Alternative mechanisms guiding salespersons’ ambidextrous product selling

Ambidextrous product-selling strategies, in which companies’ salespeople concurrently pursue the sale of existing and new products, are hard to implement. Previous studies have addressed this issue for relatively simple consumer settings with the manager in close proximity to the salespersons and focusing on different levels of control and autonomy to resolve this issue. However, little is known about how field salespeople can be influenced to pursue such dual goals proactively for more complex business-to-business products. In this study, the authors distinguish between salespeople’s proactive selling behaviour for new and existing products, and study the impact of two alternative mechanisms: a situational mechanism (i.e. perceived manager product-selling ambidexterity) and a structural mechanism (i.e. salesperson organizational identification). Using a time-lagged, multisource data set from a large ambidextrous company, the authors demonstrate that both mechanisms contribute to salespeople’s proactive selling of new and existing products, but also act as each other’s substitutes. The results suggest two most likely strategies for salespeople to obtain overall sales targets: focusing on existing product selling; or acting ambidextrously. The latter approach offers the benefits of better achieving ambidextrous company sales goals and of greater performance stability, and is thus preferred.

The effects of servant leadership on follower performance and well-being:underlying mechanisms, boundary conditions, and the role of training

Based on a review of the servant leadership, well-being, and performance literatures, the first study develops a research model that examines how and under which conditions servant leadership is related to follower performance and well-being alike. Data was collected from 33 leaders and 86 of their followers working in six organizations. Multilevel moderated mediation analyses revealed that servant leadership was indeed related to eudaimonic well-being and lead-er-rated performance via followers’ positive psychological capital, but that the strength and di-rection of the examined relationships depended on organizational policies and practices promot-ing employee health, and in the case of follower performance on a developmental team climate, shedding light on the importance of the context in which servant leadership takes place. In addi-tion, two more research questions resulted from a review of the training literature, namely how and under which conditions servant leadership can be trained, and whether follower performance and well-being follow from servant leadership enhanced by training. We subsequently designed a servant leadership training and conducted a longitudinal field experiment to examine our sec-ond research question. Analyses were based on data from 38 leaders randomly assigned to a training or control condition, and 91 of their followers in 36 teams. Hierarchical linear modeling results showed that the training, which addressed the knowledge of, attitudes towards, and ability to apply servant leadership, positively affected leader and follower perceptions of servant leader-ship, but in the latter case only when leaders strongly identified with their team. These findings provide causal evidence as to how and when servant leadership can be effectively developed. Fi-nally, the research model of Study 1 was replicated in a third study based on 58 followers in 32 teams drawn from the same population used for Study 2, confirming that follower eudaimonic well-being and leader-rated performance follow from developing servant leadership via increases in psychological capital, and thus establishing the directionality of the examined relationships.

Engineering access control for distributed enterprise applications

Access control (AC) is a necessary defense against a large variety of security attacks on the resources of distributed enterprise applications. However, to be effective, AC in some application domains has to be fine-grain, support the use of application-specific factors in authorization decisions, as well as consistently and reliably enforce organization-wide authorization policies across enterprise applications. Because the existing middleware technologies do not provide a complete solution, application developers resort to embedding AC functionality in application systems. This coupling of AC functionality with application logic causes significant problems including tremendously difficult, costly and error prone development, integration, and overall ownership of application software. The way AC for application systems is engineered needs to be changed. ^ In this dissertation, we propose an architectural approach for engineering AC mechanisms to address the above problems. First, we develop a framework for implementing the role-based access control (RBAC) model using AC mechanisms provided by CORBA Security. For those application domains where the granularity of CORBA controls and the expressiveness of RBAC model suffice, our framework addresses the stated problem. ^ In the second and main part of our approach, we propose an architecture for an authorization service, RAD, to address the problem of controlling access to distributed application resources, when the granularity and support for complex policies by middleware AC mechanisms are inadequate. Applying this architecture, we developed a CORBA-based application authorization service (CAAS). Using CAAS, we studied the main properties of the architecture and showed how they can be substantiated by employing CORBA and Java technologies. Our approach enables a wide-ranging solution for controlling the resources of distributed enterprise applications. ^

Thioredoxin and Jab1 control estrogen- and antiestrogen-mediated progression of the cell cycle through p27 interactions

A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and protein-protein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

Temporal and Spatial Variability of Mesozooplankton in a Shallow Sub-Tropical Bay: Influence of Top-Down Control

Quantifying the relationship between mesozooplankton and water quality parameters identifies the factors that structure the mesozooplankton community and can be used to generate hypotheses regarding the mechanisms that control the mesozooplankton population and potentially the trophic network. To investigate this relationship, mesozooplankton and water quality data were collected in Florida Bay from 1994 to 2004. Three key characteristics were found in the mesozooplankton community structure: (1) there are significant differences between the four sub-regions of Florida Bay; (2) there is a break in May of 1997 with significant differences before and after this date; and (3) there is a positive correlation between mesozooplankton abundance and salinity. The latter two characteristics are closely correlated with predator abundance, indicating the importance of top-down control. Hypersaline periods appear to provide a refuge from predators, allowing mesozooplankton to increase in abundance despite the increased physiological stress.

