• Title/Summary/Keyword: Central action

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Classification of HDAC8 Inhibitors and Non-Inhibitors Using Support Vector Machines

  • Cao, Guang Ping;Thangapandian, Sundarapandian;John, Shalini;Lee, Keun-Woo
    • Interdisciplinary Bio Central
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    • v.4 no.1
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    • pp.2.1-2.7
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    • 2012
  • Introduction: Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from ${\varepsilon}$-N-acetyl lysine amino acids of histone proteins. Their action is opposite to that of histone acetyltransferase that adds acetyl groups to these lysines. Only few HDAC inhibitors are approved and used as anti-cancer therapeutics. Thus, discovery of new and potential HDAC inhibitors are necessary in the effective treatment of cancer. Materials and Methods: This study proposed a method using support vector machine (SVM) to classify HDAC8 inhibitors and non-inhibitors in early-phase virtual compound filtering and screening. The 100 experimentally known HDAC8 inhibitors including 52 inhibitors and 48 non-inhibitors were used in this study. A set of molecular descriptors was calculated for all compounds in the dataset using ADRIANA. Code of Molecular Networks. Different kernel functions available from SVM Tools of free support vector machine software and training and test sets of varying size were used in model generation and validation. Results and Conclusion: The best model obtained using kernel functions has shown 75% of accuracy on test set prediction. The other models have also displayed good prediction over the test set compounds. The results of this study can be used as simple and effective filters in the drug discovery process.

Low Non-NMDA Receptor Current Density as Possible Protection Mechanism from Neurotoxicity of Circulating Glutamate on Subfornical Organ Neurons in Rats

  • Chong, Wonee;Kim, Seong Nam;Han, Seong Kyu;Lee, So Yeong;Ryu, Pan Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.2
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    • pp.177-181
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    • 2015
  • The subfornical organ (SFO) is one of circumventricular organs characterized by the lack of a normal blood brain barrier. The SFO neurons are exposed to circulating glutamate ($60{\sim}100{\mu}M$), which may cause excitotoxicity in the central nervous system. However, it remains unclear how SFO neurons are protected from excitotoxicity caused by circulating glutamate. In this study, we compared the glutamate-induced whole cell currents in SFO neurons to those in hippocampal CA1 neurons using the patch clamp technique in brain slice. Glutamate ($100{\mu}M$) induced an inward current in both SFO and hippocampal CA1 neurons. The density of glutamate-induced current in SFO neurons was significantly smaller than that in hippocampal CA1 neurons (0.55 vs. 2.07 pA/pF, p<0.05). To further identify the subtype of the glutamate receptors involved, the whole cell currents induced by selective agonists were then compared. The current densities induced by AMPA (0.45 pA/pF) and kainate (0.83 pA/pF), non-NMDA glutamate receptor agonists in SFO neurons were also smaller than those in hippocampal CA1 neurons (2.44 pA/pF for AMPA, p<0.05; 2.34 pA/pF for kainate, p< 0.05). However, the current density by NMDA in SFO neurons was not significantly different from that of hippocampal CA1 neurons (1.58 vs. 1.47 pA/pF, p>0.05). These results demonstrate that glutamate-mediated action through non-NMDA glutamate receptors in SFO neurons is smaller than that of hippocampal CA1 neurons, suggesting a possible protection mechanism from excitotoxicity by circulating glutamate in SFO neurons.

The Electrophysiological Studies of the Trapezius Muscle in Patients with Amyotrophic Lateral Sclerosis (근위축성 측상경화증 환자에서 등세모근의 신경생리학적 검사)

