Production of the glucocorticoid hormone cortisol in response to a stressor is initiated by activation of the hypothalamic-pituitary-interrenal (HPI) axis in fish. Serotonin (5-HT) and negative feedback regulate cortisol production at the whole-animal level; the objective of the present thesis was to investigate their roles in regulating cortisol production by interrenal cells of rainbow trout (Oncorhynchus mykiss). Messenger ribonucleic acid (mRNA) for the 5-HT4 receptor was present in low abundance in interrenal cells. In addition, cortisol production was significantly increased for in vitro head kidney preparations incubated with 5-HT, and this elevated cortisol production was blocked by the 5-HT4 receptor antagonist 5-fluoro-2-methoxy-[1-[2-[(methylsulphonyl) amino] ethyl]-4-piperidinyl]-1h-indole-3-methylcarboxylate sulphamate (GR125487). Thus, 5-HT acts at the head kidney level to regulate cortisol production, probably via the 5-HT4 receptor. Chronic social stress did not appear to regulate the expression of key proteins involved in cortisol biosynthesis or corticosteroid receptors (CR). However, head kidney tissue incubated in vitro with cortisol for 2-8 h showed a reduction in adrenocorticotropic hormone-stimulated cortisol production compared to controls, suggesting the existence of an ultra-short-loop negative feedback mechanism. Thus, the high circulating levels of cortisol in trout experiencing chronic social stress may activate this ultra-short-loop negative feedback mechanism to suppress cortisol production at the head kidney level.

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<p>Many cells spontaneously establish a polarity axis even in the absence of directional cues, a process called symmetry breaking. A central question concerns how cells polarize towards one, and only one, randomly oriented "front". The conserved Rhotype GTPase Cdc42p is an essential factor for both directed and spontaneous polarization in various organisms, whose local activation is thought to define the cell's front. We previously proposed that in yeast cells, a small stochastic cluster of GTP-Cdc42p at a random site on the cortex can grow into a large, dominating cluster via a positive feedback loop involving the scaffold protein Bem1p. As stochastic Cdc42p clusters could presumably arise at many sites, why does only one site become the dominating "front"? We speculated that competition between growing clusters for limiting factors would lead to growth of a single winning "front" at the expense of the others. Utilizing time-lapse imaging with high spatiotemporal resolution, we now document initiation of multiple polarized clusters that competed rapidly to resolve a winning cluster. Such multicluster intermediates are observed in wild-type yeast cells with functional directional cues, but the locations where they are initiated are biased by the spatial cues. In addition, we detected an unexpected oscillatory polarization in a majority of the cells breaking symmetry, in which polarity factors initially concentrated very brightly and then dimmed in an oscillatory manner, dampening down to a final intermediate level after 2-3 peaks. Dampened oscillation suggests that the polarity circuit contains an in-built negative feedback loop. Mathematical modeling predicts that negative feedback would confer robustness to the polarity circuit and make the kinetics of competition between polarity factor clusters relatively insensitive to polarity factor concentration.</p><p>We are trying to understand how competition between clusters occurs. We find that the yeast guanine-nucleotide dissociation inhibitor (GDI), Rdi1p, is needed for rapid competition between clusters. In the absence of Rdi1p the initial clustering of polarity</p><p>factors is slowed, and competition is also much slower: in some cases cells still have two clusters at the time of bud emergence and they form two buds. We suggest that in the absence of Rdi1p, the clusters compete for a limiting pool of Cdc42p, and that slow</p><p>exchange of Cdc42p on and off the membrane in the absence of Rdi1p leads to slow competition.</p> / Dissertation

