22,377 research outputs found
a key condition for economic convergence among middle income countries in Latin America
No full textThesis(Master) --KDI School:Master of Public Policy,2014masterpublishedJi-Hye Lee
Hye In Lee, violin, Thursday, November 8, 2012
No full textIn partial fulfillment of the requirements for the degree of
Master of Musi
Hye In Lee, violin, Thursday, May 24, 2012
No full textIn partial fulfillment of the requirements for the degree of
Master of Musi
Lee, Hye-Sun
No full text학위논문(석사)----아주대학교 일반대학원 :신경과학기술과정,2008. 2뇌졸증 후 뇌 손상을 줄이기 위한 방법은 재 관류를 통한 혈액 공급만이 가장 좋은 치료 방법이다. 하지만 delayed neuronal cell death는 재 관류 후 몇 시간 이내에 일어나게 된다. 현재 뇌졸증 치료재 개발에 많은 노력을 하고 있지만 효과적인 therapeutic effect를 볼 수 있는 cell death molecules에 대한 profiling에 대한 연구가 제대로 되어 있지 않다. 본 연구에서는 cell death marker을 통하여 시간에 따라 공간에 따라 진행되는 cell death에 대하여 profiling을 하였다. MCAo medel을 reperfusion 0h~7day까지 유도한 후 mitochondria disfunction을 나타낼 수 있는 TTC staining을 통하여 뇌손상의 진행을 관찰한 결과 reperfusion 2h대부터 ipsilateral cortex에서부터 뇌 손상이 시작되며 6h대에는 striatum, 24h~3day에는 infarct area가 peak를 이루는 것을 볼 수 있었다. 하지만 reperfusion 7day에는 infarct area가 감소 하는데 이는 penumbra region에서 angiogenesis가 활발히 일어나서 spontaneous recovery가 일어남을 확인 할 수 있었다. 뇌 손상이 cortex에서 striatum으로 진행됨을 확인을 한 후 infarct core in cortex, striatum and penumbra 순으로 cell death가 어떻게 일어나는지 HE staining을 통하여 관찰한 결과 reperfusion 2h대부터 neuronal condensation이 일어나기 시작하며 12h에는 모든 region에서 nenronal condensation이 일어나 24h~3day에는 cytoplasmic vacuoles가 나타는 것을 관찰 할 수 있었다. Cell death가 region dependent 하게 time dependent 하게 일어나는 것을 확인을 한 후 강력한 apoptosis를 일으키는 Factor X에 대하여 관찰하였다. Normal 상태에서 Factor X은 cytoplasm에 있다가 cell death가 유도되면 핵안으로 translocation 된다고 알려져 있다. MCAo model 안에서 Factor X은 occlusion 상태인 reperfusion 0h에서부터 core region인 cortex부터 핵 안으로 이동하며 6h에는 모든 region까지 이동하는 것을 볼 수 있었다. 또한 acute phage 인 reperfusion 24h~3day에는 condensation 된 모든 region까지 Factor X이 이동되었으며 이는 mitochondria disfunction을 나타내는 TTC staining 결과보다 먼저 앞서서 일어남에 따리 Factor X은 cell death를 detection 할 수 있는 earlist marker임을 확인 할 수 있었다. 또한 Factor X은 caspase-8을 거쳐 cell death를 유도 함을 cleaved caspase-3을 통하여 볼 수 있었다. Cleaved caspase-3는 reperfusion 6h에 cortex의 cytoplasm에서 보이기 시작을 하였다가 12h에는 cortex의 nuclei에서 expression 하였으며 24h~3day에는 모든 cell 에서 cleaved caspase-3 expression을 관찰 할 수 있었다. Cleaved caspase-3에 의해 DNA repair 기능을 잃은 cleaved PARP는 reperfusion 24h~3day까지 수가 증가함을 볼 수 있었다. Caspase -independent molecues중 하나인 AIF에 대하여 profiling 한 결과 normal상태일 때 보이지 않던 AIF가 reperfusion 2h에 ipsilateral cortex부터 핵 안으로 이동하기 시작하여 12h에는 모든 region에서 AIF가 이동 한 것을 관찰 할 수 있었으며 3day까지 AIF의 이동이 점차적으로 증가하는 것을 볼 수 있었다. 이는 TTC staining을 통한 mitochondrial disfunction과 일치하는 것을 볼 수 있었다. 이러한 molecules에 의해 24h~3day일 때 apoptosis가 peak로 일어남을 TUNEL assay를 통하여 관찰 할 수 있었으며 reperfusion 7day에는 DNA break가 많이 일어나 TUNEL positive 한 cell 이 감소 한 것 임을 NeuN staining을 통해 관찰 할 수 있었다. Inflammation 또 한 brain injury에 많은 영향을 준다고 알려져 있다. Microglia와 monocyte marker인 Iba1으로 시간에 따른 microglia의 response를 관찰한 결과 normal 상태에서 small cell body과 long processor 가진 microglia 가 reperfusion 0h~12h까지 enlarge cell body와 processor fragmentation 이 일어나는 것을 관찰 할 수 있었다. Reperfusion 12h~24h에는 resident microglia death가 일어나서 Iba1 positive한 cell 수가 감소함을 관찰 할 수 있었으며 (Ji et al., 2007) reperfusion 3day~7day에 증가하는 Iba1 positive cell 은 blood bone microphage 임을 evans blue를 통한 BBB leakage를 통해 확인 할 수 있었다. Cell death related molecules profiling을 통하여 cell death를 억제 하고 inflammaion을 감소 시키고 neurogenesis를 증진 시킬수 있는 therapeutic time window 제시를 통해 뇌졸증 치료에 대한 효과적인 effect를 볼 수 있을 것이라 생각한다.ABSTRACT = ⅰ
LIST OF FIGURES = ⅴ
LIST OF TABLES = ⅵ
Ⅰ. INTRODUCTION = 1
A. Characteristics of focal cerebral ischemia = 2
B. Cell death = 3
C. Cell death related molecules = 4
1. Factor X = 4
2. Apoptosis inducing factor = 5
3. Caspase-3 = 6