  • Cho, Joong-Yang;Chun, Jong-Un;Lee, Kwang-Woo
    • Annals of Clinical Neurophysiology
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    • v.6 no.2
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    • pp.85-91
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    • 2004
  • Background: Needle electromyography (EMG) and motor evoked potential (MEP) of the genioglossus (tongue) are difficult to perform in evaluations of the craniobulbar region in amyotrophic lateral sclerosis (ALS). Therefore, we investigated the yields of needle EMG and MEP recorded from the upper trapezius, since it receives innervation from the lower medulla and upper cervical cord. Methods: Needle EMG and MEP of the upper trapezius were obtained in 17 consecutive ALS patients. The needle EMG parameters recorded included abnormal spontaneous activity and motor unit action potential (MUAP) morphology. An upper motor neuron (UMN) lesion was presumed when either response to cortical stimulation was absent, or the central conduction time was delayed (>mean+2SD). Results: Of the five patients with bulbar-onset ALS, four had abnormalities in the upper trapezius and four in the tongue by needle EMG. In contrast, of the 12 patients with limb-onset ALS, 11 had abnormalities in the upper trapezius, and only five in the tongue. When MEP was performed, it was found that three of the five patients with bulbar symptoms and three of the six patients with isolated limb involvement had abnormal MEP findings. Conclusions: Electrophysiological studies of the upper trapezius are more sensitive those of the tongue in patients without bulbar symptoms. Thus, needle EMG and MEP of the upper trapezius are alternative tools for assessing bulbar and rostral neuraxial involvement in the diagnosis of ALS.

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A Study about Control of real working through the synchronized 3D Game Character and Motion Capture System (3D게임 캐릭터와 모션 캡쳐 시스템의 연동을 통한 실사 움직임(Real Working) 제어 연구)

  • Kim, Tae-Yul;Ryu, Seuc-Ho;Kyung, Byung-Pyo
    • Proceedings of the Korea Contents Association Conference
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    • 2006.11a
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    • pp.278-281
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    • 2006
  • In the Contents industry, especially in the field of game contents the area receiving the most spotlight is 3D. With qualitative and quantitative developments in games continue, interest in 3D is becoming more significant. As a result studies and actual application in the area of 3D in the game industry are being most actively conducted. It is true that 3D game characters do not have the same level of natural movement compared to the previous 2D characters. In order to overcome the limitations of movement control of the Key frame method, the method that is currently being rapidly developed is a movement control method using motion capture system. In this study, the focus is placed in production of natural character animation through movement control through linkage of 3D game characters and motion capture system. Hence, production of natural 3D game character animation through a single central action was established as the purpose of this study.

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Effects of TGF ${\beta}_1$ on the Growth and Biochemical Changes in Cultured Rat Glial Cells (Transforming growth factor ${\beta}_1$이 배양랫트 신경교세포의 성장 및 생화학적 변화에 미치는 영향)

  • Kim, Yong-Sik;Youn, Yong-Ha;Park, Nan-Hyang;Park, Chan-Woong
    • The Korean Journal of Pharmacology
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    • v.30 no.2
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    • pp.167-179
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    • 1994
  • Recent evidence indicates that glial cells have a wide range of funtions which are critical for maintaining a balanced homeostatic environment in the central nervous system(CNS) peripheral nervous system(PNS). Morever, astrocytes are known to participate in the tissue repair and neuroimmunologic events within the CNS through many kinds of growth factors and cytokines. We investigated the effect of $TGF\;{\beta}_1$, on the growth and biochemical changes of rat glial cells in culture. The proliferative effect was determined by $^3H-thymidine$ uptake and the double immunostain with anti-cell-specific marker and anti-Bromodeoxyuridine(BrdU) antibody. To check the effect of biochemical changes we compared the amounts of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) in astrocyte. And the amounts of myelin basic protein and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocyte and the amounts of peripheral myelin in Schwann cell. When $TGF\;{\beta}_1$, was treated for 2 days with cultured glial cell, $TGF\;{\beta}_1$, decreased the $^3H-thymidine$ uptake and proliferation index of double immunostain of astrocytes, which indicates the inhibition of astroglial DNA synthesis, but stimulated the growth of Schwann cell. Also, $TGF\;{\beta}_1$, decrease the GS activity and increased the amounts of GFAP in astrocyte. In the case of Schwann cells the amounts of peripheral myelin was increased when treated with $TGF\;{\beta}_1$. However, $TGF\;{\beta}_1$, didn't show any effect on the proliferation and biochemical changes in oligodendrocyte. These results suggest that $TGF\;{\beta}_1$, might have a critical action in the regulation of proliferation and biochemical changes in glial cells, especially astrocyte.