The effect of male -male competition and its underlying regulatory mechanisms on the electric signal of the gymnotiform fish Brachyhypopomus gauderio

Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.

The Effect of male-male competition and its Underlying Regulatory Mechanisms on the Electric Signal of the Gymnotiform fish Brachyhypopomus gauderio

Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.

Engineering access control for distributed enterprise applications

Access control (AC) is a necessary defense against a large variety of security attacks on the resources of distributed enterprise applications. However, to be effective, AC in some application domains has to be fine-grain, support the use of application-specific factors in authorization decisions, as well as consistently and reliably enforce organization-wide authorization policies across enterprise applications. Because the existing middleware technologies do not provide a complete solution, application developers resort to embedding AC functionality in application systems. This coupling of AC functionality with application logic causes significant problems including tremendously difficult, costly and error prone development, integration, and overall ownership of application software. The way AC for application systems is engineered needs to be changed. In this dissertation, we propose an architectural approach for engineering AC mechanisms to address the above problems. First, we develop a framework for implementing the role-based access control (RBAC) model using AC mechanisms provided by CORBA Security. For those application domains where the granularity of CORBA controls and the expressiveness of RBAC model suffice, our framework addresses the stated problem. In the second and main part of our approach, we propose an architecture for an authorization service, RAD, to address the problem of controlling access to distributed application resources, when the granularity and support for complex policies by middleware AC mechanisms are inadequate. Applying this architecture, we developed a CORBA-based application authorization service (CAAS). Using CAAS, we studied the main properties of the architecture and showed how they can be substantiated by employing CORBA and Java technologies. Our approach enables a wide-ranging solution for controlling the resources of distributed enterprise applications.

Bounds on end-to-end performance of networks employing erasure control coding

Erasure control coding has been exploited in communication networks with an aim to improve the end-to-end performance of data delivery across the network. To address the concerns over the strengths and constraints of erasure coding schemes in this application, we examine the performance limits of two erasure control coding strategies, forward erasure recovery and adaptive erasure recovery. Our investigation shows that the throughput of a network using an (n, k) forward erasure control code is capped by r =k/n when the packet loss rate p ≤ (te/n) and by k(l-p)/(n-te) when p > (t e/n), where te is the erasure control capability of the code. It also shows that the lower bound of the residual loss rate of such a network is (np-te)/(n-te) for (te/n) < p ≤ 1. Especially, if the code used is maximum distance separable, the Shannon capacity of the erasure channel, i.e. 1-p, can be achieved and the residual loss rate is lower bounded by (p+r-1)/r, for (1-r) < p ≤ 1. To address the requirements in real-time applications, we also investigate the service completion time of different schemes. It is revealed that the latency of the forward erasure recovery scheme is fractionally higher than that of the scheme without erasure control coding or retransmission mechanisms (using UDP), but much lower than that of the adaptive erasure scheme when the packet loss rate is high. Results on comparisons between the two erasure control schemes exhibit their advantages as well as disadvantages in the role of delivering end-to-end services. To show the impact of the bounds derived on the end-to-end performance of a TCP/IP network, a case study is provided to demonstrate how erasure control coding could be used to maximize the performance of practical systems. © 2010 IEEE.

Control of the innate immune response by the mevalonate pathway.

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.

Neural Mechanisms of Young Adult Sexual Decision-Making and Risk Behavior

Sexual risk behavior among young adults is a serious public health concern; 50% will contract a sexually transmitted infection (STI) before the age of 25. The current study collected self-report personality and sexual history data, as well as neuroimaging, experimental behavioral (e.g., real-time hypothetical sexual decision making data), and self-report sexual arousal data from 120 heterosexual young adults ages 18-26. In addition, longitudinal changes in self-reported sexual behavior were collected from a subset (n = 70) of the participants. The primary aims of the study were (1) to predict differences in self-report sexual behavior and hypothetical sexual decision-making (in response to sexually explicit audio-visual cues) as a function of ventral striatum (VS) and amygdala activity, (2) test whether the association between sexual behavior/decision-making and brain function is moderated by gender, self-reported sexual arousal, and/or trait-level personality factors (i.e., self-control, impulsivity, and sensation seeking) and (3) to examine how the main effects of neural function and interaction effects predict sexual risk behavior over time. Our hypotheses were mostly supported across the sexual behavior and decision-making outcome variables, such that neural risk phenotypes (heightened reward-related ventral striatum activity coupled with decreased threat-related amygdala activity) were associated with greater lifetime sexual partners at baseline measured and over time (longitudinal analyses). Impulsivity moderated the relationship between neural function and self-reported number of sexual partners at baseline and follow up measures, as well as experimental condom use decision-making. Sexual arousal and sensation seeking moderated the relationship between neural function and baseline and follow up self-reports of number of sexual partners. Finally, unique gender differences were observed in the relationship between threat and reward-related neural reactivity and self-reported sexual risk behavior. The results of this study provide initial evidence for the potential role for neurobiological approaches to understanding sexual decision-making and risk behavior. With continued research, establishing biomarkers for sexual risk behavior could help inform the development of novel and more effective individually tailored sexual health prevention and intervention efforts.

