다중 참여자를 위한 동형암호 통합 프레임워크

학위논문(석사) -- 서울대학교대학원 : 공과대학 컴퓨터공학부, 2023. 8. 송용수.동형암호(Homomorphic Encryption)는 암호화된 상태에서 복호화 없이 연산을 가능하게 하는 암호 체계입니다. 일반적인 동형암호는 같은 키로 암호화된 암호문에 대해서만 연산을 지원하기 때문에, 여러 참여자가 있는 경우 권한이 (단일) 비밀 키를 소유한 참여자에게 집중되는 문제가 있습니다. 이 문제를 해결하기 위해 두 가지 다른 동형암호 스킴인 다자간 동형 암호(Multi-Party Homomorphic Encryption)와 다중키 동형암호(Multi-Key Homomorphic Encryption)가 개발되었습니다. 다자간 동형암호는 효율적이지만 키 생성 시 참여자 간 상호 작용이 필요하며, 참여자 집합이 고정되어야 합니다. 반면, 다중키 동형암호는 참여자 수에 비례하여 성능이 저하되지만, 연산 중간에 새로운 참여자를 추가할 수 있는 장점이 있습니다. 본 연구에서는 비대화식 키 생성을 가지는 첫 번째 다자간 동형암호를 제안합니다. 제시한 다자간 동형암호는 재선형화 키가 비밀 키에 대해 선형적이기 때문에 참여자들이 생성한 키들의 합산으로 계산될 수 있습니다. 이로 인해 각 참여자가 상호작용 없이 독립적으로 키를 생성할 수 있습니다. 또한 새로운 동형암호 스킴인 그룹간 동형암호 (Multi-Group Homomorphic Encryption) 를 제안합니다. 그룹간 동형암호는 다자간 동형암호와 다중키 동형암호를 통합한 스킴으로, 이 두 가지의 장점을 모두 가집니다. 그룹간 동형암호에서는 각 참여자 그룹이 다자간 동형암호와 같이 공동 키를 생성하여 데이터를 암호화하고, 그룹 안에서 연산을 하는 경우 다자간 동형암호와 같이 동작합니다. 그러나 그룹 간 연산을 수행할 때에는 다중키 동형암호와 같이 연산하여 새로운 그룹이 연산에 참여할 수 있습니다. 마지막으로, 제안한 그룹간 동형암호를 이용하여 다자간 연산 프로토콜을 구축하고 그 안전성을 검증합니다. 또한 그룹간 동형암호를 이용하여 다자간 동형암호와 같이 학습을 수행하고 다중키 동형암호와 같이 추론을 수행하는 로지스틱 회귀 모델을 제시합니다.Homomorphic Encryption (HE), first demonstrated in 2009, is a class of encryption schemes that enables computation over encrypted data. The standard HE, however, poses an authority issue when multiple parties are involved, as the authority is concentrated solely to whom that owns the (single) secret key. To solve this issue, variants of HE have emerged in the context of multiple parties, resulting in the development of two different lines of HE schemes – Multi-Party HE (MPHE) and Multi-Key HE (MKHE). MPHE schemes tend to be much more efficient; but require the interaction between parties in the key generation and the set of parties is fixed throughout the entire evaluation. On the other hand, MKHE schemes have poor scaling with the number of parties but allow us to add new parties to the joint computation anytime. In this work, we construct the first MPHE scheme that features a non-interactive key generation. We refactor the evaluation key to be nearly linear, allowing it to be computed by simple summation. As a result, our MPHE allows each party to independently and asynchronously broadcasts its key. In addition, we propose a new HE primitive, called Multi-Group HE (MGHE). Stated informally, an MGHE scheme provides seamless integration between MPHE and MKHE, and combines the best of both these primitives. In an MGHE scheme, a group of parties generates a public key jointly which results in compact ciphertexts and efficient homomorphic operations, similar to MPHE. However, unlike MPHE, it also supports computations on encrypted data under different keys, a property enjoyed by MKHE schemes. We present a construction of MGHE from the BFV scheme and provide a proof-of-concept implementation to demonstrate its concrete performance. Finally, we describe a general approach to construct a multi-party protocol from MGHE. We provide a proof-of-concept implementation of a logistic regression model where our MGHE interpolates between MPHE (where the training is performed) and MKHE (where the inference is performed).1 Introduction 1 1.1 Our Contributions 2 1.2 Technical Overview 3 1.3 Related Work 5 2 Background 6 2.1 Notation 6 2.2 Ring Learning with Errors 6 2.3 Gadget Decomposition and External Product 6 2.4 Variants of HE for Multiple Parties 7 3 MPHE with Non-Interactive Setup 10 3.1 Basic Scheme 11 3.2 Basic Operations 13 3.3 Security 15 4 Construction of MGHE 16 4.1 Formalizing MGHE 16 4.2 Basic Scheme 18 4.3 Basic Operations 19 4.4 Security 23 5 Constructing MPC from MGHE 24 5.1 Overview 24 5.2 MPC Protocol Secure Against Semi-Malicious Corruptions 26 6 Experimental Results 30 6.1 Basic Operations 31 6.2 Application to Machine Learning Service 31 Bibliography 34 Appendix 38 A Construction of MGHE with CKKS 38 A.1 MPHE with Non-Interactive Setup 38 A.2 Extension to MGHE with CKKS 39 B Noise analysis 40 B.1 Encryption 40 B.2 Relinearization 40 B.3 Multiplication 41 Abstract in Korean 43석

