• Title/Summary/Keyword: Drug design

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Optimization of Dual Layer Phoswich Detector for Small Animal PET using Monte Carlo Simulation

  • Y.H. Chung;Park, Y.;G. Cho;Y.S. Choe;Lee, K.H.;Kim, S.E.;Kim, B.T.
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2003.09a
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    • pp.44-44
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    • 2003
  • As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.

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Predicting the Fetotoxicity of Drugs Using Machine Learning (기계학습 기반 약물의 태아 독성 예측 연구)

  • Myeonghyeon Jeong;Sunyong Yoo
    • Journal of Life Science
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    • v.33 no.6
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    • pp.490-497
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    • 2023
  • Pregnant women may need to take medications to treat preexisting diseases or diseases that develop during pregnancy. However, some drugs may be fetotoxic and lead to, for example, teratogenicity and growth retardation. Predicting the fetotoxicity of drugs is thus important for the health of the mother and fetus. The fetotoxicity of many drugs has not been established because various challenges hinder the ability of researchers to determine their fetotoxicity. The need exists for in silico-based fetotoxicity assessment models, as they can modernize the testing paradigm, improve predictability, and reduce the use of animals and the costs of fetotoxicity testing. In this study, we collected data on the fetotoxicity of drugs and constructed fetotoxicity prediction models based on various machine learning algorithms. We optimized the models for more precise predictions by tuning the hyperparameters. We then performed quantitative performance evaluations. The results indicated that the constructed machine learning-based models had high performance (AUROC >0.85, AUPR >0.9) in fetotoxicity prediction. We also analyzed the feature importance of our model's predictions, which could be leveraged to identify the specific features of drugs that are strongly associated with fetotoxicity. The proposed model can be used to prescreen drugs and drug candidates at a lower cost and in less time. It provides a predictive score for fetotoxicity risk, which may be beneficial in the design of studies on fetotoxicity in human pregnancy.

erratum : A Study on Developing Safety and Performance Assessment Guideline for Electronic Warm-Acupuncture Apparatus (erratum : 전기식 온침기에 대한 안전성 및 성능평가 가이드라인 개발 연구)

  • Hansol Jang;U-Ryeong Chung;Jeong-Hyun Moon;Seong-Kyeong Choi;Won-Suk Sung;Min-Seop Hwang;Seung-Deok Lee;Kyung-Ho Kim;Jong-Hwa Yoon;Eun-Jung Kim
    • The Journal of Korean Medicine
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    • v.44 no.1
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    • pp.128-128
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    • 2023
  • Objectives: This research aimed to develop a guideline for evaluating safety and performance of electronic warm-acupuncture apparatus. With the development of medical devices like electronic warm-acupuncture apparatus with improved performance, convenience and safety measures compared to traditional warm-acupuncture needling, safety and performance guideline is a necessity. Methods: By referring to existing standards and guidelines of other electronic devices for Korean medicine with heating function, guideline for safety and performance assessment of electronic warm-acupuncture apparatus was drafted Results: The guideline, presents explanation for adequate temperature and settings of the apparatus, and safety measurements providing against thermal runaway situations along with guidelines for the manual. Guideline for detailed test method for the performance of the apparatus such as accuracy of temperature increase and the timer, and safety unit was also provided. The test items and suggested test methods for the requirements of biological, electrical and electromagnetic safety were referred to Korean approval documents of ministry of Food and Drug Safety. Conclusion: We proposed the relevant items to verify performance and safety of warm-acupuncture apparatus to assure patient safety and improve the quality of currently developing devices for application in clinical field.