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Experimental Study of Concrete Beam with FRP Plank as Formwork and Reinforcement (FRP 판을 거푸집 및 보강재로 활용한 콘크리트 보의 실험적 연구)

  • Yoo, Seung-Woon;Bae, Han-Ug;Oliva, Michael;Bank, Lawrence
    • Journal of the Korea Concrete Institute
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    • v.19 no.1
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    • pp.67-74
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    • 2007
  • We perform an experimental study of concrete beam with pultruded fiber reinforced polymer(FRP) plank using as a permanent formwork and the tensile reinforcement. A satisfactory bond at the interface between the smooth surface of the pultruded plank and the concrete must be developed for the FRP plank and the concrete to act as a composite structural member. Two kinds of aggregate were bonded to the FRP plank using a commercially available epoxy. No additional flexural or shear reinforcement was provided in the beams. For comparison we test two types of control specimen. One control did not have any aggregate bonded to the FRP plank and the other control had infernal steel reinforcing bars instead of the FRP plank. The beams were loaded by central patch load to their ultimate capacity. The experimental results were compared to current ACI 318 (2005) and ACI 440 (2006) code predictions. This study demonstrates that the FRP plank has the potential to serve as formwork and reinforcing for concrete structures.

Revealing the complexity of ionized gas outflows in powerful Type 2 AGN in the local Universe

  • Karouzos, Marios;Woo, Jong-Hak;Bae, Hyun-Jin
    • The Bulletin of The Korean Astronomical Society
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    • v.40 no.2
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    • pp.32.3-33
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    • 2015
  • There exist scaling relations that link the mass of supermassive black holes with both the velocity dispersion and the mass of the central stellar cusp of their host galaxies. This implies that these two components grow in tandem. Feedback from actively accreting supermassive black holes (AGN), in the form of multi-phase gas outflows, has been argued to be the agent of this co-evolution. Here we employ the powerful GMOS integral field spectroscopy unit on the 8.2m Gemini-North telescope to investigate ionized gas outflows of luminous Type 2 AGN in the local Universe (z<0.1). Our sample of 6 galaxies is drawn from the Sloan Digital Sky Survey (SDSS) and was selected based on their [OIII] dust-corrected luminosity (>1042 erg/s) and signatures of outflows in the [OIII] line profile of their spatially integrated SDSS spectra. These are arguably the best candidates to explore AGN feedback in action since they are < 1% of a large local type 2 AGN SDSS sample selected based on their [OIII] kinematics. We combine a careful spectral decomposition of the [OIII] and $H{\alpha}$ line profiles with spatial information on ~0.5kpc scales to understand the outflow kinematics and energetics in these objects. We find clear evidence for strong outflows in [OIII] and occasionally $H{\alpha}$ that are clearly driven by the ionizing radiation of the AGN. We kinematically and spatially decompose outflowing and rotating ionized gas components. We find [OIII] to be a better tracer of AGN outflows, while $H{\alpha}$ appears to be strongly affected by both stellar rotation and outflows induced by ongoing star formation. The observed kinematics and spatial distribution of the ionized gas imply a large opening angle for the outflow. Finally, we find the projected outflow velocity to decrease as a function of distance, while its dispersion shows a more complex structure with a potentially initially increasing trend (out to 0.5-1kpc distances).

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Effect of Visual and Somatosensory Information Inputs on Postural Sway in Patients With Stroke Using Tri-Axial Accelerometer Measurement

