Search for single top quark production in pp̅ collisions at √s=1.96 TeV in the missing transverse energy plus jets topology

We report a search for single top quark production with the CDF II detector using 2.1 fb-1 of integrated luminosity of pbar p collisions at sqrt{s}=1.96 TeV. The data selected consist of events characterized by large energy imbalance in the transverse plane and hadronic jets, and no identified electrons and muons, so the sample is enriched in W -> tau nu decays. In order to suppress backgrounds, additional kinematic and topological requirements are imposed through a neural network, and at least one of the jets must be identified as a b-quark jet. We measure an excess of signal-like events in agreement with the standard model prediction, but inconsistent with a model without single top quark production by 2.1 standard deviations (sigma), with a median expected sensitivity of 1.4 sigma. Assuming a top quark mass of 175 GeV/c2 and ascribing the excess to single top quark production, the cross section is measured to be 4.9+2.5-2.2(stat+syst)pb, consistent with measurements performed in independent datasets and with the standard model prediction.

Language and Letters of the Bluestocking Network : Sociolinguistic Issues in Eighteenth Century Epistolary English

This study deals with language change and variation in the correspondence of the eighteenth-century Bluestocking circle, a social network which provided learned men and women with an informal environment for the pursuit of scholarly entertainment. Elizabeth Montagu (1718 1800), a notable social hostess and a Shakespearean scholar, was one of their key figures. The study presents the reconstruction of Elizabeth Montagu s social networks from her youth to her later years with a special focus on the Bluestocking circle, and linguistic research on private correspondence between Montagu and her Bluestocking friends and family members between the years 1738 1778. The epistolary language use is investigated using the methods and frameworks of corpus linguistics, historical sociolinguistics, and social network analysis. The approach is diachronic and concerns real-time language change. The research is based on a selection of manuscript letters which I have edited and compiled into an electronic corpus (Bluestocking Corpus). I have also devised a network strength scale in order to quantify the strength of network ties and to compare the results of the linguistic research with the network analysis. The studies range from the reconstruction and analysis of Elizabeth Montagu s most prominent social networks to the analysis of changing morphosyntactic features and spelling variation in Montagu s and her network members correspondence. The linguistic studies look at the use of the progressive construction, preposition stranding and pied piping, and spelling variation in terms of preterite and past participle endings in the regular paradigm (-ed, - d, -d, - t, -t) and full / contracted spellings of auxiliary verbs. The results are analysed in terms of social network membership, sociolinguistic variables of the correspondents, and, when relevant, aspects of eighteenth-century linguistic prescriptivism. The studies showed a slight diachronic increase in the use of the progressive, a significant decrease of the stigmatised preposition stranding and increase of pied piping, and relatively informal but socially controlled epistolary spelling. Certain significant changes in Elizabeth Montagu s language use over the years could be attributed to her increasingly prominent social standing and the changes in her social networks, and the strength of ties correlated strongly with the use of the progressive in the Bluestocking Corpus. Gender, social rank, and register in terms of kinship/friendship had a significant influence in language use, and an effect of prescriptivism could also be detected. Elizabeth Montagu s network ties resulted in language variation in terms of network membership, her own position in a given network, and the social factors that controlled eighteenth-century interaction. When all the network ties are strong, linguistic variation seems to be essentially linked to the social variables of the informants.

Cellular and network mechanisms generating spontaneous population events in the immature rat hippocampus

