On the Effect of Semantically Enriched Context Models on Software Modularization

Many of the existing approaches for program comprehension rely on the linguistic information found in source code, such as identifier names and comments. Semantic clustering is one such technique for modularization of the system that relies on the informal semantics of the program, encoded in the vocabulary used in the source code. Treating the source code as a collection of tokens loses the semantic information embedded within the identifiers. We try to overcome this problem by introducing context models for source code identifiers to obtain a semantic kernel, which can be used for both deriving the topics that run through the system as well as their clustering. In the first model, we abstract an identifier to its type representation and build on this notion of context to construct contextual vector representation of the source code. The second notion of context is defined based on the flow of data between identifiers to represent a module as a dependency graph where the nodes correspond to identifiers and the edges represent the data dependencies between pairs of identifiers. We have applied our approach to 10 medium-sized open source Java projects, and show that by introducing contexts for identifiers, the quality of the modularization of the software systems is improved. Both of the context models give results that are superior to the plain vector representation of documents. In some cases, the authoritativeness of decompositions is improved by 67%. Furthermore, a more detailed evaluation of our approach on JEdit, an open source editor, demonstrates that inferred topics through performing topic analysis on the contextual representations are more meaningful compared to the plain representation of the documents. The proposed approach in introducing a context model for source code identifiers paves the way for building tools that support developers in program comprehension tasks such as application and domain concept location, software modularization and topic analysis

Trust-Based Control of (Semi)Autonomous Mobile Robotic Systems

Despite great achievements made in (semi)autonomous robotic systems, human participa-tion is still an essential part, especially for decision-making about the autonomy allocation of robots in complex and uncertain environments. However, human decisions may not be optimal due to limited cognitive capacities and subjective human factors. In human-robot interaction (HRI), trust is a major factor that determines humans use of autonomy. Over/under trust may lead to dispro-portionate autonomy allocation, resulting in decreased task performance and/or increased human workload. In this work, we develop automated decision-making aids utilizing computational trust models to help human operators achieve a more effective and unbiased allocation. Our proposed decision aids resemble the way that humans make an autonomy allocation decision, however, are unbiased and aim to reduce human workload, improve the overall performance, and result in higher acceptance by a human. We consider two types of autonomy control schemes for (semi)autonomous mobile robotic systems. The first type is a two-level control scheme which includes switches between either manual or autonomous control modes. For this type, we propose automated decision aids via a computational trust and self-confidence model. We provide analytical tools to investigate the steady-state effects of the proposed autonomy allocation scheme on robot performance and human workload. We also develop an autonomous decision pattern correction algorithm using a nonlinear model predictive control to help the human gradually adapt to a better allocation pattern. The second type is a mixed-initiative bilateral teleoperation control scheme which requires mixing of autonomous and manual control. For this type, we utilize computational two-way trust models. Here, mixed-initiative is enabled by scaling the manual and autonomous control inputs with a function of computational human-to-robot trust. The haptic force feedback cue sent by the robot is dynamically scaled with a function of computational robot-to-human trust to reduce humans physical workload. Using the proposed control schemes, our human-in-the-loop tests show that the trust-based automated decision aids generally improve the overall robot performance and reduce the operator workload compared to a manual allocation scheme. The proposed decision aids are also generally preferred and trusted by the participants. Finally, the trust-based control schemes are extended to the single-operator-multi-robot applications. A theoretical control framework is developed for these applications and the stability and convergence issues under the switching scheme between different robots are addressed via passivity based measures

인체 유방암에서 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1)과의 직접 결합을 통한 Nrf2의 안정화 연구

