Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Abstract Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

The role of soil characteristics on temperature sensitivity of soil organic matter

The uncertainty associated with how projected climate change will affect global C cycling could have a large impact on predictions of soil C stocks. The purpose of our study was to determine how various soil decomposition and chemistry characteristics relate to soil organic matter (SOM) temperature sensitivity. We accomplished this objective using long-term soil incubations at three temperatures (15, 25, and 35°C) and pyrolysis molecular beam mass spectrometry (py-MBMS) on 12 soils from 6 sites along a mean annual temperature (MAT) gradient (2–25.6°C). The Q10 values calculated from the CO2 respired during a long-term incubation using the Q10-q method showed decomposition of the more resistant fraction to be more temperature sensitive with a Q10-q of 1.95 ± 0.08 for the labile fraction and a Q10-q of 3.33 ± 0.04 for the more resistant fraction. We compared the fit of soil respiration data using a two-pool model (active and slow) with first-order kinetics with a three-pool model and found that the two and three-pool models statistically fit the data equally well. The three-pool model changed the size and rate constant for the more resistant pool. The size of the active pool in these soils, calculated using the two-pool model, increased with incubation temperature and ranged from 0.1 to 14.0% of initial soil organic C. Sites with an intermediate MAT and lowest C/N ratio had the largest active pool. Pyrolysis molecular beam mass spectrometry showed declines in carbohydrates with conversion from grassland to wheat cultivation and a greater amount of protected carbohydrates in allophanic soils which may have lead to differences found between the total amount of CO2 respired, the size of the active pool, and the Q10-q values of the soils.

A comparative study of the number and mass of fine particles emitted with diesel fuel and marine gas oil (MGO)

The current investigation reports on diesel particulate matter emissions, with special interest in fine particles from the combustion of two base fuels. The base fuels selected were diesel fuel and marine gas oil (MGO). The experiments were conducted with a four-stroke, six-cylinder, direct injection diesel engine. The results showed that the fine particle number emissions measured by both SMPS and ELPI were higher with MGO compared to diesel fuel. It was observed that the fine particle number emissions with the two base fuels were quantitatively different but qualitatively similar. The gravimetric (mass basis) measurement also showed higher total particulate matter (TPM) emissions with the MGO. The smoke emissions, which were part of TPM, were also higher for the MGO. No significant changes in the mass flow rate of fuel and the brake-specific fuel consumption (BSFC) were observed between the two base fuels.

Adaptive sizing of populations and number of islands in distributed genetic algorithms

Deciding the appropriate population size and number of is- lands for distributed island-model genetic algorithms is often critical to the algorithm’s success. This paper outlines a method that automatically searches for good combinations of island population sizes and the number of islands. The method is based on a race between competing parameter sets, and collaborative seeding of new parameter sets. This method is applicable to any problem, and makes distributed genetic algorithms easier to use by reducing the number of user-set parameters. The experimental results show that the proposed method robustly and reliably finds population and islands settings that are comparable to those found with traditional trial-and-error approaches.

Dynamic optimization of migration topology in internet-based distributed genetic algorithms

Distributed Genetic Algorithms (DGAs) designed for the Internet have to take its high communication cost into consideration. For island model GAs, the migration topology has a major impact on DGA performance. This paper describes and evaluates an adaptive migration topology optimizer that keeps the communication load low while maintaining high solution quality. Experiments on benchmark problems show that the optimized topology outperforms static or random topologies of the same degree of connectivity. The applicability of the method on real-world problems is demonstrated on a hard optimization problem in VLSI design.

Cabin crew rostering at KLM: optimization of reserves

In this paper, we will discuss the issue of rostering jobs of cabin crew attendants at KLM. Generated schedules get easily disrupted by events such as illness of an employee. Obviously, reserve people have to be kept 'on duty' to resolve such disruptions. A lot of reserve crew requires more employees, but too few results in so-called secondary disruptions, which are particularly inconvenient for both the crew members and the planners. In this research we will discuss several modifications of the reserve scheduling policy that have a potential to reduce the number of secondary disruptions, and therefore to improve the performance of the scheduling process.