Bakgrunden till vår uppsats är att återkoppling behövs som verktyg på en arbetsplats för att få medarbetare att trivas. Detta har i grund och botten anknytning till vårt behov av att känna oss accepterade och av att känna samhörighet. Forskning har visat att bekräftelse från omvärlden är en viktig del för individens självbild. Särskilt i en projektorganisation är återkoppling betydelsefullt, eftersom projektgrupper ofta består av nya konstellationer av människor som snabbt måste lära sig att samarbeta. Om ett bra arbete med återkoppling sker kan detta få positiva effekter på arbetsprestationer. Problematiken kring att ge återkoppling handlar om att ge den på ett konstruktivt sätt som får mottagaren att ta åt sig. Genom att granska tidigare forskning undersökte vi varför det finns ett behov av återkoppling i pro-jektgrupper, vad forskningen säger att givaren bör tänka på när det handlar om återkoppling samt vad konsekvenserna och resultatet kan bli av återkoppling. Vårt syfte är att utifrån den forskning som idag finns undersöka hur arbetet med åter-koppling ser ut i praktiken för fem stycken projektledare. Vi ställde oss bland an-nat frågeställningarna: Ger projektledare återkoppling? På vilka sätt? Hur ser de på arbete med återkoppling? Vet de hur teorin ser ut kring ämnet? Arbetar de med att bli bättre på att ge återkoppling? För att undersöka frågeställningarna använde vi oss av en kvalitativ metod i form av semistrukturerade intervjuer. Projektle-darna arbetar alla inom samma bransch, fastighetsförvaltningsbranschen. Våra intervjudata bearbetades genom transkribering samt kodning efter förutbestämda teman. I vår analys jämförs den teoretiska bakgrunden med den empiriska datan vi insamlat. En matris med en sammanställning av det insamlade materialet återfinns i bilaga 2. Vår slutsats är bland annat att projektledare mest arbetar med positiv återkoppling och att negativ återkoppling kan vara problematiskt att ge. Vi fann även att projektledarna inte hade någon teoretisk kunskap om ämnet återkoppling utan de färdigheter de besatt hade de lärt sig genom erfarenhet. / The background of our paper is that feedback is needed as a tool on during work to make the individuals feel comfortable. This is basically related to our need of feeling accepted and to feel affinity. Research has demonstrated that the confirmation from the outside world is an important part of the individual's selfimage. In a project based environment, feedback is important, as project groups often consist of new constellations of people who quickly must learn to work together. If feed-back could be used successfully, this can have positive effects on work perfor-mance. The problem of providing feedback is how to give it in a constructive way so the receiver to take in the information and accept it. By examining past research, we examined why there is a need for feedback in project teams, what the research says that the giver should consider when it comes to feedback, and what consequences and results of feedback could be. Our purpose is, based on existing research, to examine how feedback is used in practice for five project managers. We asked ourselves following questions: Do project managers provide feedback? In what ways? How do they work with feedback? Do they know how the theory looks about the topic? How do they work to become better at giving feedback? To examine the issues, we used a qualitative approach in the form of semi-structured interviews. The interview subjects were all working in the same indus-try, the real estate industry. Our interview data were processed by transcribing and coding by predetermined themes. In our analysis we compared the theoretical background of the empirical data we collected. A matrix with a compilation of the collected data is presented in appendix 2. Our conclusion is that project managers mostly work with positive feedback and that giving negative feedback is perceived problematic. We also discovered that the project managers lacked a theo-retical knowledge about the subject and that the skills they possessed, had they learned through experience.

This research demonstrates that experience with uncontrollable reinforcement, here defined as continuous non-contingent positive feedback to solution attempts of insoluble problems, fails to produce the proactive interference phenomenon, learned helplessness, while uncontrollable aversive events, here defined as negative feedback to solution attempts of insoluble problems, produces that phenomenon. These results partially support the "learned helplessness" hypothesis of Seligman (1975) which predicts that experience with uncontrollable reinforcement, the offset of negative events or the onset of positive ones, results in learning that responding is independent of reinforcement and that learning transfers to subsequent situations. This research further demonstrates that experience with controllability, here defined as solubility, results in enhanced competence.

In this paper I examine the validity of technical analysis for the Swedish stock index OMXS30 between 2001-12-28 and 2011-12-30.  Results indicate that OMXS30 followed a non-random walk and that technical trading rules had predictive power over future price movements. Results also suggest that technical trading rules could be used to outperform a buy-and-hold strategy.

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The issue of eddy currents induced by the rapid switching of magnetic field gradients is a long-standing problem in magnetic resonance imaging. A new method for dealing with this problem is presented whereby spatial harmonic components of the magnetic field are continuously sensed, through their temporal rates of change, and corrected. In this way, the effects of the eddy currents on multiple spatial harmonic components of the magnetic field can be detected and corrections applied during the rise time of the gradients. Sensing the temporal changes in each spatial harmonic is made possible with specially designed detection coils. However to make the design of these coils possible, general relationships between the spatial harmonics of the field, scalar potential, and vector potential are found within the quasi-static approximation. These relationships allow the vector potential to be found from the field – an inverse curl operation – and may be of use beyond the specific problem of detection coil design. Using the detection coils as sensors, methods are developed for designing a negative feedback system to control the eddy current effects and optimizing that system with respect to image noise and distortion. The design methods are successfully tested in a series of proof-of-principle experiments which lead to a discussion of how to incorporate similar designs into an operational MRI.

