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Search Results: 1 - 10 of 20899 matches for " Doo-Sik Kim "
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ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function
Sanghoon Kwon, Dongbum Kim, Jae Rhee, Jeong-A Park, Dae-Won Kim, Doo-Sik Kim, Younghee Lee, Hyung-Joo Kwon
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-23
Abstract: We found that a variant of ASB9 that lacks the SOCS box (ASB9ΔSOCS) was naturally detected in human cell lines but not in peripheral blood mononuclear cells or normal hepatocytes. We also identified ubiquitous mitochondrial creatine kinase (uMtCK) as a new target of ASB9 in human embryonic kidney 293 (HEK293) cells. The ankyrin repeat domains of ASB9 can associate with the substrate binding site of uMtCK in a SOCS box-independent manner. The overexpression of ASB9, but not ASB9ΔSOCS, induces ubiquitination of uMtCK. ASB9 and ASB9ΔSOCS can interact and colocalise with uMtCK in the mitochondria. However, only expression of ASB9 induced abnormal mitochondrial structure and a decrease of mitochondrial membrane potential. Furthermore, the creatine kinase activities and cell growth were significantly reduced by ASB9 but not by ASB9ΔSOCS.ASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential expression and function of ASB9 and ASB9ΔSOCS may be a key factor in the growth of human cell lines and primary cells.The largest family of suppressor of cytokine signalling (SOCS) box-containing superfamily proteins are the ankyrin repeat and SOCS box proteins (Asbs; ASBs in humans). Although 18 members of the Asb family have been identified in mice and humans, the function of Asbs has not been clearly defined. The Asbs have two functional domains, a SOCS box and a variable number of N-terminal ankyrin (ANK) repeats [1]. The SOCS box of Asb proteins has two subdomains: a BC box and a Cul2/Cul5 box. Highly conserved amino acid sequences of the BC box and the Cul5 box, which are essential for ensuring that the interaction with elongins B/C and Cullin 5-Rbx2 forms E3 ubiquitin (Ub) ligase complexes, are important in a ubiquitination-mediated proteolysis pathway [2-6]. While SOCS family members use the SH2 domain to recruit substrates, the ANK repeat regions of Asb family members serve as specific protein-protein interaction platforms to recr
Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity
David Nguyen, Ping Deng, Elizabeth A Matthews, Doo-Sik Kim, Guoping Feng, Anthony H Dickenson, Zao C Xu, Z David Luo
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-6
Abstract: Chronic pain derived from nerve injuries, or neuropathic pain, is a common clinical problem affecting over 50 million people in the United States [1]. Neuropathic pain may manifest as spontaneous pain, pain resulting from stimuli that are normally innocuous (allodynia), and increased pain responses to suprathreshold stimuli (hyperalgesia), all of which affect adversely the quality of patients' daily-life. Unfortunately, neuropathic pain tends to be long-term, and difficult to manage due to the poor efficacies and severe side effects associated with current conventional analgesic treatments. It appears that neuropathic pain with various etiologies can lead to similar behavioral endpoints that response differentially to pharmacological agents, suggesting that different mechanisms may underlie specific neuropathic pain states deriving from different pathological conditions. Thus, the development of target specific, safe and effective agents for neuropathic pain management relies on new insights into mechanisms of different neuropathic pain states.Findings from previous studies have indicated that peripheral nerve injury induces a dramatic upregulation of the voltage-gated calcium channel (VGCC) α2δ1 subunit (Cavα2δ1) in sensory neurons and spinal dorsal horn [2-6], which correlates with neuropathic pain development [2,3,7]. Knocking down of injury-induced Cavα2δ1 upregulation in dorsal spinal cord with intrathecal antisense oligodeoxynucleotides results in allodynia reversal in spinal nerve injured rats [7]. In addition, transgenic mice overexpressing Cavα2δ1 in neuronal tissue display tactile allodynia similar to nerve injury models that can be blocked by intrathecal gabapentin [8], a drug that binds to the Cavα2δ1 proteins with high affinity [9] and has anti-neuropathic pain properties in patients and experimental animal models [2,3,10-16]. Furthermore, blocking axonal transport of injury-induced Cavα2δ1 from DRG neurons to their pre-synaptic terminals in spinal dors
Production of antibodies with peptide-CpG-DNA-liposome complex without carriers
Dongbum Kim, Sanghoon Kwon, Jae Rhee, Kwang Kim, Young-Eun Kim, Cheung-Seog Park, Myeong Choi, Jun-Gyo Suh, Doo-Sik Kim, Younghee Lee, Hyung-Joo Kwon
BMC Immunology , 2011, DOI: 10.1186/1471-2172-12-29
