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Comparative Molecular Similarity Indices Analysis of Caspase-3 Inhibitors

  • Babu, Sathya;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.7 no.4
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    • pp.227-233
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    • 2014
  • Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Activation of caspases-3 stimulates a signaling pathway that ultimately leads to the death of the cell. Hence, caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage. In this work, comparative molecular similarity indices analysis (CoMSIA) was performed on a series of 3,4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMSIA model ($q^2$ = 0.586, $r^2$ = 0.955). The predictive ability of test set ($r^2_{pred}$) was 0.723. Statistical parameters from the generated QSAR models indicated the data is well fitted and have high predictive ability. Our theoretical results could be useful to design novel and more potent caspase-3 derivatives.

The Effect of the Extents of Pleural Thickening in Tuberculous Pleurisy on the Impairment of Pulmonary Function (흉막비후의 정도가 폐기능에 미치는 영향)

  • Lee, Young-Kyoung;Na, Moon-Jun;Yun, Bo-Ra;Lee, Won-Young
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.3
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    • pp.240-247
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    • 2001
  • Background : Tuberculous pleurisy treatments improve symptoms such as fever, chest pain, cough, and prevents the progression to active pulmonary tuberculosis and the development of residual pleural thickening that decrease diaphragm and rib cage movement This study investigated how the degree of residual pleural thickening affects the pulmonary function. Methods : Fifty seven patients who were initially diagnosed as having tuberculous pleurisy, were treated with anti-tuberculous medication for 6 months and had residual pleural thickening between May 1998 and January 2000 at the Eulji university hospital were reviewed. A chest X-ray and pulmonary function test(PFT, Sensormedics 2200) were performed. The predicted value(%) of the forced vital capacity(FVC), forced inspiratory vital capacity(FNC) and total lung capacity(TLC) were measured. The residual pleural thickening was defined the average of the summation in the lateral chest at the level of the imaginary line intersecting from the cardiophrenic angle to the diaphragmatic dome and the lowest part of the costophrenic angle between them. The results were sorted into three grades according to pleural thickness ; <2mm(grade I), 2~10mm(grade II), 10mm(grade III). Results : 1. FVC(% pred) and FIVC(% pred) were statistically different between grade I and III, and II and III. However, there was no difference between the TLC(% pred) between each of the groups. 2. The pleural thickness that cause restrictive dysfunction(FVC<80%) and a statistically difference, is 3mm. Conclusion : The larger the extent of the residual pleural thickness after antituberculous medication, the greater the reduction in the FVC, FIVC, TLC. A pleural thickness of 3mm is recommended as a guideline for diagnosing a restrictive pulmonary dysfunction.

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Long-term oxygen therapy in patients with chronic respiratory failure in one university hospital (호흡부전환자의 재택산소치료 실태: 한 대학병원에서의 관찰)

  • Huh, Jin Won;Lee, Jung Yeon;Hong, Sang-Bum;Oh, Yeon Mok;Shim, Tae Sun;Lim, Chae-Man;Lee, Sang Do;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Koh, Younsuck
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.2
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    • pp.160-166
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    • 2005
  • Background : Although home oxygen therapy in hypoxemic patients with chronic lung disease has been increasing over the decade in Korea, the present state has not been known well. This study was done to know the situation of home oxygen therapy in a Korean university hospital. Methods : Between January 1, 2000 and August 31, 2003, 86 patients prescribed home oxygen therapy by the pulmonary physicians of Asan Medical Center were investigated using their medical record and questionnaire. Results : Patients (52 men, mean age of 61 years) with home oxygen therapy were increasing by every year. Underlying diseases were COPD (n=29), tuberculous destroyed lung (n=18), bronchiectasis (n=15), ILD (n=12), and others. Baseline $FEV_1/FVC$, FVC, and $FEV_1$ of patients were $58.4{\pm}25.2%$, $54.5{\pm}17.1%$ of predicted, and $41.7{\pm}20.6%$ of pred. Mean oxygen flow was 1.5 L/min and mean duration per day was 14.5 hours. During therapy, mean $PaO_2$ values have increased from 51.2 to 77.7 mm Hg and $PaCO_2$ values have increased from 47.5 to 49.6 mm Hg. Only 16.5% of the subjects were monitored by visiting nurses or pulse oximeter. Three year survival rate was 56.6% and hypercapnic patients showed better prognosis. Conclusion : The patients with home oxygen therapy were increasing yearly and a part of them were monitored. The hypercapnea respiratory failure patients would have better prognosis.