The issue of eddy currents induced by the rapid switching of magnetic field gradients is a long-standing problem in magnetic resonance imaging. A new method for dealing with this problem is presented whereby spatial harmonic components of the magnetic field are continuously sensed, through their temporal rates of change, and corrected. In this way, the effects of the eddy currents on multiple spatial harmonic components of the magnetic field can be detected and corrections applied during the rise time of the gradients. Sensing the temporal changes in each spatial harmonic is made possible with specially designed detection coils. However to make the design of these coils possible, general relationships between the spatial harmonics of the field, scalar potential, and vector potential are found within the quasi-static approximation. These relationships allow the vector potential to be found from the field – an inverse curl operation – and may be of use beyond the specific problem of detection coil design. Using the detection coils as sensors, methods are developed for designing a negative feedback system to control the eddy current effects and optimizing that system with respect to image noise and distortion. The design methods are successfully tested in a series of proof-of-principle experiments which lead to a discussion of how to incorporate similar designs into an operational MRI.

<p>One of the key mechanisms that mediate renal autoregulation is the tubuloglomerular feedback (TGF) system, which is a negative feedback loop in the kidney that balances glomerular filtration with tubular reabsorptive capacity. In this dissertation, we develop several mathematical models of the TGF system to study TGF-mediated model dynamics. </p><p>First, we develop a mathematical model of compliant thick ascending limb (TAL) of a short loop of Henle in the rat kidney, called TAL model, to investigate the effects of spatial inhomogeneous properties in TAL on TGF-mediated dynamics. We derive a characteristic equation that corresponds to a linearized TAL model, and conduct a bifurcation analysis by finding roots of that equation. Results of the bifurcation analysis are also validated via numerical simulations of the full model equations. </p><p>We then extend the TAL model to explicitly represent an entire short-looped nephron including the descending segments and having compliant tubular walls, developing a short-looped nephron model. A bifurcation analysis for the TGF loop-model equations is similarly performed by computing parameter boundaries, as functions of TGF gain and delay, that separate differing model behaviors. We also use the loop model to better understand the effects of transient as well as sustained flow perturbations on the TGF system and on distal NaCl delivery.</p><p>To understand the impacts of internephron coupling on TGF dynamics, we further develop a mathematical model of a coupled-TGF system that includes any finite number of nephrons coupled through their TGF systems, coupled-nephron model. Each model nephron represents a short loop of Henle having compliant tubular walls, based on the short-looped nephron model, and is assumed to interact with nearby nephrons through electrotonic signaling along the pre-glomerular vasculature. The characteristic equation is obtained via linearization of the loop-model equations as in TAL model. To better understand the impacts of parameter variability on TGF-mediated dynamics, we consider special cases where the relation between TGF delays and gains among two coupled nephrons is specifically chosen. By solving the characteristic equation, we determine parameter regions that correspond to qualitatively differing model behaviors. </p><p>TGF delays play an essential role in determining qualitatively and quantitatively different TGF-mediated dynamic behaviors. In particular, when noise arising from external sources of system is introduced, the dynamics may become significantly rich and complex, revealing a variety of model behaviors owing to the interaction with delays. In our next study, we consider the effect of the interactions between time delays and noise, by developing a stochastic model. We begin with a simple time-delayed transport equation to represent the dynamics of chloride concentration in the rigid-TAL fluid. Guided by a proof for the existence and uniqueness of the steady-state solution to the deterministic Dirichlet problem, obtained via bifurcation analysis and the contraction mapping theorem, an analogous proof for stochastic system with random boundary conditions is presented. Finally we conduct multiscale analysis to study the effect of the noise, specifically when the system is in subcritical region, but close enough to the critical delay. To analyze the solution behaviors in long time scales, reduced equations for the amplitude of solutions are derived using multiscale method.</p> / Dissertation