Outcomes with perioperative fat emulsions containing omega-3 fatty acid: A meta-analysis of randomized controlled trials

Purpose. Results of a meta-analysis of data from clinical studies comparing patient outcomes and hospital length of stay (LOS) in surgical patients receiving fish oil (FO)-containing i.v. fat emulsions (IVFEs) versus non-FO-containing IVFEs are presented. Methods. Computerized searches of the MEDLINE, Embase, and Coch rane CENTRAL databases were performed in August 2014 to identify Englishlanguage articles on randomized controlled trials (RCTs) comparing FO-containing and non-FO-containing IVFEs in adult surgical patients receiving parenteral nutrition. Selected articles were analyzed for methodological and publication bias and study heterogeneity (I2 statistic). Results. Data from 19 RCTs (total n = 1,167) were included in the meta-analysis. Compared with use of non-FO-containing IVFEs (products based in soybean oil [SO], medium-chain triglycerides, or olive oil), use of FO-containing IVFEs was associated with reduced infectious morbidity (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.30-0.65; p < 0.0001; I2 = 0%); the effect size was greatest for FO-containing versus SO-based IVFEs. Relative to use of SO-based IVFEs, use of FO-containing IVFEs was associated with a significant reduction in hospital LOS (weighted mean difference, -2.70 days; 95% CI, -3.60 to -1.79 days; p < 0.00001; I2 = 0%). Conclusion. The results of the meta-analysis indicated that FO-containing IVFEs could improve infectious morbidity and LOS. The overall effect of reducing infectious morbidity and LOS was found to be the greatest in comparison with the SO-based IVFEs. Copyright © 2017, American Society of Health-System Pharmacists, Inc. All rights

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived

Determination of amosulalol in human plasma using solid-phase extraction combined with liquid chromatography and ultraviolet detection

Amosulalol is an antihypertensive drug with selective postsynaptic alpha 1 and non-selective beta blocking effects. A simple solid-phase extraction and high-performance liquid chromatographic (HPLC) method has been developed and validated for the quantitative determination of amosulalol in human plasma. A reversed phase C18 column was used for the separation of amosulalol and ethyl paraben (internal standard) with a mobile phase composed of 0.025 M phosphate buffer (pH 6.0)·acetonitrile (73:27, v/v) at a flow rate of 1.5 mL/min. The ultraviolet detector was operated at the 272 nm wavelength. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 30 ng/mL. Recovery of amosulalol from human plasma was >95.6%. Amosulalol was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of a single 20 mg dose of amosulalol hydrochloride to 16 healthy volunteers. © 2004 Published by Elsevier B.V

Pharmacokinetics of formulated tenoxicam transdermal delivery systems

To investigate the feasibility of developing a new tenoxicam transdermal delivery system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were evaluated and compared with values following oral administration of tenoxicam and with application of a piroxicam plaster (Trast) marketed in Korea. Based on previous in-vitro study results, a mixture of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%) was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing effect; the area under the plasma concentration-time profile (AUC) decreased in the order of caprylic acid > linoleic acid ≥ oleic acid > lauric acid > capric acid. Compared with oral administration, maximum plasma concentration (C max) was significantly lower, and time to reach C max (T max) delayed with all formulated tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral formulation, except for TDS containing caprylic acid, although the difference was statistically significant only with capric acid. The AUC for all the formulated tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster. Even though the T max of tenoxicam TDS was not significantly different from that of the piroxicam plaster, C max was higher; formulations containing caprylic acid and linoleic acid increased C max by 7.39- and 8.76-fold, respectively. In conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good candidate for developing a new tenoxicam TDS to maintain a comparable extent of absorption to oral delivery while attaining a prolonged effect with fewer toxic events. © 2008 The Authors