Intratherapist reliability in the rating of scapula posture in multiple planes of reference

Background: Evaluation of scapular posture is a fundamental component in the clinical evaluation of the upper quadrant. This study examined the intrarater reliability of scapular posture ratings. Methods: A test-retest reliability investigation was undertaken with one week between assessment sessions. At each session physical therapists conducted visual assessments of scapula posture (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane). These five plane ratings were performed for four different scapular posture perturbating conditions (rest, isometric shoulder; flexion, abduction, and external rotation). Results. A total of 100 complete scapular posture ratings (50 left, 50 right) were undertaken at each assessment. The observed agreement between the test and retest postural plane ratings ranged from 59% to 87%; 16 of the 20 plane-condition combinations exceeded 75% observed agreement. Kappa (and prevalence adjusted bias adjusted kappa) values were inconsistent across the postural planes and perturbating conditions. Conclusions: This investigation generally revealed fair to moderate intrarater reliability in the rating of scapular posture by visual inspection. However, enough disagreement between assessments was present to warrant caution when interpreting perceived changes in scapula position between longitudinal assessments using visual inspection alone.

Socioeconomic inequalities in cardiovascular mortality and the role of childhood socioeconomic conditions and adulthood risk factors : a prospective cohort study with 17-years of follow up

Background The mechanisms underlying socioeconomic inequalities in mortality from cardiovascular diseases (CVD) are largely unknown. We studied the contribution of childhood socioeconomic conditions and adulthood risk factors to inequalities in CVD mortality in adulthood. Methods The prospective GLOBE study was carried out in the Netherlands, with baseline data from 1991, and linked with the cause of death register in 2007. At baseline, participants reported on adulthood socioeconomic position (SEP) (own educational level), childhood socioeconomic conditions (occupational level of respondent’s father), and a broad range of adulthood risk factors (health behaviours, material circumstances, psychosocial factors). This present study is based on 5,395 men and 6,306 women, and the data were analysed using Cox regression models and hazard ratios (HR). Results A low adulthood SEP was associated with increased CVD mortality for men (HR 1.84; 95% CI: 1.41-2.39) and women (HR 1.80; 95%CI: 1.04-3.10). Those with poorer childhood socioeconomic conditions were more likely to die from CVD in adulthood, but this reached statistical significance only among men with the poorest childhood socioeconomic circumstances. About half of the investigated adulthood risk factors showed significant associations with CVD mortality among both men and women, namely renting a house, experiencing financial problems, smoking, physical activity and marital status. Alcohol consumption and BMI showed a U-shaped relationship with CVD mortality among women, with the risk being significantly greater for both abstainers and heavy drinkers, and among women who were underweight or obese. Among men, being single or divorced and using sleep/anxiety drugs increased the risk of CVD mortality. In explanatory models, the largest contributor to adulthood CVD inequalities were material conditions for men (42%; 95% CI: −73 to −20) and behavioural factors for women (55%; 95% CI: -191 to −28). Simultaneous adjustment for adulthood risk factors and childhood socioeconomic conditions attenuated the HR for the lowest adulthood SEP to 1.34 (95% CI: 0.99-1.82) for men and 1.19 (95% CI: 0.65-2.15) for women. Conclusions Adulthood material, behavioural and psychosocial factors played a major role in the explanation of adulthood SEP inequalities in CVD mortality. Childhood socioeconomic circumstances made a modest contribution, mainly via their association with adulthood risk factors. Policies and interventions to reduce health inequalities are likely to be most effective when considering the influence of socioeconomic circumstances across the entire life course and in particular, poor material conditions and unhealthy behaviours in adulthood.

