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1

Deng, Guangkuan, Jianyu Zhang, and Zhiwen Fan. "Influence of marketing channel conflicts on channel innovation capability: the mediating role of channel cohesion and the moderating role of channel network structure." Nankai Business Review International 12, no. 2 (December 1, 2020): 173–93. http://dx.doi.org/10.1108/nbri-11-2019-0059.

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Purpose In this paper, extending the research on the positive effects of marketing channel conflicts, this paper aims to examine how functional and dysfunctional conflicts influence channel innovation capability by triggering channel cohesion and investigate the moderating role of a distributor’s network structure. Design/methodology/approach Based on social network theory and Coser’s conflict theory, this paper develops a framework, tested using Chinese manufacturers’ data, which incorporated six key variables, namely, functional conflict, dysfunctional conflict, channel cohesion, channel innovation capability, network density and network centrality. Findings The empirical results revealed that functional conflict can arouse channel cohesion and that distributor network density and centrality positively moderates this relationship; dysfunctional conflict negatively affects channel cohesion, but distributor network density negatively moderates this relationship; channel cohesion had a mediating effect on the relationship between channel conflict and channel innovation capability. Originality/value This paper contributes to the research on channel conflict by incorporating the entire channel system’s innovation capability as a positive consequence of channel conflict and expands the channel conflict literature that adopts a network structure perspective.
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Rajala, Anni, and Annika Tidström. "Unmasking conflict in vertical coopetition." Journal of Business & Industrial Marketing 36, no. 13 (May 18, 2021): 78–90. http://dx.doi.org/10.1108/jbim-08-2019-0381.

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Purpose The purpose of this study is to increase understanding about vertical coopetition from the perspective of interrelated conflict episodes on multiple levels. Design/methodology/approach The empirical part is based on a qualitative single case study of a coopetitive buyer-supplier relationship in the manufacturing sector. Findings Conflicts in vertical coopetition evolve from being merely functional and task-related to becoming dysfunctional and relationship-related, as the level of competition increases. The nature of conflict episodes influences the development of vertical coopetition, and therefore, the interrelatedness of conflict episodes is important to acknowledge. Practical implications Although a conflict is considered functional within a company, it may still be dysfunctional as far as the coopetitive relationship with the buyer or seller is concerned. Competition may trigger conflicts related to protecting own technology and knowledge, which may lead to termination of the cooperation, therefore coopetition should be managed in a way that balance sharing and protecting important knowledge to get advantages of coopetition. Originality/value The findings enhance prior research on vertical coopetition by offering new perspectives on causes of conflicts, their management, outcomes and types. The value of taking a multilevel approach lies in the ability to show how conflicts occur and influence other conflicts through the interrelatedness of conflict elements on different levels.
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Claro, Danny P., Denys Vojnovskis, and Carla Ramos. "When channel conflict positively affect performance: evidence from ICT supplier-reseller relationship." Journal of Business & Industrial Marketing 33, no. 2 (March 5, 2018): 228–39. http://dx.doi.org/10.1108/jbim-11-2016-0272.

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Purpose This paper aims to study the positive impact of functional conflict and conflict management in improving supplier–reseller relationship performance in multi-channel setting (reseller together with supplier’s sales reps). The authors develop four hypotheses, including direct and mediated effects, about conflict management, conflict and the impact on channel performance. Design/methodology/approach The authors’ sample of suppliers in the information and communication technology (ICT) industry in Brazil consists of an interesting setting of multi-channel distribution, as suppliers deal with sales reps in combination with reseller channels to offer products to customers. The sample is representative of the industry, including more than 60 per cent of the ICT suppliers. The model was tested with partial least squares in the context of ICT industry in Brazil. Findings The empirical test shows that although an increase in functional conflict improves channel performance (direct effect), an excessive increase may amplify the dysfunctional conflict, thereby damaging channel performance (indirect effect). The negative interplay between the two natures of conflicts is counterbalanced with conflict management. Results show that conflict management improves channel performance by decreasing the harmful effects of dysfunctional conflict. This paper contributes to the theory by deepening our understanding of conflict, a critical challenge underlying supplier–reseller relationships in marketing channels. For managers, this research clarifies the importance of considering and managing conflict of different nature in the context of multi-marketing channels. Originality/value The contribution of the authors’ study is twofold. First, they develop an integrative mediating model with key constructs of multi-channels’ conflict and channel performance. They incorporate the causal relationships between functional and dysfunctional conflict, conflict management and channel performance into a single conceptual framework. This integrative mediating model to the best of their knowledge has not been developed before. Second, they provide managers with a broad understanding of conflict management implications to supplier’s multi-channel strategy, and how functional conflict can actually be beneficial for channel performance.
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Agustina, Granit, and Feby Febrian. "CONFLICT MODEL ON WORK MOTIVATION." Dinasti International Journal of Management Science 2, no. 3 (January 25, 2021): 494–505. http://dx.doi.org/10.31933/dijms.v2i3.713.

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Each agency must be able to manage employees by applying appropriate conflict models according to organizational needs that can increase a person's work motivation for a job. This study aims to determine whether the functional and functional effects on employee work motivation. This research is a descriptive and verification research using path analysis, where the population of respondents is all employees of the tourism and culture office of West Java province as many as 200 people with a sample of 67 respondents using SPSS 24 software. From the results of the respondents' responses that have been distributed So simultaneously the test results show that the conflict model affects work motivation with a functional effect of 0.493 and a significant effect on dysfunctional 0.198 and simultaneously the effect of the two variables on work motivation is 0.295. From the research results partially know that functional is more dominant in influencing work motivation than dysfunctional in the conflict model.
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Leckie, Civilai, Robert E. Widing, and Gregory J. Whitwell. "Manifest conflict, customer orientation and performance outcomes in international buyer-seller relationships." Journal of Business & Industrial Marketing 32, no. 8 (October 2, 2017): 1062–72. http://dx.doi.org/10.1108/jbim-11-2014-0235.

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Purpose The purpose of this paper is to test the impact of manifest conflict on performance outcomes. In particular, this paper aims to examine the moderating effect of the supplier’s customer orientation (CO) as perceived by the buyer on the conflict-performance outcomes relationships in international channel relationships. Design/methodology/approach A survey of 162 Australian importers was conducted to elucidate the associations among manifest conflict, CO and performance outcomes. Findings Manifest conflict was found to be negatively related to the importer’s evaluation of the exporter’s overall performance, which is consistent with previous work. However, CO was found to moderate the negative direct effect of manifest conflict on two outcome measures, “satisfaction with business outcomes” and the “evaluation of the exporter’s overall performance”. Moreover, it actually changed the effect from dysfunctional to functional for “evaluation of the exporter’s overall performance”. That is, CO changes the nature of the manifest conflict–outcome relationship by turning it from negative to positive. Research limitations/implications This research helps answer the appeal for research on the conditions in which conflict causes dysfunctional and functional outcomes. From a practical standpoint, providing the importer views the exporter as being customer-oriented, conflict should not be avoided if it stems from disagreements that arise due to the exporter acting in the best interests of the importer. The power of CO in affecting the functionality of outcomes resulting from conflict should be highlighted. Originality/value Conflict is a fact of life in channel relationships, but little is known about its functional and dysfunctional effects (Frazier, 1999; Skarmeas, 2006). The empirical evidence largely points to conflict being dysfunctional; however, research also indicates that context can play an important role in moderating the functionality of conflict. In this paper the authors ask: what role does CO play as a determinant of the functionality of manifest conflict in channel relationships? They argue that the exporter’s CO changes the context in which the importer and the exporter interact and, thereby, changes the way in which the importer interprets the supplier’s actions.
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Endila, Virona. "Pengaruh Konflik Kerja Terhadap KIinerja Perangkat Nagari dalam Pengelolaan Keuangan Nagari." JESS (Journal of Education on Social Science) 4, no. 1 (May 30, 2020): 99. http://dx.doi.org/10.24036/jess.v4i1.277.

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This study aimed to determine the effect of work conflict on the performance of nagari apparatus in village financial management in several villages (nagari) of Limapuluh Kota District, especially in Situjuah Limo Nagari and Mungka Sub-Districts. This research was conducted because of indications of conflict that occurred in the two Sub-Districts related to nagari financial management. The method used in this study was a quantitative method with associative model. The population in this study were all nagari apparatus in Limapuluh Kota District, totaling 75 respondents. The sample in this study consisted of 63 nagari apparatus determined using the Slovin formula with a 5% error rate and the use of Multi Stage Random Sampling techniques. Data in this study were collected through questionnaires distributed to respondents with Likert scale measurements. The data are then analyzed using multiple linear regression. The results of the study showed that the effect of the functional sub-variables of work conflict on performance was around 11.5%; and this functional work conflict has a significant influence on the performance of nagari apparatus in managing nagari finances. While the dysfunctional work conflict sub-variables have an influence of 3.5%; and this dysfunctional work conflicts do not have a significant effect on the performance of nagari apparatus. But overall, work conflict had a significant effect with a value of 17.7%, and this work conflict had a significant influence on the performance of nagari apparatus in managing nagari (village) finance.
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Indraswari, Citra Rahayu, and Muhammad Nafik HR. "Pengelolaan Konflik Aktivitas Bisnis Perspektif Islam Pada Manajemen Pasar Induk Puspa Agro Jawa Timur." Jurnal Ekonomi Syariah Teori dan Terapan 1, no. 5 (December 2, 2015): 346. http://dx.doi.org/10.20473/vol1iss20145pp346-362.

