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Genetic Dissection of Quantitative Trait Loci for Substances of AbuseHarenza, Jo Lynne 19 July 2013 (has links)
It has been reported that an individual’s initial level of response to a drug might be predictive of his or her future risk of becoming dependent, thus basal gene expression profiles underlying those drug responses may be informative for both predicting addiction susceptibility and determining targets for intervention. This dissertation research aims to elucidate genetic risk factors underlying acute alcohol and nicotine dependence phenotypes using mouse genetic models of addiction. Phenotyping, brain region-specific mRNA expression profiling, and genetic mapping of a recombinant inbred panel of over 25 mouse strains were performed in order to identify quantitative trait loci (QTL) harboring candidate genes that may modulate these phenotypes. Previous BXD (B6 x D2) behavioral studies performed in our laboratory identified an ethanol-induced anxiolysis-like QTL (Etanq1) in the light dark box (LDB). We hypothesized that genetic variation within Nin (a gene within the Etanq1 support interval involved in microtubule-anchoring) may modulate anxiolytic-like responses to acute ethanol in the LDB as well as other preclinical models of anxiety, the elevated plus maze (EPM), and marble burying (MB) task. Molecular studies have allowed us to confirm cis regulation of Nin transcript levels in the NAc. To elucidate potential mechanisms mediating Etanq1, the pharmacological tools, diazepam and HZ166 (a benzodiazepine derivative) were utilized to interrogate whether GABAA receptor activation modulates ethanol’s anxiety-like behaviors in the LDB. We show that the LDB phenotype, percent time spent (PTS) in the light following a brief restraint stress, is not being modulated through direct activation of GABAA α2/α3 receptor subunits. To genetically dissect Etanq1 as well as parse the ethanol anxiolytic-like phenotype, we have assayed 8 inbred strains, selected based on genotypes at Nin, in various preclinical models of anxiety. Principal components analysis of these behavioral data suggests that the gene(s) modulating the ethanol anxiolytic-like component in the LDB do not overlap with similar phenotypes in the elevated plus maze (EPM), nor the MB phenotype. Furthermore, site-specific delivery of an sh-Nin lentivirus into the NAc of D2 mice revealed that Nin may modulate one LDB endophenotype, latency to enter the light side of the LDB, which loaded as a part of the “anxiolysis” principal component. These data strongly imply that basal neuronal Nin expression in the NAc is important for acute ethanol anxiolytic-like behavior, perhaps through a novel mechanism involving synaptic remodeling. In separate behavioral QTL mapping studies, we hypothesized that genetic variation regulating expression of Chrna7 modulates the reward-like phenotype, conditioned place preference (CPP), for nicotine. We provide evidence for genetic regulation of Chrna7 across the BXD panel of mice and through pharmacological and genetic behavioral studies, confirm Chrna7 as a quantitative trait gene modulating CPP for nicotine in mice. Microarrays, followed by network analyses, allowed us to identify a genetically co-regulated network within the nucleus accumbens (NAc), differentially expressed in mice null for Chrna7, which was similarly correlated in the BXD panel of mice. Our network and molecular analyses suggest a putative role for Chrna7 in regulating insulin signaling in the NAc, which together, may contribute to the enhanced sensitivity to nicotine observed in strains of mice that lack or have low mRNA levels of Chrna7 in the NAc. Overall, this research has elucidated and confirmed new genetic risk factors underlying alcohol and nicotine dependence phenotypes and has enabled a better understanding of the neurogenomic bases of alcohol and nicotine addiction. Future studies that further investigate the signaling pathways and/or gene interactions involving Nin and Chrna7 may lead the field to new candidates for pharmacotherapies that may be tailored for use in individuals with susceptible genotypes. Supported by NIAAA grants P20AA017828 and R01AA020634 to MFM, NIDA T32DA007027 to WLD, and NIDA R01DA032246 to MFM and MID.
