No description available.

<p>On the 13th of June 2005 the Minister of Defence, Leni Björklund, was subjected to a formal complaint addressed to the Committee on the Constitution concerning her handling of a specific co-operation project with France. The project concerned the development of a technology demonstrator for an UCAV called Neuron. The reason for the complaint was that the Minister of Defence had failed to present the project to the parliament and thus bypassed a parliamentary decision. Such negligence might be considered unlawful under the Swedish Constitution. The issue became public during an unscheduled meeting with the Committee on Defence, a meeting that was arranged at the request of the Minister of Defence. During that meeting the Minister announced that the Government in a couple of days planned to take the decision to “go ahead” with the Neuron project without a formal decision by the Parliament. The then estimated cost for the project was about 700 million SEK. The “verdict” from the Committee on the Constitution was “not guilty” according to the Constitution. The Committee on the Constitution limits its investigations to the relation between the Parliament and the Government, which is its main task. The purpose of my essay is to investigate the relation between  the Government and the Swedish Armed Forces. This investigation is conducted in order to find out what kind of role the Armed Forces as a Government Agency has played in the formulation of defence policy regarding the Neuron project. The foundation of a representative democratic system is based on the premise that the formulation of political objectives is the exclusive right of politicians. Only the elected politicians are supposed to have this power, since they are performing their duties on a mandate from the electorate, the people. The formulation of political objectives is, according to this foundation, not something that civil servants, in or out of uniform, should be doing. If and when that however happens we are facing what is normally called “a democratic black hole”.  </p><p>In order to fulfil the purpose of my essay I investigate the communication between the Government and the Armed Forces. The empirical study is performed on two kinds of documents from the Armed Forces. These documents are regularly used as basis for the Government’s decisions and propositions to the Parliament. The first kind is the Armed Force’s yearly reports concerning Long Term Planning, the second kind is documents that the Government needs for the yearly Budgetary Proposition. Both documents are wholly or partly prepared according to instructions from the Government.</p> / <p>Den 13 juni 2005 blir försvarsminister Leni Björklund KU - anmäld för sin sätt att hantera ett svenskt deltagande i projektet Neuron. Neuron-projektet handlar om försvarsmaterielsamarbete med Frankrike om att utveckla en demonstrator av en UCAV, obemannad beväpnad flygfarkost, som kallas Neuron. Anmälan handlar om att försvarsministern och därmed regeringen inte har givit riksdagen möjlighet att fatta beslut om Neuron-projektet. Regeringen hade inte med Neuron-projektet i någon proposition som riksdagen har kunnat ta ställning till, innan den 13 juni 2005. Hela frågan uppdagas när försvarsministern den 7 juni 2005 sammankallar riksdagens försvarsutskott. Vid detta möte informerar försvarsministern utskottets ledamöter om att regeringen har för avsikt att två dagar senare fatta beslut om att inleda samarbetet med Frankrike om Neuron-projektet som då ska kosta ca. 700 miljoner kronor. När KU har granskat frågan färdigt, våren 2006 blir försvarsministern trots allt inte fälld för ”brott” mot Regeringsformen. KU granskade enbart relationen mellan regeringen och riksdagen. Det jag gör i uppsatsen är att granska relationen mellan regeringen och Försvarsmakten. Detta görs för att pröva de tidigare leden i det som kallas den demokratiska styrkedjan och som beskriver hur makt och ansvar bör gå till i en folkstyrd demokrati. Den demokratiska styrkedjan består av: Folket, Riksdagen, Regeringen, Förvaltningen</p><p>Med förvaltningen menas myndigheterna. Styrningen, dvs. maktutövningen, förutsätts gå från vänster till höger, medan ansvarigheten skall gå i den motsatta riktningen. Om det uppstår brott i kedjan eller om den ’börjar gå baklänges’ uppstår något av en ’demokratins svarta hål’.  I Regeringsformen stadgas att regeringen styr riket och att myndigheterna, exempelvis Försvarsmakten, lyder under regeringen. Grundtanken vad gäller relationen mellan regering och myndigheter är att politikerna styr genom att formulera mål och riktlinjer för myndigheterna, medan myndigheterna genomför de politiska målen. Kedjan går baklänges om det istället skulle vara så att myndigheterna börjar formulera målen.</p><p>Efter KU:s granskning stod det klart att det inte fanns något formellt problem mellan riksdagen och regeringen när det gäller hur makt och ansvar hanterades. KU granskade inte, som nämnts ovan, relationen mellan regeringen och Försvarsmakten vilket är det jag gör i uppsatsen. I uppsatsen undersöker jag de underlag Försvarsmakten överlämnar till regeringen. Dessa är årliga budgetunderlag och PerP-rapporter. Budgetunderlagen utarbetas helt efter regeringens anvisningar medan PerP-rapporterna har en dubbelroll. De är både Försvarsmaktens egen perspektivplanering och i delar utarbetade efter regeringens anvisningar.</p>