Premotor Mechanisms for Orofacial Coordination

The mouth, throat, and face contain numerous muscles that participate in a large variety of orofacial behaviors. The jaw and tongue can move independently, and thus require a high degree of coordination among the muscles that move them to prevent self-injury. However, different orofacial behaviors require distinct patterns of coordination between these muscles. The method through which motor control circuitry might coordinate this activity has yet to be determined. Electrophysiological, immunohistochemical, and retrograde tracing studies have attempted to identify populations of premotor neurons which directly send information to orofacial motoneurons in an effort to identify sources of coordination. Yet these studies have not provided a complete picture of the population of neurons which monosynaptically connect to jaw and tongue motoneurons. Additionally, while many of these studies have suggested that premotor neurons projecting to multiple motor pools may play a role in coordination of orofacial muscles, no clear functional roles for these neurons in the coordination of natural orofacial movements has been identified.

In this dissertation, I took advantage of the recently developed monosynaptic rabies virus to trace the premotor circuits for the jaw-closing masseter muscle and tongue-protruding genioglossus muscle in the neonatal mouse, uncovering novel premotor inputs in the brainstem. Furthermore, these studies identified a set of neurons which form boutons onto motor neurons in multiple motor pools, providing a premotor substrate for orofacial coordination. I then combined a retrogradely traveling lentivirus with a split-intein mediated split-Cre recombinase system to isolate and manipulate a population of neurons which project to both left and right jaw-closing motor nuclei. I found that these bilaterally projecting neurons also innervate multiple other orofacial motor nuclei, premotor regions, and midbrain regions implicated in motor control. I anatomically and physiologically characterized these neurons and used optogenetic and chemicogenetic approaches to assess their role in natural jaw-closing behavior, specifically with reference to bilateral masseter muscle electromyogram (EMG) activity. These studies identified a population of bilaterally projecting neurons in the supratrigeminal nucleus as essential for maintenance of an appropriate level of masseter activation during natural chewing behavior in the freely moving mouse. Moreover, these studies uncovered two distinct roles of supratrigeminal bilaterally projecting neurons in bilaterally synchronized activation of masseter muscles, and active balancing of bilateral masseter muscle tone against an excitatory input. Together, these studies identify neurons which project to multiple motor nuclei as a mechanism by which the brain coordinates orofacial muscles during natural behavior.

Experimental and Theoretical Models to Probe Mechanisms of Biological Charge Flow

Nature is challenged to move charge efficiently over many length scales. From sub-nm to μm distances, electron-transfer proteins orchestrate energy conversion, storage, and release both inside and outside the cell. Uncovering the detailed mechanisms of biological electron-transfer reactions, which are often coupled to bond-breaking and bond-making events, is essential to designing durable, artificial energy conversion systems that mimic the specificity and efficiency of their natural counterparts. Here, we use theoretical modeling of long-distance charge hopping (Chapter 3), synthetic donor-bridge-acceptor molecules (Chapters 4, 5, and 6), and de novo protein design (Chapters 5 and 6) to investigate general principles that govern light-driven and electrochemically driven electron-transfer reactions in biology. We show that fast, μm-distance charge hopping along bacterial nanowires requires closely packed charge carriers with low reorganization energies (Chapter 3); singlet excited-state electronic polarization of supermolecular electron donors can attenuate intersystem crossing yields to lower-energy, oppositely polarized, donor triplet states (Chapter 4); the effective static dielectric constant of a small (~100 residue) de novo designed 4-helical protein bundle can change upon phototriggering an electron transfer event in the protein interior, providing a means to slow the charge-recombination reaction (Chapter 5); and a tightly-packed de novo designed 4-helix protein bundle can drastically alter charge-transfer driving forces of photo-induced amino acid radical formation in the bundle interior, effectively turning off a light-driven oxidation reaction that occurs in organic solvent (Chapter 6). This work leverages unique insights gleaned from proteins designed from scratch that bind synthetic donor-bridge-acceptor molecules that can also be studied in organic solvents, opening new avenues of exploration into the factors critical for protein control of charge flow in biology.

Diffusible Signal Factor (DSF)-dependent quorum sensing in pathogenic bacteria and its exploitation for disease control

Cell-to-cell signals of the Diffusible Signal Factor (DSF) family are cis-2-unsaturated fatty acids of differing chain length and branching pattern. DSF signalling has been described in diverse bacteria to include plant and human pathogens where it acts to regulate functions such as biofilm formation, antibiotic tolerance and the production of virulence factors. DSF family signals can also participate in interspecies signalling with other bacteria and interkingdom signaling such as with the yeast Candida albicans. Interference with DSF signalling may afford new opportunities for the control of bacterial disease. Such strategies will depend in part on detailed knowledge of the molecular mechanisms underlying the processes of signal synthesis, perception and turnover. Here, I review both recent progress in understanding DSF signalling at the molecular level and prospects for translating this knowledge into approaches for disease control.

ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.