학위논문 (박사) -- 서울대학교 대학원 : 융합과학기술대학원 분자의학 및 바이오제약학과, 2020. 8. Surh Young-Joon.Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically recognizes phosphorylated serine or threonine of a target protein and isomerizes the adjacent proline residue. Overexpression of Pin1 has been found in many types of malignancies, suggesting its oncogenic function. Recent studies have revealed constitutive activation of Nrf2, a transcription factor that regulates cellular redox homeostasis, in some transformed or cancerous cells, conferring an advantage for their growth and survival. Silencing of Pin1 by using siRNA or pharmacologic inhibition blocked the accumulation of Nrf2, thereby suppressing proliferation and clonogenicity of MDA-MB-231 human breast cancer cells and xenograft tumor growth in nude mice. Since Nrf2 harbours pSer/Thr-Pro motifs, I investigated whether Pin1 could directly interact with Nrf2 in the context of its implications in breast cancer development and progression. I found that Pin1 binds to Nrf2 which stabilizes this transcription factor by hampering proteasomal degradation. Notably, the interaction between Pin1 and Nrf2 was dependent on the phosphorylation of Nrf2 at Ser 215, 408 and 577. In another study, Keap1, the main inhibitor of Nrf2, was found to be phosphorylated at Ser 104 and Thr 277. These amino acids are preceded by proline and hence can be the putative binding sites for Pin1. I found the direct interaction between Keap1 and Pin1, and this was abolished upon substation of Ser 104 and Thr 277 with Alanine. The interaction of Nrf2 with Keap1 was markedly increased when Pin1 was downregulated. On the other hand, Keap1 knockout embryonic fibroblasts exhibited the enhanced interaction between Nrf2 and Pin1. Therefore, it is likely that Pin1 and Nrf2 may compete with each other for Keap1 binding. In conclusion, Pin1 plays a role in stabilization and constitutive activation of Nrf2 interfering the interaction between Nrf2 and Keap1.단백질의 인산화는 세포내 신호전달 단백질들의 활성에 영향을 미치며, 세포내 기능 조절을 위해 매우 중요한 역할을 담당한다. 인산화 부위 중 세린/트레오닌 다음에 특이적으로 프롤린 (pSer/Thr-Pro)이 위치할 경우 CDKs, MAPKs, and GSK-3β등과 같은 proline directed kinase들 (에 의해 인산화된다. 프롤린은 cis나 trans의 conformation을 모두 채택할 수 있어 단백질의 접힘이나 기능 활성을 조절한다. Pin1 (peptidyl-prolyl isomerase family of proteins)은 프롤린 잔기의 cis/trans의 이성화반응을 촉매하는 효소로서 인산화된 세린/트레오닌 다음에 프롤린이 오는 motif에 유일하게 결합하여 cis/trans 이성질화를 촉진한다. Pin1의 구조는 N-말단에 있는 WW 도메인과 C-말단에 있는 PPIase 도메인으로 이루어져 있으며, WW 도메인은 기질 단백질과 결합하고 PPIase 도메인은 인산화된 세린/트레오닌-프롤린 (pSer/Thr-Pro) 모티프의 프롤린 이성질화를 통한 구조 변화에 관여한다. Pin1에 의한 기질 단백질의 구조 변화는 단백질의 활성, 단백질 상호결합 및 세포내 분포와 안정성에 영향을 미친다. Pin1은 세포 주기 발달에서 중요한 역할을 하는 단백질들을 조절하는 것으로 알려져 세포내의 Pin1 단백질 발현 수준의 변화는 세포의 과도한 증식과 관련된 질병인 암의 발생 및 진행에 영향을 줄 수 있다 Nrf2는 산화적 스트레스에 의해 유발되는 염증, 암 발생, 심혈관계 질환, 및 당뇨등의 병리학적 과정에 관여하여 세포를 보호해 준다. 정상적인 상태에서 Nrf2는 저해단백질인 kelch-like ECH-associated protein 1 (Keap1)에 결합된 비활성 상태로 세포질내에 존재한다. 하지만 세포가 활성산소종 또는 친전자성 물질에 의해 자극되면 Nrf2의 인산화 또는 Keap1이 thiol modification을 통해 Keap1으로부터 Nrf2가 분리된다. 이후 Nrf2는 핵내로 이동하고, 핵내에 존재하는 small Maf 단백질과 복합체를 이룬후 항산화 효소의 프로모터 지역에 결합함으로써 phase II 항산화/해독화 효소의 발현을 조절한다. 그러나 스트레스에 반응하여 일시적으로 활성화되는 정상세포의 경우와 달리 악성 종양 세포에서 Nrf2의 과도한 지속적인 발현은 암세포의 성장을 촉진시키고 항암치료의 효과를 감소시킨다. Nrf2 단백질에도 다수의 Pin1 결합부위 (pSer/Thr-Pro motifs)가 존재하므로, Pin1과 Nrf2과의 상호작용과 이를 통한 유방암 증식 및 진행에 미치는 영향에 관하여 연구하였다. 특히, Nrf2 단백질의 세린 215, 408 and 577의 인산화 잔기가 Pin1 과의 결합 부위임을 확인하였고, Pin1과 Nrf2의 결합은 Nrf2의 프로테아좀에 의한 분해를 억제함으로써 Nrf2의 안정화에 관여함을 알 수 있었다. 한편, Nrf2의 주요 억제 단백질인 Keap1은 유방암 세포내에서 세린 104번 잔기와 트레오닌 277번 잔기에서의 인산화가 이루어짐을 ESI-LC-MS 분석을 통하여 확인하였고, 세린 104번 잔기와 트레오닌 277번 잔기의 인산화가 차단된 돌연변이 세포는 Pin1과의 직접적 결합이 Keap1 wild type 세포에 비해 현저히 감소함을 확인 할 수 있었다. 또한 Pin1 siRNA를 처리한 MDA-MB-231 세포에서는 control siRNA 그룹에 비해 Nrf2와 Keap1의 결합이 증가하였으며, Keap1 knockout 마우스 배아에서 분리한 섬유아세포(embryonic fibroblasts)에서는 Nrf2와 Pin1의 결합이 증가되었다. 이를 통하여 Pin1과 Nrf2는 Keap1과의 결합에 있어서 서로 경쟁적 역할을 함을 확인하였다. 그러므로 Pin1은 Nrf2와 Keap1사이의 결합을 방해하며 Nrf2 단백질의 활성화와 안정화에 관여할 것으로 사료된다.CHAPTER I General verview 1 1. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) in cancer 2 1.1. Pin1 has critical roles in breast cancer development and progression 2 1.2. Regulation of Pin1 gene expression in human breast cancer 3 1.3. Expression, post-translational modifications and subcellular localization of Pin1 4 1.4. The significance of Pin1 phosphorylation 8 1.5. Pin1 regulates signaling molecules associated with cancer and cancer stem cells. 8 1.6. Pin1 mediates drug resistance of breast cancer 9 1.7. Pin1 inhibitors 9 2. Nrf2 in cancer 12 2.1. Nrf2 promotes tissue invasion and metastasis 12 2.2. Role of Nrf2 in resistance to chemotherapy 13 2.3. Keap1 as an inhibitor of Nrf2 13 2.4. Keap1-independent regulation of Nrf2 14 2.5. Post-translational modifications of Nrf2 15 2.6. Protein stabilization of Nrf2. 17 REFERENCES 19 STATEMENT OF PURPOSE 36 CHAPTER II 37 Pin1 stabilizes Nrf2 in a Keap1 independent manner in breast cancer . 37 ABSTRACT 38 1. INTRODUCTION. 40 2. MATERIALS AND METHODS 43 3. RESULTS. 55 4. DISCUSSION. 99 REFERENCES. 104 CHAPTER III 111 H-Ras induces Nrf2-Pin1 interaction: Implications for breast cancer progression. 111 ABSTRACT. 112 1. INTRODUCTION. 113 2. MATERIALS AND METHODS 116 3. RESULTS. 124 4. DISCUSSION. 144 REFERENCES. 149 ABSTRACT IN KOREAN.. 160 CURRIULUM VITAE 165Docto