  • Chung, Jae-yeop
    • Physical Therapy Korea
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    • v.23 no.1
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    • pp.87-93
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    • 2016
  • Background: Posture balance control is the ability to maintain the body's center of gravity in the minimal postural sway state on a supportive surface. This ability is obtained through a complicated process of sensing the movements of the human body through sensory organs and then integrating the information into the central nervous system and reacting to the musculoskeletal system and the support action of the musculoskeletal system. Motor function, including coordination, motor, and vision, vestibular sense, and sensory function, including proprioception, should act in an integrated way. However, more than half of stroke patients have motor, sensory, cognitive, and emotional disorders for a long time. Motor and sensory disorders cause the greatest difficulty in postural control among stroke patients. Objects: The purpose of this study is to determine the effect of visual and somatosensory information on postural sway in stroke patients and carrying out a kinematic analysis using a tri-axial accelerometer and a quantitative assessment. Methods: Thirty-four subjects posed four stance condition was accepted various sensory information for counterbalance. This experiment referred to the computerized dynamic posturography assessments and was redesigned four condition blocking visual and somatosensory information. To measure the postural sway of the subjects' trunk, a wireless tri-axial accelerometer was used by signal vector magnitude value. Ony-way measure analysis of variance was performed among four condition. Results: There were significant differences when somatosensory information input blocked (p<.05). Conclusion: The sensory significantly affecting the balance ability of stroke patients is somatosensory, and the amount of actual movement of the trunk could be objectively compared and analyzed through quantitative figures using a tri-axial accelerometer for balance ability.

Studies on the anti-inflammatory action of Chilbokyeum extract in central nervous system (중추신경계(中樞神經系)에서 칠복음(七福飮)의 항염증작용(抗炎症作用)에 관한 연구(硏究))

  • Min Sang-Jun;Lee Sung-Ryull;Kang Hyung-Won;Lyu Yeoung-Su;Jeon Chang-Hwan
    • Journal of Oriental Neuropsychiatry
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    • v.12 no.2
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    • pp.173-183
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    • 2001
  • Substance P can stimulate secretion of tumor necrosis $factor-\;{\alpha}\;(TNF-\;{\alpha}\;)$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Chilbogeum can modulate cytokines secretion from primary cultures of rat astrocytes. Chilbogeum $(10\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and Substance P. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Chilbogeum $(10,\;100\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and Substance P decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and Substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in Alzheimer's disease (AD) pathology, during which they themselves may produce still more inflammatory cytokines. Chilbogeum $(10,\;100\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by CCF-STTG1 astrocytoma cells stimulated with $A\;{\beta}$ and IL-1. These results suggest that Chilbogeum may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Chilbogeum has an antiinflammatory activity in AD brain.

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Primary Health Care and Desirable Policy Directions in Korea (1차보건의료와 바람직한 정책방향)

  • 박형종;김공현
    • Health Policy and Management
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    • v.1 no.1
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    • pp.95-108
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    • 1991
  • The World Health Organization and its member states, in 1978, declared that primary health care is a key to attain the goal of Health for All by the goal of Health for All by the yeas 2000. As a member state of WHO, the Republic of Korea has participated in the declaration of ALMA-ATA and committed to put national efforts for devedoping and implementing primary health care approach with the spirit and content of this Declaration. Since 1978, to translate the spirit of the Declaration into realization, Korean goverment has developed a new category of health manpower such as Community Health Practitioners serving people living in remote rural areas and Village Health Workers serving voluntarily their own village, strengthened the function of Health Centers and Health Subcenters through their reorientation and improved the infrastructure by their new construction or renovation. While primary health care is viewed as an essential health care in Korea, there are some circles who follow a narrow definition in referring to the health care at the periphey of a health system, which is erroneous. Considering the PHC is accepted as the best alternative approach to health care to solve problems that modern health systems are facing, we propose the followings as desirable health policy directions that modern health systems are facing, we propose the followings as desirable health policy directions which might translate the persopective into action at the national level after reviewing past and current PHC approach in Korea : 1. To improve the equity through the reduction of gaps between those who have access to health care and those who have not. 2. To reinforce multisectoral approach and intersectoral coordination through the re- establishment of the National Health Council or establishment of equivalent organization at the central level. 3. To stengthen community participation through lacal people's empowerment by leadership training, changing planning process from the top-down approach to bottom-up and giving the priority to human resources rater than technology, 4. To reinforce the Ministries of Health and Social Affairs through upgrading its role and function to Coordinate Ministries which involve human welfare policies, and creating a Division which is in charge of PHC in the Ministry.

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