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Conflict is something that can not be separated in the process of management of the company. Conflict that managed well will be able to make a positive contribution to the business activities and the achievement of corporate goals. This study used a qualitative research methodology with a case study approach. The selection of a qualitative methodology based on the problem formulation used in this studyThe results of this study indicate that the conflicts that happened in management Central Market Puspa Agro caused by internal and external factor. Internal factor is derived from obscurity powers, functions and roles, monitoring and evaluation weakness, slowness of responds to the problems, the competence of individual differences, the target and task interdependence. External factors consist of the presence of government policies and industry demands. The effect of conflicts are functional and dysfunctional. Conflicts levels are low, optimal and high.Conflict management is applied by stimulation, reduction of conflict and conflict resolution methods. Conflict stimulation methods include the application of the system of reward and punishment and the different treatment of habit . Conflict reduction methods include the provision of a forum for dialogue, joint activities and creating new challenges. Conflict resolution methods include the expansion of resources, compromise, change the variable structure of the company, avoiding and otorative command.
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Cain, Gerard, and André du Plessis. "TEACHERS’ PERCEPTIONS OF THE CONSEQUENCES OF INTERPERSONAL CONFLICT: A CASE STUDY IN THREE PRIMARY SCHOOLS." Problems of Management in the 21st Century 8, no. 1 (December 10, 2013): 25–41. http://dx.doi.org/10.33225/pmc/13.08.25b.

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The purpose of this qualitative intrinsic interpretive case study, which formed part of a larger Master in Education Study, is to report on the perceptions of teachers in three primary schools regarding the consequences of conflict among educators. Fifty nine educators, including principals, participated in this study that utilised an open-ended questionnaire, semi-structured interviews and focus-group interviews. The rationale for this study was to ascertain what the perceived consequences of conflict are, in order that these schools as well as the district office of the Department of Basic Education could have a sense of what the perceived consequences are as portrayed by the participants. Hence, participants were able to tell their stories through using text and voice. The findings suggest that the consequences of conflict can be categorised as functional (positive) and dysfunctional (negative) outcomes, each with subsidiary themes. Overall, conflict was experienced as a negative force in general, that is perceived as causing defiant attitudes, intolerance, poor cooperation and teamwork, poor relationships, division of unity, poor morale and work ethic, has a negative impact on wellness, leads to absenteeism and ultimately adversely impact on the learners’ learning. On the other hand the positive consequences were improved relationships among staff, greater understanding, improved attitudes, positive change and even personal growth. Keywords: Conflict, conflict theories, consequences, dysfunctional conflict, functional conflict
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Soubagleh, Moussa Khaireh. "Exploring Conflict Management Strategies among School Administrators: A Case Study of an International Islamic School in Malaysia." IIUM Journal of Educational Studies 7, no. 1 (February 4, 2020): 3–14. http://dx.doi.org/10.31436/ijes.v7i1.158.

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AbstractAs educational organizations, schools are vulnerable to experiencing conflict. Notwithstanding the views of many scholars in the existence of functional conflict in a formal organization like school setting, proper management of conflict is required to be established by school administrators in order to ensure the smooth running of the school. The aim of this study was to explore the understanding of sources of conflict and conflict management among Islamic school administrators with the aim of formulating practical and effective strategies in conflict management within the school setting. The researchers used the qualitative case study method to explore the strategies adopted by three Islamic school administrators in handling conflict. The findings show that individual differences, commodification of education, school system and policy, human resource issues and practices, and attitude were the main factors giving rise to school conflict, while depression was identified as its resulting effect. The school needs to build trust, respect, stability, and teamwork into its atmosphere, culture and practices in order to prevent misunderstanding and conflict within its community.Keywords: Conflict management, functional conflict, dysfunctional conflict, Muslim administrators, Islamic schools, Islamic administration
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Bobot, Lionel. "Functional and dysfunctional conflicts in retailer‐supplier relationships." International Journal of Retail & Distribution Management 39, no. 1 (February 2011): 25–50. http://dx.doi.org/10.1108/09590551111104468.

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Bergiel, Erich B., Thomas W. Gainey, and Blaise J. Bergiel. "Understanding the relationship between mental models, conflict and conflict asymmetry." Team Performance Management 21, no. 7/8 (October 12, 2015): 320–38. http://dx.doi.org/10.1108/tpm-02-2015-0009.

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Purpose – The purpose of this study is to test theoretically based hypotheses linking task and team-shared mental models (SMMs) with multiple dimensions of conflict and conflict asymmetry. SMMs are viewed as an underlying mechanism of team processes. While current research has begun to clarify their influence on functional team processes, their influence on dysfunctional processes is still unknown. Design/methodology/approach – The survey was administered to 17 graduate business classes working on intense semester-long group projects. A total of 295 individual responses were received which comprised 90 (N = 90) teams. Findings – Results suggest that team SMMs reduce all dimensions of conflict and relationship conflict asymmetry, while task SMMs increase all dimensions of conflict and relationship conflict asymmetry. Research limitations/implications – This study captured the influence of SMMs on conflict at one stage of group development. Future research should examine the impact of SMMs on conflict at multiple stages of group development. Originality/value – This study contributes to the literature on both mental models and conflict. In addition, based on our literature review, it was the first to empirically link SMMs and conflict asymmetry.
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Pfajfar, Gregor, Aviv Shoham, Maja Makovec Brenčič, Dimitrios Koufopoulos, Constantine S. Katsikeas, and Maciej Mitręga. "Power source drivers and performance outcomes of functional and dysfunctional conflict in exporter–importer relationships." Industrial Marketing Management 78 (April 2019): 213–26. http://dx.doi.org/10.1016/j.indmarman.2017.03.005.

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Massey, Graham R., and Philip L. Dawes. "The antecedents and consequence of functional and dysfunctional conflict between Marketing Managers and Sales Managers." Industrial Marketing Management 36, no. 8 (November 2007): 1118–29. http://dx.doi.org/10.1016/j.indmarman.2006.05.017.

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Wu, Guangdong, Xianbo Zhao, and Jian Zuo. "Effects of inter-organizational conflicts on construction project added value in China." International Journal of Conflict Management 28, no. 5 (October 9, 2017): 695–723. http://dx.doi.org/10.1108/ijcma-03-2017-0025.

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Purpose The purpose of this research is to investigate the effects of inter-organizational conflicts on the project added value in the Chinese construction industry, and also to examine the mediating effect of conflicts on project added value and the moderating effect of conflict management strategies. Design/methodology/approach A conceptual model was developed, and a structured questionnaire survey was conducted with 667 professionals. The structural equation modeling technique was used to analyze the data. Findings The results showed that task conflict, relationship conflict and process conflict were influenced by subject characteristics of project participants, bilateral relationship characteristics and project characteristics. Similarly, these three types of conflicts interact with each other. Meanwhile, these three types of conflicts influence the added value in construction projects, which are moderated by conflict management strategies. Under a collaborating strategy, task conflict and process conflict were positively associated with project added value, and relationship conflict was negatively associated with project added value. Under a competing strategy, task conflict, process conflict and relationship conflict were negatively associated with added value in construction projects. Therefore, the constructive and destructive effects of conflicts on project added value under different conflict management strategies are verified in Chinese construction projects. Research limitations/implications The variables may not be exhaustive for construction projects and most of them were applied in construction projects for the first time. As a result, their rationality and effectiveness could be further improved. The results implied that inter-organizational conflicts had a constructive effect on project added value and should attract broad attention for future research. Additionally, different driving factors had different influences on these conflicts, and even the driving factors can be divided into different dimensions. Practical implications This study provides a better understanding of the relationship between inter-organizational conflicts and added value in construction projects, and a reliable reference for the project manager to effectively deal with these conflicts. In addition, this research reveals the effects of conflicts on project added value and the path of conflicts transformation. This provides a useful reference for project managers to take advantage of the positive effect of task conflict and process conflict, and to avoid the negative effect of relationship conflict. Originality/value Very few studies attempted to examine the effects of inter-organizational conflicts on project added value in construction projects. Therefore, this research makes significant theoretical and practical contributions to the existing body of knowledge on the conflict management and project added value. This research provides an empirical evidence to support the viewpoint that different types of conflicts can be mutually transformed. Similarly, this study explains how conflicts present functional and dysfunctional effects in construction projects. Both of them are potential theoretical contributions to the existing body of knowledge.
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Swain, Jordon, James Tuite, and John Borland. "Office space: a leadership challenge." CASE Journal 14, no. 5 (September 10, 2018): 593–603. http://dx.doi.org/10.1108/tcj-02-2018-0032.

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Synopsis The case describes the dilemma a young leader, First Lieutenant Toomey, faces after arriving at a new organization. Toomey’s subordinate (sergeant first class Rodgers) is more experienced and accomplished and has enjoyed a degree of autonomy under Toomey’s predecessor. Rodger’s demeanor and the physical setup of the joint office space speak to a dysfunctional dynamic in an organization that values a traditional hierarchy and relatively high power distance between supervisor and subordinate. The potential for conflict exists as Toomey contemplates how to address the dysfunctional norms he has observed while maintaining a functional relationship and reputation as an effective leader in his new unit. Research methodology The case was created via an interview of the protagonist. Relevant courses and levels This case is designed for use in undergraduate and graduate level courses on leadership and management. The case is useful for teaching lessons (or electives) on power, influence, conflict management, culture and leading change.
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Menon, A., S. G. Bharadwaj, and R. Howell. "The Quality and Effectiveness of Marketing Strategy: Effects of Functional and Dysfunctional Conflict in lntraorganizational Relationships." Journal of the Academy of Marketing Science 24, no. 4 (September 1, 1996): 299–313. http://dx.doi.org/10.1177/0092070396244002.

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Butler, Mark C., and Sanford B. Ehrlich. "Positional Influences on Job Satisfaction and Job Performance: A Multivariate, Predictive Approach." Psychological Reports 69, no. 3 (December 1991): 855–65. http://dx.doi.org/10.2466/pr0.1991.69.3.855.

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This study examined relationships between job attitudes, work environment perceptions, and supervisors' ratings of job performance among health care employees occupying both medical care and administrative positions in ambulatory clinic settings. Between-group differences were noted on the perceived relationship with the supervisor, level of job/role conflict, and working conditions. Results are discussed in terms of functional and dysfunctional aspects of control systems and path-goal theory of leadership.
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Gendrin, Dominique M., and Barbara L. Werner. "Internal Dialogues about Conflict: Implications for Managing Marital Discord." Imagination, Cognition and Personality 16, no. 2 (October 1996): 125–38. http://dx.doi.org/10.2190/fqbf-m75m-r3r1-ku8u.

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Studies in social cognition suggest that people in relationships engage in imagined interactions to develop appropriate lines of actions for actual conflict situations. Additionally, imagined interactions about disputes, in the absence of actual communication, has a “mulling” effect, tends to increase the severity of conflict and the likelihood partners are blamed. However, prolonged thought about disputes may have an attenuating effect when it is associated with frequent communication and when interactions are integrative. This study examines the role of imagined interactions, as one type of cognition, in processing marital disputes. The study showed that Traditionals, Independents, and Separates rely on different mental conflict schemata. An examination of the “linkage” function of imagined interactions revealed a functional impact in processing marital disputes for Traditionals and Independents. Imagined interactions about disputes were dysfunctional for Separates.
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Ubillos-Landa, Silvia, Alicia Puente-Martínez, Gina Arias-Rodríguez, Marcela Gracia-Leiva, and José Luis González-Castro. "Coping Strategies Used by Female Victims of the Colombian Armed Conflict: The Women in the Colombian Conflict (MUCOCO) Program." SAGE Open 9, no. 4 (July 2019): 215824401989407. http://dx.doi.org/10.1177/2158244019894072.

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The effects of armed conflict on women in post-conflict situations are an area of analysis for social disciplines. This study will analyze the situation in Colombia, currently involved in a peace restoration process. The aim is to verify the efficacy of a coping and emotion regulation program analyzing victimization as well as the coping strategies employed in response to these violent acts. The program focuses on 62 women contacted through the Ruta Pacífica de las Mujeres, a nongovernmental organization. The program had a positive effect on women, reporting lower levels of posttraumatic stress, more functional coping strategies, and less use of dysfunctional strategies. All emotional cognitive and social indicators improved. Women felt emotionally better, perceiving greater social support and more trust in institutions. Survivors had more self-confidence to achieve their goals and solve their problems. The implications in a context of peace reconstruction and search for social cohesion are discussed.
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Cohen-Chen, Smadar, Ruthie Pliskin, and Amit Goldenberg. "Feel Good or Do Good? A Valence–Function Framework for Understanding Emotions." Current Directions in Psychological Science 29, no. 4 (July 8, 2020): 388–93. http://dx.doi.org/10.1177/0963721420924770.

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Previous thinking has often categorized emotions as either pleasant or unpleasant or examined to what extent they are functional or dysfunctional. We suggest that researchers should consider the positivity or negativity of discrete emotions on both dimensions: subjective feelings and constructiveness of outcomes. We discuss how, across contexts, a specific emotion can potentially be categorized differently within the framework. We further suggest that this approach is particularly useful in unique, complex contexts that involve clashes among goals, interests, or values, such as violent intergroup conflicts. Using this context, we demonstrate how emotions that feel good to people can lead to behaviors and attitudes that sustain violence and thwart conflict resolution, whereas emotions that promote conflict resolution are often unpleasant. Such clashes may depend on the presence of embedded contextual factors, such as group membership and relative power. Thus, this framework will be useful for examining specific emotions while taking contextual factors into consideration. Finally, we examine several important questions stemming from our framework and suggest directions for future research.
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Battu, Nagaraju, and Ch R. B. Alias Kalyan Ram. "Interpersonal Conflict Management– Inevitable but Manageable (with Reference to M/S Karvy Computershare Pvt. Ltd, Hyderabad & M/S Anand Rathi, Bangalore)." IRA-International Journal of Management & Social Sciences (ISSN 2455-2267) 7, no. 2 (June 10, 2017): 320. http://dx.doi.org/10.21013/jmss.v7.n2.p23.

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<div><p><strong><em>Introduction</em></strong>: A conflict has generally been defined as a situation in which two or more parties strive to acquire the same scarce resources at the same time. Scholars generally agree that there needs to be more than one part to have a conflict, and that the time factor is important. What does cause concern is the term scarce resource.</p><p><strong><em>Objective of the Study</em></strong>: To examine the effect of strategies adopted for managing interpersonal conflict on organizational performance, to examine the perceptions of the employees in the organization under study and to offer suggestions to minimize the inter-personal conflicts and to improve conducive environment for organizational success</p><p><strong><em>Method of the Study</em></strong>: The study employed both descriptive survey design and explanatory research design. It targeted a population of 650 employees of purposively selected units under study. A sample size comprising 450 employees from M/s Karvy Computershare and 200 from M/s Anand Rathi were selected using stratified random sampling techniques.</p><p><strong><em>Results of the Study</em></strong>: Conflict escalation has according to this study it’s foundation in emotional involvement. A person focused conflict has a higher risk of escalation and to evolve towards becoming dysfunctional. Through this study it has been revealed that conflict management can be divided into two areas, prevention of conflicts and management of functional conflicts. Feedback can be counted as preventive tools to help develop employee’s behaviour and to ensure that the opinions and feelings are passed on through controlled communication channels. </p></div>
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Dudija, Nidya. "Strategi Penanganan Konflik pada Proses Penggabungan Perguruan Tinggi Swasta." Psikohumaniora: Jurnal Penelitian Psikologi 3, no. 1 (August 2, 2018): 37. http://dx.doi.org/10.21580/pjpp.v3i1.970.

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<p><strong>Abstract:</strong> Merger of academies to be one university is a way to perform effectivity and efficiency of the foundation as the organizer of education. The process of conveying the idea will face challenges and conflicts such as opposition to the idea of merging universities. Conflict can be a functional and dysfunctional role in the organization, depending on how the organization is able to manage the conflict and use appropriate conflict management strategies. The research was conducted at one of the private universities in Bandung that has combined four academies to form the University. This research uses a qualitative approach case study. The results of this study indicate that the foundation has an important role during the merging process, the foundation selects direct leaders (Rector of the University) from external parties to facilitate the process of forming a new culture, then the Foundation manages the conflict using a compromise strategy and collaboration to all academic communities so that conflicts arise functional role and improve post-merge University performance.</p><p><strong>Abstrak:</strong> Penggabungan sekolah tinggi menjadi universitas adalah salah satu cara untuk me­lakukan efektifitas dan efisiensi yayasan sebagai penyelenggara pendidikan. Proses menyampaikan ide akan menghadapi tantangan dan konflik seperti oposisi terhadap gagasan menggabungkan universitas. Konflik dapat berperan fungsional dan disfungsional dalam organisasi, tergantung pada bagaimana organisasi mampu mengelola konflik dan menggunakan strategi manajemen konflik yang tepat. Penelitian ini dilakukan di salah satu universitas swasta di Bandung yang telah menggabungkan empat sekolah tinggi untuk membentuk universitas. Penelitian ini menggunakan pendekatan kualitatif <em>case study</em>. Hasil penelitian ini menunjukkan bahwa yayasan memiliki peran penting selama proses penggabungan, yayasan memilih langsung pemimpin (Rektor Universitas) dari pihak eksternal untuk memfasilitasi proses pembentukan budaya baru, kemudian Yayasan me­ngelola konflik menggunakan strategi kompromi dan kolaborasi untuk semua komunitas akademis sehingga konflik muncul peran fungsional dan meningkatkan kinerja universitas pasca-penggabungan.</p>
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Hänggi, Yves. "Social Coping in Everyday Life and in Crisis Situations: An Evolutionary Psychology Perspective." Swiss Journal of Psychology 67, no. 3 (September 2008): 153–63. http://dx.doi.org/10.1024/1421-0185.67.3.153.

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An online questionnaire-based survey investigated which action heuristics are activated for social coping in everyday life and in biologically relevant crisis situations. A total of 187 participants (86% women, mean age 35) from all parts of German-speaking Europe provided information about how they would cope in social conflict situations. In everyday life situations, participants reported more functional coping when dealing with youths than when dealing with adults. Coping strategies were most dysfunctional when dealing with one’s partner. Conversely, social coping strategies in biologically significant crisis situations were more functional within the nuclear family than with outsiders. The results are discussed against the background of display rules for social coping and the theory of inclusive fitness.
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Amason, Allen C. "Distinguishing the Effects of Functional and Dysfunctional Conflict on Strategic Decision Making: Resolving a Paradox for Top Management Teams." Academy of Management Journal 39, no. 1 (February 1996): 123–48. http://dx.doi.org/10.5465/256633.

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Amason, A. C. "DISTINGUISHING THE EFFECTS OF FUNCTIONAL AND DYSFUNCTIONAL CONFLICT ON STRATEGIC DECISION MAKING: RESOLVING A PARADOX FOR TOP MANAGEMENT TEAMS." Academy of Management Journal 39, no. 1 (February 1, 1996): 123–48. http://dx.doi.org/10.2307/256633.

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26

Anicich, Eric M., Roderick I. Swaab, and Adam D. Galinsky. "Hierarchical cultural values predict success and mortality in high-stakes teams." Proceedings of the National Academy of Sciences 112, no. 5 (January 20, 2015): 1338–43. http://dx.doi.org/10.1073/pnas.1408800112.

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Functional accounts of hierarchy propose that hierarchy increases group coordination and reduces conflict. In contrast, dysfunctional accounts claim that hierarchy impairs performance by preventing low-ranking team members from voicing their potentially valuable perspectives and insights. The current research presents evidence for both the functional and dysfunctional accounts of hierarchy within the same dataset. Specifically, we offer empirical evidence that hierarchical cultural values affect the outcomes of teams in high-stakes environments through group processes. Experimental data from a sample of expert mountain climbers from 27 countries confirmed that climbers expect that a hierarchical culture leads to improved team coordination among climbing teams, but impaired psychological safety and information sharing compared with an egalitarian culture. An archival analysis of 30,625 Himalayan mountain climbers from 56 countries on 5,104 expeditions found that hierarchy both elevated and killed in the Himalayas: Expeditions from more hierarchical countries had more climbers reach the summit, but also more climbers die along the way. Importantly, we established the role of group processes by showing that these effects occurred only for group, but not solo, expeditions. These findings were robust to controlling for environmental factors, risk preferences, expedition-level characteristics, country-level characteristics, and other cultural values. Overall, this research demonstrates that endorsing cultural values related to hierarchy can simultaneously improve and undermine group performance.
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27

Korhonen, Outi. "Deconstructing the Conflict in Ukraine: The Relevance of International Law to Hybrid States and Wars." German Law Journal 16, no. 3 (July 2015): 452–78. http://dx.doi.org/10.1017/s2071832200020940.

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In Ukraine, spheres of political, military, and economic control are contested, non-transparent, and shifting. As the Ukrainian government lost control over the rebellious Eastern oblasts (regions) of the country, Russia denies its authority over various pro-Russian separatists and vigorously rejects any responsibility for the abuses by the unidentified “green men,” both before and after the annexation of Crimea. Even during the decades before this conflict, the rule of law in Ukraine was “thin” at best. Meaningful political control was sporadic and dispersed, often wielded by the mix of public, private, and other shady actors occupying the grey area between a functional and a dysfunctional state. If state actors never effectively took control over the events at the state-level during peaceful times, it is not surprising that it is more difficult once a “hot” conflict breaks out. It is not unreasonable to assume that Minsk agreements—signed in an effort to stop the hemorrhaging of the conflict—will not hold if the signatories do not effectively control the diverse public and private actors who possess the actual capacity to influence the dynamic on the ground. Before rendering any kind of juridical judgment, the complicated political and socioeconomic configuration of the conflict in Ukraine forces us to first confront a factual puzzle: Who and what influence the current situation? Which concrete actors really drive the conflict and what interests animate them?
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Parrinello, Nunziatina, Alessandra Romano, Concetta Conticello, Maide Cavalli, Alessia La Fauci, Giuseppina Rizzo, Piera La Cava, et al. "Neutrophils Of Multiple Myeloma Are Dysfunctional and Immunosuppressive." Blood 122, no. 21 (November 15, 2013): 3138. http://dx.doi.org/10.1182/blood.v122.21.3138.3138.

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Abstract Introduction Multiple Myeloma (MM) is a plasma cell malignancy with a well documented immune dysfunction. However the role and function of neutrophils in MM and monoclonal gammopathy of undetermined significance (MGUS) has been poorly investigated. Methods on neutrophils (N) of 65 MM at diagnosis, 74 MGUS and 30 healthy subjects we evaluated, by flow cytometer, phagocytic activity and surface expression of CD64, CD16, CD62L and CD11b, markers of neutrophil activation. We tested also the immunosuppressive properties of N isolated from MGUS or MM patients, through functional assays, based on in vitro co-culture of N isolated from patients and T-lymphocytes from healthy subjects and we evaluated the expression of the immunosuppressive molecule arginase-1 (Arg-1) by RT-PCR. Results Despite no differences in the absolute number of N between MM, MGUS and healthy subjects, we found a functional impairment in MM not evident in MGUS patients. The phagocytic activity of MM-N was significantly reduced compared to healthy subjects-N (p<0.001) and MGUS-N (p<0.0001) and restored after induction chemotherapy (p=0.02). Expression of CD64 was significantly elevated in MM-N compared to MGUS-N or healthy subjects-N (p=0.01 and p= 0.007 respectively) and was inversely correlated with phagocytic activity (p=0,01). No differences were observed among MM, MGUS and healthy subjects for the other surface markers evaluated. MM-N exhibit an increased expression of ARG-1 compared to MGUS and healthy subjects (25.5 vs 6.2 vs 1 fold changes in gene expression, p=0.003), confirmed by functional assay of enzymatic activity of ARG-1, positively correlated with advanced disease. After PHA-P stimulation,T-lymphocytes isolated from healthy subjects missed the expression of activation markers such CD71, CD69, CD25, CD3ζ in the presence of MM-N for 72 hours, and in a less extensive way in the presence of MGUS-N. Conclusion Compared to controls, neutrophils obtained from MM patients have a reduced phagocytic activity, a greater expression of Arg-1 and exhibit an immunosuppressive function on T lymphocytes. Taken together, these findings indicated that neutrophils may contribute to impairment of immune function that characterizes MM patients. Disclosures: No relevant conflicts of interest to declare.
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Philip, Mary, Lauren Fairchild, Liping Sun, Agnes Viale, Taha Merghoub, Jedd D. Wolchok, Christina S. Leslie, and Andrea Schietinger. "Chromatin State Dynamics Underlying CD8 T Cell Differentiation and Dysfunction in Cancer." Blood 128, no. 22 (December 2, 2016): 861. http://dx.doi.org/10.1182/blood.v128.22.861.861.

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Abstract T cells recognizing tumor-specific antigens are detected in cancer patients but are dysfunctional. Upon antigen encounter, T cells differentiate into discrete phenotypic and functional states. Cellular differentiation is driven by epigenetic remodeling, however, it is not known whether and how epigenetic programming establishes and regulates tumor-specific T cell (TST) dysfunction and determines a T cell's ability to respond to therapeutic interventions such as immune checkpoint blockade (PD-1 and CTLA-4). Here for the first time, we (1) identify chromatin dynamics underlying T cell differentiation to the dysfunctional state in mouse and human tumors and (2) provide insights into the epigenetic and transcriptional regulatory mechanisms determining T cell susceptibility to therapeutic reprogramming. Using a genetic cancer mouse model, we previously showed that CD8 TST become unresponsive early during carcinogenesis at the pre-malignant stage, even before the emergence of a pathologically-defined malignant tumor. While T cell dysfunction was initially reversible, it ultimately became a fixed state that could not be rescued by therapeutic interventions such as PD1 checkpoint blockade. To identify the hierarchical changes in chromatin states resulting in "dysfunction imprinting," we used the Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq) to map the genome-wide changes in chromatin accessibility in TST cells over the course of cancer development. In parallel, we carried out RNA-Seq to determine the interplay between chromatin remodeling and transcriptional networks. Substantial chromatin remodeling occurred during early T cell activation in the pre-malignant lesion (days 5-7) followed by a second wave of chromatin accessibility changes between days 7 and 14. Strikingly, after the second wave, no further CD8 T cell chromatin remodeling occurred during carcinogenesis, even after progression to an advanced late-stage tumor with an immunosuppressive microenvironment. Interestingly, these 2 distinct chromatin accessibility patterns in TST correlated temporally with the plastic and fixed dysfunctional states and susceptibility to therapeutic reprogramming in vivo. To understand the transition from plastic to fixed dysfunction, we analyzed the differential expression of transcription factors (TF) in conjunction with changes in peak accessibility at TF-binding motifs genome-wide. We identified a network including CD8 T cell regulatory TF such as TCF1, LEF1, BLIMP1, and BACH2 as well as less-well-characterized TF (NR4A2, TOX) potentially controlling differentiation to the dysfunctional state. Moreover, ATAC-Seq analysis of human tumor-infiltrating CD8 T cells revealed similar tumor-associated changes in peak accessibility, and studies are ongoing to assess the associated TF networks. In this study, we have defined discrete chromatin states and associated transcriptional networks underlying plastic and fixed dysfunction in TST, thus providing new insights into the genomic control circuitry of T cell differentiation/dysfunction that may point to new strategies for cellular reprogramming of T cells for cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.
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Jacoby, Meagan A., Rigoberto de Jesus, and Matthew J. Walter. "Dysfunctional Double-Strand DNA Break Repair In Primary t-AML/t-MDS Myeloblasts." Blood 116, no. 21 (November 19, 2010): 3366. http://dx.doi.org/10.1182/blood.v116.21.3366.3366.

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Abstract Abstract 3366 The gross chromosomal aberrations in treatment-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/t-MDS) cells suggest that disease initiation and progression may result from the inability of cells to appropriately respond to double-strand DNA breaks (DSBs) induced by prior exposure to radiation, alkylator, or topoisomerase II inhibitor therapy. We hypothesize that dysregulation of DSB repair by homology-directed repair (HDR) or nonhomologous end joining (NHEJ) contributes to the development of t-AML/t-MDS. Dysregulation of DSB repair in t-AML/t-MDS may result from inherited variants or acquired mutations in HDR/NHEJ pathway genes. To directly test this possibility, we used next-generation sequencing technology and an array CGH platform to identify inherited and somatic genetic variants, including small indels and copy number alterations, in 21 canonical HDR and 9 NHEJ DNA repair genes, as well as a subset of 7 DNA damage response genes using tumor DNA and paired normal DNA obtained from 30 t-AML/t-MDS patients. All the data has been acquired and the analysis is ongoing. Because dysregulation of DNA repair pathways can result from epigenetic changes or post-translational modifications in DNA repair genes and would not be detected using sequencing and array CGH, we are also performing functional studies to interrogate DSB repair using primary bone marrow cells from 16 of these t-AML/t-MDS patients and CD34+ cells from 5 normal healthy controls. We performed a flow-based assay for DSB formation and repair by measuring the phosphorylated form of the variant histone H2AX (pH2AX), which is rapidly phosphorylated upon DSB formation, in myeloblasts (CD45 dim, low side scatter) and lymphocytes (a surrogate for normal cells) from leukemic bone marrow. Baseline measurements of unmanipulated primary bone marrow cells and a time course to measure the kinetics of DSB repair after gamma irradiation are used to assess a cell's basal DSB burden and the response to acute damage. We have validated this assay in a defined genetic system using isogenic cells deficient or not in BRCA2, a gene central to the HDR pathway, and were able to demonstrate that cells lacking BRCA2 have elevated pH2AX levels at 4–24 hours post DSB induction compared to controls (p=0.01). In addition, we have evaluated the ability of the cells to form nuclear foci of pH2AX and RAD51 (a protein central to the repair of DSB by HDR) by quantifying the relative numbers of immunofluorescent nuclear foci upon irradiation. We have performed these functional assays for 8 t-AML/t-MDS samples and 3 normal donors. We identified one t-AML/t-MDS sample whose myeloblasts show 2–3 fold greater pH2AX at baseline, compared to control CD34+ cells (p=0.006). Interestingly, the clearance of pH2AX is significantly faster in this sample compared to controls (p=0.001) despite showing elevated baseline pH2AX levels. This patient had a translocation involving chromosome 11q23. One additional patient in our cohort with an 11q23 translocation also showed similar increased baseline pH2AX levels. In addition, we identified abnormalities in a third t-AML/t-MDS sample that trends towards impaired maximal pH2AX induction (p=0.052). Furthermore, myeloblasts from a fourth t-AML/t-MDS sample, a known heterozygous BRCA2 mutation carrier, show a trend towards delayed pH2AX clearance (p=0.07). As predicted, bone marrow cells from this BRCA2 carrier also have 3.5 fold less RAD51 nuclear foci formation compared to control cells (8.6% vs 30%). Collectively, these results show that primary t-AML bone marrow cells can be used to assess the functional integrity of DSB response, and suggest that a large proportion of samples (4/8) may contain genetic alterations in DNA DSB response and/or repair genes. Functional studies of an additional 8 samples are ongoing. Next generation sequencing and array CGH data for the 37 HDR/NHEJ genes has been completed and will be correlated with the functional studies for each sample. Identification of abnormal DSB repair in leukemic patients may not only elucidate the molecular pathogenesis of the disease, but may provide rationale for testing agents to achieve selective killing of leukemic cells, as defects in one DNA repair pathway may increase reliance on another, making these cancer cells particularly susceptible to killing by inhibitors targeting the extant pathway(s). Disclosures: No relevant conflicts of interest to declare.
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31

Stamatelopoulos, Kimon, Marita Lyka, Christos Papamichail, Maria Roussou, Maria Gavriatopoulou, Constantinos Pamboucas, Evangelos Terpos, Meletios A. Dimopoulos, and Efstathios Kastritis. "Hemodynamic, Functional and Structural Markers of Vascular Involvement in Primary Systemic Light Chain (AL) Amyloidosis." Blood 124, no. 21 (December 6, 2014): 2029. http://dx.doi.org/10.1182/blood.v124.21.2029.2029.

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Abstract Light chain (AL) amyloidosis is characterized by the extracellular deposition of clonal light chain-derived amyloid fibrils in various tissues. Kidneys and heart are most commonly affected; clinically non detectable deposits in other tissues may also result in significant dysfunction. Amyloid deposits within the wall of the arteries or direct toxicity of light chains may cause arterial dysfunction in patients with AL amyloidosis, with cardiovascular consequences. Endothelial dysfunction, subclinical atherosclerosis of the carotid arteries and stiffening of the arterial tree are commonly found as deleterious vascular phenotypes and are considered surrogate markers of cardiovascular disease and outcome. Matrix metalloproteases, advanced glycation products, endothelial dysfunction and neuroendocrine signaling are implicated in arterial dysfunction and are affected in AL amyloidosis. However, arterial involvement in AL has not been evaluated thoroughly. In order to evaluate vascular dysfunction in patients with AL amyloidosis we evaluated non-invasively acquired markers which may be indicative of vascular involvement: hemodynamic [reflected waves and aortic blood pressures (BP)], functional [flow-mediated dilatation and carotid-femoral pulse wave velocity (PWV)] and structural [intima-media thickness (IMT) and the presence of plaques in the carotid arteries] markers of vascular damage were measured. Ninety-one (91) consecutive newly diagnosed patients with systemic AL were prospectively studied and compared to 91 controls matched 1:1 for traditional risk factors of cardiovascular disease (age, gender, smoking, hypertension, hyperlipidemia, diabetes) and for the presence of coronary artery disease. The median age of patients with AL was 65 years (range 40-83), 56% were males, 77% had renal and 57% cardiac involvement. Median NTproBNP was 1420 pg/ml, 25%, 49% & 26% were Mayo stage 1, 2 & 3 respectively, median eGFR was 66 ml/min/1.73 m2and median involved FLC (iFLC) level was 189 mg/L. First we compared indices of vascular damage between AL patients and matched controls: arterial stiffness (PWV: 10.4±3.0 vs 8.6±3.7 m/sec, p=0.002) and arterial wall thickness in the internal carotid artery (IMT: 0.76±0.21 vs 0.68±0.21 mm, p=0.017) were significantly higher in AL patients. Thus, subclinical vascular damage, independent from traditional factors of vascular dysfunction, is present in patients with AL. Peripheral systolic and diastolic blood pressure and aortic systolic, diastolic and pulse pressure (p≤0.001) and reflected waves (augmentation index (AI), p=0.045) were significantly lower in AL patients than in controls. After adjustment for NTproBNP levels, as a marker of cardiac dysfunction, the differences in blood pressures (systolic, diastolic and pulse pressure) remained significant (p≤0.008 for all). Thus, despite increased arterial stiffness, dysfunctional vasculature results in paradoxically lower systolic and diastolic blood pressure, a hallmark of AL amyloidosis, independently from the degree of cardiac dysfunction. We then examined possible associations of markers of AL with the indices of vascular dysfunction, after adjustment for risk factors of cardiovascular disease. The level of iFLCs was an independent determinant of lower peripheral systolic (p=0.021) and aortic systolic (p=0.009) and pulse pressure (p=0.013), hsTnT (p=0.016) and NTproBNP (p=0.001) levels were independent determinants of arterial stiffness (PWV). In a multivariate model mean blood pressure and NTproBNP were the only determinants of PWV. NTproBNP also correlated with the presence of plaques in the internal carotid arteries (p=0.006) independently of other risk factors of vascular disease. Thus, markers of cardiac dysfunction and the load of FLCs were associated with vascular dysfunction. Our results suggest vascular involvement in patients with AL amyloidosis, reflected at low aortic blood pressures, increased arterial stiffness and wall thickness in the internal carotid arteries. The association of the amount of light chains with aortic blood pressure suggests a role of the toxic light chain. The observed association of arterial stiffness with markers of heart involvement is indicative of a parallel process of heart and vascular injury in AL amyloidosis. Further research, to assess the clinical utility of markers of vascular damage in AL amyloidosis is needed. Disclosures No relevant conflicts of interest to declare.
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Gottman, John Mordechai, and Robert Wayne Levenson. "Dysfunctional Marital Conflict." Journal of Divorce & Remarriage 31, no. 3-4 (September 1, 1999): 1–17. http://dx.doi.org/10.1300/j087v31n03_01.

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33

Tonino, Sanne H., Jacoline M. van Laar, Marinus H. J. van Oers, Jean Y. J. Wang, Eric Eldering, and Arnon P. Kater. "ROS-Mediated Upregulation of Noxa Overcomes Drug-Resistance Due to P53-Dysfunction in Chronic Lymphocytic Leukemia." Blood 114, no. 22 (November 20, 2009): 2382. http://dx.doi.org/10.1182/blood.v114.22.2382.2382.

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Abstract Abstract 2382 Poster Board II-359 Although recent advances in treatment-strategies for chronic lymphocytic leukemia (CLL) have resulted in increased remission rates and response duration, the disease eventually relapses, which necessitates repeated cycles of therapy. Eventually most patients develop chemo-resistant disease which infers a very poor prognosis. The activity of purine-analogs and alkylating agents, the backbone of current treatment regimens, depends on functional p53 and chemo-resistance is highly associated with a dysfunctional p53-response. P53-independent sensitization of CLL cells to these compounds could represent a novel strategy to overcome chemo-resistance. Platinum-based compounds have been successfully applied in relapsed lymphoma and recently also in high-risk CLL. In various cancer-types, the activity of such compounds has been found to be p53-independent and in part mediated by p73. In this study we investigated the efficacy and mechanism of action of platinum-based compounds in chemo-refractory CLL. Neither cisplatinum nor oxaliplatin as a single agent induced cell death in clinically relevant doses. However, independent of p53-functional status, platinum-based compounds acted synergistically with fludarabine, which was found to be caspase-dependent. Combination-treatment resulted in strong upregulation of the pro-apoptotic BH3-only protein Noxa. We did not find evidence for a role of p73; however, the observed synergy was found to involve generation of reactive oxygen species (ROS). Co-treatment with ROS-scavengers completely abrogated Noxa-upregulation and cell-death upon combination treatment in p53-dysfunctional CLL. Noxa RNA-interference markedly decreased sensitivity to combination treatment, supporting a key role for Noxa as mediator between ROS signaling and apoptosis induction. In addition to these findings, we tested the effects of platinum-based compounds and fludarabine on drug-resistance resulting from CD40-ligand stimulation of CLL cells, which represents a model for CLL cells in the protective micro-environment of the secondary lymph node-tissue (Hallaert et al Blood 2008 112(13):5141). Combination treatment could overcome CD40-ligand induced chemo-resistance and was, at least in part, mediated by the generation of ROS and marked induction of expression of Noxa. Our data indicate that interference with the cellular redox-balance represents an interesting target to overcome drug resistance due to both p53-dysfunction as well as micro-environmental protective stimuli in CLL. Disclosures: No relevant conflicts of interest to declare.
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34

Delalibera, Mayra, Joana Presa, Alexandra Coelho, António Barbosa, and Maria Helena Pereira Franco. "Family dynamics during the grieving process: a systematic literature review." Ciência & Saúde Coletiva 20, no. 4 (April 2015): 1119–34. http://dx.doi.org/10.1590/1413-81232015204.09562014.

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The loss of a loved one can affect family dynamics by changing the family system and creating the need for family members to reorganize. Good family functioning, which is characterized by open communication, expression of feelings and thoughts and cohesion among family members, facilitates adaptive adjustment to the loss. This study conducted a systematic review of the literature on family dynamics during the grieving process. A search was conducted in the EBSCO, Web of Knowledge and Bireme databases for scientific articles published from January 1980 to June 2013. Of the 389 articles found, only 15 met all the inclusion criteria. The selected studies provided evidence that dysfunctional families exhibit more psychopathological symptoms, more psychosocial morbidity, poorer social functioning, greater difficulty accessing community resources, lower functional capacity at work, and a more complicated grieving process. Family conflicts were also emphasized as contributing to the development of a complicated grieving process, while cohesion, expression of affection and good communication in families are believed to mitigate grief symptoms.
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35

Nelson, H. Wayne. "Dysfunctional Health Service Conflict." Health Care Manager 31, no. 2 (2012): 178–91. http://dx.doi.org/10.1097/hcm.0b013e31825206f3.

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36

Sorokman, T. V., L. Yu Khlunovska, and I. Ya Lozyuk. "Frequency of involvement different parts of the gastrointestinal tract in the pathological process in children with biliary dysfunction." Modern pediatrics. Ukraine, no. 4(116) (May 26, 2021): 24–28. http://dx.doi.org/10.15574/sp.2021.116.24.

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The close anatomical and physiological connection of the digestive organs leads to a significant spread of functional disorders in various diseases. Purpose — to investigate the frequency and features of the clinical course of biliary dysfunction (BD) in children. Materials and methods. 66 children aged 10–18 years with BD were examined. The study included a complete clinical examination of children, laboratory and instrumental methods. To assess the severity of clinical symptoms in the examined patients was used traditional score scale of symptoms (0–3 points) and the frequency index (FI). Results. In most children, the database was combined with other functional and organic lesions of the digestive tract (n=56, 84.8%). The database was most often combined with chronic gastritis and duodenitis, as well as with functional motor disorders. FI in children with BD involved in the pathological process of the stomach and duodenum was the highest (0.59), and IR in children with BD and intestinal involvement was the lowest (0.23). The relationship between the frequency of combined pathology and the frequency of cases of increase in the size of the gallbladder (χ2=22.87 at a critical value of χ2=9.33 for the significance level p<0.01). Hyper- or hypofunctions of the biliary tract occurred with the same frequency. Conclusions. Biliary dysfunction in children is significantly more often combined with chronic gastritis and duodenitis, as well as with other functional disorders of the gastrointestinal tract (duodenogastric reflux). In children with biliary dysfunction and involvement in the pathological process of other parts of the gastrointestinal tract there is an increase in the frequency of exacerbations, more pronounced signs of dyspeptic syndrome on the background of pain with the same intensity and more often ultrasound reveals signs of gallbladder dysformation. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, biliary dysfunction.
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37

Skopin, I. I., I. V. Slivneva, M. S. Latyshev, D. V. Murysova, T. V. Asatryan, N. O. Sokolskaya, A. V. Vavilov, and N. O. Toporkov. "Assessment of the predictors of persistence/progression of functional mitral insufficiency in patients undergoing the interventional treatment of aortic valve diseases." Patologiya krovoobrashcheniya i kardiokhirurgiya 23, no. 2 (October 15, 2019): 9. http://dx.doi.org/10.21688/1681-3472-2019-2-9-19.

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<p>Mitral insufficiency usually accompanies numerous aortic valve diseases. At present, concomitant pronounced mitral regurgitation remains a fairly urgent problem in the transcatheter treatment of aortic valve diseases. During the postoperative period of transcatheter aortic valve replacement, mitral insufficiency tends to decrease in majority of the patients; however, in certain patients, mitral insufficiency persists as well as progresses, highlighting the advantages of this approach over open two-valve surgery. This article presents an analysis of research devoted to functional mitral insufficiency in patients undergoing the interventional treatment of aortic valve diseases. This study included high-risk patients (according to the STS scale of operational risk ≥8%), representing an older age group with a broad spectrum of comorbid pathologies. Some cases were categorised as the New York Heart Association functional class IV, presented with pronounced systolic dysfunction of the left ventricle or were considered inoperable. Based on the systematic review of eight studies, predictors of potential mitral insufficiency progression were identified, and treatment algorithms for this category of patients were studied for the interventional treatment of aortic valve disease. The intervention aims to optimise long-term prognosis, both in open surgery and minimally invasive interventions. The results of the present study will help improve immediate and long-term postoperative outcomes of the interventional treatment of aortic valve diseases. Determining the prognostic development of mitral regurgitation will help select the best management tactics for this complex group of patients, thereby improving treatment outcomes and long-term prognosis of both open surgery and minimally invasive interventions.</p><p>Received 26 June 2019. Revised 23 August 2019. Accepted 26 August 2019.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p>
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Ferrer, Gerardo, Xiao-Jie Yan, Brendan Franca, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, and Nicholas Chiorazzi. "Chronic Lymphocytic Leukemia Patients and Eµ-TCL1 Mice Share a Phenotype of Functional Granulocyte-like and Dysfunctional Monocyte-like Myeloid Derived Suppressor Cells." Blood 126, no. 23 (December 3, 2015): 614. http://dx.doi.org/10.1182/blood.v126.23.614.614.

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Abstract Immune imbalance is a common characteristic of patients with chronic lymphocytic leukemia (CLL). This feature is shared with Eμ-TCL1 transgenic mice that, like CLL patients, exhibit an expansion of CD5+ B cells with associated non-B-cell defects. In patients and in mice, T-cell responses are often ineffective. This alteration is generally considered due to the direct effects of the leukemic cells. The expansion of myeloid derived suppressor cells (MDSCs), which play a major role in helping tumor cells escape immune surveillance by inhibiting T-cell responses, is promoted by many cancers. MDSCs are a heterogeneous population of cells that are subdivided into monocyte-like (m-MDSC) and granulocyte-like (g-MDSC) subsets, both in humans and mice. There we have investigated the extent that patients with CLL have expansions of MDSCs, what are their types and functions, and how these correlate with the Eμ-TCL1 mice model. Using flow cytometry on cryopreserved PBMCs, we found that the absolute numbers of MDSCs (HLA-DRlo/CD11b+/CD33+) in 49 untreated CLL patients were significantly higher than 15 healthy controls (HCs) (966 446 vs. 163 578 cells/ml, P<0.001). Moreover, we observed that the absolute numbers of MDSCs significantly correlated with CLL B-cell counts in the blood (P=0.005, Spearman r=0.423). Of note, the distribution between m-MDSCs (CD14+) and g-MDSCs (CD15+) was dramatically different, with CLL patients exhibiting significantly higher numbers and percentages of g-MDSCs than HCs (702 296 vs. 26 818 cells/ml, P<0.001; 50.89 vs. 16.98%, P<0.001).In line with these results, when we explored the MDSC populations (CD11b+/GR1+) in Eμ-TCL1 mice of 5-16 months of age with leukemia cell blood counts ranging from 0.1 to 100 x 106 cell/ml. This analysis indicated a positive correlation between MDSCs and leukemic CD19+ CD5+ cells (P=0.003; Spearman r=0.328). Furthermore, the dot-plot analysis of GR1 and CD11b showed three well defined cell populations: one monocytic (Ly6-C+) and two granulocytic (Ly6-G+ CD11blo and Ly6-G+ CD11bhi). As in patients, the g-MDSC population was larger than the m-MDSC population (884 100 vs. 454 700,P=0.016). However in this case, the m-MDSCs correlated with the numbers of circulating leukemic cells (P<0.001; Spearman r=0.463) and the g-MDSCs did not. The latter was the case even when they were subdivided into both CD11blo and CD11bhi subgroups. A similar pattern was observed when analyzing single cell suspensions from murine spleens. When we evaluated the ability of MDSCs to inhibit autologous T-cell proliferation in CLL patients (n=7), we observed a consistent reduction of proliferation only when co-culturing with g-MDSCs(P=0.034). In contrast, the effects of m-MDSCs on T-cell expansion were varied and insignificant statistically. In 5 CLL samples, we induced m-MDSCs (im-MDSCs) from purified CD33+ cells in vitro with GM-CSF, IL10, and IL6; the im-MDSCs effectively suppressed T-cell proliferation in 4 of 5 cases at an average inhibition of 33% (range: 10-79%). Thus, dysfunctional m-MDSC suppression was not inherent and functional suppression could be achieved by stimulation of CLL precursor cells. Similarly in 3 independent experiments performed with MDSCs from Eμ-TCL1 mice (12-14 months of age), we observed a reduction of in vitro proliferation with g-MDSCs (P=0.049) and not with m-MDSCs. In addition, for those Eμ-TCL1 animals for which sufficient sample was available, we subdivided the g-MDSC population into the two subpopulations based on CD11b density; the CD11blo subset present less nuclear segmentation and higher suppressive activity. In summary, absolute numbers of MDSCs in the blood of CLL patients and Eμ-TCL1 mice are elevated and correlate with the levels of expansion of the leukemia. The major subtype in both situations was g-MDSCs.These g-MDSCs were functionally competent suppressors, whereas m-MDSCs were impaired in this function. In CLL patients, this m-MDSC suppressor defect could be corrected by in vitro stimulation with growth factors that support monocyte differentiation. The high similarity between CLL patients and Eμ-TCL1 mice in relation to MDSC number and function suggest that an imbalance in g-MDC vs. m-MDSC function may affect CLL development and expansion, altering interactions with members of the microenvironment such as T cells. Disclosures No relevant conflicts of interest to declare.
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39

Alekseenko, Anastasia. "Dysfunctions of Russian Market of Mergers and Acquisitions: Causes, Consequences, Methods of Overcoming." Vestnik Volgogradskogo gosudarstvennogo universiteta. Ekonomika, no. 3 (December 2019): 29–35. http://dx.doi.org/10.15688/ek.jvolsu.2019.3.3.

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The article deals with studying the institutional dysfunction of the Russian market of mergers and acquisitions. It proves that problems of functioning and quality of formal regulating institutions hinder its effective development. The contradiction of interests between the state as a subject of regulation and the state as a participant of the market resulted in forming institutional microdysfunctions connected with “double standards” of law enforcement for different types of owners, striving to obtain bureaucracy rent, intertwining functional actions of the state as a regulator and the state as a market participant. This contributed to the regular blocking of the trap effect in applying valuation norms in the antitrust law, causing impossibility to effectively prevent unfair deals and at the same time hinder fair and effective deals in the Russian market of mergers and acquisitions. To settle this problem it is required to use changes aimed at reducing asymmetric information between subjects of the Russian market of mergers and acquisitions and the state, and also blocking informal institutions which are in conflict with formal regulating institutions. Improving evaluation methods of economic analysis in the antitrust practice, expanding informal control (such as making independent expert research of future substantial deals and also analyzing performed deals) will contribute to overcoming the existing dysfunctions of the Russian market of mergers and acquisitions.
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40

Hamamci, Zeynep. "DYSFUNCTIONAL RELATIONSHIP BELIEFS IN MARITAL CONFLICT." Journal of Rational-Emotive & Cognitive-Behavior Therapy 23, no. 3 (September 2005): 245–61. http://dx.doi.org/10.1007/s10942-005-0013-y.

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41

Mucci, A., S. Galderisi, P. Rocca, A. Rossi, A. Bertolino, and M. Maj. "Neurocognitive Predictors of Social Cognition in Subjects with Schizophrenia and their First-degree Relatives." European Psychiatry 41, S1 (April 2017): S40. http://dx.doi.org/10.1016/j.eurpsy.2017.01.182.

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IntroductionSocial cognition is a complex construct that refers to the functions required to understand other people's mental states and behavior. In people with schizophrenia, social cognition deficits account for a proportion of variance in functional outcome, independent of symptomatology. However, the relationships among social cognition, neurocognitive functioning and functional outcome are still unclear. Previous investigations had several limitations including small sample size, heterogeneous and limited measures of social cognition and neurocognitive functions.AimsWithin the study of the Italian Network for Research on Psychoses, we investigated factors influencing outcome in patients with schizophrenia and their unaffected relatives. Psychopathology, including depression, neurocognition, social cognition and outcome were assessed using instruments designed to overcome some of the previous limitations.MethodsStructural equation modeling was used to test direct and indirect effects of neurocognition, social cognition and functional capacity on vocational and interpersonal functioning. Tests of facial emotion recognition, emotional intelligence and theory of mind were included to assess social cognition. The MATRICS Consensus Cognitive Battery (MCCB) was used to investigate neurocognition.ResultsIn both subjects with schizophrenia and their first-degree relatives, social cognition was found to be independent of negative symptoms and to have a direct impact on outcome. Neurocognition was a predictor of functional capacity and social cognition, which both mediated its impact on outcome. Social cognition was independent of functional capacity and negative symptoms.ConclusionsBetter understanding of how neurocognitive dysfunction and social cognition deficits relate to one another may guide efforts toward targeted treatment approaches.Disclosure of interestAM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter.All other Authors declare no potential conflict of interest.
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42

SULLIVAN, FRANCIS J. "Dysfunctional Workers, Functional Texts." Written Communication 14, no. 3 (July 1997): 313–59. http://dx.doi.org/10.1177/0741088397014003002.

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43

Skopin, I. I., and M. S. Latyshev. "Reconstructive operations on subvalvular structures of the mitral valve during remodelling of the left ventricle. Papillary muscle interventions." Patologiya krovoobrashcheniya i kardiokhirurgiya 24, no. 3 (September 30, 2020): 32. http://dx.doi.org/10.21688/1681-3472-2020-3-32-44.

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<p>The optimal treatment strategy for secondary mitral regurgitation of type IIIb (A. Carpentier classification) remains debatable. The use of a standard surgical technique for treating secondary mitral regurgitation and undersized ring annuloplasty demonstrates suboptimal results in several patients (about 30% of the patients exhibit postoperative hemodynamically significant mitral regurgitation with the absence of effective reverse remodelling of the left ventricle). Such suboptimal results are associated with the unification of only the mitral valve reconstruction technique, irrespective of the state of the left ventricle (degree of dysfunction, dilatation, tethering/tenting, and papillary muscle displacement); this is not entirely justified because of the disease complexity (valve and ventricular), and it is crucial to influence both the components of the disease. Particularly, modern researchers are inclined toward the need of using additional reconstructive interventions on the subvalvular structures that contribute to a more effective reverse remodelling of the left ventricle.<br />Here, we present a review of recent studies on the surgical treatment of functional mitral insufficiency of type IIIb (A. Carpentier classification) with effects on the subvalvular structures (pupillary muscle relocation and approximation).</p><p>Revised 19 April 2020. Revised 5 May 2020. Accepted 28 May 2020.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p>
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44

Hinge, Ashwini S., Jingyi He, Eucabeth Mose, Jose Javier, James Bartram, Ellen Fjellman, Hiromi Sesaki, H. Leighton Grimes, Nathan Salomonis, and Marie-Dominique Filippi, PhD. "Mitochondrial Morphology Controls Hematopoietic Stem Cell Self-Renewal and Confers Them Divisional Memory." Blood 130, Suppl_1 (December 7, 2017): 633. http://dx.doi.org/10.1182/blood.v130.suppl_1.633.633.

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Abstract Hematopoietic stem cells (HSC) have extensive regenerative potential but limited self-renewal ability. The repopulation potential is gradually lost with HSC divisions and during stress hematopoiesis. Hence, we hypothesize that activation or inactivation of signaling pathways or other mechanisms, inherently occurring during HSC activation into cycle, drives their progressive functional decline. To address this, we used single cell RNA-sequencing and compared the transcriptome of HSCs [Lin-c-Kit+Sca-1+CD48-CD150+] that is expressed upon exit from quiescence and the one that is inherited by daughter cells upon HSC division. We compared HSCs with full self-renewal activity to HSCs that have lost self-renewal activity [i.e. before (NT-HSC) and after transplantation (T-HSC), respectively]. Analysis of the data was performed using unsupervised methods, namely iterative clustering and guide-gene selection (ICGS), [Olsson et al, Nature, 2016] and principal component (PCA) analysis. Each revealed that genes categorized in mitochondrial organization were dramatically upregulated in activated NT-HSC and remained highly expressed in their daughter cells. Remarkably, ICGS revealed at least 2 distinct regulatory states within T-HSC; one that clustered within NT-HSC, and another one that was clearly separated from NT-HSC. The latter was exclusively comprised of daughter T-HSCs, and quite unexpectedly was demarcated by a lack of expression of mitochondrial genes along with changes in expression of genes related to cytoskeleton organization. Using EGFP-mitochondria reporter mice; which labels mitochondria regardless of their membrane potential and activated state, we found that NT-HSC had 4-fold higher mitochondrial content than progenitors. High resolution confocal imaging indicated that mitochondria were punctuated and the network was dispersed in the entire cell volume in NT-HSC. However, in T-HSCs, mitochondria formed one or a few larger aggregates. Mitochondrial membrane potential was also severely reduced in T-HSC in vivo, indicating that HSC accumulate dysfunctional mitochondria after replicative stress during stress hematopoiesis. During cell division, in vitro, mitochondria were unequally distributed to daughter cells of single T-HSC division [one daughter cell had more aggregated mitochondria], whereas mitochondria were equally partitioned during division of NT-HSC, suggesting that HSC lose mitochondrial quality control after replicative stress. Further, mitochondria aligned along the microtubule network in NT-HSC but not in T-HSC. Mitochondrial morphology and distribution are maintained through regulated cycles of fission and fusion, which is essential for maintaining a functional organelle and for equal mitochondrial inheritance during division. We found that the mitochondrial fission protein Drp1, which normally accumulated and wrapped around mitochondria in NT-HSC during cell activation, failed to do so in T-HSCs, perhaps due to impaired mitochondrial-cytoskeleton association. Genetic loss of Drp1 caused severe mitochondrial aggregation in HSCs, and impaired HSC self-renewal and repopulation ability in competitive transplant studies, indicating that accumulation of aggregated and dysfunctional mitochondria causes HSC functional defects. To understand whether HSCs accumulated abnormal mitochondrial morphology with divisional history during homeostatic conditions, we used the GFP label-retaining H2B mouse model. Remarkably, mitochondria were well dispersed and homogeneously distributed in GFP labeled-retaining HSCs (i.e. HSC that had not divided), while HSCs with history of cell division (no GFP) had larger and more compact aggregates. Hence, once HSCs exit from quiescence, they irreversibly accumulate dysfunctional mitochondria over the course of divisions due to lack of mitochondrial quality control mechanisms, which drives gradual heterogeneity and loss of self-renewal ability. Thus, HSCs use mitochondrial architecture to remember their divisions, in turn affecting their self-renewal ability. Therefore, drugs or pharmacological inhibitors targeting mitochondrial organization or its quality can be new therapeutic approach to improve HSC function following transplantation. Disclosures No relevant conflicts of interest to declare.
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Kordasti, Shahram Y., Judith C. W. Marsh, Sufyan Al-Khan, Jie Jiang, Alexander E. Smith, Azim M. Mohamedali, Pilar Perez Abellan, et al. "Functional Characterization of CD4+ T-Cells in Aplastic Anemia (AA)." Blood 118, no. 21 (November 18, 2011): 1340. http://dx.doi.org/10.1182/blood.v118.21.1340.1340.

