Despite surgical innovation, the sensory and motor outcome after peripheral nerve injury is incomplete. In this thesis, the biological pathways potentially responsible for the poor functional recoveries were investigated in both the distal nerve stump/target organ, spinal motoneurons and dorsal root ganglia (DRG). The effect of delayed nerve repair was determined in a rat sciatic nerve transection model. There was a dramatic decline in the number of regenerating motoneurons and myelinated axons found in the distal nerve stumps of animals undergoing nerve repair after a delay of 3 and 6 months. RT-PCR of the distal nerve stumps showed a decline in expression of Schwann cells (SC) markers, with a progressive increase in fibrotic and proteoglycan scar markers, with increased delayed repair time. Furthermore, the yield of SC which could be isolated from the distal nerve segments progressively fell with increased delay in repair time. Consistent with the impaired distal nerve stumps the target medial gastrocnemius (MG) muscles at 3- and 6-months delayed repair were atrophied with significant declines in wet weights (61% and 27% compared with contralateral sides). The role of myogenic transcription factors, muscle specific microRNAs and musclespecific E3 ubiquitin ligases in the muscle atrophy was investigated in both gastrocnemius and soleus muscles following either crush or nerve transection injury. In the crush injury model, the soleus muscle showed significantly increased recovery in wet weight at days 14 and 28 (compared with day 7) which was not the case for the gastrocnemius muscle which continued to atrophy. There was a significantly more pronounced up-regulation of MyoD expression in the denervated soleus muscle compared with the gastrocnemius muscle. Conversely, myogenin was more markedly elevated in the gastrocnemius versus soleus muscles. The muscles also showed significantly contrasting transcriptional regulation of the microRNAs miR-1 and miR-206. MuRF1 and Atrogin-1 showed the highest levels of expression in the denervated gastrocnemius muscle. Morphological and molecular changes in spinal motoneurons were compared after L4-L5 ventral root avulsion (VRA) and distal peripheral nerve axotomy (PNA). Neuronal degeneration was indicated by decreased immunostaining for microtubule-associated protein-2 in dendrites and synaptophysin in presynaptic boutons after both VRA and PNA. Immunostaining for ED1-reactive microglia and GFAPpositive astrocytes was significantly elevated in all experimental groups. qRT-PCR analysis and Western blotting of the ventral horn from L4-L5 spinal cord segments revealed a significant upregulation of apoptotic cell death mediators including caspases-3 and -8 and a range of related death receptors following VRA. In contrast, following PNA, only caspase-8 was moderately upregulated. The mechanisms of primary sensory neuron degeneration were also investigated in the DRG following peripheral nerve axotomy, where several apoptotic pathways including those involving the endoplasmic reticulum were shown to be upregulated. In summary, these results show that the critical time point after which the outcome of regeneration becomes too poor appears to be 3-months. Both proximal and distal injury affect spinal motoneurons morphologically, but VRA induces motoneuron degeneration mediated through both intrinsic and extrinsic apoptotic pathways. Primary sensory neuron degeneration involves several different apoptotic pathways, including the endoplasmic reticulum.

No description available.

