Humans are well-known for being adept at using intuition and expertise in many situations. However, human experts are still susceptible to errors in judgment or execution, and failure to recognize the limits of knowledge. This would happen especially in semi-structured situations, in multi-disciplinary settings, under time or other stress, under uncertainty, or when knowledge is outdated Human errors are caused by cognitive biases, attentional slips/memory lapses, cultural motivations, and missing knowledge. The purpose of this research is to study errors of human experts committed in judgment and the general idea of critiquing systems as corresponding plan. Compared to expert systems, critiquing systems are narrowly focused programs useful in limited situations for collaborating with and supporting experts in their task activities. It supports an expert by detecting the human's errors by deploying various strategies that stimulate humans to improve their performance. A variety of types of critiquing systems has spread through numerous application areas.

This study demonstrated the effects of extracts from the mushroom Keumsa sangwhang(Phellinus linteus) (KPLE) on fasting glucose and cholesterol levels in human blood. In this double-blind, placebo-controlled human intervention study, healthy volunteers were randomized to receive 3.3 g of KPLE (n=31) or placebo (n=31) per day by oral administration for 8 weeks. The cholesterol and fasting serum glucose levels were evaluated before and after treatment. The fasting serum glucose level was significantly decreased by KPLE administration (p<0.01), but the total cholesterol, triglyceride, HDLcholesterol and LDL-cholesterol concentrations did not change. This study suggests a possibility that KPLE may be useful as a functional food for the prevention of diabetes mellitus.

Cyto kinc production by epiclerma l keratinocytes has been investiga ted ext ensive ly cluring the past decacle in the skm Furthermore‘ cyto kines produced by pidermal kerat inocytes may be regar decl as important regulators in inflammation, 1 nunune responses‘ and during wound healing, The associa tion of specific cytokine patterns in proliferative a ncl/or infl ammatory related cha nges in the s kin suggests a role in the pathogenesis of certain skin diseases, Although it is conceiva b1e that the pa ttern of cytokine express ion in o1'al kera tinocytes might be sirnilar t o tha t of epidermal origin, the1'e a re only sparse reports that have s hown t his experi menta lly, In addition, there is s ome evidence that there may be differe n ces in the proliferative capacity of oral versus epidermal keratinocytes, Since t his may be crucial for better un clerstanding the biologica l processes in the oral mucosa and how they may differ from the e pidennis, we a na lyzed the cyto kine expression pat tern of human oral kera tinocy tes, The purpose of this study were to investigate mRNA & protein express ion 0 1' va rious cy tokines between NHOK and NHEK by RT-PCR & immunoslot blotting, and to apply its results 1‘0 1' bet ter understancling t he pathological processes in the o1'al mucosal d1seases Cultured NHEK showecl larger a rea of cel lula r s tratil'icat ion tha n cul tu ++ 1'ed NHOK in 0 05mM Ca concentra tion, 1L - 1α , IL- 6 mRNA expression 0 1' cult ured NHOK we1'e hi gher than that of NHEK, TNF- mRNA expression of NHEK was about 1, 2 folds than that 0 1' NHOK, ICAM- 1 mRNA expression of NHOK was a bout 13 folds t han that of NHOK, while NHEK was weakly detected, 1L- 1a , IL-6 pro tein expression of cul tured NHOK were hi gher t han t ha t of NHEK TNF-a protein expression of NHEK was about 1, 2 fo lds than that of NHOK, 1CAM- 1 protein expression of NHOK was about 40 folcls than that of NHOK, whil e NHEK was weakly detectecl , mRNA express ion was associa ted wi th prot ein expression in cul tured NHOK ancl NHEK, It s uggestecl that lL- 1a ‘ 11-6 and ICAM-1 mRNA and protein be highl y expressecl in cultured NHOK, Especially, ICAM- 1 would be a useful ma rker for the pathogenesis of oral mucosal di sease,

Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and have the capacity to differentiate into various types of cells in the body. Hence, these cells may potentially be an indefinite source of cells for cell therapy in various degenerative diseases including neuronal disorders. For clinical applications of human ES cells, directed differentiation of these cells would be necessary. The objective of this study is to develop the culture condition for the expansion of neural precursor cells derived from human ES cells. Human ES cells were able to differentiate into neural precursor cells upon a stepwise culture condition. Neural precursor cells were propagated up to 5000-fold in cell numbers over 12-week period of culture and evaluated for their characteristics. Expressions of sox1 and pax6 transcripts were dramatically up-regulated along the differentiation stages by RT-PCR analysis. In contrast, expressions of oct4 and nanog transcripts were completely disappeared in neural precursor cells. Expressions of nestin, pax6 and sox1 were also confirmed in neural precursor cells by immunocytochemical analysis. Upon differentiation, the expanded neural precursor cells differentiated into neurons, astrocytes, and oligodendrocytes. In immunocytochemical analysis, expressions of type III β-tubulin and MAP2ab were observed. Presence of astrocytes and oligodendrocytes were also confirmed by expressions of GFAP and O4, respectively. Results of this study demonstrate the feasibility of long-term expansion of human ES cell-derived neural precursor cells in vitro, which can be a potential source of the cells for the treatment of neurodegenerative disorders.

Epigenetic modification dependent DNA methyltransferases (DNMTs) play an important role in tissue- and stage-specific gene regulation and normal mammalian development. In this study, we show that DNMTs are expressed at different levels during hematopoietic stem cell (HSC) differentiation to proerythrocytes. DNMT1, DNMT3A, and DNMT3B were highly expressed at day 7 after differentiation. We used specific siRNA as a tool to probe the relationship between the expression of DNMTs and erythropoietic differentiation. When introduced siRNA of DMNT1 and DMNT3b in human CD34+ cells, these more differentiated into erythrocytes. This was confirmed by glycophorin A (GPA) positive cell analysis and globin gene expression. GPA+ cells increased up to 20～30%, and γ- and ε-globin genes increased in siRNA transfected cells. Therefore, our data suggest that suppression of DNA methylation can affect positively differentiation of HSC and may contribute to expression of erythrocyte lineage genes including GPA and globins.

Embryonic stem (ES) cells are known to have an infinite proliferation and pluripotency that are associated with complex processes. The objective of this study was to examine expression of genes differentially regulated during differentiation of human ES cells by suppression subtractive hybridization (SSH). Human ES cells were induced to differentiate into neural precursor cells via embryoid body. Neural precursor cells were isolated physically based on morphological criteria. Immunocytochemical analysis showed expression of pax6 in neural precursor cells, confirming that the isolated cells were neural precursor cells. Undifferentiated human ES cells and neural precursor cells were subject to the SSH. TPX2 (Targeting Protein for Xklp2 (Xenopus centrosomal kinesin-like protein 2)) was identified, cloned and analyzed during differentiation of human ES cells into neural lineages. Expression of TPX2 was gradually down-regulated in embryoid bodies and neural precursor cells relative to undifferentiated ES cells. Targeting Protein for Xklp2 has been shown to be involved in cell division by interaction with microtubule development in cancer cells. Taken together, result of this study suggests that TPX2 may be involved in proliferation and differentiation of human ES cells.

Cordyceps militaris is well known as a traditional herbal ingredient, which has been used for patients suffering from cancer in oriental medicine. In this study we have investigated the biochemical mechanisms of anti-proliferative effects by C. militaris extract(CBE) in human breast cancer MDA-MB-231 cells. It was found that CBE treatment induced chromatin condensation, mitochondrial energization, annexin V staining and sub-G1 phase DNA content. These indicators of apoptosis correlate with the mitochondrial dependent pathway, which results in the activation of caspase-3 activity. Both the cytotoxic effect by CBE treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in the observed cytotoxic effect. Co-treatment of CBE and LY294002, resulted in significantly induction of apoptosis. These results indicate that caspase-3 is a key regulator of apoptosis in response to CBE in human breast cancer MDA-MB-231 through down regulation of Akt, and that the C. militaris extract may therefore have therapeutic potential against human breast cancer.

