Formation of Modern Literary Field: Intersection of Gender and Coloniality in Korean History.

This dissertation begins with several questions regarding colonial modernity, gender and nationalism in colonial Korea. Why do some New Women, especially female writers, get memorialized as ideal models, and others do not? If gendered nationalism produced the model of an ideal women and suppressed and regulated women to fit that frame, where can we locate the subjectivity of New Women? Even though male nationalists seem so powerful when they construct and enforce a model for ideal women, is their power undermined by their own status as the colonized? In order to answer these sequential questions, this dissertation follows writers’ lives and their works in colonial Korea. The literary world, with its writers’ groups, was the place to practice modernity because, in the colonial context, the participation of Koreans in the economic and political realms was restricted. As a consequence, the literary realm became especially important, and it offers us a valuable opportunity for observing the discourse and behavior of these colonial subjects. Using the comparative method, I argue that gaining access to economic resources and maintaining favorable public opinion contribute to the success of female writers. Although both successful and unsuccessful female writers had several marriages, divorces, and love affairs, the more successful second generation of female writers use several strategies such as making politically expedient marriages, and publishing ideologically uncontroversial stories to maintain their popularity. In short, they learned the lessons of their first-generation predecessors. While male writers tried to control the behaviors of Korean New Women, they also attempted to overcome their own insecure position as the colonized by imagining Japanese women as their inferior. The literary world of colonial Korea, in the form of novels, newspaper and magazine articles, and barriers to publication, clearly reflects these struggles and conflicts. At the same time, the colonial writers contributed to the construction and practice of social norms. Examining these multi-layered conflicts and the construction of norms in the colonial context, this dissertation suggests that no single category or duality, whether male/female or colonizer/colonized, fully explains the colonial structure or the struggles that took place within it.Ph.D.SociologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/75884/1/junh_1.pd

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway

Synthesis and Applications of Dicationic Iodide Materials for Dye-Sensitized Solar Cells

Dye-sensitized solar cells (DSSCs) have been receiving growing attentions as a potential alternative to order photovoltaic devices due to their high efficiency and low manufacturing cost. DSSCs are composed of a photosensitizing dye adsorbed on a mesoporous film of nanocrystalline TiO2 as a photoelectrode, an electrolyte containing triiodide/iodide redox couple, and a platinized counter electrode. To improve photovoltaic properties of DSSCs, new dicationic salts based on ionic liquids were synthesized. Quite comparable efficiencies were obtained from electrolytes with new dicationic iodide salts. The best cell performance of 7.96% was obtained with dicationic salt of PBDMIDI

A critical role for hepatic protein arginine methyltransferase 1 isoform 2 in glycemic control

Appropriate control of hepatic gluconeogenesis is essential for the organismal survival upon prolonged fasting and maintaining systemic homeostasis under metabolic stress. Here, we show protein arginine methyltransferase 1 (PRMT1), a key enzyme that catalyzes the protein arginine methylation process, particularly the isoform encoded by Prmt1 variant 2 (PRMT1V2), is critical in regulating gluconeogenesis in the liver. Liver‐specific deletion of Prmt1 reduced gluconeogenic capacity in cultured hepatocytes and in the liver. Prmt1v2 was expressed at a higher level compared to Prmt1v1 in hepatic tissue and cells. Gain‐of‐function of PRMT1V2 clearly activated the gluconeogenic program in hepatocytes via interactions with PGC1α, a key transcriptional coactivator regulating gluconeogenesis, enhancing its activity via arginine methylation, while no effects of PRMT1V1 were observed. Similar stimulatory effects of PRMT1V2 in controlling gluconeogenesis were observed in human HepG2 cells. PRMT1, specifically PRMT1V2, was stabilized in fasted liver and hepatocytes treated with glucagon, in a PGC1α‐dependent manner. PRMT1, particularly Prmt1v2, was significantly induced in the liver of streptozocin‐induced type 1 diabetes and high fat diet‐induced type 2 diabetes mouse models and liver‐specific Prmt1 deficiency drastically ameliorated diabetic hyperglycemia. These findings reveal that PRMT1 modulates gluconeogenesis and mediates glucose homeostasis under physiological and pathological conditions, suggesting that deeper understanding how PRMT1 contributes to the coordinated efforts in glycemic control may ultimately present novel therapeutic strategies that counteracts hyperglycemia in disease settings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/10/fsb221018-sup-0005-FigS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/9/fsb221018-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/8/fsb221018-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/7/fsb221018-sup-0008-FigS8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/6/fsb221018-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/5/fsb221018_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/4/fsb221018.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/3/fsb221018-sup-0007-FigS7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/2/fsb221018-sup-0006-FigS6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163465/1/fsb221018-sup-0004-FigS4.pd

Directing ricin-based immunotoxins with targeting affibodies and KDEL signal peptide to cancer cells effectively induces apoptosis and tumor suppression

<jats:title>Abstract</jats:title><jats:p>The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based ???magic bullets??? to effectively suppress tumors that are resistant to conventional anti-cancer drugs.</jats:p> <jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p&gt

Demonstration of P-Type Stack-Channel Ternary Logic Device Using Scalable Dntt Patterning Process

A p-type ternary logic device with a stack-channel structure is demonstrated using an organic p-type semiconductor, dinaphtho[2,3-b:2\u27,3\u27-f]thieno[3,2-b]thiophene (DNTT). A photolithography-based patterning process is developed to fabricate scaled electronic devices with complex organic semiconductor channel structures. Two layers of thin DNTT with a separation layer are fabricated via the low-temperature deposition process, and for the first time, p-type ternary logic switching characteristics exhibiting zero differential conductance in the intermediate current state are demonstrated. The stability of the DNTT stack-channel ternary logic switch device is confirmed by implementing a resistive-load ternary logic inverter circuit

Dual-Channel P-Type Ternary Dntt-Graphene Barristor

P-type ternary switch devices are crucial elements for the practical implementation of complementary ternary circuits. This report demonstrates a p-type ternary device showing three distinct electrical output states with controllable threshold voltage values using a dual-channel dinaphtho[2,3-b:2\u27,3\u27-f]thieno[3,2-b]-thiophene-graphene barristor structure. to obtain transfer characteristics with distinctively separated ternary states, novel structures called contact-resistive and contact-doping layers were developed. The feasibility of a complementary standard ternary inverter design around 1 V was demonstrated using the experimentally calibrated ternary device model

A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A

Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7±8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand

The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury

Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT). Hv1 mediated voltage-gated proton currents in spinal microglia and mice lacking Hv1 (Hv1 KO) display attenuated pain hypersensitivities after SNT compared with wildtype (WT) mice. In addition, microglial production of reactive oxygen species (ROS) and subsequent astrocyte activation in the spinal cord was reduced in Hv1 KO mice after SNT. Cytokine screening and immunostaining further revealed that IFN-γ expression was compromised in spinal astrocytes in Hv1 KO mice. These results demonstrate that Hv1 proton channel contributes to microglial ROS production, astrocyte activation, IFN-γ upregulation, and subsequent pain hypersensitivities after SNT. This study suggests Hv1-dependent microglia-astrocyte communication in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.The work was supported by the National Institutes of Health grants (R01NS110825 and R01NS088627) to L.J.W and National Research Founda‑tion of Korea grants (NRF-2017M3C7A1025602, 2018R1A5A2024418 and 2021R1A2C3003334) from Korean government MSIT (Ministry of Science and ICT) to S.B.O

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis

In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child–Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2months, p = 0.070) and PFS (4.6 vs 2.4months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96–2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC