The challenge of operating and managing complex and dynamic environments, known as complex endeavors, has become a central issue in the C2 research community. NATO research groups have studied how to combat the negative effects of endeavor complexity on performance. Essential to these efforts is the study of C2 Agility, which is the ability of an entity to cope with change and employ different C2 approaches based on the requirements imposed by—and changes in—the current operational environment. An important aspect in accomplishing this research goal is to study how operational environments are constituted, as this would enable research into how the effectiveness of different C2 approaches is affected by different endeavors. The Endeavor Space model, which represents endeavor complexity in three dimensions, was developed for this purpose. In an effort to continue research on the Endeavor Space, the current study set out to implement the dimensions in a C2 research platform called ELICIT. Three ELICIT scenarios were created to represent different regions of the Endeavor Space. Additionally, the study designed, developed, and tested a prototype self-assessment instrument—the ESSAI—to capture how the Endeavor Space dimensions—Tractability, Dynamics, and Dependencies—were experienced by operators. Eight teams completed the scenarios and rated their complexity using the ESSAI. No significant differences in perceived complexity could be found between the scenarios. However, all Endeavor Space dimensions indicated correlational relationships with perceived difficulty, and most of them correlated with ELICIT performance. This is indicative of underlying patterns that were not thoroughly revealed in the current study. Implications and improvements for future research are discussed.

Expression of the cellular prion protein (PrPC) from the PRNP gene is crucial for the development of a group of fatal neurodegenerative disorders called prion diseases. During prion infection a misfolded protein homologue of PrPC, PrPSc causes further misfolding on interaction with native PrPC molecules. PrPSc is highly resistant to proteinase K and aggregation of this protein is considered a hallmark of infection. Sheep are considered a model of natural infection and susceptibility to scrapie in sheep is defined by polymorphisms in the PRNP gene. It is still not fully understood how these polymorphisms regulate the conversion process or which other co-factors are involved. One such factor may be the truncation of PrPC via proteolytic processing in the form of two main cleavage events, known as α- and β-cleavage. In sheep α-cleavage cuts at amino acid 115, creating two truncated proteins C1 and N1 and represents the main cleavage event in healthy brain. β-Cleavage creates a longer C-terminal fragment, C2 and corresponding N-terminal fragment N2, cutting around amino acid 92 in sheep. Truncated forms of PrPC have been shown to represent around 50 % of total residual PrP in brain and may be an important determinant of disease through both decreasing the amount of full length PrPC available for conversion and through functions associated with the truncated fragments. The research presented has shown that increased production of an α-cleavage fragment C1 in brain is associated with TSE resistant genotype ARR/ARR, while the presence of C2 fragment is affiliated with scrapie susceptible PRNP genotypes in brain. There was no difference in the levels of full length PrPC in these genotypes suggesting that PrP expression does not directly correlate to susceptibility in this model. To assess if PrPC fragments could affect the conversion during disease in-vitro fibrillisation assays were performed using novel truncated recombinant proteins. These truncated proteins, although not thought to convert to PK resistant PrPSc during disease, can form amyloid fibrils. However, these fibrils appear to be less neurotoxic when compared to fibrils produced by full length PrPC. Only the truncated fragments derived from the ARR allele inhibit in-vitro fibrillisation of other allelic PrPC variants. Furthermore, treatment of infected cells in culture with recombinant C1ARR led to a decrease in the formation of disease associated PrPSc. In conclusion, genetic variations in levels of PrP truncated fragments may add to the complexity of genetic determinants of prion disease. In parallel with polymorphism-dependant conversion abilities, varying α-cleavage of ovine PrPC may help to explain genetic resistance in sheep. The inhibitory effects of C1, illustrated in-vitro may represent a therapeutic avenue in the treatment of prion disease.

In this thesis, experiments into artificially guiding neuronal growth cones using tightly focused laser beams were performed and evaluated. The experiments are performed by focusing a laser beam to the leading edge of a developing growth cone and attempting to change the direction of growth cone. These experiments were carried out using Gaussian, line and asymmetric line beam profiles. There was no noticeable change in the success rate with different beam profiles. Following this, I assisted my colleague Dr Michael Mazilu in the construction of a mathematical model of filopedia in an optical field in order to help explain the mechanism for optically guided neuronal growth which suggests that optical trapping forces on filopedia are responsible. Next, I set about implementing a system to automate the process of laser guided neuron growth by employing a spatial light modulator and a custom-built computer program. This allowed the computer to track a developing growth cone and automatically adjust the position of the laser beam as the growth cone developed. This program was successfully employed to artificially grow neuronal growth cones towards a user-inputted target point. The use of the spatial light modulator to beam shape was also demonstrated with the use of a Bessel beam being used to guide neurons for the first time. I also used a transgenic cell line of neurons to show for the first time that HSP70 is not involved in this phenomenon. This was accomplished by transfecting NG108’s with a plasmid containing HSP70 promoter tagged GFP. Under enough thermal or mechanical stress, the cells would express HSP70 which would produce a detectable GFP signal. No GFP was detected in cells after being exposed to laser irradiation of a power higher than would normally be used to guide neurons. Combined, these experiments show that the beam profile of the operating laser does not significantly affect the success of artificial growth and that the optical force on filopedia near the laser beam is likely to be the mechanism for this phenomenon. A possible heating effect of the laser has also been shown to not be strong enough to elicit a heat shock stress response from the cell. The demonstration of an automatic system which incorporates beam shaping has also been shown and such a system shows the potential to advance the investigation of artificial neuron growth using lasers.

<p>Command and Control (C2) refers to the process or function of commanding and controlling military or civilian units. For most military context C2 is exercised in an adversarial environment where two or more forces are fighting against each other. In these situations it is desirable to constrain the adversarial forces in order to prevent them from achieving their objectives. By maintaining an accurate view of the possible dependencies and couplings within the own forces and between the own and adversarial forces, constraints can be managed and coordinated.</p><p>The purpose of this thesis is to develop a model that is capable of capturing these dependencies and couplings. This model is developed using the Functional Resonance Analysis Method (FRAM; Hollnagel, 2004). FRAM builds on the assumption that all parts of the system can be described as functional units. These functional units can then be linked together to form large systems. The links themselves are defined by how a function may affect other functions or in turn be affected by them. This enables the model to incorporate complex interactions within the system as well as between two adversarial systems.</p><p>The microworld “Dynamiskt Krigsspel för Experiment” (DKE) was used to develop the model. A scenario with two teams battling in this adversarial microworld setting was analyzed in detail for this purpose. The developed model uses three different layers, or resolutions, of functions to capture all potential couplings between functions. The lowest level of functions, called the tactical level, is the physical actions of the units in the microworld. The next level, the operational level, concerns the more overarching goals for which the tactical functions are used. Last, the strategic level consists of the C2 functions, such as data collection, sensemaking and planning.</p><p>The developed model is then applied to the scenario in DKE and shown to be able to describe and explain all actions by the two adversary systems as well as the couplings and dependencies between them.</p>

<p><strong>OBJECTIVE:</strong> This thesis had two purposes. The main one was to examine how mixed conditions affect a Command & Control (C²) system, particularly in terms of shared understanding, situation awareness (SA), performance and workload. Mixed conditions refer here to when subsystems of a larger C²-system differ in terms of capabilities, particularly those capabilities influencing the understanding of a situation e.g. sensors or communication, which could affect the C²-capabilities when working toward a common goal. The second purpose of this thesis was to investigate a newly developed tool for measuring shared understanding, Shared Priorities, in terms of validity and usefulness.</p><p><strong>METHOD:</strong> A number of hypotheses were constructed and investigated by a controlled experiment using a microworld, C3Fire, where two-man teams fought a simulated forest fire. The independent variable manipulated was the type of support system used. One condition used one computer interface per participant, the second was mixed conditions where one participant used the computer interface and one used a paper map, and the last condition was both participants using a paper map. Different questionnaires developed to measure SA, workload etc. was used to measure the dependent variables.</p><p><strong>RESULTS:</strong> The statistical analysis performed on the collected data showed that the performance and SA was comparatively better when both participants used the computer interface than the mixed condition, which in turn was better than when both participants used a paper map. For workload and teamwork, no differences between the mixed condition and the dual map condition were found. As for the Shared Priorities measurement, no differences were found between any of the conditions.</p><p><strong>CONCLUSION: </strong>A C²-system in which some additional capabilities are introduced for some but not all subsystems may not benefit in some regards, e.g. workload and teamwork, but could improve in others, e.g. SA and performance. A Structural Equation Model (SEM) shows that the theoretical constructs of SA, workload, teamwork and performance are related and affect each other, so that the workload of the system negatively affects the teamwork and SA, while the teamwork may affect SA positively and a high SA enables high performance. </p>