Distinct endogenous network events, generated independently of sensory input, are a general feature of various structures of the immature central nervous system. In the immature hippocampus, these type of events are seen as "giant depolarizing potentials" (GDPs) in intracellular recordings in vitro. GABA, the major inhibitory neurotransmitter of the adult brain, has a depolarizing action in immature neurons, and GDPs have been proposed to be driven by GABAergic transmission. Moreover, GDPs have been thought to reflect an early pattern that disappears during development in parallel with the maturation of hyperpolarizing GABAergic inhibition. However, the adult hippocampus in vivo also generates endogenous network events known as sharp (positive) waves (SPWs), which reflect synchronous discharges of CA3 pyramidal neurons and are thought to be involved in cognitive functions. In this thesis, mechanisms of GDP generation were studied with intra- and extracellular recordings in the neonatal rat hippocampus in vitro and in vivo. Immature CA3 pyramidal neurons were found to generate intrinsic bursts of spikes and to act as cellular pacemakers for GDP activity whereas depolarizing GABAergic signalling was found to have a temporally non-patterned facilitatory role in the generation of the network events. Furthermore, the data indicate that the intrinsic bursts of neonatal CA3 pyramidal neurons and, consequently, GDPs are driven by a persistent Na+ current and terminated by a slow Ca2+-dependent K+ current. Gramicidin-perforated patch recordings showed that the depolarizing driving force for GABAA receptor-mediated actions is provided by Cl- uptake via the Na-K-C1 cotransporter, NKCC1, in the immature CA3 pyramids. A specific blocker of NKCC1, bumetanide, inhibited SPWs and GDPs in the neonatal rat hippocampus in vivo and in vitro, respectively. Finally, pharmacological blockade of the GABA transporter-1 prolonged the decay of the large GDP-associated GABA transients but not of single postsynaptic GABAA receptor-mediated currents. As a whole the data in this thesis indicate that the mechanism of GDP generation, based on the interconnected network of bursting CA3 pyramidal neurons, is similar to that involved in adult SPW activity. Hence, GDPs do not reflect a network pattern that disappears during development but they are the in vitro counterpart of neonatal SPWs.

VEGFR-3 and Tie pathways in vascular network formation

The blood and lymphatic vascular systems are essential for life, but they may become harnessed for sinister purposes in pathological conditions. For example, tumors learn to grow a network of blood vessels (angiogenesis), securing a source of oxygen and nutrients for sustained growth. On the other hand, damage to the lymph nodes and the collecting lymphatic vessels may lead to lymphedema, a debilitating condition characterized by peripheral edema and susceptibility to infections. Promoting the growth of new lymphatic vessels (lymphangiogenesis) is an attractive approach to treat lymphedema patients. Angiopoietin-1 (Ang1), a ligand for the endothelial receptor tyrosine kinases Tie1 and Tie2. The Ang1/Tie2 pathway has previously been implicated in promoting endothelial stability and integrity of EC monolayers. The studies presented here elucidate a novel function for Ang1 as a lymphangiogenic factor. Ang1 is known to decrease the permeability of blood vessels, and could thus act as a more global antagonist of plasma leakage and tissue edema by promoting growth of lymphatic vessels and thereby facilitating removal of excess fluid and other plasma components from the interstitium. These findings reinforce the idea that Ang1 may have therapeutic value in conditions of tissue edema. VEGFR-3 is present on all endothelia during development, but in the adult its expression becomes restricted to the lymphatic endothelium. VEGF-C and VEGF-D are ligands for VEGFR-3, and potently promote lymphangiogenesis in adult tissues, with direct and remarkably specific effects on the lymphatic endothelium in adult tissues. The data presented here show that VEGF-C and VEGF-D therapy can restore collecting lymphatic vessels in a novel orthotopic model of breast cancer-related lymphedema. Furthermore, the study introduces a novel approach to improve VEGF-C/VEGF-D therapy by using engineered heparin-binding forms of VEGF-C, which induced the rapid formation of organized lymphatic vessels. Importantly, VEGF-C therapy also greatly improved the survival and integration of lymph node transplants. The combination of lymph node transplantation and VEGF-C therapy provides a basis for future therapy of lymphedema. In adults, VEGFR-3 expression is restricted to the lymphatic endothelium and the fenestrated endothelia of certain endocrine organs. These results show that VEGFR-3 is induced at the onset of angiogenesis in the tip cells that lead the formation of new vessel sprouts, providing a tumor-specific vascular target. VEGFR-3 acts downstream of VEGF/VEGFR-2 signals, but, once induced, can sustain angiogenesis when VEGFR-2 signaling is inhibited. The data presented here implicate VEGFR-3 as a novel regulator of sprouting angiogenesis along with its role in regulating lymphatic vessel growth. Targeting VEGFR-3 may provide added efficacy to currently available anti-angiogenic therapeutics, which typically target the VEGF/VEGFR-2 pathway.