Background: Previous studies show that recommendations accuracy partly can be explained by numerous variables. Prior research leave out several variables, which based on theoretical support, may have a connection with accuracy, such as the cash flows’ volatility. Based on the DCF-model’s structure, accuracy of target prices is assumed to have a positive relationship with companies that have stable cash flows. Purpose: The purpose of this thesis is to analyze the accuracy of stock analysts' target prices and their connection with stable cash flows. The purpose of the study is also to analyze the role of less highlighted variables’ relationship with the accuracy of target prices, in combination with earlier investigated variables. Completion: Including less highlighted variables is supported by theory about corporate valuation, where cash flows’ volatility is the main focus of this study. The accuracy of the target prices is analyzed by regression analysis for three time horizons, where the dependent variable is the absolute margin of error and the dependent variables are represented by the explanatory factors that the study examines. The relationships are estimated by OLS, due to the fact that data are unbalanced. Conclusion:  Stock analysts’ target prices present relationships with numerous of the variables examined in the study. The strongest relationships with the accuracy of target prices are shown by cash flows’ variation, the number of stock analysts, goodwill in terms of total capital and companies’ size. The results show that companies with stable cash flow have a positive relationship with the accuracy of target prices, which supports the theories of the DCF-model for valuation of companies with stable cash flow. The estimations show that the accuracy of target prices also is explained by other factors than those this very study investigates. The results show that the accuracy is higher for shorter time horizons. / Bakgrund: Tidigare studier finner att prognosers träffsäkerhet delvis kan förklaras av flertalet variabler. De variabler som studeras i tidigare forskning visar bitvis på tvetydigheter och utelämnar flertalet variabler som utifrån teoretiskt stöd kan ha ett samband med träffsäkerheten, som exempelvis kassaflödens volatilitet. Utifrån DCF-modellens uppbyggnad antas riktkursers träffsäkerhet ha ett positivt samband med bolag som har stabila kassaflöden. Syfte: Studiens syfte är att ekonometrisk analysera träffsäkerheten i aktieanalytikers riktkurser och söka systematiska förklaringsfaktorer till avvikelser mellan riktkurser och de faktisk realiserade kurserna. Fokus ligger på att, i kombination med tidigare undersökta variabler, analysera tidigare mindre uppmärksammade variablers så som kassaflödens samband med riktkursers precision.   Genomförande: Från teori kring bolagsvärdering hämtas stöd för mindre belysta faktorer som kan tänkas påverka riktkursers träffsäkerhet, där kassaflödens volatilitet är studiens huvudsakliga fokus. Riktkursernas träffsäkerhet analyseras via regressionsanalys för tre olika tidshorisonter, där beroendevariabeln är den absoluta felmarginalen i riktkursen och de oberoende variablerna representeras av företagens kassaflöden och övriga påverkansfaktorer som identifierats i tidigare forskning. Studien bygger på data från den amerikanska aktiemarknaden. Slutsats: Aktieanalytikers riktkurser uppvisar samband med flertalet av de variabler studien undersöker. Starkast samband med riktkursers träffsäkerhet visar kassaflödens variation, antalet aktieanalytiker, goodwill i termer av totalt kapital och bolags storlek. Resultaten visar att bolag med stabila kassaflöden har ett positivt samband med riktkursers träffsäkerhet. Detta ger stöd åt DCF-modellens teorier vid värdering av bolag med stabila kassaflöden. Skattningarna visar att riktkursers träffsäkerhet även förklaras av andra faktorer än de som studien undersöker. Resultaten visar att träffsäkerheten är högre för kortare tidshorisonter.

In 2001, the FASB (Financial Accounting Standard Board) introduced accounting regulations SFAS 141 and SFAS 142 to improve the relevance, representational faithfulness, and comparability of financial reporting. The new standards have profoundly changed the accounting for business combinations and goodwill under US GAAP by requiring reporting entities to no longer amortize goodwill over its expected useful life, but to test for impairment annually. However, the new regulation has met sharp criticism for creating a scope for high levels of managerial discretion which may be exercised opportunistically in the accounting for goodwill. This study examines whether the proportion of purchase price allocated to goodwill differs between public and private acquisitions. We try to answer this question by carrying out a quantitative study on 481 observations, between the period of 2001 to 2005 by studying the relationship between acquirer type (Public vs. Private) and target firm characteristic on goodwill allocated, and we find the following results: 1) Public acquirers allocate higher levels of goodwill in comparison to private acquirers. (2) Market-to-book values of private target firms are not positively correlated with recorded goodwill levels.