OBJECTIVE: This thesis had two purposes. The main one was to examine how mixed conditions affect a Command &amp; Control (C2) system, particularly in terms of shared understanding, situation awareness (SA), performance and workload. Mixed conditions refer here to when subsystems of a larger C2-system differ in terms of capabilities, particularly those capabilities influencing the understanding of a situation e.g. sensors or communication, which could affect the C2-capabilities when working toward a common goal. The second purpose of this thesis was to investigate a newly developed tool for measuring shared understanding, Shared Priorities, in terms of validity and usefulness. METHOD: A number of hypotheses were constructed and investigated by a controlled experiment using a microworld, C3Fire, where two-man teams fought a simulated forest fire. The independent variable manipulated was the type of support system used. One condition used one computer interface per participant, the second was mixed conditions where one participant used the computer interface and one used a paper map, and the last condition was both participants using a paper map. Different questionnaires developed to measure SA, workload etc. was used to measure the dependent variables. RESULTS: The statistical analysis performed on the collected data showed that the performance and SA was comparatively better when both participants used the computer interface than the mixed condition, which in turn was better than when both participants used a paper map. For workload and teamwork, no differences between the mixed condition and the dual map condition were found. As for the Shared Priorities measurement, no differences were found between any of the conditions. CONCLUSION: A C2-system in which some additional capabilities are introduced for some but not all subsystems may not benefit in some regards, e.g. workload and teamwork, but could improve in others, e.g. SA and performance. A Structural Equation Model (SEM) shows that the theoretical constructs of SA, workload, teamwork and performance are related and affect each other, so that the workload of the system negatively affects the teamwork and SA, while the teamwork may affect SA positively and a high SA enables high performance.

FER-1 is required for fusion of specialized vesicles, called membranous organelles, with the sperm plasma membrane during Caenorhabditis elegans spermiogeneis. To investigate the role of FER-1 in membranous organelle fusion, I first examined ten fer-1 mutations and found that they all cause the same defect in membrane fusion. FER-1 and the ferlin protein family are membrane proteins with four to seven C2 domains which commonly mediate Ca2+-dependent lipid-processing events. Most of the fer-1 mutations fall within these C2 domains, showing that they have distinct, non-redundant functions. I found that membranous organelle fusion requires intracellular Ca2+ and that C2 domain mutations alter Ca2+ sensitivity. This suggests that the C2 domains are involved in Ca2+ sensing and further supports their independent function. Using two immunological approaches we found three FER-1 isoforms, two of which may arise from FER-1 by proteolysis. By both light and electron microscopy these FER-1 proteins are localized to membranous organelle membranes. Together, these results suggest that the ferlin family members may share a conserved mechanism to regulate cell-type specific membrane fusion.In Chapter III, I present additional results toward studying the function of FER-1 using several broad-based approaches. First, I present a bioinformatics analysis of FER-1 C2 domains and the preliminary results of their calcium-dependent phospholipid binding capabilities. Second, preliminary interactions found with individual FER-1 functional domains by a yeast-two hybrid screen are discussed. Lastly, I present results from a candidate-gene approach to identify additional regulators of MO fusion, the sperm-specific synaptobrevins.