Automatic Lameness Detection in a Milking Robot : Instrumentation, measurement software, algorithms for data analysis and a neural network model

The aim of this thesis is to develop a fully automatic lameness detection system that operates in a milking robot. The instrumentation, measurement software, algorithms for data analysis and a neural network model for lameness detection were developed. Automatic milking has become a common practice in dairy husbandry, and in the year 2006 about 4000 farms worldwide used over 6000 milking robots. There is a worldwide movement with the objective of fully automating every process from feeding to milking. Increase in automation is a consequence of increasing farm sizes, the demand for more efficient production and the growth of labour costs. As the level of automation increases, the time that the cattle keeper uses for monitoring animals often decreases. This has created a need for systems for automatically monitoring the health of farm animals. The popularity of milking robots also offers a new and unique possibility to monitor animals in a single confined space up to four times daily. Lameness is a crucial welfare issue in the modern dairy industry. Limb disorders cause serious welfare, health and economic problems especially in loose housing of cattle. Lameness causes losses in milk production and leads to early culling of animals. These costs could be reduced with early identification and treatment. At present, only a few methods for automatically detecting lameness have been developed, and the most common methods used for lameness detection and assessment are various visual locomotion scoring systems. The problem with locomotion scoring is that it needs experience to be conducted properly, it is labour intensive as an on-farm method and the results are subjective. A four balance system for measuring the leg load distribution of dairy cows during milking in order to detect lameness was developed and set up in the University of Helsinki Research farm Suitia. The leg weights of 73 cows were successfully recorded during almost 10,000 robotic milkings over a period of 5 months. The cows were locomotion scored weekly, and the lame cows were inspected clinically for hoof lesions. Unsuccessful measurements, caused by cows standing outside the balances, were removed from the data with a special algorithm, and the mean leg loads and the number of kicks during milking was calculated. In order to develop an expert system to automatically detect lameness cases, a model was needed. A probabilistic neural network (PNN) classifier model was chosen for the task. The data was divided in two parts and 5,074 measurements from 37 cows were used to train the model. The operation of the model was evaluated for its ability to detect lameness in the validating dataset, which had 4,868 measurements from 36 cows. The model was able to classify 96% of the measurements correctly as sound or lame cows, and 100% of the lameness cases in the validation data were identified. The number of measurements causing false alarms was 1.1%. The developed model has the potential to be used for on-farm decision support and can be used in a real-time lameness monitoring system.

Data mining for telecommunications network log analysis

Telecommunications network management is based on huge amounts of data that are continuously collected from elements and devices from all around the network. The data is monitored and analysed to provide information for decision making in all operation functions. Knowledge discovery and data mining methods can support fast-pace decision making in network operations. In this thesis, I analyse decision making on different levels of network operations. I identify the requirements decision-making sets for knowledge discovery and data mining tools and methods, and I study resources that are available to them. I then propose two methods for augmenting and applying frequent sets to support everyday decision making. The proposed methods are Comprehensive Log Compression for log data summarisation and Queryable Log Compression for semantic compression of log data. Finally I suggest a model for a continuous knowledge discovery process and outline how it can be implemented and integrated to the existing network operations infrastructure.

The Most Probable Bayesian Network and Beyond

This doctoral dissertation introduces an algorithm for constructing the most probable Bayesian network from data for small domains. The algorithm is used to show that a popular goodness criterion for the Bayesian networks has a severe sensitivity problem. The dissertation then proposes an information theoretic criterion that avoids the problem.

