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There is an increasing interest in developing next-generation wearable ultrasound patch systems because of their wide range of applications, such as home healthcare systems and continuous monitoring systems for physiological conditions. A wearable ultrasound patch system requires a stable interface to the skin, an ultrasound coupling medium, a flexible transducer array, and miniaturized operating circuitries. In this study, we proposed a patch composed of calcium (Ca)-modified silk, which serves as both a stable interface and a coupling medium for ultrasound transducer arrays. The Ca-modified silk patch provided not only a stable and conformal interface between the epidermal ultrasound transducer and human skin with high adhesion but also offered acoustic impedance close to that of human skin. The Ca-modified silk patch was flexible and stretchable (∼400% strain) and could be attached to various materials. In addition, because the acoustic impedance of the Ca-modified silk patch was 2.15 MRayl, which was similar to that of human skin (1.99 MRayl), the ultrasound transmission loss of the proposed patch was relatively low (∼0.002 dB). We also verified the use of the Ca-modified silk patch in various ultrasound applications, including ultrasound imaging, ultrasound heating, and transcranial ultrasound stimulation for neuromodulation. The comparable performance of the Ca-modified patch to that of a commercial ultrasound gel and its durability against various environmental conditions confirmed that the Ca-modified silk patch could be a promising candidate as a coupling medium for next-generation ultrasound patch systems.

Live-streaming commerce business is growing as the consumption of video content and Smartphone shopping increases. This study examines the following three aspects: whether para-social interaction influences perceived interactivity; whether seller trust affects satisfaction with the experience; whether relationships are controlled by a moderated mediator of self-image congruity. An online survey was conducted with 203 women aged 20-30 years. They were asked to respond to the survey after watching a beauty category live-streaming commerce broadcast. The results revealed that the para-social interaction had a significant effect on perceived interactivity, seller trust and satisfaction with the experience. The findings also indicated that the perceived interactivity and seller trust mediated the relationship between para-social interaction and satisfaction with the experience. Regarding the mediated moderation effect of self-image congruity, it was statistically significant between para-social interaction and perceived interactivity through seller trust. A higher level of consumer’s self-image congruity influenced the greater effect of para-social interaction on live commerce experience. This study makes important theoretical contributions to the para-social interaction in mobile commerce industry by emphasizing the mediating role of perceived interactivity and seller trust. This is achieved by examining the moderating effects of self-congruity on satisfaction with the experience. The results also verify the seller’s crucial role in live-streaming commerce market which leads to the consumers greater fulfillment.

The released NOx during fuel combustion is one of the major air pollutants, directly related to acid rain and photochemical smog. At present, there is not an economical and effective method of inhibiting NOx emission from sintering flue gas. Therefore, controlling the conditions of fuel combustion is extremely required for the reduction in NOx. The current research investigated the effects of different combustion parameters on the formation of NOx for three type of coals. The formation of NOx decreased with increasing temperature and heating rate while it increased when oxygen content in an atmosphere increased. Anthracite coal replacement with coke up to 100 pct promoted a decrease in the formed NOx amount and XNO by 21 and 53 pct, respectively. The addition of CaO and FeO enhanced the conversion of nitrogen to NOx, especially at temperatures below 1273 K (1000 °C). Taking both the oxidation reaction to form NOx and reduction reaction of NOx to form N2 into account, the activation energy (EA) values of anthracite and coke were evaluated to be 2.2 and 3.6 kJ/mol, respectively. The combustion of semi-anthracite coal emitted the largest amount of NOx, but the anthracite coal containing less fuel-N than other coals showed the highest value of XNO, which indicates that nitrogen content in coal is not the major factor affecting the formation of NOx. The change in nitrogen functionality after combustion process might be the reason for the unpredicted results in the XNO. The pyrrolic-N in anthracite coal might be considered to be the major functional form that directly affects the conversion of nitrogen to NO.