Men’s Jeans Fit Based on Body Shape Categorization

The purpose of this study was to categorize lower body shape in men and to investigate the interplay between body shape and fitting issues appearing in men’s jeans. More specifically, the goal of the study was to improve apparel fit based on body shape. The detailed objectives of the study were to: (1) Categorize male body shapes using statistical analysis; (2) use 3D virtual fitting technology to assess fit and develop a shape-driven pants block pattern for each body shape. This quantitative study was conducted in three stages: (1) categorizing the body shape of 1420 male scans, aged 18-35, from the SizeUSA dataset, (2) develop a shape-driven pants block pattern for each identified body shape, and (3) validate the developed blocks by virtually trying the shape-driven block pattern on fit testers from different body shape groups. Exploratory Factor Analysis (EFA) and cluster analysis were used for body shape categorization, which resulted in three different body shapes: (1) Flat-Straight, (2) Moderate Curvy-Straight, and (3) Curvy. Three fit models were selected from each identified body shape group and then patterns were developed using Armstrong’s (2005) jeans foundation method. Patterns were modified and fitted to the selected representative fit models of each body shape group. The developed shape-driven block patterns were simulated on the fit testers to further explore the relationship between body shape and fit issues. This study suggests that two individuals with identical body measurements may experience very different fit problems tailored to their different body shapes. It was found that each body shape would exclusively experience unique fit issues. Furthermore, the shape driven block patterns were found to be highly correlated with their host body shape category. This research implies that if the mass customization process starts with block patterns that are engineered for specific body shape categories significantly less fit issues would appear and the desired fit would be achieved in fewer fitting sessions