Summative Usability Assessment of Software for Ventilator Central Monitoring System (인공호흡기 중앙감시시스템 소프트웨어의 사용적합성 총괄평가)

  • Ji-Yong Chung;You Rim Kim;Wonseuk Jang
    • Journal of Biomedical Engineering Research
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    • v.44 no.6
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    • pp.363-376
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    • 2023
  • According to the COVID-19, development of various medical software based on IoT(Internet of Things) was accelerated. Especially, interest in a central software system that can remotely monitor and control ventilators is increasing to solve problems related to the continuous increase in severe COVID-19 patients. Since medical device software is closely related to human life, this study aims to develop central monitoring system that can remotely monitor and control multiple ventilators in compliance with medical device software development standards and to verify performance of system. In addition, to ensure the safety and reliability of this central monitoring system, this study also specifies risk management requirements that can identify hazardous situations and evaluate potential hazards and confirms the implementation of cybersecurity to protect against potential cyber threats, which can have serious consequences for patient safety. As a result, we obtained medical device software manufacturing certificates from MFDS(Ministry of Food and Drug Safety) through technical documents about performance verification, risk management and cybersecurity application.The purpose of this study is to conduct a usability assessment to ensure that ergonomic design has been applied so that the ventilator central monitoring system can improve user satisfaction, efficiency, and safety. The rapid spread of COVID-19, which began in 2019, caused significant damage global medical system. In this situation, the need for a system to monitor multiple patients with ventilators was highlighted as a solution for various problems. Since medical device software is closely related to human life, ensuring their safety and satisfaction is important before their actual deployment in the field. In this study, a total of 21 participants consisting of respiratory staffs conducted usability test according to the use scenarios in the simulated use environment. Nine use scenarios were conducted to derive an average task success rate and opinions on user interface were collected through five-point Likert scale satisfaction evaluation and questionnaire. Participants conducted a total of nine use scenario tasks with an average success rate of 93% and five-point Likert scale satisfaction survey showed a high satisfaction result of 4.7 points on average. Users evaluated that the device would be useful for effectively managing multiple patients with ventilators. However, improvements are required for interfaces associated with task that do not exceed the threshold for task success rate. In addition, even medical devices with sufficient safety and efficiency cannot guarantee absolute safety, so it is suggested to continuously evaluate user feedback even after introducing them to the actual site.

Development and Testing of the Model of Health Promotion Behavior in Predicting Exercise Behavior

  • O'Donnell, Michael P.
    • Korean Journal of Health Education and Promotion
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    • v.2 no.1
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    • pp.31-61
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    • 2000
  • Introduction. Despite the fact that half of premature deaths are caused by unhealthy lifestyles such as smoking tobacco, sedentary lifestyle, alcohol and drug abuse and poor nutrition, there are no theoretical models which accurately explain these health promotion related behaviors. This study tests a new model of health behavior called the Model of Health Promotion Behavior. This model draws on elements and frameworks suggested by the Health Belief Model, Social Cognitive Theory, the Theory of Planned Action and the Health Promotion Model. This model is intended as a general model of behavior but this first test of the model uses amount of exercise as the outcome behavior. Design. This study utilized a cross sectional mail-out, mail-back survey design to determine the elements within the model that best explained intentions to exercise and those that best explained amount of exercise. A follow-up questionnaire was mailed to all respondents to the first questionnaire about 10 months after the initial survey. A pretest was conducted to refine the questionnaire and a pilot study to test the protocols and assumptions used to calculate the required sample size. Sample. The sample was drawn from 2000 eligible participants at two blue collar (utility company and part of a hospital) and two white collar (bank and pharmaceutical) companies located in Southeastern Michigan. Both white collar site had employee fitness centers and all four sites offered health promotion programs. In the first survey, 982 responses were received (49.1%) after two mailings to non-respondents and one additional mailing to secure answers to missing data, with 845 usable cases for the analyzing current intentions and 918 usable cases for the explaining of amount of current exercise analysis. In the follow-up survey, questionnaires were mailed to the 982 employees who responded to the initial survey. After one follow-up mailing to non-respondents, and one mailing to secure answers to missing data, 697 (71.0%) responses were received, with 627 (63.8%) usable cases to predict intentions and 673 (68.5%) usable cases to predict amount of exercise. Measures. The questionnaire in the initial survey had 15 scales and 134 items; these scales measured each of the variables in the model. Thirteen of the scales were drawn from the literature, all had Cronbach's alpha scores above .74 and all but three had scores above .80. The questionnaire in the second mailing had only 10 items, and measured only outcome variables. Analysis. The analysis included calculation of scale scores, Cronbach's alpha, zero order correlations, and factor analysis, ordinary least square analysis, hierarchical tests of interaction terms and path analysis, and comparisons of results based on a random split of the data and splits based on gender and employer site. The power of the regression analysis was .99 at the .01 significance level for the model as a whole. Results. Self efficacy and Non-Health Benefits emerged as the most powerful predictors of Intentions to exercise, together explaining approximately 19% of the variance in future Intentions. Intentions, and the interaction of Intentions with Barriers, with Support of Friends, and with Self Efficacy were the most consistent predictors of amount of future exercise, together explaining 38% of the variance. With the inclusion of Prior Exercise History the model explained 52% of the variance in amount of exercise 10 months later. There were very few differences in the variables that emerged as important predictors of intentions or exercise in the different employer sites or between males and females. Discussion. This new model is viable in predicting intentions to exercise and amount of exercise, both in absolute terms and when compared to existing models.