본 연구는 조선후기 실학의 한 양상을 보여준다고 평가되는 五洲衍文長箋散稿의 구성상의 특징을 살피고, 이와 관련하여 五洲 李圭景(1788-1856)의 공부법 가운데 하나를 밝힘으로써 조선후기 일부 지식인들에게 보이던 지적 풍토를 究明하는 것을 목적으로 한다. 이 과정에서 다음 사항들이 검토되었다.첫째, 기존에 알려진 五洲의 작품 五洲衍文長箋散稿 五洲書種 詩家點燈 이외에 五洲의 손에서 이루어진 다른 서적이 있는가를 검토하였다. 五洲衍文長箋散稿에 대한 분석만으로도 이상 3종 이외에 약 20여종의 서적이 五洲의 저작임을 확인할 수 있었다. 둘째, 그렇다면 이 많은 저작들을 남길 수 있었던 것은 어째서인가? 이는 무엇보다 五洲衍文長箋散稿에서 보이는 構成上의 문제를 염두에 두지 않을 수 없다. 즉, 이 책은 일정한 주제에 관해 沈潛된 사고를 바탕으로 저자의 견해를 피력하는 데에 주안을 두었다기보다는, 일정한 주제에 관해 기존의 관련정보들을 갈무리해두는 방식을 택하고 있다. 다시 말해, 짧은 기간에 많은 저작을 남긴 것은 오히려 깊이 있는 沈潛이 결여된 成冊 방식이 큰 몫을 한 듯 하다. 셋째, 정보를 갈무리하는 성책방식은 단순한 독서를 통해 이루어진다기보다는 해당 정보를 직접 ‘보유’하고 있을 필요가 있다. 이 과정에서 크게 활용된 공부법이 바로 抄였으며, 抄는 抄하는 과정에서 정보의 습득을 가져오지만 또 다른 측면으로 보자면 정보의 구축, 즉 성책의 수단이기도 하였다. 따라서 五洲衍文長箋散稿라는 책은 五洲가 지녔던 癖에 가까운 抄라는 공부법이 이루어낸 결과물이라는 것을 알 수 있었다.

The purpose of this article is to examine the relationship between unsafe behavior, human factor and human error. For the object, several correlation analyses for those three elements were implemented. Several hypotheses for the relationship between them was suggested. The suggested hypotheses were verified by a comprehensive survey received from 132 safety manager of manufacturing industry. The conclusions were proven from the hypotheses verificaiton as belows; 1) The dependent relation items between unsafe behavior and human factor are dress protection tool, machine(equipment) and working rule have a dependent relation. 2) The dependent relation items between human factor and human error are uncommunication, control, slaps, fatigue, education, system, unmonitoring, failure. 3) The dependent relation items between human error and unsfafe behavior are decline and product/working method,failure and uncommunication have a dependent relation.

Macrophage inflammatory prote in -3α (M1P-3a 01' CCL20) is an intr땅uing molecule in CanCel‘ irrununotherapy‘ but M1P-3 a expr ession and signaling are not well under s tood in oral cancer cell s. We investigated CCL20 expression a nd signal trans duction by treating immortal ized hllman oral keratinocyte (IHO찌 and oral ca ncer (뻐 4) cells with defe roxa llline (DFO) and examined the mRNA express ion 01' CCL20 using RT- PCR and ELI8A. lHOK and HN4 cells treated with DFO sbowed increased mRNA and protein expression 01' CCL20. and the upregulation 01' DFO-induced CCL20 expression was higher in IHOK cells than in HN4 cells 8elective inhibitors of p38 and ERKl/2 abol ished DF'O- induced CCL20 expression in both lHOK and HN12 cells. and p38 and ERKl/2 inhibitors prevented DFO- induceddegradati on 01' 1 -κ B and NF'-K B activation. Activation 01' c-fos and c-jun also occmred fo l lowing DFO treatment in IHOK and HN4 cells Collectively, these results suggest that DFO-indllced M1 P- 3a. which is involved in the MAP kinase‘ c-fos, c-jun, and NF-K B pathways, may be an important mediator of the a ntitumor immune response in oral keratinocytes ancl warrants con sideration as a target molecule for oral cancer t reatment

