• 제어로봇시스템학회:학술대회논문집
• /
• 제어로봇시스템학회 2003년도 ICCAS
• /
• pp.1951-1956
• /
• 2003

It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we find that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

• 생물정신의학
• /
• 제18권1호
• /
• pp.36-45
• /
• 2011

Objectives : Though a proportion of Alzheimer's disease(AD) patients treated with donepezil have shown positive response on cognition, but the responders' characteristics are still uncertain. This study attempts to identify whether a single oral dose of donepezil(5mg) can change cognition and the relationship between single dose responder items and long-term responder are examined. Methods : Twenty-three AD patients for single donepezil challenge study group and eleven AD patients for controls were participated in the study. Seven days after baseline study for neuropsychological test and EEG, same studies were rechecked after donepezil medication in study group. In donepezil study groups, 12 weeks after donepezil medication, neuropsychological test and EEG were rechecked. Results : After single donepezil challenge, forward digit span, Rey-Osterrieth Complex Figure Test copy, SVLT delayed recall were significantly improved, and beta spectra power in anterior, theta spectra power in posterior field were significantly decreased. According to linear regression analysis, forward digit span after single donepezil challenge was significantly positive correlated with long-term responders. Conclusions : This study suggests that single donepezil medication can significantly change cognitive functions and EEG in AD patients. Among these responsive items, forward digit span was significantly correlated with long-term responder.

• Nuclear Engineering and Technology
• /
• 제50권5호
• /
• pp.745-750
• /
• 2018

New exercise technology such as the virtual reality (VR)-based exercise system is required to meet soaring demand for target participants in exercises and to alleviate the difficulties in personnel mobilization through an alternative approach to the exercise system. In a previous study, event tree methodologies were introduced in setting up an exercise scenario of a VR-based radiological exercise system. In the scenario, the locations at which major events occur are rephrased as nodes, routes as paths, and public response actions as protective actions or contents of an exercise at individual locations. In the study, a model for estimating effective doses to the participants is proposed to evaluate the exercise system, using the effective dose rates at particular times and locations derived from a computer program. The effective dose received by a student when she/he follows a successful route is about a half of the dose received when she/he does not follow the exercise guide directions. In addition, elapsed time to finish an exercise when following a successful route is less than one-third of the time spent to finish an exercise when following the guide's directions.

• Molecular & Cellular Toxicology
• /
• 제2권1호
• /
• pp.48-53
• /
• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• 한국환경보건학회지
• /
• 제43권4호
• /
• pp.247-256
• /
• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• 대한기관식도과학회지
• /
• 제15권2호
• /
• pp.49-56
• /
• 2009

Purpose : To evaluate the treatment outcome for patients with locally advanced, unresectable esophageal cancer treated with relatively high dose radiation therapy(RT). Materials and Methods : From January 2000 to December 2008, 32 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated with radiation therapy(RT) with or without concurrent chemotherapy. Ten patients were excluded from analysis because of distant metastasis and drop off. Patient distributions according to AJCC stages II, III IVa were 7(31.8%), 12(54.6%), 3(13.6%) respectively. The locations of tumor were cervical/upper thorax 3 (13.6%), mid thorax 13(59.1%), and lower thorax/abdominal 6(27.3%), respectively. Eleven patients received RT only, and 11 patients received cisplatin based concurrent chemoradiotherapy(CCRT). Median radiation dose was 65 Gy(range 57.6~72 Gy). Results : The median follow-up was 9.1 months(range 1.9~43.8 months). The response rates for complete response, Partial response, stable disease and Persistent disease were 6(27.3%), 11(50.0%), 4(18.2%) and 1(4.5%), respectively. Two patients(9.1%) suffered from esophageal stenosis and stents were inserted. Two patients(9.1%) had Grade 3 radiation pneumonitis and one of them expired due to acute respiratory distress syndrome(ARDS) at 36 days after completion of radiation therapy. The recurrence rate was 11(50.0%). The patterns of recurrence were persistent disease and local progression in 5(22.7%), local recurrence 3(13.7%) and concomitant local and distant recurrence in 3(13.7%). The overall survival(OS) rate was 32.1% at 2 years and 21.4% at 3 years(median 12.0 months). Disease free survival(DFS) rate was 17.3% at 2 and 3 years. All patients who had no dysphagia at diagnosis showed complete response after treatment and 100% OS at 3 years(p=0.0041). The OS for above 64.8 Gy group and 64.8 Gy or below group at 3 years were 60.6% and 9.1%(p=0.1341). The response to treatment was the only significant factor affecting OS(p=0.004). Conclusion : Relatively high dose radiation therapy in unresectable esophageal cancer tended to have a better outcome without increased complication rate. Further study with more patients is warranted to justify improved result.