Uppsatsen syftar till att analysera hur försvarsmakten omhändertar krigsvetenskapens variabler för ledning –teknik, människa och metod– i dess tre nivåer; den militärstrategiska, den operativa samt den taktiska.Metoden som används utgörs av en kvalitativ metod som analyserar försvarsmaktens inriktande och styrande dokumentation.Resultatet visar att försvarsmakten till stor del omhändertar krigsvetenskapens teorier om ledningssystem.Det finns idag en otydlighet hur begreppet ledning omhändertas av försvarsmakten. Från att historiskt varit en egenskap hos en befälhavare har ledning i nutid utvecklats till något som har karaktäriserats till att utgöra ett system där människor möter metoder och teknik med syfte att skapa en planerad samordning av en given verksamhet med givna komponenter i en mer eller mindre känd kontext. Ledning inom försvarsmakten definieras olika beroende på vilket reglemente, doktrin eller anvisning som behandlar området.Forskningsmässigt är ämnesområdet är relativt nytt, även om företeelsen ledning troligvis har funnits så länge som människan har ägnat sig åt strid och krigskonst. Genom systematisering, vetenskapligt intresse och inte minst en teknisk utveckling, har behovet av att studera krigets ledning ökat för att kunna behålla och utveckla krigföringsförmåga.

This article investigates the determinants of entry and exit in the Austrian manufacturing sector based on 1981 to 1994 data. We study the response of entry, exit and other indicators of firm dynamics to changes in average plant size, size heterogeneity, concentration, incentives and vertical integration. By applying Bayesian simulation methods we estimate random coefficient models and study the symmetry of the determinants of entry and exit. Our empirical analysis shows that entry and exit rates are driven by the same determinants. The impacts of these determinants are nearly homogeneous for both, entry rates and exits rates, respectively. Moreover, we find (i) that changes in average plant size, size heterogeneity and concentration are not symmetric with respect to entry and exit, (ii) that changes in the growth of sales is weakly symmetric and (iii) that the growth rate of employment is strongly asymmetric across industries in Austrian manufacturing. Furthermore, we infer from the data that the turnover of firms influences the changes in the number of competitors. Low entry rates go hand in hand with low net entry rates and a low turnover. (author's abstract) / Series: Working Papers Series "Growth and Employment in Europe: Sustainability and Competitiveness"

This was an investigation into the relationship between quality of care and staff views of, and responses to, challenging behaviour in adults with learning disabilities. Cognitive representations have been identified as a determinant of therapeutic outcomes in a variety of health care settings. There were two main aims of this study. First, to describe and measure the cognitive representations of challenging behaviour among staff working with adults with learning disabilities and second, to evaluate the effects of training on these views held by staff. Existing literature was reviewed. A Likert type questionnaire, the Challenging Behaviour Representation Questionnaire (CBRQ) was developed to record staff views. The CBRQ draws on two existing measures: the Illness Perception Questionnaire (IPQ) and the Challenging Behaviour Attributions Scale (CHABA). The CBRQ will give a new method of evaluating the staff views most often associated with evidence-based practice, helping behaviours and positive outcomes. Questionnaire items were generated from responses by 300 staff, to assess the applicability of Leventhal's Self Regulatory model in the context of challenging behaviour. The rating scales in the questionnaire were theoretically derived, based on the dimensions of Leventhal's model (identity, cause, consequences, treatment/control, time-line). An 'emotional-reaction' dimension was added, suggested by more recent research. The use of the Leventhal model was supported, with the exception of the 'time line' component. The questionnaire was tested for reliability and validity then administered before and after training to staff in three different groups. Targeted training changed cognitive representation of challenging behaviour overall, as measured by the CBRQ, and this change was statistically significantly in two of the five dimensions for the experimental group. Other results suggest that dimensions of cognitive representation are affected in different and complex ways by training. The statistical and the practical significance of the results are discussed in relation to staff training and therapeutic outcomes for people with learning disabilities. A 'staff-regulatory' model of cognitive representation is proposed linking cognitive representation and challenging behaviour.