Abstract: We present that a particular form of natural phosphodiester bond CpG-DNA encapsulated in a specific liposome complex (Lipoplex(O)) induces potent immunomodulatory activity in humans as well as in mice. Additionally, Lipoplex(O) enhances the production of IgG2a specific to antigenic protein in mice. Most importantly, immunization of mice with several peptides co-encapsulated with Lipoplex(O) without carriers significantly induces each peptide-specific IgG2a production in a TLR9-dependent manner. A peptide-specific monoclonal antibody produced against hepatocellular carcinoma-associated antigen has functional effects on the cancer cells.Our overall results show that Lipoplex(O) is a potent adjuvant and that complexes of peptide and Lipoplex(O) are extremely useful for B cell epitope screening and antibody production without carriers. Therefore, our strategy may be promptly used for the development of therapeutic antibodies by rapid screening of potent B cell epitopes.Synthetic oligodeoxynucleotides (ODNs) and bacterial DNA containing unmethylated CpG dinucleotides flanked by specific base sequences (CpG-DNA) have significant immunomodulatory effects on B lymphocytes, macrophages, dendritic cells, and natural killer cells [1-4]. Experimental evidence suggests that CpG-DNA induces the regulation of Th1/Th2 immune responses, antigen-presenting cell activity, and immunoglobulin (Ig) isotype switching [5-7]. Therefore, CpG-DNA has gained attention for its potential use as an immune adjuvant and in therapeutics for allergic and infectious diseases [8,9].Phosphorothioate-modified types of CpG-DNA (PS-ODN), which are resistant to nuclease activity and can be efficiently delivered into cells [10,11], have been utilized in clinical applications [9]. The immunomodulatory activities of PS-ODN are enhanced by liposome-encapsulation [12-14]. However, several studies have suggested that PS-ODN induces backbone-related side effects, such as transient splenomegaly [15], lymphoid folli
Impact of adjuvant chemotherapy for gliomatosis cerebri
Doo-Sik Kong, Sung Kim, Jung-Il Lee, Yeon-Lim Suh, Do Lim, Won Kim, Ki-Hoon Kwon, Kwan Park, Jong Kim, Do-Hyun Nam
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-424
Abstract: Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.Gliomatosis cerebri (GC) is a rare variant of glioma. It is characterized by a diffuse infiltration of malignant glial cells throughout large regions of the central nervous system [1-6] and a relative preservation of the neural architecture. Since Nevin first used the term gliomatosis cerebri in 1938, describing the histological finding of glial overgrowth of the brain [7], the World Health Organization now defines GC as a diffuse glial tumor that extensively infiltrates the brain and involves more than multiple lobes (frequently bilaterally) [8]. Jennings et al. reported that GC can be divided into two forms based on descriptive neuropathological grounds [9,10]. Type I GC consists of well-differentiated low-grade gliomas without contrast enhancement and its clini
Prevention and Therapy of Hepatocellular Carcinoma by Vaccination with TM4SF5 Epitope-CpG-DNA-Liposome Complex without Carriers
Sanghoon Kwon, Dongbum Kim, Byoung Kwon Park, Sunhee Cho, Kwang Dong Kim, Young-Eun Kim, Cheung-Seog Park, Hyun-Jong Ahn, Jae-Nam Seo, Kyung-Chan Choi, Doo-Sik Kim, Younghee Lee, Hyung-Joo Kwon
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033121
Abstract: Although peptide vaccines have been actively studied in various animal models, their efficacy in treatment is limited. To improve the efficacy of peptide vaccines, we previously formulated an efficacious peptide vaccine without carriers using the natural phosphodiester bond CpG-DNA and a special liposome complex (Lipoplex(O)). Here, we show that immunization of mice with a complex consisting of peptide and Lipoplex(O) without carriers significantly induces peptide-specific IgG2a production in a CD4+ cells- and Th1 differentiation-dependent manner. The transmembrane 4 superfamily member 5 protein (TM4SF5) has gained attention as a target for hepatocellular carcinoma (HCC) therapy because it induces uncontrolled growth of human HCC cells via the loss of contact inhibition. Monoclonal antibodies specific to an epitope of human TM4SF5 (hTM4SF5R2-3) can recognize native mouse TM4SF5 and induce functional effects on mouse cancer cells. Pre-immunization with a complex of the hTM4SF5R2-3 epitope and Lipoplex(O) had prophylactic effects against tumor formation by HCC cells implanted in an mouse tumor model. Furthermore, therapeutic effects were revealed regarding the growth of HCC when the vaccine was injected into mice after tumor formation. These results suggest that our improved peptide vaccine technology provides a novel prophylaxis measure as well as therapy for HCC patients with TM4SF5-positive tumors.