• 한국의학물리학회지:의학물리
• /
• 제14권2호
• /
• pp.74-80
• /
• 2003

본 연구의 목적은 핵의학 분야에서 생체 내 흡수선량의 직접 측정에 사용될 수 있는, 테프론을 씌운 TLD의 수행성을 알아보고, 흡수선량 측정 시 테프론의 영향에 대하여 분석하고자 한다. 테프론 캡슐에 든 LiF TLD-100의 반응감도를 고체 팬텀 내에서의 깊이를 달리 하며 측정하였다 성인 인체모형 팬텀을 이용하여 테프론을 씌운 TLD로써 생체 내 흡수선량을 측정하였다. 테프론을 씌우지 않은 보통의 TLD를 이용하여 구한 PDD, TMR, 그리고 생체흡수선량과 테프론을 씌운 TLD로 구한 값을 비교하였다. 보통의 TLD를 이용하여 구한 반응값과 테프론을 씌운 TLD로 구한 값의 차이는 build-up이상의 깊이에서는 같은 조건하에서 3％ 이내였다. 그러나 팬텀 표면 부근에서는 테프론 켑슐의 두께에 기인한 build-up 효과로 인해 큰 차이를 보였다. 본 연구에서 테프론 켑슐로 인하여 수 메가볼트의 방사선에 대한 TLD의 흡수선량 측정에 미치는 변화는 미미한 것으로 나타났다. 따라서 치료 환경 하에서 테프론을 씌운 TLD가 생체 내 선량측정에 매우 적합한 것으로 사료된다.

• IMMUNE NETWORK
• /
• 제6권2호
• /
• pp.93-101
• /
• 2006

Background: Memory T lymphocytes of the immune system provide long-term protection in response to bacterial or viral infections/immunization. Ag concentration has also been postulated to be important in determining whether T cell differentiation favors effector versus memory cell development. In the present study we hypothesized that naive Ag-specific $CD4^+$ T cells briefly stimulated with different Ag doses at the primary exposure could affect establishment of memory cell pool after secondary immunization. Methods: To assess this hypothesis, the response kinetics of DO11.10 TCR $CD4^+$ T cells primed with different Ag doses in vitro was measured after adoptive transfer to naive BALB/c mice. Results: Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide $(OVA_{323-339})$, whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low $OVA_{323-339}$ peptide dose showed least contraction and established higher number of memory cells than other treated groups. When the cell division was analyzed after adoptive transfer, the high dose Ag-stimulated donor cells have undergone seven rounds of cell division at 3 days post-adoptive transfer. However, there was very few division in naive and low dose of peptide-treated group. Conclusion: These results suggest that primary stimulation with a low dose of Ag leads to better memory $CD4^+$ T cell generation after secondary immunization. Therefore, these facts imply that optimally primed $CD4^+$ T cells is necessary to support effective memory pool following administration of booster dose in prime-boost vaccination.

• 한국환경성돌연변이발암원학회지
• /
• 제22권2호
• /
• pp.97-105
• /
• 2002

Nowadays a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms are developed and manufactured with safety evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. This study was carried out to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice. In this study, doses which we determined to expose to mice were 40 cigarettes for 6 hours a day to mice in single dose and 20 (high dose), 10 (middle dose) and 5 cigarettes (low dose) a day for 28 days in repeated dose inhalation toxicity, in vivo chromosome aberration test and micronucleus test. The particulate substances from H menthol herbal cigarettes also were gathered and used in the Salmonella typhimurium/microsome assay (Salmonella test; Ames test). We could find neither significant changes between control and treatment groups nor dose-response effects of test material at all except serum Ca level of female middle dose treatment group in repeated dose inhalation toxicity test. In conclusion, H menthol herbal cigarettes, when applied clinically intended dose we used, might not show any toxic and/or mutagenic effect.

• 한국환경보건학회지
• /
• 제49권1호
• /
• pp.1-10
• /
• 2023

Low-dose radiation exposure has received considerable attention because it reflects the general public's type and level of exposure. Still, controversy remains due to the relatively unclear results and uncertainty in risk estimation compared to high-dose radiation. However, recent epidemiological studies report direct evidence of health effects for various types of low-dose radiation exposure. In particular, international nuclear workers' studies, CT exposure studies, and children's cancer studies on natural radiation showed significantly increased cancer risk among the study populations despite their low-dose radiation exposure. These studies showed similar results even when the cumulative radiation dose was limited to an exposure group of less than 100 mGy, demonstrating that the observed excess risk was not affected by high exposure. A linear dose-response relationship between radiation exposure and cancer incidence has been observed, even at the low-dose interval. These recent epidemiological studies include relatively large populations, and findings are broadly consistent with previous studies on Japanese atomic bomb survivors. However, the health effects of low-dose radiation are assumed to be small compared to the risks that may arise from other lifestyle factors; therefore, the benefits of radiation use should be considered at the individual level through a balanced interpretation. Further low-dose radiation studies are essential to accurately determining the benefits and risks of radiation.