Strain engineering of perovskite quantum dots (pQDs) enables widely tunable photonic device applications. However, manipulation at the single-emitter level has never been attempted. Here, we present a tip-induced control approach combined with tip-enhanced photoluminescence (TEPL) spectroscopy to engineer strain, bandgap, and the emission quantum yield of a single pQD. Single CsPbBrxI3-x pQDs are clearly resolved through hyperspectral TEPL imaging with ∼10 nm spatial resolution. The plasmonic tip then directly applies pressure to a single pQD to facilitate a bandgap shift up to ∼62 meV with Purcell-enhanced PL increase as high as ∼105 for the strain-induced pQD. Furthermore, by systematically modulating the tip-induced compressive strain of a single pQD, we achieve dynamical bandgap engineering in a reversible manner. In addition, we facilitate the quantum dot coupling for a pQD ensemble with ∼0.8 GPa tip pressure at the nanoscale estimated theoretically. Our approach presents a strategy to tune the nano-opto-electro-mechanical properties of pQDs at the single-crystal level.

OBJECTIVES: Polyunsaturated fatty acids (PUFA) such as n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n-6 PUFA, arachidonic acid (AA) may mediate inflammatory responses. Vitamin B6 deficiency has been shown to alter plasma PUFA levels. This perturbation of PUFA metabolism in vitamin B6 deficiency measured by pyridoxal-5’-phosphate (PLP) may contribute to inflammation. Thus, we aimed to examine the associations of 1) dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level, 2) plasma AA/(EPA + DHA) and PLP with C-reactive protein (CRP), a marker for inflammation, and 3) dietary EPA + DHA, and vitamin B6 with CRP level, using NHANES. METHODS: NHANES datasets (2003–2004) with subjects ≥20 years were analyzed, accounting for survey design and sample weights (n = 4486). The significance level was P < 0.05. Covariates were age, gender, ethnicity, BMI, smoking, alcohol, total energy, dietary supplements, physical activity, and NSAIDs, depending on analyses. Multiple linear regression assessed the association of dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level (Low: 3 mg/L); then, dietary EPA + DHA, and B6 with CRP level. RESULTS: In the low PLP level, dietary EPA + DHA was negatively associated with plasma ratio of AA/(EPA + DHA) (B = ─5.29, SE = 0.84, P = < .0001), but B6 intake was not, whereas, in the high PLP level, both dietary EPA + DHA (B = ─2.99, SE = 0.53, P = < .0001) and dietary vitamin B6 (B = ─0.21, SE = 0.04, P = 0.0001) were inversely associated with plasma AA/(EPA + DHA). Further, low PLP level was associated with greater odds of moderate to high CRP level compared to high PLP level (adjusted OR (aOR): 2.8, 95% CI: 1.93–4.04, P = < .0001), but plasma AA/(EPA + DHA) was not. In addition, both dietary EPA + DHA (aOR: 0.5, 95% CI: 0.23–0.98, P = 0.04) and vitamin B6 (aOR: 0.8, 95% CI: 0.68–0.95, P = 0.009) were inversely associated with moderate to high CRP level. CONCLUSIONS: Our findings show that low plasma PLP level and low vitamin B6 intake are associated with inflammation, and the relationship may be through their effect on PUFA metabolism, suggesting that increased intake of vitamin B6 and EPA and DHA may protect against inflammation. FUNDING SOURCES: N/A.

Methylammonium lead halide (MAPbI3) perovskites are considered as promising materials owing to their excellent optical and electrical properties. However, perovskite materials suffer from degradation in air, which limits their practical applications. Here, we demonstrate successful passivation of the MAPbI3 photodetectors through monochloro-para-xylylene (Parylene-C) deposition. The time-dependent photocurrent characteristics were systematically investigated, and we achieved significantly improved device performance and stability with Parylene-C passivation. Based on the excitation-power-dependent photoluminescence (PL) data, we confirmed that Parylene-C can reduce the carrier losses in MAPbI3, leading to the enhancement of photocurrent and PL in MAPbI3 photodetectors.