Design and evaluation of levodopa methyl ester intranasal delivery systems

Objectives: This study aimed to examine the feasibility of nasal powder formulations for the delivery of levodopa (L-dopa) into the brain using highly water-soluble levodopa methyl ester hydrochloride (LDME). Methods: For designing nasal LDME powders, pH-rate stabilities of LDME in buffer solutions and their enzymatic degradations in rabbit nasal mucosal and serosal extracts were investigated. In vitro permeation studies were carried out with four LDME nasal powders. Results: LDME was degraded fast in weakly acidic and neutral solutions, but relatively stable in acidic solutions. In nasal extracts, LDME (50 and 200 μg/mL) was rapidly hydrolyzed, forming L-dopa, and there were no significant differences in first-order degradation rates between mucosal and serosal extracts. From the in vitro permeation studies, LDME powder formulations resulted in faster appearance rates (1.07 ± 0.39 mg/cm2/hr) of L-dopa than solution formulations (0.35 ± 0.08 mg/cm2/hr). Conclusions: These results suggested that LDME nasal powder formulations could be useful delivery systems of L-dopa. © 2011 - IOS Press and the authors. All rights reserved

Enhanced bioavailability of piroxicam via salt formation with ethanolamines

Piroxicam can be ionized as a zwitterion that has two pKa values (pKa 1 = 1.86 and pKa2 = 5.46). Consequently, piroxicam has a low solubility in both polar and nonpolar media, and a low lipophilicity, which results in a low permeability. Three piroxicam-ethanolamine salts were prepared, which had a higher area under the curve (AUC) than piroxicam. There were minimal differences in the AUC among the salt forms. It was reported that the piroxicam triethanolamine salt had a lower permeability across the skin than piroxicam but it had a higher oral bioavailability. Piroxicam monoethanolamine showed the highest Cmax followed by piroxicam diethanolamine and piroxicam triethanolamine. The dissolution rates of piroxicam and its salts were similar at pH 1.2. Piroxicam monoethanolamine showed the highest dissolution rate at pH 6.8, which was followed by the piroxicam diethanolamine and piroxicam triethanolamine salts. The order of dissolution rate at pH 6.8 matched the order of Cmax or the AUC after oral administration. © 2005 Elsevier B.V. All rights reserved

Low cyclosporine concentrations in children and time to acute graft versus host disease

BackgroundAchievement of target blood concentrations of cyclosporine (CsA) early after transplantation is known to be highly effective for reducing the incidence of acute graft versus host disease (aGVHD). However, no research has been conducted for predicting aGVHD occurrence with low CsA concentrations at different time periods. The objective of this study was to investigate the risk of aGVHD according to low CsA concentrations at lag days in children with allogenic hematopoietic stem cell transplantation (HSCT).MethodsThe records of 61 consecutive children who underwent allogeneic HSCT and received CsA as prophylaxis against aGVHD between May 2012 and March 2015 were retrospectively evaluated. The main outcome was any association between low CsA concentrations at lag days and aGVHD occurrence, which was examined for the first month after transplantation. Mean CsA concentrations at three lag periods were calculated: lag days 0-6, 7-13, and 14-20 before aGVHD occurrence.ResultsPatients whose mean CsA concentrations at lag days 0-6 did not reach the initial target concentration had 11.0-fold (95% confidence interval [CI]: 2.3-51.9) greater incidence of aGVHD. In addition, the AORs of low CsA concentrations at lag days 7-13 and 14-20 for developing aGVHD were 108.2 (95% CI: 7.7-1515.5) and 12.1 (95% CI: 1.1-138.1), respectively.ConclusionsAfter low CsA concentrations are detected, careful attention needs to be paid to prevent aGVHD

Adequate intensity of warfarin therapy for Korean patients with mechanical cardiac valves.

The study aim was to identify adequate therapeutic ranges of the International Normalized Ratio (INR) in Korean patients receiving warfarin after prosthetic mechanical heart valve replacement. Retrospective chart reviews were conducted of 818 patients for a total follow up period of 8,100 patient-years; all details of major complication events of thromboembolism and bleeding were recorded. The INR-incidence of complication curve was plotted, and an adequate INR determined from the intersections of 95% confidence interval (CI) curves of complication rates to ensure the lowest incidences of both thromboembolic and bleeding complications. An analysis of a subgroup of patients with atrial fibrillation (AF) was performed to evaluate the complication occurrence. A total of 69 complications occurred, of which 36 were thromboembolic events and 33 were bleeding. The adequate ranges of INR were determined as: 2.0-2.5 for patients with aortic or mitral valve replacement; 2.1-2.6 for those with aortic plus mitral valve replacement; and 2.3-2.8 for those with tricuspid valve replacement with or without other valves. It has been shown that, by keeping the INR levels within these therapeutic ranges, complication risks could be significantly reduced by up to 51%. The overall incidence of complications was increased if the patients had AF (hazards risk (HR) = 1.27, 95% CI = 1.05-1.52). The study results may provide evidence for the application of low-intensity warfarin therapies in Asian patients, including Koreans. In addition, the method of determining adequate INR levels by using INR-incidence of complications curves might be employed in many clinical settings