The Role of Ubiquitin-conjugating Enzymes as Therapeutic Targets in Cancer (암 치료 표적으로써 유비퀴틴 접합 효소 UBE2의 기능)
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- Journal of Life Science
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- v.33 no.6
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- pp.523-529
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- 2023
Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.
The subsea power cables are increasingly important for harvesting renewable energies as we develop offshore wind farms located at a long distance from shore. Particularly, the continuous flexural motion of inter-array dynamic power cable of floating offshore wind turbine causes tremendous fatigue damages on the cable. As the subsea power cable consists of the helical structures with various components unlike a mooring line and a steel pipe riser, the fatigue analysis of the cables should be performed using special procedures that consider stick/slip phenomenon. This phenomenon occurs between inner helically wound components when they are tensioned or compressed by environmental loads and the floater motions. In particular, Vortex-induced vibration (VIV) can be generated by currents and have significant impacts on the fatigue life of the cable. In this study, the procedure for VIV fatigue analysis of the dynamic power cable has been established. Additionally, the respective roles of programs employed and required inputs and outputs are explained in detail. Demonstrations of case studies are provided under severely sheared currents to investigate the influences on amplitude variations of dynamic power cables caused by the excitation of high mode numbers. Finally, sensitivity studies have been performed to compare dynamic cable design parameters, specifically, structural damping ratio, higher order harmonics, and lift coefficients tables. In the future, one of the fundamental assumptions to assess the VIV response will be examined in detail, namely a narrow-banded Gaussian process derived from the VIV amplitudes. Although this approach is consistent with current industry standards, the level of consistency and the potential errors between the Gaussian process and the fatigue damage generated from deterministic time-domain results are to be confirmed to verify VIV fatigue analysis procedure for slender marine structures.
The emergence of the field of organizational buying behavior in the mid-1960’s with the publication of Industrial Buying and Creative Marketing (1967) set the stage for a new paradigm of thinking about how business was conducted in markets other than those serving ultimate consumers. Whether it is "industrial marketing" or "business-to-business marketing" (B-to-B), organizational buying behavior remains the core differentiating characteristic of this domain of marketing. This paper explores the impact of several dynamic factors that have influenced how organizations relate to one another in a rapidly increasing interdependence, which in turn can impact organizational buying behavior. The paper also raises the question of whether or not the major conceptual models of organizational buying behavior in an interdependent world are still relevant to guide research and managerial thinking, in this dynamic business environment. The paper is structured to explore three questions related to organizational interdependencies: 1. What are the factors and trends driving the emergence of organizational interdependencies? 2. Will the major conceptual models of organizational buying behavior that have developed over the past half century be applicable in a world of interdependent organizations? 3. What are the implications of organizational interdependencies on the research and practice of organizational buying behavior? Consideration of the factors and trends driving organizational interdependencies revealed five critical drivers in the relationships among organizations that can impact their purchasing behavior: Accelerating Globalization, Flattening Networks of Organizations, Disrupting Value Chains, Intensifying Government Involvement, and Continuously Fragmenting Customer Needs. These five interlinked drivers of interdependency and their underlying technological advances can alter the relationships within and among organizations that buy products and services to remain competitive in their markets. Viewed in the context of a customer driven marketing strategy, these forces affect three levels of strategy development: (1) evolving customer needs, (2) the resulting product/service/solution offerings to meet these needs, and (3) the organization competencies and processes required to develop and implement the offerings to meet needs. The five drivers of interdependency among organizations do not necessarily operate independently in their impact on how organizations buy. They can interact with each other and become even more potent in their impact on organizational buying behavior. For example, accelerating globalization may influence the emergence of additional networks that further disrupt traditional value chain relationships, thereby changing how organizations purchase products and services. Increased government involvement in business operations in one country may increase costs of doing business and therefore drive firms to seek low cost sources in emerging markets in other countries. This can reduce employment opportunitiesn one country and increase them in another, further accelerating the pace of globalization. The second major question in the paper is what impact these drivers of interdependencies have had on the core conceptual models of organizational buying behavior. Consider the three enduring conceptual models developed in the Industrial Buying and Creative Marketing and Organizational Buying Behavior books: the organizational buying process, the buying center, and the buying situation. A review of these core models of organizational buying behavior, as originally conceptualized, shows they are still valid and not likely to change with the increasingly intense drivers of interdependency among organizations. What will change however is the way in which buyers and sellers interact under conditions of interdependency. For example, increased interdependencies can lead to increased opportunities for collaboration as well as conflict between buying and selling organizations, thereby changing aspects of the buying process. In addition, the importance of communication processes between and among organizations will increase as the role of trust becomes an important criterion for a successful buying relationship. The third question in the paper explored consequences and implications of these interdependencies on organizational buying behavior for practice and research. The following are considered in the paper: the need to increase understanding of network influences on organizational buying behavior, the need to increase understanding of the role of trust and value among organizational participants, the need to improve understanding of how to manage organizational buying in networked