With the anticipation for a more connected world through the Internet of Things, there is still a strong demand for miniaturized chemical sensors. Here, we report on a miniaturized resonant chemical sensor based on a Capacitive Micromachined Ultrasonic Transducer (CMUT) with a low operating voltage suitable for portable gas sensor applications. Previously reported CMUT chemical sensors required a DC operating voltage (16∼50 V) higher than the supply voltages of common circuits (e.g., 1.8–5 V). Thus, additional circuitry such as a charge pump circuit often was required as a part of the sensor interface circuits to supply the DC voltage to CMUT. This resulted in additional power consumption and a larger footprint. In this work, the vacuum gap of the CMUT which determines the operating voltage was reduced to 50 nm through the development of a double oxidation process with a high wafer-level yield. We achieved a significantly smaller pull-in voltage (

Non-invasive brain stimulation is a promising alternative therapeutic means for people suffering from brain disorders. Among various direct brain stimulation modalities, ultrasound provides distinct advantages such as non-invasiveness, focusing capability, in-depth targeting, and technical maturity of ultrasound technology. However, the mechanism, therapeutic effects, and safety of ultrasound neuromodulation are yet to be determined. To uncover these fundamental aspects of ultrasound neuromodulation, development of enabling technology, such as miniature ultrasound neuromodulation devices suitable for in vivo and in vitro studies, is essential. Recently, our group has developed a miniature MEMS ultrasound transducer, Capacitive Ultrasonic Micromachined Transducer (CMUT) ring array, that enables non-invasive neuromodulation for freely-moving small animals. The design, implementation, and in vivo results of our system are described.

OBJECTIVES: Previous evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP

This plan explores the marketing potential for the use of Big Data along with visual analytics in neonatal intensive care units. The goal of this technology is to provide more efficient and streamlined data collection and display methods for an extremely vulnerable segment of the population. The applicability of this technology is explored through various business models which address the short, medium, and long term marketing goals, such as SWOT, TOWS, and a Strategic Road Map. The results provide strong support for potential market application in Korea as well as abroad.

After experiencing Apple iPhone’s capabilities and mobile app ecosystem named ‘App Store’, Koreans realized the importance of the software. Government and commercial companies are now seeking ways to develop software potentials aligned with hardware potentials and secure qualified experts such as software architects. How one can make senior software professionals like software architects earn respect and Received (January 29, 2016), Review Result (February 16, 2016) Accepted (February 23, 2016), Published (July 31, 2016) 156-743 Department of IT Policy and Management, Soongsil Univ., Seoul, Korea email: hyojungkim20000@gmail.com 156-743 Department of IT Policy and Management, Soongsil Univ., Seoul, Korea email: jaekul75@gmail.com 156-743 Department of IT Policy and Management, Soongsil Univ., Seoul, Korea email: hoonyjung9999@gmail.com 156-743 Graduate School of Software, Soongsil University, Sangdo-dong, Dongjak-gu, Seoul, Korea email: keita89@naver.com (Corresponding Author)156-743 Department of IT Policy and Management, Soongsil Univ., Seoul, Korea email: kjb123@ssu.ac.kr How to Promote Software Architects in Korea Copyright c 2016 HSST 2 position in the marketplace is very important to make Korea be more competitive globally. Generally speaking, software architects are neither well-known nor respected in Korea. In this paper, who software architects are and what they provide in the market, and how to promote software architect are examined via case studies in marketing and self reinforcing perspectives with implications. As a simple but effective leverage point to make better market ecosystem in labor supply chain related to IT industry, adopting marketing perspective to the software architect is recommended to get interests from individuals, commercial companies and government agencies. Branding with self motivation help the software architect be considered from virtual, invisible potentials to more tangible and visible potentials as we can see the Open Group in WW and KOSTA in Korea.

Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years, 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires, plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.