Heme oxygenase-l (HO-l) exhibits cyt oprotective effects in many different cell types and is induced by nicotine exposure in human gingival fibroblasts‘ However‘ therole of HO- l in cancer cells exposed to nicotine has not previously been descnbed We investigated the effects of nicotine on HO-l protein expression and cell viability in immortalized (IHOK) and malignant (HN12) human ora l keratinocyte cells using the MTT assay and Western blotting. We al so examined the involvement of t he phosphoinosit ide-3-0H- kinase (PI3K), mitogen-acti vated protein kinase (MAPK) , and nucJear factor-κ B (NF-κ B) signaling pathways in nicotine-induced cytotoxicity and HO- l levels in IHOK and HN12 cell s‘ Nicotine induced HO- l pro ducti on and had cytotoxic effects on cells in both a concentration- and time-dependent manner. Nicotine-induced cytotox icity and accumulation of HO- l were greater in JJ-IOK cells than in HN12 cells Molecular inhibitors of the ERK, p38 MAP kinase, PI3K, and NF-κ B signaling pathways blocked the cytotoxic effects and induction of J-IO-l expression by nicotine. Treatmen t with an t ioxida nts (bil irubin, N-acetyl cysteine) protected cells against nicotine-induced cytotoxicity and blocked the upregula tion of J-IO- l, the effects of which were more pronounced in II-IOK cells than in HN12 cells Collecti vely, these results suggest that J-IO- l plays a principal role in the protective response to nicotine in oral cancel and immortalized keratinocytes. Moreover, the addition of exogenous antioxidants may help to protect oral epithelial cells as chemopreventive agents against nicotine-induced oxidative stress.

Heme oxygenase-l (HO-l) exhibits cyt oprotective effects in many different cell types and is induced by nicotine exposure in human gingival fibroblasts‘ However‘ therole of HO- l in cancer cells exposed to nicotine has not previously been descnbed We investigated the effects of nicotine on HO-l protein expression and cell viability in immortalized (IHOK) and malignant (HN12) human ora l keratinocyte cells using the MTT assay and Western blotting. We al so examined the involvement of t he phosphoinosit ide-3-0H- kinase (PI3K), mitogen-acti vated protein kinase (MAPK) , and nucJear factor-κ B (NF-κ B) signaling pathways in nicotine-induced cytotoxicity and HO- l levels in IHOK and HN12 cell s‘ Nicotine induced HO- l pro ducti on and had cytotoxic effects on cells in both a concentration- and time-dependent manner. Nicotine-induced cytotox icity and accumulation of HO- l were greater in JJ-IOK cells than in HN12 cells Molecular inhibitors of the ERK, p38 MAP kinase, PI3K, and NF-κ B signaling pathways blocked the cytotoxic effects and induction of J-IO-l expression by nicotine. Treatmen t with an t ioxida nts (bil irubin, N-acetyl cysteine) protected cells against nicotine-induced cytotoxicity and blocked the upregula tion of J-IO- l, the effects of which were more pronounced in II-IOK cells than in HN12 cells Collecti vely, these results suggest that J-IO- l plays a principal role in the protective response to nicotine in oral cancel and immortalized keratinocytes. Moreover, the addition of exogenous antioxidants may help to protect oral epithelial cells as chemopreventive agents against nicotine-induced oxidative stress.

Sulfur is commonly used in Asia as a n herba l medicine to treat infl ammation and cancel‘. and potent chemopreventive effects have been demonstrated in various in vivo and in vitromodels for sulfur-containing compounds found in naturally occun‘ ing products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developedhigh- purity eclible sulfur (ES) on immortali zecl human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral can cer (HN4‘ HN12) basecl on an 3-(4. 5-Dimethylt hiazol-2-yl)-2.5-cliphenyl tetrazolium bromide (MTT) a ssay, Western blotting, cell cycle analysis, ancl nuclear staining. The puri ty of the ES used in th is s tucly was verified by high performance liquid chromat ography (HPLC) , amino acid analysis and energy di spersive spectroscopy (EDS). ES inhibitecl the proliferation of immor talized and malignant oral kerati nocytes in a dose- and time-dependent manner FITC-Annexin V staining. DNA fragmentation testing. and Hoechst 33258 staining revealed that ES inhibits cell growth via apoptosis . ES blocked cell-cycle progression at the sub- Gl phase, with decreased expression 0 1' cyclins Dl, D2, and E, and t heir activating partners cdk2, cdk4, and cdk6‘ and a concomitant induction of p53 and p21/WAF1. Furthermore, ES treatment increased the cytosolic level of cytochrome c a nd resulted in caspase-3 activation‘ and thi s effect was correlated wi th Bax up- regulation and Bcl-2 down- regulation Taken together, these clata suggest that ES is a potential chemopreventive and chemotherapeutic agent for oral cancel