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Clinical Efficacy of Erdosteine in Patients with Acute or Chronic Bronchitis -A Randomized, Double Blind, Comparative Study vs. Ambroxol- (급.만성 기관지염 환자에서 엘도스$^{(R)}$(Erdosteine)의 임상효과 -염산 암브록솔과의 무작위 이중맹검 비교시험-)

  • Kim, Seok-Chan;Lee, Sang-Hoak;Song, So-Hyang;Kim, Young-Kyoon;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1296-1307
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    • 1997
  • Background : Erdosteine is a thiol derivative developed for the treatement of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis. Erdosteine has mucomodulating and antioxidant properties and especially exhibits excellent gastrointestinal tolerability. Methods : The study was conducted as a prospective evaluation, with 2 comparative groups orally treated with erdosteine 300mg (bid.) or ambroxol 30mg (b.i.d.) for 7 days and the design of trial was double-blind. The treatments have been assigned randomly to patients (n=80) with acute or chronic bronchitis. The primary end-point used to determine efficacy in this study was subjective symptoms including expectorating frequence, expectoration volume, expectorating difficulty, expectoration viscosity, cough intensity and dyspnea. The secondary end-points of efficacy was the result of arterial blood gas analysis and pulmonary function test. Safety was evaluated with adverse drug reactions and laboratory tests monitoring. 61 patients was included in the efficacy analysis, due to the fact that 19 patients drop-out for different reasons. The obtained values have been analyzed with paired Hest., ANOVA test., multivariate $t^2$-test, repeated measures analysis of covariance, two sample t-test, loglinear-logit model analysis, Fisher's exact test. Results : 1) There was no significant difference on demographic data and vital signs between erdosteine and ambroxol treated groups. 2) The comparison between erdosteine and ambroxol treated groups showed no significant difference in improvement of each symptom in spite of the more favorable efficacy obtained with erdosteine. No difference on the contrary was observed for arterial blood gas analysis and pulmonary function test. 3) As safety is concerned, no clinical significant changes in laboratory test and symptom were induced in erdosteine and ambroxol treated group and two patients in ambroxol treated group drop-out for adverse reactions in symptom. 4) In the evaluation of final clinical efficacy, erdosteine improved more effectively patient's overall symptoms {very good effect (11/31), good effect (12/31), moderate effect (6/31), no effect (2/31), aggravation (0/31)} than ambroxol {very good effect (6/30), good effect (14/30), moderate effect (5/30), no effect (4/30), aggravation (2/30)}. And the probability of symptomatic improvement by erdosteine compared to ambroxol was 2.5 times. (p<0.05). Conclusion : This study showed that erdosteine was clinically effective and safe drug for treatment of acute and chronic bronchitis.