New Perspectives On Firm Growth

This insightful volume presents a collection of innovative works by two of the leading researchers of firm growth: Per Davidsson, Director, Australian Centre for Entrepreneurship Research and Professor of Entrepreneurship, Queensland University of Technology, Australia and Jönköping International Business School, Sweden and Johan Wiklund, Professor of Entrepreneurship, Syracuse University, US and Jönköping International Business School, Sweden. The studies extend previous research by providing stronger theoretical underpinnings and using longitudinal databases that can separate in time the firms’ growth from its presumed causes. They also break new ground by examining different modes of growth, such as sales growth vs. employment growth, and organic growth vs. acquisition-based expansion. Further, the studies investigate the drivers of firm growth and take a critical look at the effects, such as under what circumstances high growth is associated with high profitability. The issue of how firm growth is achieved and managed, and what consequences it has for different stakeholders is both theoretically interesting and practically important. The book will strongly appeal to academics of entrepreneurship, small business management and strategy.

Introduction

The issue of firm growth - how it is achieved and managed, and what consequences it has for different stakeholders - is both theoretically interesting and practically important. It is also an area of scholarly enquiry that has expanded very significantly since we started doing research on it in the 1980s and 1990s. In this volume we present and comment upon the most recent contributions we have made to this field of inquiry - separately, jointly and with various colleagues (who are included in the 'we/us article authors' used in the remainder of this introduction). While the chapters have been published before in various places, we think it valuable to gather them in one easily accessible place, which also allows space for our reflective commentary across the individual chapters. We hope readers will find the work a useful and worthwhile addition to the extant body of knowledge about firm growth. We also hope they will find that it- as its title suggests- brings new•/ perspectives on firm growth and its study, and that it can inspire future contributions by other researchers. This is important, because despite the growing volume of research on firm growth, many important questions still lack satisfactory answers. The current volume may be regarded as a follow-up of a previous collection where we- and Frederic Delmar- presented and commented on eight articles on (mostly small) firm growth that we had jointly or separately published up until that time (Davidsson et al., 2006). In that volume we organised the works under three broad themes: the conceptual and empirical complexity of the firm growth phenomenon; growth aspirations and motivations; and patterns and determinants of actual growth The current volume builds on and extends these themes. Only one of the chapters in the previous volume directly addressed the issue of drivers of actual growth. We add three more in this book, two of which expand on the (aspirations and motivations' theme by relating growth aspirations and motivations (or lack thereof) of the owner-manager to the actual growth achieved in the subsequent period.

Asset specificity and behavioral uncertainty as moderators of the sales growth-employment growth relationship in emerging ventures

New venture growth is a central topic in entrepreneurship research. Although sales growth is emerging as the most commonly used measure of growth for emerging ventures, employment growth has also been used frequently. However, empirical research demonstrates that there are only very low to moderately sized correlations between the two (Delmar et aL, 2003; Weinzimmer, et al., 1998). In addition) sales growth and employment growth respond differently to a wide variety of criteria (Baum et al., 2001; Delmar et al., 2003). In this study we use transaction cost economics (Williamson, 1996) as a theoretical base to examine transaction cost influences on the addition of new employees as emerging ventures experience sales growth. \\le theorize that transaction cost economics variables will moderate the relationship between sales growth and employment growth. W'e develop and test hypotheses related to asset specificity, behavioral uncertainty, and the influence of resource munificence on the strength of the sales growth/ employment growth relationship. Asset specificity is theorized to be a positive moderator of the relationship between sales growth and employment growth. When the behavioral uncertainty associated with adding new employees is greater than that of outsourcing or subcontracting, it is hypothesized to be a negative moderator of the sales growth/employment growth relationship. We also hypothesize that resource scarcity will strengthen those relationships.

Towards an integrative framework for future research on small firm growth

Our review has demonstrated that small firm growth is a complex phenomenon. The concept ‘growth’ denotes both a change in amount and the process by which that change is attained. Further, the growth can be achieved in different ways and with varying degrees of regularity, and it manifests itself along several different dimensions such as sales, employment, and accumulation of assets. This complexity has naturally led researchers to adopt different approaches to studying growth and to use different measures to assess it. Further, although our review shows that it can fruitfully be regarded as a growth issue, the research on small firms' internationalization has largely developed as a separate stream. Similarly, other relatively separate literatures have evolved, which effectively focus on different modes of growth although mostly without regarding the studies first and foremost as growth studies. This goes for topics such as mergers and acquisitions, diversification, and integration - research streams which have largely ignored the particularities of small firms and which in turn have been largely ignored among researchers focusing on small firm growth.