3D-QSAR Analysis on the Fungicidal Activity with N-Phenylbenzenesulfonamide Analogues against Phytophthora blight (Phytophthora capsici) and Prediction of Higher Active Compounds (고추역병균(Phytophthora capsici)에 대한 N-Phenylbenzenesulfonamide 유도체들의 살균활성에 관한 3D-QSAR 분석과 고활성 화합물의 예측)

  • Soung, Min-Gyu;Kang, Kyu-Young;Cho, Yun-Gi;Sung, Nack-Do
    • Applied Biological Chemistry
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    • v.50 no.3
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    • pp.192-197
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    • 2007
  • 3D-QSARs on the fungicidal activity of N-phenylbenzenesulfonamide and N-phenyl-2-thienylsulfonamide analogues (1-37) against Phytophthora blight (Phytophthora capsici) were studied quantitatively using CoMFA and CoMSIA methods. The statistical results of the optimized CoMFA (2) model ($r^2_{cv.}(q^2)$ = 0.692 & $r^2_{ncv.}$= 0.965) show better predictability and fitness than CoMSIA (2) model ($r^2_{cv.}(q^2)$ = 0.796 & $r^2_{ncv.}$= 0.958). The fungicidal activities according to the information of the optimized CoMFA (2) model were dependent upon the steric and electrostatic fields of the molecules. Therefore, from the contribution contour maps of CoMFA (2) model, it is expected that 63% contribution was caused by the steric bulk of meta-substituent ($R_1$) on the S-phenyl ring. Also, the other contribution level of 32.9% was represented by the positive charged $R_4-group$ ($R_1$) on the N-phenyl ring and para-substituent ($R_1$) on the S-phenyl ring. A series of higher active compounds, $R_1$= 3-decyl substituent ($pred.pI_50$= 5.88) etc. were predicted based on the findings.

Relationship between Pulmonary Function and Apnea-Hypopnea Index in Asthmatic Children: The Preliminary Study (천식 환아의 폐기능과 수면무 호흡의 연관성: 예비연구)

  • Kang, Seung-Gul;Lee, Heon-Jeong;Lee, Seung-Hwan;Yoo, Young;Choung, Ji-Tae;Kim, Leen
    • Sleep Medicine and Psychophysiology
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    • v.16 no.2
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    • pp.74-78
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    • 2009
  • Objective: It has been reported that the sleep apnea syndrome in the asthmatic patients is prevalent, however, the systematic study in this field using polysomnography has rarely been performed. The aim of this study is to investigate the relationship between the apnea-hypopnea index (AHI) and the pulmonary function in asthmatic children. Methods: This study enrolled 19 male and 12 female asthmatic children aged 6-13 years (average $8.2{\pm}1.7$ years old). Complete overnight polysomnography and pulmonary function test were performed for the participants. Results: Of the 31 asthmatic children, 21 (67.7%) met the diagnostic criteria of the pediatric sleep apnea and the average AHI was $1.7{\pm}1.5/h$. The children with higher AHI showed poorer pulmonary function ($FEV_1$/FVC ratio: p=0.002, $FEV_1$%pred: p=0.047). Conclusion: These results suggest that the prevalence of the pediatric sleep apnea could be very high among the asthmatic children and the severity of the sleep apnea correlates with the pulmonary function. However, the case-control study to compare the AHI between the asthma and control groups is absolutely necessary because few normative data are available for the children.

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An Efficient Weight Signaling Method for BCW in VVC (VVC의 화면간 가중 양예측(BCW)을 위한 효율적인 가중치 시그널링 기법)

  • Park, Dohyeon;Yoon, Yong-Uk;Lee, Jinho;Kang, Jungwon;Kim, Jae-Gon
    • Journal of Broadcast Engineering
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    • v.25 no.3
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    • pp.346-352
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    • 2020
  • Versatile Video Coding (VVC), a next-generation video coding standard that is in the final stage of standardization, has adopted various techniques to achieve more than twice the compression performance of HEVC (High-Efficiency Video Coding). VVC adopted Bi-prediction with CU-level Weight (BCW), which generates the final prediction signal with the weighted combination of bi-predictions with various weights, to enhance the performance of the bi-predictive inter prediction. The syntax element of the BCW index is adaptively coded according to the value of NoBackwardPredFlag which indicates if there is no future picture in the display order among the reference pictures. Such syntax structure for signaling the BCW index could violate the flexibility of video codec and cause the dependency issue at the stage of bitstream parsing. To address these issues, this paper proposes an efficient BCW weight signaling method which enables all weights and parsing without any condition check. The performance of the proposed method was evaluated with various weight searching methods in the encoder. The experimental results show that the proposed method gives negligible BD-rate losses and minor gains for 3 weights searching and 5 weights searching, respectively, while resolving the issues.