4. Poly(ADP-ribose) polymerase = 7
D. Brain inflammation = 8
1. Ionized calcium-binding adapter molecules = 9
2. CD8 = 10
3. ED1(CD68) = 10
Ⅱ. MATERIALS AND METHODS = 11
A. MATERIALS = 11
1. Preparation of MCAo and reperfusion model = 11
B. METHODS = 12
1. Measurement of infarct volume = 12
2. Tissue preparation and immunohistochemistry = 13
3. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining = 14
4. Determination of BBB permeability with the use of Evans Blue = 14
Ⅲ. RESULTS = 15
PARTⅠ. Spatio-temporal distribution of cell death-related molecules = 15
A. Increment of infarct volume following to ischemic injury = 15
B. Progressive neuronal cell death in the ischemic brain = 15
C. Neuron- specific expression of Factor X = 16
D. Spatio-temporal distribution of Factor X in the ischemic brain = 16
E. Spatio-temporal distribution of AIF in the ischemic brain = 17
F. Spatio-temporal assessment of caspase-3 activation = 17
G. Spatio-temporal distribution of cleaved PARP in ischemic brain = 18
H. Spatio-temporal distribution of TUNEL and NeuN positive cells in ischemic brain = 18
PARTⅡ. Spatio-temporal distribution of inflammation-related molecules = 29
A. Spatio-temporal responses of microglia in ischemic brain (Morphological changes of Iba1-positive cells) = 29
B. Iba1-positive cells are TUNEL-negative after ischemic injury = 30
C. Concomitant infiltration of blood cells upon vascular leakage = 30
Ⅳ. CONCLUSION ＆ DISCUSSION = 34
REFERENCES = 39
―국문요약― = 46MasterDelayed neuronal cell death occurring hours after reperfusion is a hallmark of ischemic stroke. The cell death processes include caspase-dependent cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-independent process such as nuclear translocation of AIF. In this study, we investigated spatial and temporal distribution of these death related molecules in rat brain following to two hours occlusion of middle cerebral artery. Immunohistological analyses revealed that sequential profiles about caspase-dependent cleavage of PARP, caspase3 activation, and nuclear translocation of caspase-independent molecules, apoptosis inducing factor (AIF), after reperfusion. Involvement of microglia and T-lymphocytes was evaluated by antibodies against ionized calcium-binding adapter molecule 1 (Iba1) and CD8 in reverse proportion to the integrity of blood brain barrier. Further studies about the effects of microglia on the infiltration of immune cells will provide information about the potential targets of treatment in patho-physiological status of
brain ischemia
Pulse Width Allocation and Clock Skew Scheduling: Optimizing Sequential Circuits Based on Pulsed Latches
No full textPulsed latches, latches driven by a brief clock pulse, offer the same convenience of timing verification and optimization as flip-flop-based circuits, while retaining the advantages of latches over flip-flops. But a pulsed latch that uses a single pulse width has a lower bound on its clock period, limiting its capacity to deal with higher frequencies or operate at lower V(dd). The limitation still exists even when clock skew scheduling is employed, since the amount of skew that can be assigned and realized is practically limited due to process variation. For the first time, we formulate the problem of allocating pulse widths, out of a small discrete number of predefined widths, and scheduling clock skews, within a predefined upper bound on skew, for optimizing pulsed latch-based sequential circuits. We then present an algorithm called PWCS Optimize (pulse width allocation and clock skew scheduling, PWCS) to solve the problem. The allocated skews are realized through synthesis of local clock trees between pulse generators and latches, and a global clock