• International journal of advanced smart convergence
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• 제12권4호
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• pp.434-442
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• 2023

The relationship between acute kidney injury (AKI) prediction and nephrotoxic drugs, or drugs that adversely affect kidney function, is one that has yet to be explored in the critical care setting. One contributing factor to this gap in research is the limited investigation of drug modalities in the intensive care unit (ICU) context, due to the challenges of processing prescription data into the corresponding drug representations and a lack in the comprehensive understanding of these drug representations. This study addresses this gap by proposing a novel approach that leverages patient prescription data as a modality to improve existing models for AKI prediction. We base our research on Electronic Health Record (EHR) data, extracting the relevant patient prescription information and converting it into the selected drug representation for our research, the extended-connectivity fingerprint (ECFP). Furthermore, we adopt a unique multimodal approach, developing machine learning models and 1D Convolutional Neural Networks (CNN) applied to clinical drug representations, establishing a procedure which has not been used by any previous studies predicting AKI. The findings showcase a notable improvement in AKI prediction through the integration of drug embeddings and other patient cohort features. By using drug features represented as ECFP molecular fingerprints along with common cohort features such as demographics and lab test values, we achieved a considerable improvement in model performance for the AKI prediction task over the baseline model which does not include the drug representations as features, indicating that our distinct approach enhances existing baseline techniques and highlights the relevance of drug data in predicting AKI in the ICU setting.

• 미생물학회지
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• 제38권4호
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• pp.218-218
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• 2002

Using two drugs, tunicamycin and brefeldin A, which affect protein processing, we investigated the intracellular processing mechanism of secreted aspartyl proteinase 1 (SAPl) of Candide albicans. Three intracellular forms of SAPI were detected by immunoblotting using menoclonal antibody (MAb) CAPl. Their molecular weights were approximately 40, 41 and 45 kDa, respectively. The 41 kDa protein is a glycoprotein and may be the same as the extracellular form judging by its molecular mass. The 40 kDa protein was the unglycosylated form and its molecular mass coincided with deglycosylated SAPl and the 45 kDa protein was also the unglycosylated form. Neither the 40 and 45 kDa proteins were detected in the culture supernatant of C. albicans. These suggested that the 40 and 45 kDa proteins might be intracellular precursor forms of SAPI. These results show that SAPI is translated as a 45 kDa precusor form in the endoplasmic reticulum and the 45 kDa precursor farm undergoes proteolytic cleavage after translocation into the Golgi apparatus, generating the 40 kDa precursor form. This 40 kDa precursor is converted into a 41 kDa mature form through glycosylation in the Golgi apparatus. The mature form of the 41 kDa protein is sorted into secretary vesicles and finally released into the extracellular space through membrane fusion. When the glycan region of SAPl was digested with N-glycosidase F, both stability and activity of the enzyme decreased. These results indicate that the glycan attached to the enzyme may, at least in parti be related to enzyme stability and activity.

• Molecules and Cells
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• 제43권7호
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• pp.662-670
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• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.229-254
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• 2004

The objective of this study was to scrutinize the rationale of SUPAC-MR and its application in processing postapproval changes to modified release solid oral dosage forms. The types of postapproval changes that were primarily covered with SUPAC-MR included variations in the components and composition, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. SUPAC-MR defined levels of postapproval changes that the industry might make. Classification of such categories was based on the likelihood of risk occurrence and potential impact of changes upon the safety and efficacy of approved drug products. In most cases, the changes could be classified into 3 levels. It described what chemistry, manufacturing, and control tests should be conducted for each change level. The important tests specified in SUPAC-MR were batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. It then suggested what type of a filing report should be submitted to the FDA for each change level. In general, level 1 changes could be reported in an annual report, whereas level 2 and/or 3 changes could be submitted in changes-being-effected or prior approval supplements. It could be understood that the purpose of SUPAC-MR was to maintain the safety and quality of approved modified release solid oral dosage forms undergoing certain changes. At the same time, it contributed to providing a less burdensome regulatory process with the manufacturers when they wanted to make postapproval changes. European regulatory agencies also implemented SUPAC-like regulations in handling such changes to drug products. Therefore, in this study a recommendation was made for KFDA and the Korean industry to evaluate thoroughly the usefulness of these guidances and regulations in dealing with postapproval changes to modified release solid oral dosage forms.