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Effects of Alcohol on Psychomotor Performance and Subjective Assessments In Normal Adults with Variation of Acetaldehyde Dehydrogenase I (정상성인에서 ALDH-I의 변이가 알콜의 정신운동성 수행과 주관적 평가에 미치는 영향)

  • Yoon, Bo Hyun;Yoon, Jin Sang
    • Korean Journal of Biological Psychiatry
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    • v.3 no.2
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    • pp.222-239
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    • 1996
  • The purpose of this study was to evaluate the effects of alcohol on the psychomotor performance and subjective assessment in healthy Korean adults with acetaldehyde dehydrogenase I(ALDH-I) isozyme variance. A total of 20 male subjects, half with active ALDH-I and the other half with inactive ALDH-I, were selected through both a self-reporting questionnaire examining alcohol sensitivity and the Higuchi's ethanol patch test detecting ALDH-I deficiency. In a doule-blind, placebo-controlled cross-over design, each subject consumed four doses of alcohol(0.25, 0.5, 0.75, 1.0g/kg) and placebo on five separate occasions at weekly intervals, Treatment order was fully balanced using a $5{\times}5$ Latin square, Psychomotor performance tests[coritical flicker fusion threshold(CFF) and choice reaction time(CRT)] and self-estimate questionnaires were conducted at baseline and at time points of 20, 40, 60, 90, 120, 150, 180 minutes after consuming the test drug for 20 minutes, Blood alcohol concentrations(BACs) using breath analyzer were measured at baseline and at time points of 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180 minutes after drinking, The BACs and the mean changes in the psychomotor performances and subjective assessments from pre-alcohol baseline, were compared between the two groups. The findings were summarized as follows : 1) BACs were tended to be higher in the inactive group than the active in all of the four alcohol doses. However significant group differences were only after the 0.5g/kg dose of alcohol. 2) The inactive group showed significant impairment in CFFT at most time points alter 0.75 and 1.0g/kg doses of alcohol. 3) In CRT, total reaction time(TRT) significantly prolonged in the inactive group than the active group at 20 minutes after 0.25 and 1.0g/kg doses of alcohol and at 40, 60, 90 minutes alter 0.75g/kg dose of alcohol. In the inactive group, recognition time component significantly increased at 20, 60, 90 minutes after 1.0g/kg dose of alcohol, while movement time component significantly increased at 40, 60 minutes after 0.75g/kg dose of alcohol. 4) Subjective evaluation of the effect of alcohol revealed that physical and mental conditions as well as a self-estimate of the effects of alcohol on performance were significantly worse in the inactive group than the active at some time points alter all of the lour alcohol doses, wihch were more pronounced after 0.75 and 1.0g/kg doses of alcohol. 5) Most of the group differences mentioned above, still remained statistically significant after BAC was entered as a covariate, These findings demonstrated that the alcohol sensitivity is higher in individuals with inactive ALDH-I than those with active ALDH-I both on the subjective assessments and the objective psychomotor performances. Furthermore, these results suggest thai the alcohol sensitivity may be determined by acetaldehyde concentration rather than BAC per se. In future studies, after more accurate genotyping for ALDH-I, the relationships between BAC, acetaldehyde concentration and alcohol sensitivities should be clearly defined.

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Expression of Serotonin(5-HT) Receptor Isotypes in Reproductive Organs of Male Rat (수컷 흰쥐 생식기관에서의 세로토닌 수용체 아형 유전자 발현)

  • 이성호
    • Development and Reproduction
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    • v.6 no.2
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    • pp.111-115
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    • 2002
  • 5-Hydroxytryptamine(5-HT; serotonin) system has been implicated in the modulation of male sexual behaviors and the secretion of reproductive hormones. In human males, selective serotonin re-uptake inhibitors(SSRIs) are known to improve the major male sexual dysfunction, premature ejaculation, through the central nervous system-mediated pathways. As numerous hormone and local factors, 5-HT may have peripheral role in the regulation of male sexual function. The expression of 5-HT receptor subtypes in the target tissue, however, has not been explored yet. The present study was undertaken to test whether the 5-HT receptor subtypes are expressed in the reproductive tissues of male rat, especially in ejaculatory machinery such as seminal vesicle and vas deferens. To do this, reverse transcription-polymerase chain reaction(RT-PCR) and Southern blot analysis were employed. The transcripts for the 1A, 1B and 2C subtypes of 5-HT receptor were amplified in all the tested tissues. The present study demonstrated the expression of 5-HT receptor in the rat ejaculatory machinery, suggesting that 5-HT may play a pivotal role in the male sexual function via not only central pathway but also peripheral route. Further study on the receptor subtype-specific effect and their harmonized mode of action will be needed to establish the understanding of ejaculation mechanism and drug design.