tree between a clock source and pulse generators. Experiments with 65-nm technology demonstrate that combining a small number of different pulse widths with clock skews of up to 10% of the clock period yield the minimum achievable clock period for many benchmark circuits. The results have an average figure of merit of 0.86, where 1.0 indicates a minimum clock period, and the average reduction in area by 11%. The design flow including PWCS_Optimize, placement and routing, and synthesis of local and global clock trees is presented and assessed with example circuits
Systematized Event-Aware Learning for Multi-Object Tracking
No full textWe propose an end-to-end online multi-object tracking (MOT) framework with a systematized event-aware loss, which is designed to control possible occurrences in an online MOT situation and compel the tracker to take appropriate actions when such events occur. Training samples from real candidates using a simulation tracker are generated, and a systematized event-aware association matrix is constructed for every frame to enable the tracker to learn the ideal action in a running environment. Several experiments, including ablation studies on various public MOT benchmark datasets, are conducted. The experimental results verify that each event affecting the tracking measure can be controlled, and the proposed method presents optimal results compared with recent state-of-the-art MOT methods.1
Thermal Buckling Characteristics of Composite Conical Shell Structures
No full textThermal buckling and free vibration analyses of multi-laered composite conical shells based on a layerwise displacement theory are performed. The Donnells displacement-strain relationships of conical shell structure are applied. The natural frequencies are compared with the ones existing in the previous literature for laminated conical shells with several cone semi-vertex angles. Moreover, the thermal buckling behaviors of the laminated conical shell are investigated to consider the effect of the semi-vertex angle, subtended angle, and radius to thickness ratio on the structural stability.This study has been supported by the KARI under research and development of Korea Space Launch Vehicle Project. Authors are grateful for thier wupports
Ji Eun Lee, oboe, Friday, March 29, 2013
No full textIn partial fulfillment of the requirements for the degree of
Master of Musi
Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β-Cell Dysfunction and Senescence in Type 2 Diabetes
No full textAn increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity and type 2 diabetes, imposing a tremendous economic and health burden on society. Pancreatic β-cells are crucial for controlling glucose homeostasis by properly producing and secreting the glucose-lowering hormone insulin, and the dysfunction of β-cells determines the outcomes for both type 1 and type 2 diabetes. As the native structure of insulin is formed within the endoplasmic reticulum (ER), ER homeostasis should be appropriately maintained to allow for the proper metabolic homeostasis and functioning of β-cells. Recent studies have found that cellular senescence is critically linked with cellular stresses, including ER stress, oxidative stress, and mitochondrial stress. These studies implied that β-cell senescence is caused by ER stress and other cellular stresses and contributes to β-cells’ dysfunction and the impairment of glucose homeostasis. This review documents and discusses the current understanding of cellular senescence, β-cell function, ER stress, its associated signaling mechanism (unfolded protein response), and the effect of ER stress on β-cell senescence and dysfunction
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