On the 13th of June 2005 the Minister of Defence, Leni Björklund, was subjected to a formal complaint addressed to the Committee on the Constitution concerning her handling of a specific co-operation project with France. The project concerned the development of a technology demonstrator for an UCAV called Neuron. The reason for the complaint was that the Minister of Defence had failed to present the project to the parliament and thus bypassed a parliamentary decision. Such negligence might be considered unlawful under the Swedish Constitution. The issue became public during an unscheduled meeting with the Committee on Defence, a meeting that was arranged at the request of the Minister of Defence. During that meeting the Minister announced that the Government in a couple of days planned to take the decision to “go ahead” with the Neuron project without a formal decision by the Parliament. The then estimated cost for the project was about 700 million SEK. The “verdict” from the Committee on the Constitution was “not guilty” according to the Constitution. The Committee on the Constitution limits its investigations to the relation between the Parliament and the Government, which is its main task. The purpose of my essay is to investigate the relation between  the Government and the Swedish Armed Forces. This investigation is conducted in order to find out what kind of role the Armed Forces as a Government Agency has played in the formulation of defence policy regarding the Neuron project. The foundation of a representative democratic system is based on the premise that the formulation of political objectives is the exclusive right of politicians. Only the elected politicians are supposed to have this power, since they are performing their duties on a mandate from the electorate, the people. The formulation of political objectives is, according to this foundation, not something that civil servants, in or out of uniform, should be doing. If and when that however happens we are facing what is normally called “a democratic black hole”.   In order to fulfil the purpose of my essay I investigate the communication between the Government and the Armed Forces. The empirical study is performed on two kinds of documents from the Armed Forces. These documents are regularly used as basis for the Government’s decisions and propositions to the Parliament. The first kind is the Armed Force’s yearly reports concerning Long Term Planning, the second kind is documents that the Government needs for the yearly Budgetary Proposition. Both documents are wholly or partly prepared according to instructions from the Government. / Den 13 juni 2005 blir försvarsminister Leni Björklund KU - anmäld för sin sätt att hantera ett svenskt deltagande i projektet Neuron. Neuron-projektet handlar om försvarsmaterielsamarbete med Frankrike om att utveckla en demonstrator av en UCAV, obemannad beväpnad flygfarkost, som kallas Neuron. Anmälan handlar om att försvarsministern och därmed regeringen inte har givit riksdagen möjlighet att fatta beslut om Neuron-projektet. Regeringen hade inte med Neuron-projektet i någon proposition som riksdagen har kunnat ta ställning till, innan den 13 juni 2005. Hela frågan uppdagas när försvarsministern den 7 juni 2005 sammankallar riksdagens försvarsutskott. Vid detta möte informerar försvarsministern utskottets ledamöter om att regeringen har för avsikt att två dagar senare fatta beslut om att inleda samarbetet med Frankrike om Neuron-projektet som då ska kosta ca. 700 miljoner kronor. När KU har granskat frågan färdigt, våren 2006 blir försvarsministern trots allt inte fälld för ”brott” mot Regeringsformen. KU granskade enbart relationen mellan regeringen och riksdagen. Det jag gör i uppsatsen är att granska relationen mellan regeringen och Försvarsmakten. Detta görs för att pröva de tidigare leden i det som kallas den demokratiska styrkedjan och som beskriver hur makt och ansvar bör gå till i en folkstyrd demokrati. Den demokratiska styrkedjan består av: Folket, Riksdagen, Regeringen, Förvaltningen Med förvaltningen menas myndigheterna. Styrningen, dvs. maktutövningen, förutsätts gå från vänster till höger, medan ansvarigheten skall gå i den motsatta riktningen. Om det uppstår brott i kedjan eller om den ’börjar gå baklänges’ uppstår något av en ’demokratins svarta hål’.  I Regeringsformen stadgas att regeringen styr riket och att myndigheterna, exempelvis Försvarsmakten, lyder under regeringen. Grundtanken vad gäller relationen mellan regering och myndigheter är att politikerna styr genom att formulera mål och riktlinjer för myndigheterna, medan myndigheterna genomför de politiska målen. Kedjan går baklänges om det istället skulle vara så att myndigheterna börjar formulera målen. Efter KU:s granskning stod det klart att det inte fanns något formellt problem mellan riksdagen och regeringen när det gäller hur makt och ansvar hanterades. KU granskade inte, som nämnts ovan, relationen mellan regeringen och Försvarsmakten vilket är det jag gör i uppsatsen. I uppsatsen undersöker jag de underlag Försvarsmakten överlämnar till regeringen. Dessa är årliga budgetunderlag och PerP-rapporter. Budgetunderlagen utarbetas helt efter regeringens anvisningar medan PerP-rapporterna har en dubbelroll. De är både Försvarsmaktens egen perspektivplanering och i delar utarbetade efter regeringens anvisningar.