Growing profitable or growing from profits : putting the horse in front of the cart?

Top lists of and praise for the economy's fastest growing firms abound in business media around the world. Similarly, in academic research there has been a tendency to equate firm growth with business success. This tendency appears to be particularly pronounced in-but not confined to­ entrepreneurship research. In this study we critically examine this tendency to portray firm growth as more or less universally favorable. While several theories suggest that growth drives profitability we first show that the available empirical evidence does not support the existence of a general, positive relation­ ship between growth and profitability. Using the theoretical lens of the Resource-Based View (RBV) we then argue that sound growth usually starts with achieving sufficient levels of profitability. In summary, our theoretical argument is as follows: In a population of SMEs, superior profitability is likely to be indicative of having built a resource-based competitive advantage. Building such a valuable and hard to-copy advantage may at first constrain growth. However, the underlying advantage itself and the financial resources generated through high profitability make it possible for firms in this situation to now achieve sound and sustainable growth - which may require building a series of temporary advantages- without having to sacrifice profitability. By contrast, when firms strive for high growth starting from low profitability, the latter often indicates lack of competitive advantage. Therefore growth must be achieved in head-to-head competition with equally attractive alternatives, leading to profitability deterioration rather than improvement. In addition, these low profitability firms are unlikely to be able to finance strategies toward building valuable and difficult-to-imitate advantages while growing.

Organic and acquisitive growth : re-examining, testing and extending Penrose’s growth theory

The Theory of the Growth of The Firm by Edith Penrose, first published in 1959, is a seminal contribution to the field of management. Penrose's intention was to create a theory of firm growth which was logically consistent and empirically tractable (Buckley and Casson, 2007). Much attention, however, has been focused on her unintended contribution to the resource-based view (henceforth RBV) (e.g. Kor and Mahoney, 2004; Lockett and Thompson, 2004) rather than her firm growth theory. We feel that this is unfortunate because despite a rapidly growing body of empirical work, conceptual advancement in growth studies has been limited (Davidsson and Wiklund, 2000; Davidsson et ai., 2006; Delmar, 1997; Storey, 1994). The growth literature frequently references Penrose's work, but little explicit testing of her ideas has been undertaken. This is surprising given that Penrose's work remains the most comprehensive theory of growth to date. One explanation is that she did not formality present her arguments, favouring verbal exposition over formalized models (Lockett, 2005; Lockett and Thompson, 2004). However, the central propositions and conclusions of her theory can be operationalized and empirically tested.

Performance configurations over time: implications for growth-and profit-oriented strategies

Entrepreneurship research and practice places emphasis on company growth as a measure of entrepreneurial success. In many cases, there has been a tendency to give growth a very central role, with some researchers even seeing growth as the very essence of entrepreneurship (Cole, 1949; Sexton, 1997; Stevenson & Gumpert, 1991). A large number of empirical studies of the performance of young and/or small firms use growth as the dependent variable (see reviews by Ardishvili, Cardozo, Harmon, & Vadakath, 1998; Delmar, 1997; Wiklund, 1998). By contrast, the two most prominent views of strategic management – strategic positioning (Porter, 1980) and the resource-based view (Barney, 1991; Wernerfelt, 1984) – are both concerned with achieving competitive advantage and regard achieving economic rents and profitability relative to other competitors as the central measures of firm performance. Strategic entrepreneurship integrates these two perspectives and is simultaneously concerned with opportunity seeking and advantage seeking (Hitt, Ireland, Camp, & Sexton, 2002; Ireland, Hitt, & Sirmon, 2003). Consequently, both company growth and relative profitability are together relevant measures of firm performance in the domain of strategic entrepreneurship.