• 정보과학회 논문지
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• 제42권1호
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• pp.15-22
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• 2015

본 논문에서는 대규모의 계산 작업을 고성능으로 처리해야 하는 신약재창출 시뮬레이션 분야에 분산 슈퍼컴퓨팅 기술을 적용한 사례에 대해 논의하고자 한다. 신약재창출이란 기존에 알려진 약물의 새로운 적응증을 규명하는 것을 의미하며, 이러한 신약재창출은 비교적 짧은 수행시간을 갖는 대규모의 도킹(docking) 연산들을 고성능으로 처리해야한다는 점에서 Many-Task Computing (MTC) 성격을 지니고 있다. 이러한 MTC 응용들의 대표 사례로서 신약재창출 시뮬레이션을 분산 슈퍼컴퓨팅 환경 기반의 HTCaaS 시스템에 적용하였으며, 이를 통해 효율적인 작업 배포, 동적인 자원 할당 및 로드 밸런싱, 안정성 및 다양한 자원들의 효율적인 통합 등이 이러한 과학 응용들을 지원하는 데 있어 필수적인 기능임을 확인할 수 있었다.

• 대한한의학방제학회지
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• 제20권2호
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• pp.137-151
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• 2012

Objectives : provides the basis on steaming processing method (SPM) which was stated in 'Dongeuibogam' and 'Euihakipmun'. Methods : Drugs and prescriptions listed in 'Dongeuibogam' and 'Euihakipmun' were investigated by following criteria; (i) name and prescription of SPM-applied drugs, (ii) protocols on the use of the supporting materials, (iii) kind of supporting materials, (iv) processing period, (v) part of the herb plants, (vi) efficacy of herbal drugs, (vii) tastes of herbal drugs, (viii) meridian tropism of the herbal drugs. Results : 1. The number of herbs was 92 species of from 'Dongeuibogam', 87 from 'Euihakipmun', and the number of prescriptions was 197 from 'Dongeuibogam' and 119 from 'Euihakipmun'. 2. Infiltrating steaming and mixing and steaming procedures were used to process supporting materials. 3. The abundance of supporting materials was in the order of alcohol and ginger juice. 4. A twelve hour-period was most frequently used. 5. The herbal parts used most were in the order of fruit, seed, roots, and stem. 6. According to an efficacy category, a drug supplementing invigoration was used most frequently and a drug eliminating heat followed next. 7. Based on four spirit features, herbs showing warm, cold, and mild features were used most. 8. In considering five tastes, herbs showing sweet and bitter tastes were used most. 9. The herbs supporting the function of liver, kidneys, spleen, stomach, and lung were used in SPM. The herbs converging to the kidneys and the liver were conducted most in 'Dongeuibogam' and 'Euihakipmun' respectively. No case for herbal drug converging to 'Samcho' was reported. Conclusions : Our investigation on the use of SPM from 'Dongeuibogam' and 'Euihakipmun' revealed that there are special principles underlying the use of supporting materials, SPM period, parts and efficacy.

• 정보처리학회논문지D
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• 제13D권7호
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• pp.977-984
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• 2006

본 연구는 RFID를 이용하여 특수의약품의 생산, 유통, 병원으로 이어지는 약품의 흐름을 추적 관리하는데 목적이 있다. 이는 유통과정에서 약품의 위변조를 막고, 유통흐름의 투명성을 제고하기 위해 의약품의 생산시점에 RFID Tag를 부착하여, 유통과정 각 단계에서 의약품의 흐름을 추적 관리하여 최종 사용자가 안심하고 사용할 수 있도록 한다. 또한 부가적으로 유통흐름상의 각 단계의 주체들에게 재고관리 정보를 제공하여 의약품 수급 및 관리에 대해 편의성을 제공하고 입출고 작업을 원활하게 수행할 수 있도록 한다. 본 연구는 의약품 분야에 FRID 적용가능성을 검토하는 연구로서 약품코드에 대한 RFID코드 표준안의 적용과 국산 미들웨어의 적용을 시도하였고 향후 의약품 분야의 이력관리를 할 수 있는 E-pedigree의 기초를 마련하고자 한다 또한 기술적으로 유통분야에 많이 쓰이는 90Mhz 대역의 리더 적용 및 약품에 적합한 RFID Tag의 설계 및 선정 결과를 제시한다.