Algorithms for 13C metabolic flux analysis

The metabolism of an organism consists of a network of biochemical reactions that transform small molecules, or metabolites, into others in order to produce energy and building blocks for essential macromolecules. The goal of metabolic flux analysis is to uncover the rates, or the fluxes, of those biochemical reactions. In a steady state, the sum of the fluxes that produce an internal metabolite is equal to the sum of the fluxes that consume the same molecule. Thus the steady state imposes linear balance constraints to the fluxes. In general, the balance constraints imposed by the steady state are not sufficient to uncover all the fluxes of a metabolic network. The fluxes through cycles and alternative pathways between the same source and target metabolites remain unknown. More information about the fluxes can be obtained from isotopic labelling experiments, where a cell population is fed with labelled nutrients, such as glucose that contains 13C atoms. Labels are then transferred by biochemical reactions to other metabolites. The relative abundances of different labelling patterns in internal metabolites depend on the fluxes of pathways producing them. Thus, the relative abundances of different labelling patterns contain information about the fluxes that cannot be uncovered from the balance constraints derived from the steady state. The field of research that estimates the fluxes utilizing the measured constraints to the relative abundances of different labelling patterns induced by 13C labelled nutrients is called 13C metabolic flux analysis. There exist two approaches of 13C metabolic flux analysis. In the optimization approach, a non-linear optimization task, where candidate fluxes are iteratively generated until they fit to the measured abundances of different labelling patterns, is constructed. In the direct approach, linear balance constraints given by the steady state are augmented with linear constraints derived from the abundances of different labelling patterns of metabolites. Thus, mathematically involved non-linear optimization methods that can get stuck to the local optima can be avoided. On the other hand, the direct approach may require more measurement data than the optimization approach to obtain the same flux information. Furthermore, the optimization framework can easily be applied regardless of the labelling measurement technology and with all network topologies. In this thesis we present a formal computational framework for direct 13C metabolic flux analysis. The aim of our study is to construct as many linear constraints to the fluxes from the 13C labelling measurements using only computational methods that avoid non-linear techniques and are independent from the type of measurement data, the labelling of external nutrients and the topology of the metabolic network. The presented framework is the first representative of the direct approach for 13C metabolic flux analysis that is free from restricting assumptions made about these parameters.In our framework, measurement data is first propagated from the measured metabolites to other metabolites. The propagation is facilitated by the flow analysis of metabolite fragments in the network. Then new linear constraints to the fluxes are derived from the propagated data by applying the techniques of linear algebra.Based on the results of the fragment flow analysis, we also present an experiment planning method that selects sets of metabolites whose relative abundances of different labelling patterns are most useful for 13C metabolic flux analysis. Furthermore, we give computational tools to process raw 13C labelling data produced by tandem mass spectrometry to a form suitable for 13C metabolic flux analysis.