environments, the need to increase understanding of customer needs in the value network, and the need to increase understanding of the impact of emerging new business models on organizational buying behavior. In many ways, these needs deriving from increased organizational interdependencies are an extension of the conceptual tradition in organizational buying behavior. In 1977, Nicosia and Wind suggested a focus on inter-organizational over intra-organizational perspectives, a trend that has received considerable momentum since the 1990's. Likewise for managers to survive in an increasingly interdependent world, they will need to better understand the complexities of how organizations relate to one another. The transition from an inter-organizational to an interdependent perspective has begun, and must continue so as to develop an improved understanding of these important relationships. A shift to such an interdependent network perspective may require many academicians and practitioners to fundamentally challenge and change the mental models underlying their business and organizational buying behavior models. The focus can no longer be only on the dyadic relations of the buying organization and the selling organization but should involve all the related members of the network, including the network of customers, developers, and other suppliers and intermediaries. Consider for example the numerous partner networks initiated by SAP which involves over 9000 companies and over a million participants. This evolving, complex, and uncertain reality of interdependencies and dynamic networks requires reconsideration of how purchase decisions are made; as a result they should be the focus of the next phase of research and theory building among academics and the focus of practical models and experiments undertaken by practitioners. The hope is that such research will take place, not in the isolation of the ivory tower, nor in the confines of the business world, but rather, by increased collaboration of academics and practitioners. In conclusion, the consideration of increased interdependence among organizations revealed the continued relevance of the fundamental models of organizational buying behavior. However to increase the value of these models in an interdependent world, academics and practitioners should improve their understanding of (1) network influences, (2) how to better manage these influences, (3) the role of trust and value among organizational participants, (4) the evolution of customer needs in the value network, and (5) the impact of emerging new business models on organizational buying behavior. To accomplish this, greater collaboration between industry and academia is needed to advance our understanding of organizational buying behavior in an interdependent world.
One of the roles of the Semantic Web services is to execute dynamic intra-organizational services including the integration and interoperation of business processes. Since different organizations design their processes differently, the retrieval of similar semantic business processes is necessary in order to support inter-organizational collaborations. Most approaches for finding services that have certain features and support certain business processes have relied on some type of logical reasoning and exact matching. This paper presents our approach of using imprecise matching for expanding results from an exact matching engine to query the OWL(Web Ontology Language) MIT Process Handbook. MIT Process Handbook is an electronic repository of best-practice business processes. The Handbook is intended to help people: (1) redesigning organizational processes, (2) inventing new processes, and (3) sharing ideas about organizational practices. In order to use the MIT Process Handbook for process retrieval experiments, we had to export it into an OWL-based format. We model the Process Handbook meta-model in OWL and export the processes in the Handbook as instances of the meta-model. Next, we need to find a sizable number of queries and their corresponding correct answers in the Process Handbook. Many previous studies devised artificial dataset composed of randomly generated numbers without real meaning and used subjective ratings for correct answers and similarity values between processes. To generate a semantic-preserving test data set, we create 20 variants for each target process that are syntactically different but semantically equivalent using mutation operators. These variants represent the correct answers of the target process. We devise diverse similarity algorithms based on values of process attributes and structures of business processes. We use simple similarity algorithms for text retrieval such as TF-IDF and Levenshtein edit distance to devise our approaches, and utilize tree edit distance measure because semantic processes are appeared to have a graph structure. Also, we design similarity algorithms considering similarity of process structure such as part process, goal, and exception. Since we can identify relationships between semantic process and its subcomponents, this information can be utilized for calculating similarities between processes. Dice's coefficient and Jaccard similarity measures are utilized to calculate portion of overlaps between processes in diverse ways. We perform retrieval experiments to compare the performance of the devised similarity algorithms. We measure the retrieval performance in terms of precision, recall and F measure? the harmonic mean of precision and recall. The tree edit distance shows the poorest performance in terms of all measures. TF-IDF and the method incorporating TF-IDF measure and Levenshtein edit distance show better performances than other devised methods. These two measures are focused on similarity between name and descriptions of process. In addition, we calculate rank correlation coefficient, Kendall's tau b, between the number of process mutations and ranking of similarity values among the mutation sets. In this experiment, similarity measures based on process structure, such as Dice's, Jaccard, and derivatives of these measures, show greater coefficient than measures based on values of process attributes. However, the Lev-TFIDF-JaccardAll measure considering process structure and attributes' values together shows reasonably better performances in these two experiments. For retrieving semantic process, we can think that it's better to consider diverse aspects of process similarity such as process structure and values of process attributes. We generate semantic process data and its dataset for retrieval experiment from MIT Process Handbook repository. We suggest imprecise query algorithms that expand retrieval results from exact matching engine such as SPARQL, and compare the retrieval performances of the similarity algorithms. For the limitations and future work, we need to perform experiments with other dataset from other domain. And, since there are many similarity values from diverse measures, we may find better ways to identify relevant processes by applying these values simultaneously.
