Search

Alzheimer's disease (AD) is a genetically complex disease for which nearly 40 loci have now been identified via genome-wide association studies (GWAS). We attempted to identify groups of rare variants (alternate allele frequency <0.01) associated with AD in a region-based, whole-genome sequencing (WGS) association study (rvGWAS) of two independent AD family datasets (NIMH/NIA; 2247 individuals; 605 families). Employing a sliding window approach across the genome, we identified several regions that achieved association p values <10-6, using the burden test or the SKAT statistic. The genomic region around the dystobrevin beta (DTNB) gene was identified with the burden and SKAT test and replicated in case/control samples from the ADSP study reaching genome-wide significance after meta-analysis (pmeta = 4.74 × 10-8). SKAT analysis also revealed region-based association around the Discs large homolog 2 (DLG2) gene and replicated in case/control samples from the ADSP study (pmeta = 1 × 10-6). In conclusion, in a region-based rvGWAS of AD we identified two novel AD genes, DLG2 and DTNB, based on association with rare variants.

CEvNS detectors could provide new opportunities in nuclear physics applications if they can improve existing parameters such as neutrino detector size, portability, their sensitivity to a large range of reactor antineutrino energies, and resources required for operation. Thus, modelling the antineutrino spectrum is a crucial step to study the reactor antineutrino spectra and the CEvNS detector response. The first objective of this paper is to study the importance of fission product libraries in the construction of antineutrino spectrum using the summation method and with various corrections. We have used ENDF/B-VIII and JEFF3.3 as our base data to model the spectrum. We have also included the TAGS data (pandemonium free) when such data is available. The isomeric transitions correction has the highest impact on the antineutrino spectra increasing the values 29% to 37% on an average in the energy range of 0.5 MeV to 2 MeV. This correction also shows an increase of 4.71% to 7.13% in the range of 0 to 2 MeV, with improving isomeric transitions using the TAGS data. Next, the spectra including the isomeric transition correction using the Gross Theory causes reduction by 11.56 % to 69.46 % in the range of 6 to 8 MeV. The finite size, radiative, and weak magnetism corrections cause no more than 3.27% difference between the corrected and uncorrected spectra. Our second objective is to calculate pulse height distributions of Ge and Si based CEvNS sensors assuming a 20eV nuclear recoil threshold. In our study, we have assumed a 100kg detector placed 10m away from the 1MW TRIGA reactor. Our results show that the detector response with corrected spectra for a natural Ge and Si detector are 44.25events/day and 7.99events/day. The biggest impact on the detector response is due to the isomeric transition correction; with 37% difference between the corrected and uncorrected detector response is observed., Comment: 41 pages, 8 tables, 17 figures

Rapid design space exploration in early design stage is critical to algorithm-architecture co-design for accelerators. In this work, a pre-RTL cycle-accurate accelerator simulator based on SystemC transaction-level modeling (TLM), AccTLMSim, is proposed for convolutional neural network (CNN) accelerators. The accelerator simulator keeps track of each bus transaction between accelerator and DRAM, taking into account the communication bandwidth. The simulation results are validated against the implementation results on the Xilinx Zynq. Using the proposed simulator, it is shown that the communication bandwidth is severely affected by DRAM latency and bus protocol overhead. In addition, the loop tiling is optimized to maximize the performance under the constraint of on-chip SRAM size. Furthermore, a new performance estimation model is proposed to speed up the design space exploration. Thanks to the proposed simulator and performance estimation model, it is possible to explore a design space of millions of architectural options within a few tens of minutes.