Where and how to conserve: Extending the scope of spatial reserve network design

Ongoing habitat loss and fragmentation threaten much of the biodiversity that we know today. As such, conservation efforts are required if we want to protect biodiversity. Conservation budgets are typically tight, making the cost-effective selection of protected areas difficult. Therefore, reserve design methods have been developed to identify sets of sites, that together represent the species of conservation interest in a cost-effective manner. To be able to select reserve networks, data on species distributions is needed. Such data is often incomplete, but species habitat distribution models (SHDMs) can be used to link the occurrence of the species at the surveyed sites to the environmental conditions at these locations (e.g. climatic, vegetation and soil conditions). The probability of the species occurring at unvisited location is next predicted by the model, based on the environmental conditions of those sites. The spatial configuration of reserve networks is important, because habitat loss around reserves can influence the persistence of species inside the network. Since species differ in their requirements for network configuration, the spatial cohesion of networks needs to be species-specific. A way to account for species-specific requirements is to use spatial variables in SHDMs. Spatial SHDMs allow the evaluation of the effect of reserve network configuration on the probability of occurrence of the species inside the network. Even though reserves are important for conservation, they are not the only option available to conservation planners. To enhance or maintain habitat quality, restoration or maintenance measures are sometimes required. As a result, the number of conservation options per site increases. Currently available reserve selection tools do however not offer the ability to handle multiple, alternative options per site. This thesis extends the existing methodology for reserve design, by offering methods to identify cost-effective conservation planning solutions when multiple, alternative conservation options are available per site. Although restoration and maintenance measures are beneficial to certain species, they can be harmful to other species with different requirements. This introduces trade-offs between species when identifying which conservation action is best applied to which site. The thesis describes how the strength of such trade-offs can be identified, which is useful for assessing consequences of conservation decisions regarding species priorities and budget. Furthermore, the results of the thesis indicate that spatial SHDMs can be successfully used to account for species-specific requirements for spatial cohesion - in the reserve selection (single-option) context as well as in the multi-option context. Accounting for the spatial requirements of multiple species and allowing for several conservation options is however complicated, due to trade-offs in species requirements. It is also shown that spatial SHDMs can be successfully used for gaining information on factors that drive a species spatial distribution. Such information is valuable to conservation planning, as better knowledge on species requirements facilitates the design of networks for species persistence. This methods and results described in this thesis aim to improve species probabilities of persistence, by taking better account of species habitat and spatial requirements. Many real-world conservation planning problems are characterised by a variety of conservation options related to protection, restoration and maintenance of habitat. Planning tools therefore need to be able to incorporate multiple conservation options per site, in order to continue the search for cost-effective conservation planning solutions. Simultaneously, the spatial requirements of species need to be considered. The methods described in this thesis offer a starting point for combining these two relevant aspects of conservation planning.

Fine-tuning of the signalling network controlling morphogenesis and stem cell development in teeth

Tooth development is regulated by sequential and reciprocal interactions between epithelium and mesenchyme. The molecular mechanisms underlying this regulation are conserved and most of the participating molecules belong to several signalling families. Research focusing on mouse teeth has uncovered many aspects of tooth development, including molecular and evolutionary specifi cs, and in addition offered a valuable system to analyse the regulation of epithelial stem cells. In mice the spatial and temporal regulation of cell differentiation and the mechanisms of patterning during development can be analysed both in vivo and in vitro. Follistatin (Fst), a negative regulator of TGFβ superfamily signalling, is an important inhibitor during embryonic development. We showed the necessity of modulation of TGFβ signalling by Fst in three different regulatory steps during tooth development. First we showed that tinkering with the level of TGFβ signalling by Fst may cause variation in the molar cusp patterning and crown morphogenesis. Second, our results indicated that in the continuously growing mouse incisors asymmetric expression of Fst is responsible for the labial-lingual patterning of ameloblast differentiation and enamel formation. Two TGFβ superfamily signals, BMP and Activin, are required for proper ameloblast differentiation and Fst modulates their effects. Third, we identifi ed a complex signalling network regulating the maintenance and proliferation of epithelial stem cells in the incisor, and showed that Fst is an essential modulator of this regulation. FGF3 in cooperation with FGF10 stimulates proliferation of epithelial stem cells and transit amplifying cells in the labial cervical loop. BMP4 represses Fgf3 expression whereas Activin inhibits the repressive effect of BMP4 on the labial side. Thus, Fst inhibits Activin rather than BMP4 in the cervical loop area and limits the proliferation of lingual epithelium, thereby causing the asymmetric maintenance and proliferation of epithelial stem cells. In addition, we detected Lgr5, a Wnt target gene and an epithelial stem cell marker in the intestine, in the putative epithelial stem cells of the incisor, suggesting that Lgr5 is a marker of incisor stem cells but is not regulated by Wnt/β-catenin signalling in the incisor. Thus the epithelial stem cells in the incisor may not be directly regulated by Wnt/β-catenin signalling. In conclusion, we showed in the mouse incisors that modulating the balance between inductive and inhibitory signals constitutes a key mechanism regulating the epithelial stem cells and ameloblast differentiation. Furthermore, we found additional support for the location of the putative epithelial stem cells and for the stemness of these cells. In the mouse molar we showed the necessity of fi ne-tuning the signalling in the regulation of the crown morphogenesis, and that altering the levels of an inhibitor can cause variation in the crown patterning.