The purpose of the study was to provide training to peer tutors to teach students with mild and moderate disabilities sales tax computation using a simultaneous prompting procedure with fidelity. Non-target information presented during training sessions and generalization to natural environment settings was assessed. A multiple probe (days) across participants design was used to evaluate the effectiveness of the intervention on the dependent variables. The results showed peer tutors could use the simultaneous prompting procedure with fidelity to teach sales tax computation and students with disabilities could acquire sales tax computation. The students acquired the non-target information presented and generalization occurred in a natural setting.

Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of small non-coding RNAs. Their main function is to target chemical modifications of ribosomal RNAs (rRNAs) and small nuclear (snRNAs). They fall into two classes, box C/D snoRNAs and box H/ACA snoRNAs, which are clearly distinguished by conserved sequence motifs and the type of modification that they govern. The box H/ACA snoRNAs are responsible for targeting pseudouridylation sites and the box C/D snoRNAs for directing 2’-O-methylation of ribonucleotides. A subclass that localize to the Cajal bodies, termed scaRNAs, are responsible for methylation and pseudouridylation of snRNAs. In addition an amazing diversity of non-canonical functions of individual snoRNAs arose. The modification patterns in rRNAs and snRNAs are retained during evolution making it even possible to project them from yeast onto human. The stringent conservation of modification sites and the slow evolution of rRNAs and snRNAs contradicts the rapid evolution of snoRNA sequences. Recent studies that incorporate high-throughput sequencing experiments still identify undetected snoRNAs even in well studied organisms as human. The snoRNAbase, which has been the standard database for human snoRNAs has not been updated ince 2006 and misses these new data. Along with the lack of a centralized data collection across species, which incorporates also snoRNA class specific characteristics the need to integrate distributed data from literature and databases into a comprehensive snoRNA set arose. Although several snoRNA studies included pro forma target predictions in individual species and more and more studies focus on non-canonical functions of subclasses a systematic survey on the guiding function and especially functional homologies of snoRNAs was not available. To establish a sound set of snoRNAs a computational snoRNA annotation pipeline, named snoStrip that identifies homologous snoRNAs in related species was employed. For large scale investigation of the snoRNA function, state-of-the-art target pedictions were performed with our software RNAsnoop and PLEXY. Further, a new measure the Interaction Conservation Index (ICI) was developed to evaluate the conservation of snoRNA function. The snoStrip pipeline was applied to vertebrate species, where the genome sequence has been available. In addition, it was used in several ncRNA annotation studies (48 avian, spotted gar) of newly assembled genomes to contribute the snoRNA genes. Detailed target analysis of the new vertebrate snoRNA set revealed that in general functions of homologous snoRNAs are evolutionarily stable, thus, members of the same snoRNA family guide equivalent modifications. The conservation of snoRNA sequences is high at target binding regions while the remaining sequence varies significantly. In addition to elucidating principles of correlated evolution it was possible, with the help of the ICI measure, to assign functions to previously orphan snoRNAs and to associate snoRNAs as partners to known but so far unexplained chemical modifications. As further pattern redundant guiding became apparent. For many modification sites more than one snoRNA encodes the appropriate antisense element (ASE), which could ensure constant modification through snoRNAs that have different expression patterns. Furthermore, predictions of snoRNA functions in conjunction with sequence conservation could identify distant homologies. Due to the high overall entropy of snoRNA sequences, such relationships are hard to detect by means of sequence homology search methods alone. The snoRNA interaction network was further expanded through novel snoRNAs that were detected in data from high-throughput experiments in human and mouse. Through subsequent target analysis the new snoRNAs could immediately explain known modifications that had no appropriate snoRNA guide assigned before. In a further study a full catalog of expressed snoRNAs in human was provided. Beside canonical snoRNAs also recent findings like AluACAs, sno-lncRNAs and extraordinary short SNORD-like transcripts were taken into account. Again the target analysis workflow identified undetected connections between snoRNA guides and modifications. Especially some species/clade specific interactions of SNORD-like genes emerged that seem to act as bona fide snoRNA guides for rRNA and snRNA modifications. For all high confident new snoRNA genes identified during this work official gene names were requested from the HUGO Gene Nomenclature Committee (HGNC) avoiding further naming confusion.

