 2.1 m/min) in three cooling conditions: dry, cryogenic, and cryogenic plus heat. Cutting force and friction coefficients were observed to evaluate the machining characteristics for each cooling condition. For the cryogenic condition, cutting force and friction coefficients increased, but decreased for the cryogenic plus heat condition

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The surface roughness and cutting forces are the important factors for the machine-part quality during the hard-turning process. The aim of this paper is to optimize hard-cutting conditions via implementation of response surface methodology (RSM). The experiments were conducted for the hard-turning process with the Box-Behnken design. The validation of the surface roughness and cutting forces was performed with the obtained 2nd order polynomial regression model. The results showed that the surface roughness was strongly dependent upon the RPM. The diminution of the cutting force was attributed to the low feed rate and the depth of cut. On the basis of the RSM, optimized cutting conditions of RPM, feed rate, and depth of cut are 3440, 0.0352 [mm/rev], and 0.03 [mm]. In this optimal cutting condition, the surface roughness can be around Ra= 0.202 ??m