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Abstract Abstract 1340 We have examined the role of CD4+ T-cells in the pathogenesis of AA in 63 patients, 48 of whom were analyzed at diagnosis and 15 following immunosuppressive therapy (IST). Absolute numbers of CD4+ regulatory T cells (Tregs, defined as CD3+CD4+CD25highCD27+Foxp3+) were lower in pre-treatment AA patients compared to 10 healthy donors (HDs) (5.5 × 106 v 1.4 × 107)(p=0.01). In patients with severe (SAA) and very severe AA (VSAA), the absolute number and frequency of Tregs were lower than non-severe AA (NSAA) (4.4 × 106/L v 1 × 107/L)(p=0.01) and HDs (4.4 × 106/L v 3 × 107/L) (p<0.001). Absolute numbers of Th1 and Th2 cells in all pre-treatment patients were higher compared to HDs (6.4 × 107/L v 1.8 × 107/L)(p=0.03) for Th1 and (2.6 × 107/L v 2.4 × 106/L)(p=0.006) Th2 cells. Although mean percentages of AA Th17 cells were higher than in HDs (1.5% v 0.15%)(p=0.04), differences in absolute numbers were not significant. Absolute numbers of Th2 and Th17 cells were increased in SAA (1.3 × 107/L v 7.4 × 106/L for Th2)(p=0.01) compared to NSAA (5.7 × 106/L v 2.15 × 106/L for Th17)(p=0.02). Ratios of Th1/Tregs (p=0.003), Th2/Tregs (p=0.02), and Th17/Tregs (p=0.001) were higher in SAA and VSAA compared to NSAA. Percentage of both activated (CD4+CD45RA−CD25highFoxp3high) and resting (CD4+CD45RA+ CD25highFoxp3low) Tregs was decreased in AA patients, compared to HDs (p=0.004 and p=0.01), whereas cytokine secreting Tregs (CD4+CD45RA−CD25high Foxp3low) were increased in AA (p<0.003). Sorted Tregs from AA patients did not suppress cytokine secretion by autologous or HD T effectors (Te) cells in 1:1 co-cultures, whereas IL-2 and IFN-γ secretion by AA Te (CD4+CD25lowCD127high) was suppressible by allogeneic Tregs from HDs, confirming Tregs dysfunction. AA Tregs did not inhibit either CD154 or CD69 expression on Te cells. Tregs from AA patients secreted significantly more IFN-γ, TNF-α and IL-17 (p=0.02, p=0.02 and p=0.01, respectively) after 4 hours stimulation with PMA/Ionomycine compared to HDs. Expression levels of FoxP3, ROR□c and T-bet in AA Tregs was normal. IFN-γ secreting cells (Th1) were enriched using enrichment kit then further enriched by FACS sorting. CDR3 region products of TCR Vβ-chain were amplified using Vβ specific forward and Cβ reverse primers. CDR3 PCR products from AA patients and HDs were subjected 454 sequencing (Roche GS FLX titanium). Sequencing was performed to yield an average ‘depth’ in excess of 1000 clonally reads (1000x) for each sample specific CDR3 PCR amp icon. Reads were processed using Roche Amp icon Variant Analyzer software (AVA). Diversity of TCR receptors (measured by spectratyping and confirmed by high throughput deep sequencing) in AA Th1 cells was lower than HDs (p=0.037), as shown by the percentage and number of consensus clusters in total sequence reads. Interestingly, percentages of the most dominant CDR3 clones, revealed by high throughput sequencing, were higher in AA compared to HDs, regardless of spectratyping pattern. Global gene expression of Tregs was compared in 3 pre-IST AA patients and 5 HDs. A unique gene signature consisting of 86 genes that were significant was identified. There were 8 down regulated genes (fold change) in the pre-treatment group; PIN4 (−4.1), OR2T12 (−3.3), AMAC1 (−2.73), PERP (−2.69), UTS2 (−2.27), RNF139 (−2.13), COMMD9 (−2.09) and LOC100128356 (−2.01). The top 10 of 78 up-regulated genes in the pre-treatment group were HBB (19.5), PSME2 (13.8), CSDA (13.07), FAM127A (7.78), EXOSC1 (7.73), BPGM (7.43), CYSLTR1 (7.17), CHPT1 (6.96) and PLAC8 (6.71). qPCR analysis for CSDA, HBB, PSMiE2, PERP, PIN4, and UTS2 confirmed a similar trend to the microarray results. Interestingly absolute number of Tregs, and Th2/Treg ratio were higher in 10 IST responsive patients compared to 5 non-responsive patients (p=0.005 and 0.02, respectively). We show that expansion of Th1, Th2, Th17, and decreased/skewed Tregs immunophenotype and function are a consistent and defining feature of SAA and VSAA. Clonal expansion of Th1 cells is likely to be antigen driven and the presence of dysfunctional Tregs aggravates this autoimmune response. Increases of Tregs, and Th2/Treg ratios following IST predicts a favourable response to this treatment. Disclosures: No relevant conflicts of interest to declare.
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46

Gottman, John M., and Janice L. Driver. "Dysfunctional Marital Conflict and Everyday Marital Interaction." Journal of Divorce & Remarriage 43, no. 3-4 (August 25, 2005): 63–77. http://dx.doi.org/10.1300/j087v43n03_04.

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47

Haferkamp, Claudia J. "Dysfunctional beliefs, self-monitoring, and marital conflict." Current Psychology 13, no. 3 (September 1994): 248–62. http://dx.doi.org/10.1007/bf02686852.

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48

Westin, Erik, Larisa Pereboeva, Divya Devadasan, Tim M. Townes, and Frederick D. Goldman. "Suppression of Antioxidant Responses in Dyskeratosis Congenita Cells." Blood 126, no. 23 (December 3, 2015): 2412. http://dx.doi.org/10.1182/blood.v126.23.2412.2412.

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Abstract Dyskeratosis Congenita (DC) is a bone marrow failure disorder characterized by a triad of leukoplakia, skin dyspigmentation and nail dystrophy. Pathologies found in these patients arise due to mutations found within a number of genes (DKC1, TERT, TERC, TINF2, TCAB1, CTC1, NOP10, C16orf57, NHP2 and PARN) that limit telomere maintenance/elongation, resulting in severely shortened telomeres. Previous studies in our lab have demonstrated impaired proliferation, limited lifespan and aberrant DNA damage response pathways in DC cells. These studies have also uncovered a significant reactive oxygen species (ROS) increase within every cell type investigated thus far. This ROS increase correlates with telomere dysfunction and the subsequent activation of the p53 DNA damage response pathway, which can be rescued by exogenous TERT or p53-shRNA expression. We have acquired skin punch biopsies from two patients with DC carrying either a TERT or DKC1 mutation. Here, we have investigated a potential candidate pathway largely characterized as a key antioxidant regulator in hematopoietic cells, NRF2 (NFE2L2). NRF2 is a redox-sensitive basic leucine zipper transcription factor that, together with its heterologous partners (small MAF proteins, cJun, ATF, etc), binds to antioxidant response elements (AREs) within gene promoters in a pro-oxidant environment. We compared the RNA expression via QRTPCR of NRF2 in control and DC skin fibroblasts and found a significant reduction in DC cells (TERT mutation: 1.5 fold; DKC1 mutation: 2.6 fold). Protein levels of NRF2 were also decreased in DC fibroblasts compared to controls. TXN is a gene whose expression is increased by NRF2 in a pro-oxidant environment. TXN expression was also significantly reduced (TERT mutation: 2.1 fold; DKC1 mutation: 2.2 fold). To test whether NRF2 suppression in DC cells is due to telomere dysfunction, we exogenously expressed TERT via retrovirus in DC and control fibroblasts. TERT expression led to dramatic increases in NRF2 (TERT mutation: 3.4 fold, DKC1 mutation: 3.7 fold) and TXN (TERT mutation: 3.7 fold, DKC1 mutation: 1.6 fold). In contrast, TERT expression in control cells increased NRF2 only 1.3 fold while TXN decreased 1.4 fold. Finally, we wanted to compare the expression of NRF2/TXN in low and elevated oxidative environments (4% vs 21% O2). Control cells increased the TXN expression in 21% O2 (NRF2: no change, TXN: 2.8 fold) while DC cells suppressed NRF2 (TERT mutation: no change, DKC1 mutation: 3 fold decrease) and TXN expression (TERT mutation: 1.4 fold decrease, DKC mutation: 2.3 fold decrease). Functional studies have found DC cells grown in low oxygen increase their proliferative capacity perhaps due to, in part, the NRF2 pathway. Together, these data support a hypothesis whereby shortened/dysfunctional telomeres suppress NRF2 activity and an antioxidant response to a pro-oxidant environment. Based upon previous research, this pathway is likely dependent on the activation of p53 as an intermediary between dysfunctional telomere signaling and the subsequent suppression of NRF2 activity. An abrogated antioxidant response in shortened telomere cells may promote entry into senescence and pathologies related to aging. Systemic pharmacological intervention that reduces ROS could reverse this process and form the basis to alleviate DC and related symptomology associated with this multi-organ disorder. Disclosures No relevant conflicts of interest to declare.
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Davis‐Sramek, Beth, Brian S. Fugate, and Ayman Omar. "Functional/dysfunctional supply chain exchanges." International Journal of Physical Distribution & Logistics Management 37, no. 1 (February 6, 2007): 43–63. http://dx.doi.org/10.1108/09600030710723318.

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50

Volpe, Umberto, Eleonora Merlotti, Armida Mucci, and Silvana Galderisi. "The contribution of brain imaging to the study of panic disorder." Epidemiology and Psychiatric Sciences 13, no. 4 (December 2004): 237–48. http://dx.doi.org/10.1017/s1121189x00001755.

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SummaryAims — The present review is aimed to evaluate the recent contribution of brain imaging techniques to the definition of neuroanatomofunctional models of panic disorder (PD). Methods — Structural and functional brain imaging studies of PD, conducted from January 1993 to October 2003 and selected through a comprehensive Medline search (key-words: panic disorder, emotions, brain imaging, EEG, Event-Related Potentials, MRI, fMRI, PET, SPECT, TC) were included in the review. The Medline search has been complemented by bibliographic cross-referencing. Results — The majority of the reviewed studies suggests that a dysfunction of a neural circuit encompassing prefrontal and temporo-Iimbic cortices is present in PD. A right hemisphere preferential involvement in PD has been shown by several studies. Conclusions — Reviewed neuroimaging studies suggest a dysfunction of frontal and temporo-Iimbic circuitries in PD. However, those studies cannot be considered conclusive because of several methodological limitations. Longitudinal and multi-modal studies involving larger patient samples, possibly integrated with population-based and genetic studies, would provide more insight into pathophysiological mechanisms of PD.Declaration of Interest: Authors declare that none of them had any known real, potential, or apparent conflict of interest and that there was no business or personal interest that might be relevant to the topic of this article.
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