Mine schedule optimization with geotechnical constraints

If a mining project consists of n stoping activities these can be scheduled in n! ways according to the duration between the activities and their precedence. Mine schedule optimization manipulates the precedence relationships and the duration of the mining activities in order to maximize the Net Present Value (NPV). However, unexpected instabilities may impede or disrupt the schedule and thus reduce the profitability and so geotechnical aspects of the operation need to be taken into account. The mine schedule optimization software considered in this work is the so-called Schedule Optimization Tool (SOT). This thesis reports the work for development of new geomechanical constraints for any mine scheduling tool to find the safest and the most profitable schedule, exemplified within the SOT framework. The core hypothesis of this research is that there is a time-dependent aspect of the rock behaviour that leads to instability, a consequence of dependence of geotechnical instability upon the sequence and duration between stoping activities. There is evidence presented in this work that supports this hypothesis. An automated procedure for timely and computationally efficient calculations of the instability metrics is presented. This can be applied to evaluate the geomechanical stability of any of the n! schedules for excavating n stopes or applied to evaluate geomechanical stability of schedules arising in the schedule optimization process. However, in practice, the number of feasible schedules is much less than n! due to the precedence constraints. The approach starts with computing n elastic stress fields induced after excavating each individual stope independently within an identical computational domain using Compute3D. The stress-time series of each iv and/or every sequence of stoping are generated through superimposition of these pre-computed stress fields, and the time stamps of blasting for excavation are allocated corresponding to the stoping timetable. Different blasts are allowed to be timetabled at the same time. By means of Hooke’s law and the 3D Kelvin-Voigt creep model the elastic strain time series and the viscoelastic strain time series are produced for the stress-time series. Based on the Mohr- Coulomb Failure criterion three (in)stability indicators are defined: i. ‘Strength Factor’ to evaluate state of stress at each stage of each schedule as a proportion of is strength ii. ‘Strainth Factor’ to evaluate state of elastic strain at each stage of each schedule as a proportion of a limiting ‘rupture’ strain iii. ‘Viscoelastic-strainth Factor’ to evaluate state of viscoelastic strain at each stage of each schedule as a proportion of a limiting ‘rupture’ strain. To provide a perspective of the (in)stability condition in the computational domain for all the feasible sequences of stoping, 12 (in)stability metrics were defined and the results of each are illustrated in the form of ‘(in)stability indicator diagrams’. The overall methodology is applied to an example of excavating 6 open stopes. Additionally, a methodology is theorized to evaluate the stability condition in the rock mass surrounding the stopes for a series of stoping and backfilling schedules. The methodology is based on pre-computing one additional stress field element for each stope, which represents the effect of the fill loading on the rock mass. The calculations for this approach are consistent with the time and computational efficiency of the original methodology. The computational effort v increases to ‘2n’ pre-computed stress fields rather than ‘n’: as problem sizes double, computational time doubles, rather than increases in polynomial or exponential time.Master of Applied Science (M.Sc.) in Natural Resources Engineerin

The Powerful Woman

The Powerful Woman is the continuation of exploration of Transformational Reconstruction, an innovative draping and pattern-making technique (Sato, 2011). I have been working with TR for past few years. With this piece I continue to expand my knowledge of creating pattern pieces in combination with knitting and felting techniques. Iranian men\u27s clothing of Bakhtiari tribe, Chogha, inspired this design. Chogha is a white upper-bodice garment with black stripes, which represent the victory of goodness over evilness (Dashtaki, 2013). The goals of creating this dress were to (a) combine cultural approach with modern origami look and (b) combine TR method with felting techniques to emulate men\u27s clothing to design a garment for powerful woman. The feeling of the power derived by Chogha was transferred into modern and wearable dress for powerful woman by accentuating the shoulder. Felting textile technique was started with knitting the skirt piece with black and white wool yarns then felted in a hot cycle of washing machine. Pattern pieces were attached together with needle felting technique, agitation and compression caused the wool fibers to capture each other