Previous in vi tro studies demonstrated that H202 or carbamide peroxide cou ld penetrate i nto pul p chambers through enamel and dentin (Benetti et a l., 2004; G okay et a l. , 2004‘ Suli eman et al .. 2005) ‘ Recently. Lee et al.(2006) demonstrated that H20Z enhanced the diffe rentiation of odontoblast like cell line, whereas it inhibited osteogenic diffe rentiation in pre 。steobl astic cell line, as seen by its efl"ecLs on an early difï"erentiation marker. ALP activity. I-lowever. the effects of HZ02 have not been well elucidated in primary cultured human pulp cells ln th is study‘ we investigated whether HO- 1 is involved in H20 2-induced cytotoxicity and examined the production 0 1" dent in sia lophosphoprotein (DSPP) and other minera li zation markers, in human pulp cells H20Z dec1'eased cell viabili ty. but increased HO-l and DSPP expression in a concentra t ion and time dependent manner. Inhibitors of guanylate cyclase, PI3K. ERK, and p38 MAP kinase blocked J-!?,0 2- induced cytot oxicity and the expression of HO-1 and DSPP mRNAs in pulp cells. These data suggest that t he induction of HO-l by H202 in pu lp cells plays a protective role against the cytotoxic effects of H202 and stimulates DSPP expression. resulting in prematu re oclontoblast differentiation th rough pathways t hat involve cGMP. p38. ancl ERK

The aim of t his study was to investigate the cytotoxic and ni t ric oxide (NO)-inducing effects of bismuth oxide (Bi203)-containi ng Portland cement (BPC) on human dental pulp cells. We also assessed whether heme oxygenase-l (HO-l) is involved in BPC-induced cytotox.icity in dental pulp cells Cytotoxicity and NO production induced by BPC were higher than those induced by Portland cement (PC) at 12 and 24 hours, and the former grad ua lly decreased to the level observed for PC. HO- l and inducible nitric oxide synthase (iNOS) mRNA expressions in the BPC group showed maximal increase at 24 hours. and it gradually decreased with increasing cultivation tlme Hemin treatment reversed the BPC-induced cytotoxicity ‘ whereas zinc protoporphyrin IX treatment increased the cytotoxicity. These results suggested that NO production by BPC correlates with HO-l exp1'ession in dental pulp cells Moreover ‘ BPC- induced HO-l expression in dental pulp cells plays a protective 1'ole against the cytotox.ic effects of BPC.

Although substance P (SP). a potent pro-inflammatory peptide, is involved in inflammation and immune responses, the effect of SP 011 the expression of macl'ophage inJlammatol'Y protein 3a (MIP-3a. CCL20) in periodontal ligament (PDL) cells a l'e unknown Equally as enigmatic is the link between SP. the stress protein heme oxygenase-l (HO-l) , and CCL20 product ion. We investigated whether SP induces the release of chemokine CCL20 from irrunortalized POL (IPDL) cells. and further claif’y SP mediated pathways . We also exarnined the relationship between HO-l and CCL20 by treating POL cells with SP Incubating IPOL cells with SP incl'eased ex pl'ession of CCL20 mRNA and CCL20 protein in a dose-time dependent manner. Highly selective p38 and ERKl/2 inhibitors abl'ogated SP-induced expression of CCL20 lD IPOL cells SP is also responsible fo l' ini tiating phosphorylation of I/( B‘ degl'adation of IK B. and activation of NF-/( B. SP induced expression of HO-l in both a concentration- and time-dependent manner. and CCL20 refl ected similal' patterns. The inductive effects of SP on HO-l and CCL20 were enhanced by HO- l inducer hemin and the membrane-permea ble cGMP analog 8-bromo-cGMP Conversely, this pathway was inhi bited by the HO-l inhibitor zinc Pl'otoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase‘ 1H- [1. 2. 4]uxad iazole[4, 3-alquinoxal i n- 1-one (ODQ) We report hel'ein the pathway that connects SP a long with other modulators 0 1' neuroimmunoregulationto the induction of HO-1 and the inflanunatol'y mediatol' MIP- 3a /CCL20 in IPDL cel ls. which play an impol'tant role in the development 0 1' pe- I'iodontitis or inflammation during ol'thodontic tooth movement