Conductive polymers (CPs) such as polypyrrole (PPY) are emerging biomaterials for use as scaffolds and bioelectrodes which interact with biological systems electrically. Still, more electrically conductive and biologically interactive CPs are required to develop high performance biomaterials and medical devices. In this study, in situ electrochemical copolymerization of polydopamine (PDA) and PPY were performed for electrode modification. Their material and biological properties were characterized using multiple techniques. The electrical properties of electrodes coated with PDA/PPY were superior to electrodes coated with PPY alone. The growth and differentiation of C2C12 myoblasts and PC12 neuronal cells on PDA/PPY was enhanced compared to PPY. Electrical stimulation of PC12 cells on PDA/PPY further promoted neuritogenesis. In vivo electromyography signal measurements demonstrated more sensitive signals from tibia muscles when using PDA/PPY-coated electrodes than bare or PPY-coated electrodes, revealing PDA/PPY to be a high-performance biomaterial with potential for various biomedical applications.

Conductive polymers (CPs) such as polypyrrole (PPY) are emerging biomaterials for use as scaffolds and bioelectrodes which interact with biological systems electrically. Still, more electrically conductive and biologically interactive CPs are required to develop high performance biomaterials and medical devices. In this study, in situ electrochemical copolymerization of polydopamine (PDA) and PPY were performed for electrode modification. Their material and biological properties were characterized using multiple techniques. The electrical properties of electrodes coated with PDA/PPY were superior to electrodes coated with PPY alone. The growth and differentiation of C2C12 myoblasts and PC12 neuronal cells on PDA/PPY was enhanced compared to PPY. Electrical stimulation of PC12 cells on PDA/PPY further promoted neuritogenesis. In vivo electromyography signal measurements demonstrated more sensitive signals from tibia muscles when using PDA/PPY-coated electrodes than bare or PPY-coated electrodes, revealing PDA/PPY to be a high-performance biomaterial with potential for various biomedical applications.

Sanghun Lee,1 Jeonghyun Joo,2 Minah Kwak,3 Kicheul Sohn,4 Songha Chon5 1Department of Medical Consilience, Graduate School, Dankook University, Yongin, Republic of Korea; 2Department of Korean Internal Medicine, Comprehensive and Integrative Medicine Hospital, Daegu, Republic of Korea; 3Department of Internal Medicine, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 4Department of Preventive Medicine, Daegu Catholic University Medical Center, Daegu, Republic of Korea; 5Department of Hemato-Oncology, Comprehensive and Integrative Medicine Hospital, Daegu, Republic of Korea Background: Small cell lung cancer (SCLC) transformation is one of the resistance mechanisms associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Rechallenge with the first-line TKI after the second-line chemotherapy is suggested as a salvage treatment despite modest efficacy. Case presentation: Here, we report the case of a 72-year-old, never-smoker female diagnosed with multiple metastatic lung adenocarcinoma (cT2aN2M1) harboring EGFR mutations in exon 21 (L858R) of the primary lesion. Despite subsequent treatment with gefitinib for more than a year, the patient developed resistance to the drug. Histological analysis based on rebiopsy at subphrenic mass revealed small cell transformation. After a partial response to irinotecan and carboplatin, the metastatic subphrenic and liver masses presented dramatic progression despite another round of cytotoxic chemotherapy. Rechallenge with erlotinib based on the original EGFR mutation (L858R) without small cell transformation confirmed by re-biopsy of hepatic mass lesions elicited only mixed response. Therefore, cytotoxic chemotherapy comprising irinotecan and carboplatin combined with erlotinib was effective against all the metastatic lesions. Conclusion: To the best of our knowledge, this is the first case of concurrent retreatments with TKIs and chemotherapy previously effective in SCL