OBJECTIVES: Antiretroviral therapy has increased life expectancy for HIV infected patients; however, this population is developing chronic illnesses associated with aging. Liver disease is a major cause of non-AIDS mortality, characterized by progressive fibrosis. Infection with HIV and with Hepatitis C Virus (HCV) promotes liver fibrogenesis. Tissue inhibitor of metalloproteinase-1 (TIMP1), inhibits fibrosis regression and is profibrogenic. Association between TIMP1 and liver disease progression in an aging population of HIV/HCV co-infected, HIV mono-infected, HCV mono-infected, and healthy groups from the Miami Adult Studies on HIV (MASH) cohort in Miami, Florida, was investigated. METHODS: Serum TIMP1 levels were determined by ELISA. A non-invasive estimate of liver fibrosis, FIB-4 score was calculated. Liver fibrosis was defined as FIB-4: Low 3.25. ANOVA with Tukey's test assessed the mean differences of FIB-4 score and TIMP1 level between groups, TIMP1 levels between 3 FIB-4 categories, and the effect of age on FIB-4 and TIMP1. Linear regression predicted the association of FIB-4 score and TIMP-1 level. RESULTS: Mean age of the cohort was 54.3 ± 8.1 years with no difference between groups. Mean FIB-4 for HIV/HCV co-infected group was the highest among the 4 groups (P

This paper reports smart wireless sensor node for Structural Health Monitoring (SHM) that is capable of operation with energy harvesting systems using piezoelectric materials. A large amount of research has focused on utilizing the impedance method for structural health monitoring but these studies required expensive and bulky impedance analyzers, which are unsuitable for field deployment. Piezoelectric materials can be used as mechanisms to transfer ambient vibrations into electrical energy that can be stored and used to power other devices. In this study, three types of piezoelectric materials were evaluated experimentally for use as power harvesting devices. In general, the power produced by the vibrations of piezoelectric devices is low, meaning that the equipment powered by the device cannot be operated effectively. Therefore, a time delay circuit and reset IC chip was used to improve the efficiency of the electrical power generated. The experimental results were used to estimate the efficiency of these devices and identified the feasibility of their use in practical applications.

We investigate how the second-order learning process moderates the relationship between innovation performance and two types of knowledge seeking behavior, namely exploration and exploitation. We reinvestigate the second-order learning process of the top 100 Korean firms from 1997 to 2007 by capturing CEO turnover, board turnover, and R&D alliances. We argue that the current findings about exploration and exploitation should be reclassified in terms of innovation input and output. We suggest that researchers investigate the organizational learning process to understand the link between innovation inputs and outputs. Our empirical results show that while innovation inputs are not related to exploratory outputs, the second-order learning process reshapes the relationship between both exploration/exploitation type innovation inputs and exploratory innovation outputs, and that the new focus of organizational learning process can refine current innovation literature.

Collecting large amounts of data is very useful in many ways, however it is only half of a larger whole. This vast amount of data needs to be analyzed and presented in such a way that it can be understood and then used by those who need it, thus the need for strong visual analytics. Development at this stage and in this environment should provide a supportive and technologically rich foundation on which to develop the technology in preparation for international expansion. We believe this can be done by providing comprehensive, collaborative, and easy to use clinical support solutions for the clinical decision makers involved in the NICU.