For decades electrophysiologists have recorded and characterized the biophysical properties of a rich diversity of neuron types. This diversity of neuron types is critical for generating functionally important patterns of brain activity and implementing neural computations. In this thesis, I developed computational methods towards quantifying neuron diversity and applied these methods for understanding the functional implications of within-type neuron variability and across-type neuron diversity. First, I developed a means for defining the functional role of differences among neurons of the same type. Namely, I adapted statistical neuron models, termed generalized linear models, to precisely capture how the membranes of individual olfactory bulb mitral cells transform afferent stimuli to spiking responses. I then used computational simulations to construct virtual populations of biophysically variable mitral cells to study the functional implications of within-type neuron variability. I demonstrate that an intermediate amount of intrinsic variability enhances coding of noisy afferent stimuli by groups of biophysically variable mitral cells. These results suggest that within-type neuron variability, long considered to be a disadvantageous consequence of biological imprecision, may serve a functional role in the brain. Second, I developed a methodology for quantifying the rich electrophysiological diversity across the majority of the neuron types throughout the mammalian brain. Using semi-automated text-mining, I built a database, Neuro- Electro, of neuron type specific biophysical properties extracted from the primary research literature. This data is available at http://neuroelectro.org, which provides a publicly accessible interface where this information can be viewed. Though the extracted physiological data is highly variable across studies, I demonstrate that knowledge of article-specific experimental conditions can significantly explain the observed variance. By applying simple analyses to the dataset, I find that there exist 5-7 major neuron super-classes which segregate on the basis of known functional roles. Moreover, by integrating the NeuroElectro dataset with brain-wide gene expression data from the Allen Brain Atlas, I show that biophysically-based neuron classes correlate highly with patterns of gene expression among voltage gated ion channels and neurotransmitters. Furthermore, this work lays the conceptual and methodological foundations for substantially enhanced data sharing in neurophysiological investigations in the future.

Trichostatin A (TSA) is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. Whether TSA specifically targets the upregulation of the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice is unclear. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-Smn mediated pathway. Daily intraperitoneal injection of TSA from postnatal day 12 to 25 was performed in the Smn2B/- mice and littermate controls. Previous work from our laboratory demonstrated that treatment with TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/-mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Here, we have shown that TSA treatment does not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. Further, qPCR analysis revealed no changes in the level of Smn transcripts in the brain or spinal cord of TSA-treated SMA mice. Similarly, western blot analysis revealed no significant increase in Smn protein levels in the brain, spinal cord, hind limb muscle, heart muscle, or the liver of TSA treated Smn2B/- mice. However, TSA has beneficial effects in the muscles of Smn2B/- mice and improves motor behavior and myofiber size. TSA improves muscle development by enhancing the activity of myogenic regulatory factors independent of the Smn gene. The beneficial effect of TSA is therefore likely through an Smn-independent manner. Identification of these protective pathways will be of therapeutic value for the treatment of SMA.

No description available.

In recent years it has become apparent that neuronal development and function relies not just on the regulation of transcription but also on post-transcriptional events. Two prevalent mRNA-based regulatory mechanisms in neurons are asymmetric mRNA localisation and the generation of different 3’UTR isoforms by alternative polyadenylation (APA). While experiments in mammalian systems indicate that subcellular mRNA localisation plays an important role in regulating local expression of proteins in neuronal processes, little is known about how mRNAs reach their destinations. It has been proposed that APA allows the production of mRNA isoforms with different roles. However, the importance of 3’UTR extensions has not been addressed in detail, particularly at the organismal level. In my PhD, I investigated the mechanisms of mRNA localisation and functional consequences of APA using the Drosophila embryonic nervous system as a genetically tractable model. I screened for mRNAs that localise in embryonic axons using an available transgenic library of 3’UTR sequences, as well as publically available in situ hybridisation data. I found that Ankyrin2 (Ank2) mRNA localises in Drosophila embryonic sensory neurons, and showed that this is dependent on the kinesin-1 motor and microtubules. These data reveal an active mRNA transport system in embryonic neurons. I also showed that the Ank2 mRNA has an extended 3’UTR that is found in axons, suggesting that APA could be relevant to axonal functions of Ank2. I demonstrated that while mRNA molecules could still localise to axons upon CRISPR-Cas9-mediated deletion of the Ank2 3’UTR extension, a fraction of the mutant embryos had a disrupted nervous system. Interestingly, embryos that lack the ability to make Ank2 protein have an overtly normal embryonic nervous system. This observation reveals that the extension does not simply promote Ank2 protein function. Further experiments revealed that the extended 3’UTR is required for efficient locomotion of adult flies. While the exact function of the Ank2 3’UTR extension requires future investigation, I show that it is unlikely to be associated with the trafficking of associated proteins into axons. RNA affinity purifications from embryonic extracts provide evidence that the 3’UTR extension selectively binds conserved RNA-binding proteins. I speculate that the extension plays a role in regulating axonal morphogenesis by regulating the relative expression level of different Ank2 protein isoforms.