Conductive polymers, including polypyrrole (PPy), have been extensively explored to fabricate electrically conductive biomaterials for bioelectrodes and tissue engineering scaffolds. For their in vivo uses, a sterilization method without severe impairment of original material properties and performance is necessary. Gamma-ray radiation has been commonly applied for sterilization of medical products because of its simple and uniform sterilization without heat generation. Herein we describe the first study on gamma-ray sterilization of PPy bioelectrodes and its effects on their characteristics. We irradiated PPy bioelectrodes with different doses (0–75 kGy) of gamma-rays. Gamma-ray irradiation of the PPy (γ-PPy) increased the oxygenation and hydrophilicity of the surfaces. Interestingly, gamma-ray irradiation did not alter the electrical impedances and conductivities of the PPy substrates. Additionally, γ-PPy prepared with various dopants (e.g., para-toluene sulfonate, polystyrene sulfonate, and chlorine) showed the electrochemical properties similar to the non-irradiated control. Gamma-ray irradiation at doses of ≥15 kGy was required for effective sterilization as evidenced by complete eradication of gram positive and negative bacteria. γ-PPy substrates also showed cytocompatibility similar to untreated control PPy, indicating no substantial alteration of cytocompatibility. In conclusion, gamma ray sterilization is a viable method of sterilization of conducting polymer-based biomaterials for biomedical applications.

Sang Hoon Lee,1 Seung Up Kim,1–3 Jeong Won Jang,4 Si Hyun Bae,4 Sanghun Lee,1,3 Beom Kyung Kim,1–3 Jun Yong Park,1–3 Do Young Kim,1–3 Sang Hoon Ahn,1–3 Kwang–Hyub Han1–31Department of Internal Medicine, 2Institute of Gastroenterology, Yonsei University College of Medicine, 3Liver Cirrhosis Clinical Research Center, 4Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground/purpose: Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA).Methods: This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.Results: This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05). On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05). Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (

By mutual agreement, in 2015, the Republic of Korea (ROK) assumes wartime operational control (OPCON) of its forces with the U.S. continuing to provide support as the ROK expands its Peninsula security responsibilities. Given North Korea's provocative stance on nuclear weapons, challenges to the Armistice Agreement, and overall belligerent attitude to the world, ROK leaders have expressed concerns over whether or not this wartime OPCON transition is a prudent move in 2015. This study begins with the primary question, Will the transfer of wartime OPCON from the U.S. to ROK pose a negative effect on the military effectiveness of the ROK / U.S. security alliance? In order to respond to the research question, this study explored the regional security framework through bilateral and multilateral lenses, and applied a critical factor analysis using an ends, ways, means, as well as strengths, weaknesses, opportunities, threats (SWOT) analysis. The findings of this study include recommendations regarding the future of the ROK / U.S. security alliance after wartime OPCON transition.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture and Planning, 1996., Includes bibliographical references (leaves 317-339)., This dissertation investigates the transformation of architectural ideals brought about by the development of iron construction during the nineteenth century in France. The emergence of iron construction paralleled the crisis of neoclassicism, in which an ambiguous compromise between classical formal norms and modem science and technology was already manifest in the iron reinforced lintel. In the crisis of neoclassicism, iron, with its impact on both technological and formal aspects of architecture, emerged as a symbolic material to create a new style of modem architecture among utopians and rationalists. However, iron construction could not create a new style on its own; nor did there exist absolute formal aesthetic principles to impose on the construction. This is a fundamental dilemma of modem architecture, an inherent contradiction of bourgeois culture. Structural rationalists during the second half of the nineteenth century tried to resolve this contradiction by attempting to create a new style of architecture based on material and constructional rationality and reason. However, their inability to create a new style was finally proved in the last decade of the nineteenth century when the Art Nouveau exploitation of iron became a passion for individual fantasies, while engineers declared the triumph of their iron construction. Subsequent rationalists' change of the material signifier of architectural modernity from iron to reinforced concrete testified to the fundamental gap between technology and form, and the dilemma of bourgeois rationalism. Early twentieth century modernist historians rediscovered nineteenth century iron construction as a precursor of modem architecture, constructing an evolutionary history of modem architecture based on the rationalist constructive tradition, from iron construction to reinforced concrete architecture. However, their "discovery" of iron construction was purely an aesthetic invention of the twentieth century based on modernis, Sanghun Lee, Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture and Planning, 1996., Includes bibliographical references (leaves 317-339)., This dissertation investigates the transformation of architectural ideals brought about by the development of iron construction during the nineteenth century in France. The emergence of iron construction paralleled the crisis of neoclassicism, in which an ambiguous compromise between classical formal norms and modem science and technology was already manifest in the iron reinforced lintel. In the crisis of neoclassicism, iron, with its impact on both technological and formal aspects of architecture, emerged as a symbolic material to create a new style of modem architecture among utopians and rationalists. However, iron construction could not create a new style on its own; nor did there exist absolute formal aesthetic principles to impose on the construction. This is a fundamental dilemma of modem architecture, an inherent contradiction of bourgeois culture. Structural rationalists during the second half of the nineteenth century tried to resolve this contradiction by attempting to create a new style of architecture based on material and constructional rationality and reason. However, their inability to create a new style was finally proved in the last decade of the nineteenth century when the Art Nouveau exploitation of iron became a passion for individual fantasies, while engineers declared the triumph of their iron construction. Subsequent rationalists' change of the material signifier of architectural modernity from iron to reinforced concrete testified to the fundamental gap between technology and form, and the dilemma of bourgeois rationalism. Early twentieth century modernist historians rediscovered nineteenth century iron construction as a precursor of modem architecture, constructing an evolutionary history of modem architecture based on the rationalist constructive tradition, from iron construction to reinforced concrete architecture. However, their "discovery" of iron construction was purely an aesthetic invention of the twentieth century based on modernis, Sanghun Lee, Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture and Planning, 1996., Includes bibliographical references (leaves 317-339)., This dissertation investigates the transformation of architectural ideals brought about by the development of iron construction during the nineteenth century in France. The emergence of iron construction paralleled the crisis of neoclassicism, in which an ambiguous compromise between classical formal norms and modem science and technology was already manifest in the iron reinforced lintel. In the crisis of neoclassicism, iron, with its impact on both technological and formal aspects of architecture, emerged as a symbolic material to create a new style of modem architecture among utopians and rationalists. However, iron construction could not create a new style on its own; nor did there exist absolute formal aesthetic principles to impose on the construction. This is a fundamental dilemma of modem architecture, an inherent contradiction of bourgeois culture. Structural rationalists during the second half of the nineteenth century tried to resolve this contradiction by attempting to create a new style of architecture based on material and constructional rationality and reason. However, their inability to create a new style was finally proved in the last decade of the nineteenth century when the Art Nouveau exploitation of iron became a passion for individual fantasies, while engineers declared the triumph of their iron construction. Subsequent rationalists' change of the material signifier of architectural modernity from iron to reinforced concrete testified to the fundamental gap between technology and form, and the dilemma of bourgeois rationalism. Early twentieth century modernist historians rediscovered nineteenth century iron construction as a precursor of modem architecture, constructing an evolutionary history of modem architecture based on the rationalist constructive tradition, from iron construction to reinforced concrete architecture. However, their "discovery" of iron construction was purely an aesthetic invention of the twentieth century based on modernis, Sanghun Lee, Ph.D.

By mutual agreement, in 2015, the Republic of Korea (ROK) assumes wartime operational control (OPCON) of its forces with the U.S. continuing to provide support as the ROK expands its Peninsula security responsibilities. Given North Korea's provocative stance on nuclear weapons, challenges to the Armistice Agreement, and overall belligerent attitude to the world, ROK leaders have expressed concerns over whether or not this wartime OPCON transition is a prudent move in 2015. This study begins with the primary question, "Will the transfer of wartime OPCON from the U.S. to ROK pose a negative effect on the military effectiveness of the ROK / U.S. security alliance?" In order to respond to the research question, this study explored the regional security framework through bilateral and multilateral lenses, and applied a critical factor analysis using an ends, ways, means, as well as strengths, weaknesses, opportunities, threats (SWOT) analysis. The findings of this study include recommendations regarding the future of the ROK / U.S. security alliance after wartime OPCON transition.