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The Role of MAGL Inhibition in Nicotine Withdrawal and RewardMuldoon, Pretal 16 November 2012 (has links)
ROLE OF MAGL INHIBITION IN NICOTINE WITHDRAWAL AND REWARD. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Pretal Ishvarlal Patel Muldoon Director: M. Imad Damaj, PhD Professor, Department of Pharmacology and Toxicology Tobacco use is one of the leading causes of preventable deaths worldwide. Nicotine, the main psychoactive component of tobacco, sustains and initiates tobacco addiction. Cessation of nicotine induces a dependence withdrawal syndrome. Recent in vivo studies indicate that the endocannabinoid (EC) system modulates both nicotine reward and withdrawal. The purpose of this proposal is to investigate the role of enhancing endogenous 2-arachidonoylglycerol (2-AG) and by blocking its degradative enzyme, monoacylglycerol lipase (MAGL) enzyme, in nicotine reward and dependence. The selective MAGL inhibitor JZL184 dose-dependently reduced both precipitated and spontaneous somatic and aversive withdrawal signs in mice. These effects were blocked by rimonabant indicating a CB1 receptor mechanism. Furthermore, repeated administration of JZL184 for 6 days did not produce tolerance to the alleviation of withdrawal and the treatment did not induce alterations in CB1 receptor levels or receptor-mediated G-protein activity in various brain regions. In addition, a decrease in 2-AG levels was found in the nucleus accumbens in nicotine-dependent mice undergoing precipitated withdrawal, suggesting that a dysregulation of this EC signaling system occurs during nicotine withdrawal. Lastly, we tested the effectiveness of a combination of low-dose JZL184 and high dose of the FAAH inhibitor PF-3845 on spontaneous nicotine withdrawal. Indeed, the combination of low-dose JZL184 and PF-3845 significantly attenuated nicotine spontaneous withdrawal signs. MAGL inhibition by JZL184 dose-dependently caused a significant blockade of nicotine reward as measured in the mouse conditioned place preference (CPP). In contrast to withdrawal, JZL184’s effect on nicotine CPP was not CB1 mediated. In addition, JZL184 treatment did not cause significant alterations in CB1 receptor levels or receptor-mediated G-protein activity in several brain regions involved in nicotine reward. The effects of JZL184 on nicotine CPP was selective since the drug failed to alter food-induced CPP and LiCl-induced conditioned place aversion in the mouse. Interestingly, active doses of JZL184 did not only cause an increases in 2-AG levels but also induced a concomitant decrease in arachidonic acid (AA) levels in various brain regions suggesting an AA cascade dependent-mechanism. In line of these changes, a cox-2 inhibitor, valdecoxib, dose-dependently blocked nicotine preference.
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Aplikace pro hodnocení výkonnosti zaměstnanců / Staff Performance Evaluation ApplicationSlivka, Lukáš January 2011 (has links)
This thesis presents the Balanced Scorecard methodology, which belongs to the most widely accepted way of measuring business performance. The work emphasizes the human resources sector and wants to highlight the role. Employees representing the most important capital of the modern organization must have an idea about the functioning of business in a deeper context. Their performance management and pay system connected with BSC of firm are essential to increase the firm's value. Automating the process at a higher number of employees is a must.
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Aplikace pro hodnocení výkonnosti zaměstnanců / Staff Performance Evaluation ApplicationSlivka, Lukáš January 2013 (has links)
This thesis presents the Balanced Scorecard methodology, which belongs to the most widely accepted way of measuring business performance. The work emphasizes the human resources sector and wants to highlight the role. Employees representing the most important capital of the modern organization must have an idea about the functioning of business in a deeper context. Their performance management and pay system connected with BSC of firm are essential to increase the firm's value. Automating the process at a higher number of employees is a must.