Quantitative Analysis and Efficient Surface Modification of Silica Nanoparticles
Hak-Sung Jung,Doo-Sik Moon,Jin-Kyu Lee
Journal of Nanomaterials , 2012, DOI: 10.1155/2012/593471
Abstract: Aminofunctional trialkoxysilanes such as aminopropyltrimethoxysilane (APTMS) and (3-trimethoxysilylpropyl)diethylenetriamine (DETAS) were employed as a surface modification molecule for generating monolayer modification on the surface of silica (SiO2) nanoparticles. We were able to quantitatively analyze the number of amine functional groups on the modified SiO2 nanoparticles by acid-base back titration method and determine the effective number of amine functional groups for the successive chemical reaction by absorption measurements after treating with fluorescent rhodamine B isothiocyanate (RITC) molecules. The numbers of amine sites measured by back titration were 2.7 and 7.7 ea/nm2 for SiO2-APTMS and SiO2-DETAS, respectively, while the numbers of effective amine sites measured by absorption calibration were about one fifth of the total amine sites, namely, 0.44 and 1.3 ea/nm2 for SiO2-APTMS(RITC) and SiO2-DETAS(RITC), respectively. Furthermore, it was confirmed that the reactivity of amino groups on the surface-modified silica nanoparticles could be maintained in ethanol for more than 1.5 months without showing any significant differences in the reactivity.
Observation of abrupt first-order metal-insulator transition in GaAs-based two-terminal device
Hyun-Tak Kim,Doo-Hyeb Youn,Byung-Gyu Chae,Kwang-Yong Kang,Yong-Sik Lim
Physics , 2004,
Abstract: An abrupt first-order metal-insulator transition (MIT) as a jump of the density of states is observed for Be doped GaAs, which is known as a semiconductor, by inducing very low holes of approximately n_p=5x10^{14} cm^{-3} into the valence band by the electric field; this is anomalous. In a higher hole doping concentration of n_p=6x10^{16} cm^{-3}, the abrupt MIT is not observed at room temperature, but measured at low temperature. A large discontinuous decrease of photoluminescence intensity at 1.43 eV energy gap and a negative differential resistance are also observed as further evidence of the MIT. The abrupt MIT does not undergo a structural phase transition and is accompanied with inhomogeneity. The upper limit of the temperature allowing the MIT is deduced to be approximately 440K from experimental data. The abrupt MIT rather than the continuous MIT is intrinsic and can explain the "breakdown" phenomenon (unsolved problem) incurred by a high electric field in semiconductor devices.
Association of Low Muscle Mass and Combined Low Muscle Mass and Visceral Obesity with Low Cardiorespiratory Fitness
Tae Nyun Kim, Man Sik Park, You Jeong Kim, Eun Ju Lee, Mi-Kyung Kim, Jung Min Kim, Kyung Soo Ko, Byoung Doo Rhee, Jong Chul Won
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100118
Abstract: Objective Previous studies have shown that low cardiorespiratory fitness (CRF), visceral obesity and low muscle mass may share pathophysiological mechanisms, such as insulin resistance and chronic inflammation. In this study, we investigated whether low CRF is associated with low muscle mass, visceral obesity, and visceral obesity combined with low muscle mass. Research Design and Methods The associations between CRF and low muscle mass and combined low muscle mass and visceral obesity were examined in 298 apparently healthy adults aged 20–70 years. Low muscle mass was defined using a skeletal muscle mass index (SMI) that was calculated using dual energy X-ray absorptiometry. Visceral obesity was defined as a visceral fat area (VFA) exceeding 100 cm2 in women and 130 cm2 in men. We classified the participants into 4 low muscle mass/visceral obesity groups according to SMI and VFA. CRF was measured using a cycle ergometer test. Results CRF level correlated positively with SMI and negatively with VFA. Individuals with low muscle mass had lower CRF values than those without low muscle mass. After adjustment for age, sex, lifestyle factors, and markers for insulin resistance and inflammation, participants in the lowest quartile of CRF had an odds ratio (OR) for low muscle mass of 4.98 compared with those in the highest quartile (95% confidence interval (CI) = 1.19–12.99; P for trend = 0.001) and an OR for combined low muscle mass and visceral obesity of 31.46 (95% CI = 4.31–229.68; P for trend = 0.001). Conclusions Individuals with lower CRF exhibited increased risk of low muscle mass and combined low muscle mass and visceral obesity. These results suggest that low CRF may be a potential indicator for low muscle mass and combined low muscle mass and visceral obesity in Korean adults.
A WKYMVm-Containing Combination Elicits Potent Anti-Tumor Activity in Heterotopic Cancer Animal Model
Sang Doo Kim, Ha Young Lee, Jae Woong Shim, Hak Jung Kim, Suk-Hwan Baek, Brian A. Zabel, Yoe-Sik Bae
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030522
Abstract: The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm), 5-fluoro-uracil (5-FU), and mature dendritic cells (mDCs) against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK) cells into the tumor. The production of two cytokines, IFN-γ and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.
Unified Platform for AI and Big Data Analytics  [PDF]
Sik Kim, Yongjin Kwon
Journal of Computer and Communications (JCC) , 2017, DOI: 10.4236/jcc.2017.58001
Abstract: This paper describes an integrated platform for machine learning and big data analysis. The integrated platform is configured in a way that builds a large distributed data processing environment in the computing environment that makes up the NVIDIA AI platform. In addition, this paper describes the background of this idea selection and the use of the software to build the unified platform. The technical details are shown in terms of how to create the proposed platform. In the anlaysis section, the methodology is provided and also the steps are explained as to how to use this integration platform. Finally, the expected effects are elaborated in the conclusion section.
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