Background: Cutaneous biophysical parameters which are measured using commercial non-invasive methods are known to reflect skin functions. Previous studies on the age-, climate, and skin care habit-related changes of biophysical parameters have mainly focused on Caucasians, and studies on Asians are in paucity. Objective: This study was aimed to investigate the variations of cutaneous biophysical parameters in Chinese and Korean women (northeast Asians) and to assess the association between those parameters and age, climate, and cosmetic habits. Methods: A cross-sectional study included 361 healthy Chinese and Korean women between 18 and 49 years of age in 4 cities (Guangzhou, Nanjing, and Shijiazhuang in China, and Suwon in Korea). We measured skin surface temperature, hydration, transepidermal water loss (TEWL), sebum, elasticity, skin pore, wrinkle, and skin tone (brightness) using non-invasive instruments. Demographic profiles and cosmetic habits were assessed using a questionnaire. Results: Skin elasticity and tone decreased, and pore size and wrinkle increased with age. Skin surface temperature, hydration, TEWL, and sebum output were not significantly influenced by aging. Four cities showed different climate (temperature and relative humidity) and cosmetic habits. Suwon (Korean) showed higher hydration level, lower TEWL and lower sebum, less severe wrinkle and brighter skin than the 3 cities in China. After adjusting for age and region, using sunscreen everyday, wearing base makeup daily, and using moisturizers improved hydration, TEWL, and elasticity significantly. Conclusions: Korean women were found to have a better profile of biophysical parameters than Chinese women, which might be attributed to cosmetic habits, besides age and climatic factors. The fact that appropriate cosmetic habits are associated with favorable skin biophysical parameters underscores the importance of daily skin care routine in preserving skin functions.

Background Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by a localized degradation of connective tissue and apoptosis of vascular smooth muscle cells. This study examined whether the ligand-activated peroxisome proliferator-activated receptor (PPAR) δ can directly antagonize angiotensin II (Ang II)-induced AAA formation in apoE-deficient mice. Methods and results Six-month-old male apoE-deficient mice were infused with Ang II and/or GW501516 (1.44 and 3.3mg/kg/day, respectively) via osmotic mini-pumps. At day 28, aortic size was measured and tissues were collected for analyses. Co-infusion of GW501516, an activator of PPARδ, attenuated both the incidence and the severity of Ang II-induced AAA in apoE-deficient mice. Ligand-activated PPARδ also reduced infiltration of macrophages, resulting in significant decreases in chemotactic proteins such as monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and inducible nitric oxide synthase. The anti-inflammatory effect of GW501516 was associated with the suppression of apoptotic cell death, along with the inhibition of medial smooth muscle cell loss and focal elastin destruction, which leads to a medial dissection and aortic rupture. These ameliorative effects of GW501516 on Ang II-induced aneurysm were correlated with increased expression of extracellular matrix (ECM) proteins, such as types I and III collagen, fibronectin, and elastin, along with the up-regulation of transforming growth factor-β1. In addition, ligand-activated PPARδ also increased the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3, while it strongly suppressed that of matrix metalloproteinase-2. Conclusions PPARδ attenuates Ang II-induced AAA formation by regulating ECM homeostasis and inflammatory responses, suggesting a novel strategy for the treatment of AAA.

We investigate how the second-order learning process moderates the relationship between innovation performance and two types of knowledge seeking behavior, namely exploration and exploitation. We reinvestigate the second-order learning process of the top 100 Korean firms from 1997 to 2007 by capturing CEO turnovers, Board turnover and R&D alliances. We argue that the current findings about exploration and exploitation should be reclassified in the form of innovation inputs and outputs. We further suggest that researchers need to investigate organizational learning process in understanding the link between innovation inputs and outputs. Our empirical results show that innovation inputs are not related to the exploratory outputs, but the second-order learning process reshapes the relationships between both exploration/exploitation-type innovation inputs and exploratory innovation outputs. Our study shows how the new focus of organizational learning process can refine the current innovation literature.