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Organisational reward strategies and performance of front line managers : analysis of Pakistani textile industryTufail, Muhammad Shahid January 2014 (has links)
The current study seeks to contribute specifically to the literature on reward management and managerial performance. In doing so, it aims to address certain gaps in the existing literature; particularly a noticeable lack of research in rewards and individual performance relationships in a developing country, Pakistan. This study has sought to examine the relationship of extrinsic rewards comprising of pay, bonuses, opportunities for promotion and intrinsic rewards such as sense of recognition, job characteristics with individual performance measured as task and contextual performance including citizenship behaviour. Furthermore, the study has sought to examine the mediation role of organisational justice elements such as procedural and distributive justice in reward performance relationships. The study aims at identifying different rewards being offered in textile organisations and their relationships with performance of front line managers in textile sector organisations. The study focuses primarily on key research questions: 1. What is the relationship between extrinsic rewards such as pay and bonus based incentives with the performance of front line managers? 2. How do opportunities for promotion relate with performance of front line managers in textile industry? 3. What is the relationship of intrinsic rewards such as sense of recognition and job characteristics with the performance of front line managers? 4. How does procedural and distributive justice influence the reward performance relationships for front line managers in textile industry? Being deductive in nature, the current study revolves around the premises of positivist philosophy. Being cross section in nature, a survey based design is selected and a quantitative strategy is used in this study for data collection and analysis. The study is facilitated by random stratified sampling for data collection and structural equation modelling technique to draw results of direct and mediation effects of study constructs. The results portray significant relationships of rewards and individual performance with relatively strong emphasis on task performance in comparison to contextual performance. The results further highlight the mediation of procedural and distributive justice particularly in extrinsic rewards and task performance relationships for front line managers. The study seeks to contribute to existing theoretical knowledge and practices in developing economies and is pioneering in its examination of rewards-individual performance relationships in Pakistan. In examining organisational rewards with task and contextual performance for front line managers in private manufacturing sector, the study tends to address the gap in existing literature on reward and performance management. Moreover, the current study further seeks to examine the mediation effects of procedural and distributive justice in reward performance relationships discovering this field of theoretical knowledge as existing literature does not reflect upon this gap. The study intends to offer help and support to concerned stakeholders in better understanding, developing and modifying rewards-performance relationships particularly for textile industry in Pakistan.
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Morotens väg till motivation : En flerfallsstudie om belöningssystem i IT-företag / The carrots way to motivation : A multivariate study of reward systems in the IT businessGustafsson, Alexandra, Langmoen, Minda, Tamme, Amanda January 2017 (has links)
Titel: Morotens väg till motivation – En flerfallsstudie om belöningssystem i IT-företag Författare: Alexandra Gustafsson, Minda Langmoen & Amanda Tamme Examinator: Elin Funck Handledare: Anders Jerreling Bakgrund & Problem: IT-branschen är en ung bransch som präglas av snabb förändring och utveckling. Utifrån Contingency-teorin kommer företags ekonomistyrning att skilja sig beroende på aspekter gällande storlek, strategi och miljö. Belöningssystem som en del av ekonomistyrningen, kan vid rätt utformning användas som ett effektivt styrmedel, men problemet ligger i att hitta lämplig utformning som sedan skapar motivation hos anställda. Syfte: Syftet med uppsatsen är att beskriva, förklara samt jämföra hur belöningssystem är utformade inom tre olika IT-företag. Vidare syftar arbetet till att utreda hur denna del av ekonomisystemet motiverar företagets medarbetare. Metod: Studien är av kvalitativ karaktär och vid insamling av empiriskt material har semistrukturerade intervjuer på IBM, NAB Solutions och Atea genomförts. Utifrån uppsatsens syfte valdes flerfallsstudie som forskningsstrategi. Det insamlade materialet presenteras först på företagsnivå sedan görs en jämförelse mellan de tre företagen. Slutsats: Samtliga företag har ett belöningssystem bestående av både monetära och icke- monetära belöningar, där de intervjuade har uppgett att det generellt sett är de icke-monetära belöningarna som bidrar till att skapa motivation. De avgörande faktorerna för företagens utformning av belöningsssystem antas vara storleken, strategin och dess ålder. Att IT- branschen är så pass ung kan leda till att företagen snabbt kan bli tvungna att göra om sina belöningssystem. Beroende på contingency-aspekterna storlek, strategi och miljö förväntas utformningen mellan företagen att skilja åt.