Trichostatin A (TSA) is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. Whether TSA specifically targets the upregulation of the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice is unclear. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-Smn mediated pathway. Daily intraperitoneal injection of TSA from postnatal day 12 to 25 was performed in the Smn2B/- mice and littermate controls. Previous work from our laboratory demonstrated that treatment with TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/-mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Here, we have shown that TSA treatment does not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. Further, qPCR analysis revealed no changes in the level of Smn transcripts in the brain or spinal cord of TSA-treated SMA mice. Similarly, western blot analysis revealed no significant increase in Smn protein levels in the brain, spinal cord, hind limb muscle, heart muscle, or the liver of TSA treated Smn2B/- mice. However, TSA has beneficial effects in the muscles of Smn2B/- mice and improves motor behavior and myofiber size. TSA improves muscle development by enhancing the activity of myogenic regulatory factors independent of the Smn gene. The beneficial effect of TSA is therefore likely through an Smn-independent manner. Identification of these protective pathways will be of therapeutic value for the treatment of SMA.

Cognition is a trait of great evolutionary importance in complex organisms, but the driving factors of its evolution are still poorly understood. It is proposed that different formula variants of the encephalization index (brain to body weight ratio) might be able to serve as predictive indicators of intelligence between species, but this remains highly controversial, predominantly because of their inability to reliably validate empirical knowledge. Another proposed predictive index for intelligence has been the total neuron count in animals’ brains. There is, though, a lack of comparative and quantitative behavioral data in support of any of the proposed models, especially across non-human mammals. Total neuron count is controlled by the process of neurogenesis during development, which is directly involved in shaping brain’s dimensions. It is known that neural stem cells increasingly shift from proliferative divisions towards differentiating (or neurogenic) divisions during development. One possible approach to alter cortical topology is by manipulating the stem cell division in order to generate more neurons. It has previously been shown that one of the main factors known to influence the type of cell division mode is the length of the cell cycle and specifically the length of G1 phase. The main constituents driving progression through G1 phase are Cdk4 and Cyclin D1 (4D for simplicity) and overexpression of these proteins in neural stem cells results in a shortening of their cell cycle, leading to expansion of the progenitor cell pool at the expense of newborn neurons. Upon silencing 4D, development is allowed to continue normally and thus, the excess of progenitor cells ultimately contributes to an increased generation of neurons. Intriguingly, transient 4D overexpression during corticogenesis in transgenic mice leads to the development of brains with increased encephalization index as a result of an increase in the total neuron count, without altering cortical lamination or preventing cortical layering. In this study, I further characterize the effects of developmentally-induced 4D neurogenesis in the developing and adult mouse brain. Moreover, with the use of different cognitive tests designed to assess differences in processes such as learning, spatial navigation, motor coordination, and context iscrimination, I attempt to identify quantifiable changes in these processes between mice with increased neuron count and controls. I hypothesize that a general intelligence ranking between groups can be obtained by analyzing collective data from several tests. Altogether, my work provides a better understanding of the contribution of increased neurogenesis both in developmental processes of the cortex as well as in animal cognition and behavior.

The objective of this thesis is to evaluate the possibility of creating a tool capable of predicting commodity prices. Along with other business strategies, tools and markets analyses for financial and capital markets, this tool should help make the best estimate of future developments on the observed markets. The main market, on which this work is focused, is the agricultural commodities market, namely corn and its related markets. The fundamental basis upon which the arguments in this thesis are built, is the use of artificial intelligence, particularly neural networks. The whole application is presented using a graphical user interface that allows even those with little or no understanding of this field to delve deeper into the interesting area - using modern computer systems to support trading activities.