// Hojin Kang 1,2,* , Rin Khang 1,2,* , Sangwoo Ham 1,* , Ga Ram Jeong 3 , Hyojung Kim 1 , Minkyung Jo 1 , Byoung Dae Lee 3 , Yun Il Lee 4 , Areum Jo 1,2 , ChiHu Park 5,6 , Hyein Kim 1,5 , Jeongkon Seo 7 , Sun Ha Paek 8 , Yun-Song Lee 1 , Jeong-Yun Choi 1 , Yunjong Lee 1 and Joo-Ho Shin 1,2 1 Department of Molecular Cell Biology, Division of Pharmacology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea 2 Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, South Korea 3 Department of Neuroscience, Department of Physiology, Neurodegeneration Control Research Center, Kyung Hee University School of Medicine, Seoul, South Korea 4 Department of New Biology, Daegu Geongbuk Institute of Science and Technology, Daegu, South Korea 5 Research Core Facility, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea 6 HuGeX Co., Ltd. Seongnam, South Korea 7 UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, South Korea 8 Department of Neurosurgery, Seoul National University College of Medicine, Seoul, South Korea * These authors have contributed equally to this work Correspondence to: Yunjong Lee, email: // Joo-Ho Shin, email: // Keywords : metformin, dopaminergic, Parkinson’s disease, PGC-1α, mitochondria, Gerotarget Received : October 10, 2016 Accepted : April 24, 2017 Published : May 24, 2017 Abstract Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson’s disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown. In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN). Consistent with this data, metformin increased mitochondrial marker proteins in SH-SY5Y neuroblastoma cells. Mitochondrial protein expression by metformin was found to be brain region specific, with metformin increasing mitochondrial proteins in the SN and the striatum, but not the cortex. As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1α promoter activity was stimulated by metformin via CREB and ATF2 pathways. PGC-1α and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex. Finally, we showed that metformin protected dopaminergic neurons and improved dopamine-sensitive motor performance in an MPTP-induced PD animal model. Together these results suggest that the metformin-ATF2/CREB-PGC-1α pathway might be promising therapeutic target for PD.

Resistive random-access memory (ReRAM) devices based on halide perovskites have recently emerged as a new class of data storage devices, where the switching materials used in these devices have attracted extensive attention in recent years. Thus far, three-dimensional (3D) halide perovskites have been the most investigated materials for resistive switching memory devices. However, 3D-based memory devices display ON/OFF ratios comparable to those of oxide or chalcogenide ReRAM devices. In addition, perovskite materials are susceptible to exposure to air. Herein, we compare the resistive switching characteristics of ReRAM devices based on a quasi-two-dimensional (2D) halide perovskite, (PEA)2Cs3Pb4I13, to those based on 3D CsPbI3. Astonishingly, the ON/OFF ratio of the (PEA)2Cs3Pb4I13-based memory devices (109) is three orders of magnitude higher than that of the CsPbI3 device, which is attributed to a decrease in the high-resistance state (HRS) current of the former. This device also retained a high ON/OFF current ratio for 2 weeks under ambient conditions, whereas the CsPbI3 device degraded rapidly and showed unreliable memory properties after 5 days. These results strongly suggest that quasi-2D halide perovskites have potential in resistive switching memory based on their desirable ON/OFF ratio and long-term stability. A type of computer memory that stores data by changing the resistance of insulating crystals can be made more durable with organic chemical additives. Resistive memory devices constructed from inorganic crystals known as halide perovskites are inexpensive and have minimal power requirements. However, they can degrade quickly in humid conditions. Hyojung Kim from Seoul National University in South Korea and colleagues now report that these stability issues can be improved by sandwiching thin layers of aromatic hydrocarbons between halide perovskite crystals. The water-repelling nature of the organic molecules helps double the lifespan of the new hybrid compared to an unmodified halide perovskite device. In addition, the organic layers augment the differences between ‘ON’ and ‘OFF’ resistive memory states, making device operation more reliable. ReRAM devices based on halide perovskites have recently emerged as a new class of data storage device, where the switching materials used in these devices have attracted huge attention in recent years. In this study, we compare the resistive switching characteristics of ReRAM devices based on a quasi-2D halide perovskite, (PEA)2Cs3Pb4I13, to those based on 3D CsPbI3. Astonishingly, the ON/OFF ratio of the (PEA)2Cs3Pb4I13-based memory devices was much higher than that of the CsPbI3 device. Also this device retained a high ON/OFF current ratio for two weeks under ambient conditions, whereas the CsPbI3 device degraded rapidly and showed unreliable memory properties after five days. We strongly believe that quasi-2D halide perovskites have potential in resistive switching memory based on their high ON/OFF ratio and long-term stability.