• 정보처리학회논문지:소프트웨어 및 데이터공학
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• 제11권1호
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• pp.11-18
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• 2022

신약 디자인은 단백질 수용체와 같은 생물학적 표적과 상호작용할 수 있는 약물 후보물질을 식별하는 과정이다. 전통적인 신약 디자인 연구는 약물 후보 물질 탐색과 약물 개발 단계로 구성되어 있으나, 하나의 신약을 개발하기 위해서는 10년 이상의 장시간이 요구된다. 이러한 기간을 단축하고 효율적으로 신약 후보 물질을 발굴하기 위하여 심층 학습 기반의 방법들이 연구되고 있다. 많은 심층학습 기반의 모델들은 SMILES 문자열로 표현된 화합물을 재귀신경망을 통해 학습 및 생성하고 있으나, 재귀신경망은 훈련시간이 길고 복잡한 분자식의 규칙을 학습시키기 어려운 단점이 있어서 개선의 여지가 남아있다. 본 연구에서는 self-attention과 variational autoencoder를 활용하여 SMILES 문자열을 생성하는 딥러닝 모델을 제안한다. 제안된 모델은 최신 신약 디자인 모델 대비 훈련 시간을 1/26로 단축하는 것뿐만 아니라 유효한 SMILES를 더 많이 생성하는 것을 확인하였다.

• 한국환경농학회지
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• 제34권3호
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• pp.230-237
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• 2015

BACKGROUND: To identify the sources of inaccuracy in LC/MS/MS methods used in the routine quantitation of small molecules are described and discussed. METHODS AND RESULTS: Various UPLC coupled to triple quadrupole mass spectrometer and time of flight (TOF) were used to identify the potential sources of inaccuracy and inducing the pitfalls of qualification and quntitation during the veterinary drug residue analysis. Some of stable isotope labelled veterinary drugs, which were used as internal standards, presented "cross-talk", regardless of manufactures of mass spectrometer and types of spectrometer. Group of sulfonamides also presented inaccuracy qualification and quantitation due to the multi-residue analytical method with the same fragment ions at the close retention times. CONCLUSION: The phenomena of "cross-talk" occurring between subsequently monitored transition from stable isotope labelled and isotope non-labelled authentic chemical were identified. To prevent errors and achieve more accurate data during the analysis of small molecules by LC/MS/MS SRM method, Followings should be taken care of and kept checking; purity and concentration of stable isotope as an internal standard, prevention of carry-over during the separation in column, minimizing the ion suppression by matrix effect, identification of retention time, precursor ion and product ion, and full knowledge of data processing including smoothing and peak integration.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2006년도 추계학술발표대회
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• pp.547-550
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• 2006

오늘날 의료기기는 내장된 소프트웨어에 의해 제어되는 전자 의료기기의 형태로 급격하게 발전하고 있다. 따라서 전자 의료기기의 품질은 내장된 의료용 소프트웨어의 품질에 의해 크게 좌우될 수 밖에 없다. 특히, 의료기기가 인간의 생명과 밀접하게 연관되어 있다는 점을 고려할 때, 프로그램 가능한 전자 의료기기의 품질 측면에서도 신뢰성 측면을 특히 고려한 평가 방법이 연구되어야 할 것으로 생각된다. 본 연구에서는 소프트웨어 제품평가에 관련된 국제표준인 ISO/IEC 9126과 ISO/IEC 12119를 기반으로 하여 국내의 프로그램 가능한 전자 의료기기의 특성을 고려하여 신뢰성에 대한 평가를 위한 방법을 구축하고자 한다.