The Search of Pig Pheromonal Odorants for Biostimulation Control System Technologies: Prediction of Pig Pheromonal Tetrahydrofuran-2-yl Family Compounds by Means of Ligand Based Approach (생물학적 자극 통제 수단으로 활용하기 위한 돼지 페로몬성 냄새 물질의 탐색: Ligand Based Approach에 의한 돼지 페로몬성 Tetrahydrofuran-2-yl 계 화합물의 예측)

  • Soung, Min-Gyu;Cho, Yun-Gi;Park, Chang-Sik;Sung, Nack-Do
    • Reproductive and Developmental Biology
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    • v.32 no.3
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    • pp.141-146
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    • 2008
  • To search a new porcine pheromonal odorant, the models of four type (2D-QSAR, HQSAR, CoMFA & CoMSlA) were derived from quantitative structure-activity relationship (QSAR) between tetrahydrofuran-2-yl family compounds and their observed binding affinity constants (Obs.p$[Od]_{50}$). The optimized CoMFA model (predictability; $r^{2}_{cv.}(q^2)$=0.886 & correlation coefficient: $r^{2}_{ncv.}$=0.984) from ligand based approaches was confirmed as the best model among them. The $N^{1}$-allyl-$N^{2}$-(tetrahydrofuran-2-yl)methyl)oxalamide (P1), 2-(4-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P5) and 2-(3-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P6) molecules predicted as porcine pheromonal odorant by the CoMFA model were showed relatively high binding affinity constant values (Pred.p$[Od]_{50}=8{\sim}10$) and very lower toxicity values against some sorts of toxicity.

Hologram Based QSAR Analysis of CXCR-2 Inhibitors

  • Sathya., B
    • Journal of Integrative Natural Science
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    • v.10 no.2
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    • pp.78-84
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    • 2017
  • CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response because the neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Hence, in the present study, Hologram based Quantitative Structure Activity Relationship Study was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The best HQSAR model was obtained using atoms, bonds, and chirality as fragment distinction parameter using hologram length 151 and 6 components with fragment size of minimum 4 and maximum 7. Significant cross-validated correlation coefficient ($q^2=0.774$) and non cross-validated correlation coefficients ($r^2=0.977$) were obtained. The model was then used to evaluate the six external test compounds and its $r^2_{pred}$ was found to be 0.614. Contribution map show that presence of cyclopropyl ring and its bulkier substituent's makes big contributions for improving the biological activities of the compounds. We hope that our HQSAR model and analysis will be helpful for future design of novel and structurally related CXCR2 antagonists.

Ligand Based HQSAR Analysis of CRTh2 Antagonists

  • Babu, Sathya;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.8 no.1
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    • pp.1-12
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    • 2015
  • CRTh2 receptor is an important mediator of the inflammatory effects and act as beneficial target for the treatment of asthma, COPD, allergic rhinitis and atopic dermatitis. In the present work, Hologram QSAR studies were conducted on a series of 50 training set CRTh2 antagonists (2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl acetic acids). The best HQSAR model was obtained using atoms, bonds, connections and donor/acceptor as fragment distinction parameter using hologram length 257 and 6 components with fragment size of minimum 7 and maximum 10. Significant cross-validated correlation coefficient ($q^2=0.786$) and non cross-validated correlation coefficients ($r^2=0.954$) were obtained. The model was then used to evaluate the 15 external test compounds which are not included in the training set and the predicted values were in good agreement with the experimental results ($r^2_{pred}=0.739$). Contribution map show that presence of C ring and its substituents makes big contributions for activities. The HQSAR model and analysis from the contribution map could be useful for further design of novel structurally related CRTh2 antagonists.

A New large-scale Pre-purification for Peroxidase from Plant Cell Cultures (식물세포 배양으로부터 Peroxidase 대량 정제를 위한 전처리 공정 개발)

  • 표상현
    • KSBB Journal
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    • v.15 no.4
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    • pp.342-345
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    • 2000
  • A novel pre-purification method was developed for producing peroxidase to guarantee high purity and yield from plant cell cultures in large-scale process. This method was a simple and efficient procedure for the isolation and pre-purification of peroxidase from the biomass consisting of active clay treatment followed by cationic exchange chromatography. The use of active clay in the pre-purification process allows for rapid and efficient separation of peroxidase from interfering compounds and dramatically increases yield and purity of crude peroxidase for purification steps compared to alternative processes. This pre-purification process serves to minimize the buffer usage size and complexity of the HPLC operations for peroxidase purification. This process is readily scalable to a pilot plant and eventually to a production environment where mass production of material are expected to be produced.

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