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Teambelöning : en studie om teambaserade belöningssystem och dess inverkan på medarbetares motivation / Team reward : a study of team-based reward system and its influence on employees motivationJansson, Johanna, Sandin, Johanna January 2016 (has links)
Syftet med studien är att undersöka upplägg och användning av ett teambaserat belöningssystem. Studien utgår från frågeställningar om vad medarbetarna i Handelsbanken har för syn på det teambaserade belöningssystemet Oktogonen som banken använder sig av. Genom att studera teambelöning så kommer det att ge kunskap om hur det fungerar samt hur de anställda uppfattar belöningssystemet. Studien har en kvalitativ metod i form av semistrukturerade intervjuer. Intervjuerna är med fem stycken medarbetare inom Handelsbanken. Vid analysering av det insamlade materialet har vi använt oss av tematisering för att ge läsaren en enkel struktur att följa och för att det tydligt ska framgå vilka huvudteman som studien bygger på. Motivation påverkar medarbetarnas arbetsprestation och Oktogonen är inte en motivationshöjande faktor i och med att utbetalningen sker i slutet av arbetslivet. Oktogonen är därför svår att greppa och påverkar inte arbetsprestationen i någon större utsträckning. Däremot stärker den teamarbetet bland personalen. / This studys purpose is to examine the setup and use of team-based rewardsystems. The study is based on questions about what employees in Handelsbanken think of their team-based rewardsystem Oktogonen. By examining team rewards knowledge will be given about how it works and what the employees think of it. The study has a qualitative formed method with semi-structured interviews with five employees in Handelsbanken. When analyzing the collected material we have used thematisation to give the reader structure and to clearly mention the main themes of the study. Motivation affect employees job performance and Oktogonen is not a motivating factor because the payment is made at the end of working life. Therefore Oktogonen is hard to grasp and do not affect work performance in any significant way, however it strengthens the teamwork among the staff.
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Belöningssystem och motivation : En flerfallsstudie på företag inom byggbranschen / Reward system and motivation : A multi-case study in the construction industryAdamsson, Philip, Petersson, Johannes, Andersson, Gabriel January 2016 (has links)
Sammanfattning Titel: Belöningssystem och motivation - En flerfallsstudie på företag inom byggbranschen Författare: Philip Adamsson, Gabriel Andersson, Johannes Petersson Program: Civilekonomprogrammets controllerfördjupning Examinator: Elin Funck Handledare: Natalia Semenova Institution: Ekonomihögskolan Linnéuniversitetet i Växjö Bakgrund och problem: Ett styrmedel som flitigt nyttjas är belöningssystem där ledningen med hjälp av ett fungerande belöningssystem kan få önskat beteende hos arbetstagaren. Hur ett belöningssystem är utformat skiljer sig mellan olika branscher och byggbranschen är en bransch kantad av intressekonflikter mellan arbetsgivare och arbetstagare. Råder det en överrensstämmelse mellan arbetsgivarens avsikt med ett belöningssystem och arbetstagaren uppfattning om belöningssystemet? Det finns flertalet olika belöningar som kan ge önskat beteende, men vad är det egentligen som motiverar arbetstagare inom byggbranschen. Syfte: Syftet med studien är att redogöra för hur belöningssystem är utformade i byggbranschen. Vidare är syftet med studien att se om arbetsgivarens avsikter med och arbetstagarens uppfattning av belöningssystemet överensstämmer. Dessutom ämnar studien behandla varför, alternativt varför inte arbetstagarna anser att belöningssystemet motiverar. Metod: Vi har genomfört en flerfallsstudie på Svensk Vattenbilningsteknik AB och TECAB Ytskyddsprodukter AB, verksamma inom byggbranschen. Empiriskt material har insamlats genom semi-strukturerade intervjuer. Studien har haft en deduktiv forskningsansats. Slutsats: Vi kan konstatera att arbetsgivare bör fokusera på vilket syfte de har med belöningssystemet för att kunna utforma ett fungerande belöningssystem. Enligt studien skall ett belöningssystem innehålla en kombination av finansiella och ickefinansiella belöningar. Slutligen bör en finansiell bonus ingå i byggföretags belöningssystem eftersom den ökar arbetstagarnas motivation och tillfredsställelse. / Abstract Title: Reward system and motivation – A multi-case study in the construction industry Authors: Philip Adamsson, Gabriel Andersson, Johannes Petersson Examiner: Elin Funck Supervisor: Natalia Semenova Background and problem: A reward system is an instrument that is widely used, where management with help of a