The purpose of this study was to develop a Science Academic Emotion Scale for Elementary Students. To make a scale, authors extract a core of 14 emotions related to science learning situations from Kim & Kim (2013) and literature review. Items on the scale consisted of 14 emotions and science learning situations. The first preliminary scale had 174 items on it. The number of 174 items was reduced and elaborated on by three science educators. Authors verified the scale using exploratory factor analysis, confirmatory factor analysis, inter-item consistency and concurrent validity. The second preliminary scale consisted of 141 items. The preliminary scale was reduced to seven factors and 56 items by applying exploratory factor analysis twice. The seven factors include: enjoyment contentment interest, boredom, shame, discontent, anger, anxiety, and laziness. The 56 items were elaborated on by five science educators. The scale with 56 items was fixed with seven factors and 35 items to get the final scale by applying confirmatory factor analysis twice. Except for Chi-square and GFI (Goodness of Fit Index), other various goodness of fit characteristics of the seven factors and 35 items model showed good estimated figures. The Cronbach of the scale was 0.85. The Cronbach of seven factors are 0.95 in enjoyment contentment interest, 0.81 in boredom, 0.87 in shame, 0.82 in discontent, 0.87 in anger, 0.77 in anxiety, 0.81 in laziness. The correlation coefficient was 0.59 in enjoyment contentment interest, 0.54 in anxiety, 0.42 in shame, and 0.28 in boredom, which were estimated using the Science Academic Emotion Scale and National Assessment System of Science-Related Affective Domain (Kim et al., 1998). Based on the results, authors judged that the Science Academic Emotion Scale for Elementary Students achieved an acceptable validity and reliability.
This dissertation aims to empirically analyze the effect of cultivation of software industry on the local economy through Inter-regional Software Input-Output Analysis. The temporal range of analysis of effect of software industry on the local economy shall be for the year 2005 since analysis is made on the basis of the Regional Industrial Input-Output Table published by the Bank of Korea in 2005, and spatial domain shall be limited to the 16 metropolitan cities and provinces, which are the standards for each administrative zone. Results of analysis of this dissertation are as follows. Firstly, average inverse matrix coefficient of software industry for each region was computed to be 1.6248, which is lower than the average inverse matrix coefficient of 1.7979 for the entire industries. Secondly, among these, inverse matrix coefficient of software industry for each region on other industry within the same region was 0.1794, which is higher than that of entire industries at 0.1382. However, average inverse matrix coefficients of software industry for each region on self-industry within the same region and entire industries in other regions were found to be 1.0119 and 0.4335, respectively, which is lower than those of entire industries at 1.0982 and 0.5616, respectively. Thirdly, domestic produces induced by final demand items of software industry for each region was the highest for Seoul with 17.3309 trillion Korean won, accounting for 81.0% of the total, followed by Gyeonggi with 2.3370 trillion Korean won, 10.9% of the total. Fourthly, distribution ratios of domestic produces induced by final demand items of software industry for each region were found to be 19.1%, 72.1% and 8.8% with respect to the weight of consumption, investment and export, respectively, thereby illustrating very high level of distribution ratios of domestic produces being induced by investment in comparison to the distribution ratios of domestic produces being induced for the entire industries at 47.3%, 19.8% and 32.9%, respectively.
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70