Recovery 01' original form ancl function from c1amaged organs 01' tissues is olltmost goal of regenera tive meclicine. Va riolls methods such as moleclll ar biology. drug c1elivery system, biomaterials. tissue engineering have been s tllcliecl and appl iecl in that field . 1'he core factor of all 01' these kinds of efforts might be the cells including stem cells 01' progenitor cell s . AclllJt progenitor 01' stem cells have many advantages for therapeutic meclicine, inclucling free form ethi cal probl em. easiness in collection and clllture. Bone marrow‘ fat tissue, peripheral blood. placenta‘ ancl umbilicaJ cord bloocl a re preferable source 01' acllllt stem cells 01' progenitors. ]-]uman umbilical cord bloocl. taken form vein of corcl after baby c1elivery‘ are known to contain many progenitor cells. Since Boyse et al reportecl bone marrow transplantation with hllman cord blood CD34+ cells f'or leukemia. functional cells in human cord blood have been the cells of great interest. 1n this study‘ the a u thors i s이 ated peripheral bloocl mononuciear celJs. endothelial progenitors‘ late outgrowth vascular endothelial-like cells‘ ancl mesenchymal stem cell- like cells from human umbilical cord blood and a pplied in bony defects, myocardiac infarction and limb ischemic lesl0n Al I of these fllnctional cells showed favorable healing capacity and their effects primarily based on enhanced anglOgenesls Conclllsively. a lthollgb the precise cha racteristics are not well-described‘ the current stucly reveals that various types of functional cell s of human umbilical cord blood have some stem cell or progenitors features and play an important r ole in ti ssue regeneration

3BK21 program for Veterinary Science, College of Veterinary Medicine‘ Seoul National University. Seoul. Korea Human Co1'd blood has been used for the alternatives of bone marrow transplantation for more 10 years. Recently Mesenchymal s tem cell s , ES-like cells and endothelial stem cells has been successfuly isolated from huam co1'd blood Presentl y. it has been reported that a bout 70 incurable ans tractible di sease was possibly cured by umbili cal cord blood-deri ved s tem cells in the clinit;al test s‘ However‘ isolation and expansion of s tem cells from human umbilical cord blood(UCB) have been very difficult and an obstrucle for the clinical use This study showed that effi cient s iolat iona and expans ion of mesenchymal stem cells from UCB Full term UCB samples were obtained from the umbi lical vein after vaginal deli ve ry with the informed consent 0 1' the mothe1' approved by Borame Hospital Institutional Review Broad (IRB). And a lso. t his work was also a pproved by Seoul National University IRB. Recently, we isolated a population of s tem cells from human corcl bloocl (UCB)‘ which expressed embryo stage specific maker. SSEA-4. ancl the multi-potential stem cell marker‘ 。c t4 And we have sucessfully developed culture methods to expand ancl subculture these cells up to 1.000 billion from one single clone. Subsequently. we were a ble to transclifferente theses stem cells into insulin- producing is let- like structures. which co-express in sulin andC-pepticle, adipocyte, neuron‘ bone and cartilage. In acldition. the isola tion rate of MSC from UCB is about 70 % from the cord blood units. This isolation rate were not affected by maternal ages. the sex of baby, isolation time from the deli very. for example. 12 hrs. 24 hrs ‘ even 48 hrs from delivery Taken together. these findings might have a s ignificant potential to aclvance human UCB clerivecl stem- cell -basecl ther apeutics fOI' clinical use in near future