functional reward system can get a desired behavior from an employee. How a reward system is designed differs between sectors. The construction industry is a sector bordered by conflicts of interest between employers and employees. Is there a match between the employer's intention with reward systems and employee’s perception of the reward system? There are multiple rewards that can provide a desired behavior, but what is it that really motivate employees in the construction industry. Purpose: The purpose of this study is to describe how the reward system is designed in the construction industry. Furthermore, the purpose of the study is to see if the employer's intentions and the employee's perception of the reward system is consistent. The study also intends to describe why, or why not employees feel that the reward system motivates them. Methods: We conducted a multi-case study of Svensk Vattenbilningsteknik AB and TECAB Ytskyddsprodukter AB. Both companies are active in the construction industry. Empirical material were obtained through semi-structured interviews. The study had a deductive research approach. Conclusion: We can conclude that employers should focus on the purpose of their reward system to design a functional system. According to the study, a reward system should contain a combination of financial and non-financial rewards. Finally, a financial bonus should be a part of a construction company´s reward system, because it increases employee motivation and satisfaction.
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Attentional Biases in Value-Based Decision-MakingSan Martin Ulloa, Rene January 2014 (has links)
<p>Humans make decisions in highly complex physical, economic and social environments. In order to adaptively choose, the human brain has to learn about- and attend to- sensory cues that provide information about the potential outcome of different courses of action. Here I present three event-related potential (ERP) studies, in which I evaluated the role of the interactions between attention and reward learning in economic decision-making. I focused my analyses on three ERP components (Chap. 1): (1) the N2pc, an early lateralized ERP response reflecting the lateralized focus of visual; (2) the feedback-related negativity (FRN), which reflects the process by which the brain extracts utility from feedback; and (3) the P300 (P3), which reflects the amount of attention devoted to feedback-processing. I found that learned stimulus-reward associations can influence the rapid allocation of attention (N2pc) towards outcome-predicting cues, and that differences in this attention allocation process are associated with individual differences in economic decision performance (Chap. 2). Such individual differences were also linked to differences in neural responses reflecting the amount of attention devoted to processing monetary outcomes (P3) (Chap. 3). Finally, the relative amount of attention devoted to processing rewards for oneself versus others (as reflected by the P3) predicted both charitable giving and self-reported engagement in real-life altruistic behaviors across individuals (Chap. 4). Overall, these findings indicate that attention and reward processing interact and can influence each other in the brain. Moreover, they indicate that individual differences in economic choice behavior are associated both with biases in the manner in which attention is drawn towards sensory cues that inform subsequent choices, and with biases in the way that attention is allocated to learn from the outcomes of recent choices.</p> / Dissertation
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Testosterone Reactivity and Neural Activation in the MID taskLee, Yoojin 18 December 2014 (has links)
The purpose of the project was to determine if testosterone reactivity and neural changes could be observed in response to a reward-seeking competitive task, respectively, and whether testosterone was related to neural activation. Forty nine undergraduate students were recruited playing the Monetary Incentive Delay (MID). We found that a subset of participants (N=20) showed testosterone reactivity to the task (ps < .05). During the EEG analyses, cue had a main effect on FRN amplitude in a trend level (p = .084): The large incentive cue triggered smaller (less negative) FRN amplitude than the small incentive cue did (p < .05), especially during the second reward seeking block (A’) (p = .065) and especially within males (p < .05). Testosterone level and reactivity were not further associated with FRN amplitude (ps > .1). Taken together, results show both testosterone and FRN amplitude may be sensitive to a complex reward-seeking and competition.
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