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Optimization of Interesterification Reaction for the Continuous Production of trans-Free Fat in a Packed Bed Enzyme Bioreactor with Immobilized Lipase (고정화 리파제를 이용한 충진형 효소생물반응기 내에서의 무-트랜스 유지 연속 생산을 위한 에스테르 교환 반응의 최적화)

  • Kim, Sang-Woo;Park, Kyung-Min;Ha, Jae-Uk;Lee, Jae-Hwan;Chang, Pahn-Shick
    • Korean Journal of Food Science and Technology
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    • v.41 no.2
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    • pp.173-178
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    • 2009
  • Epidemiological studies showed that high trans-fat consumption is closely associated with getting the risks of cardiovascular disease. The objective of this study was to produce trans-free fat through lipase-catalyzed interesterification, as a substitute for the cream margarine commonly used in industry. Optimum conditions for interesterification in a packed bed enzyme bioreactor (PBEB) were determined using response surface methodology (RSM) based on central composite design. Three kinds of reaction variables were chosen, such as substrate flow rate (0.4-1.2 mL/min), reaction temperature (60-70$^{\circ}C$), and ratio of fully hydrogenated canola oil (FHCO, 35-45%) to evaluate their effects on the degree of interesterification. Optimum conditions from the standpoint of solid fat content (SFC) were found to be as follows: 0.4 mL/min flow rate, 64.7$^{\circ}C$ reaction temperate, and 42.8% (w/w) ratio of FHCO, respectively. The half-life of immobilized lipase in PBEB with two stages at 60$^{\circ}C$ ($1^{st}$ stage) and 55$^{\circ}C$ ($2^{nd}$ stage) was about more than 30 days as estimated by extrapolating the incubation time course of tristearoyl glycerol (TS) conversion, whereas the half-life of the enzyme in PBEB with single stage at 65$^{\circ}C$ was only about 15 days. Finally, the results from SFC analysis suggest that trans-free fat produced in this study seems to be a suitable substitute for the cream margarine commonly used in industry.

Solution Structure of 21-Residue Peptide (Asp 84-Leu 104), Functional Site derived from $p16^{INK4A}$ ($p16^{INK4A}$ 단백질 활성부위(Asp 84-Leu 104)의 용액상 구조)

  • Lee, Ho-Jin;Ahn, In-Ae;Ro, Seonggu;Choi, Young-Sang;Yoon, Chang No;Lee, Kang-Bong
    • Analytical Science and Technology
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    • v.13 no.4
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    • pp.494-503
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    • 2000
  • A 21-residue peptide corresponding to amino acids 84-104 of $p16^{INK4A}$, the tumor suppressor, has been synthesized and its structure was studied by Circular Dichroism, $^1H$ NMR spectroscopy and molecular modeling. A p16-derived peptide (84-104 amino acids) forming stable complex with CDK4 and CDK6 inhibits the ability of CDK4/6 to phosphorylate pRb in vitro, and blocks cell-cycle progression through G1/S phase as shown in the function of the full-length p16. Its NMR spectral data including NOEs, $^3J_{NH-H{\alpha}}$ coupling constants, $C_{\alpha}H$ chemical shift, the average amplitude of amide chemical shift oscillation and temperature coefficients indicate that the secondary structure of a p16-derived peptide is similar to that of the same region of full-length p16, which consists of helix-turn-helix structure. The 3-D distance geometry structure based on NOE-hased distance and torsion angle restraints is characterized by ${\gamma}$-turn conformation between residues $Gly^{89}-Leu^{91}$(${\varphi}_{i+1}=-79.8^{\circ}$, ${\varphi}_{i+1}=60.2^{\circ}$) as evidenced in a single crystal structure for the corresponding region of p18 or p19, but is undefined at both the N and C termini. This compact and rigid ${\gamma}$-turn region is considered to stabilize the structure of p16-derived peptide and serve as a site recognizing cyelin dependent kinase, and this well-defined ${\gamma}$-turn structure could be utilized for the design of anti-cancer drug candidates.

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