We study the sensitivity of fixed target neutrino experiments (LSND, T2K, CENNS, and COHERENT) and proton beam dumps (MiniBooNE off-target, and SHiP) to sub-GeV dark matter. In order to reproduce the observed thermal relic abundance, these states are coupled to the Standard Model via new, low mass mediators in the form of a kinetically mixed U(1)0 vector mediator or a vector mediator gauging baryon number. We present a model for the production of low mass dark matter from proton-nucleon collisions in fixed targets. Sensitivity projections are made using signals from elastic electron- and nucleon-dark matter scattering, as well as coherent nuclear-dark matter scattering and dark matter induced inelastic π 0 production. A fixed target Monte Carlo code has been developed for this analysis, and documentation is included. We find that analyses using current and future proton fixed target experiments are capable of placing new limits on the hidden sector dark matter parameter space for dark matter masses of up to 500\,MeV and mediator masses as large as a few GeV. / Graduate

Native to Asia, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) is an invasive non-native ladybird in Europe and North America, where it was widely introduced as a biological control agent of aphids and coccids. There were three main objectives of this study: firstly, to investigate the spread and distribution of H. axyridis in Europe from the start of the invasion process; secondly, to study its ecology in Great Britain; and thirdly, to examine its effects on native ladybirds in Britain. In Europe, collaborations with a network of scientists allowed the collation of H. axyridis occurrence data from across the continent. In Great Britain, a web-based public survey (www.harlequin-survey.org) was used, leading to the receipt of over 10,000 verified records of H. axyridis between 2004 and 2008. National land cover data enabled the habitats used by H. axyridis to be identified across Great Britain. These datasets were analysed in order to study the spread and ecology of H. axyridis in Europe and Britain. Fieldwork over a three year period (2006 to 2008) was carried out to examine changes in ladybird species assemblages during the invasion phase of H. axyridis in eastern England. Laboratory work was conducted to detect intraguild predation by H. axyridis, through PCR analyses of gut contents of field-collected ladybirds. In Europe, H. axyridis has spread since 2001 at the rate of approximately 200km yr-1. It has become established in at least 23 European countries. The established range extends from Norway in the north to southern France in the south, and from Ukraine in the east to Great Britain in the west. In the first five years of establishment H. axyridis spread north through Britain at the rate of 105km yr-1 and west at the rate of 145km yr-1. Evidence of the production of two generations per year was found, giving H. axyridis an advantage over most native ladybirds in Britain. Although H. axyridis was very common in urban habitats, it increasingly used semi-natural habitats. In addition, whilst the species was most common on deciduous trees, it was increasingly found on herbaceous plants. Aceraceae, Rosaceae and Malvaceae were the dominant plant families used by H. axyridis, especially for breeding. In eastern England H. axyridis increased from 0.1% to 40% of total ladybirds in three years, whilst native aphidophagous ladybirds declined from 84% to 41% of total ladybirds in the same period. Three species in particular experienced declines: Adalia 2-punctata, Coccinella 7-punctata and Propylea 14-punctata. Harmonia axyridis was the most abundant species by the end of the study. Detection of intraguild predation by one coccinellid on another, in the field in Europe, was shown for the first time using PCR techniques: A. 2-punctata DNA was detected in the gut of one of 112 field-collected H. axyridis. Harmonia axyridis has spread very quickly since 2001 and has become one of the most widely distributed coccinellids in Europe. Populations of native aphidophagous ladybirds were negatively affected by the arrival of H. axyridis, partly through intraguild predation.

This research presents a new approach to derive recommendations for segment-specific, targeted marketing campaigns on the product category level. The proposed methodological framework serves as a decision support tool for customer relationship managers or direct marketers to select attractive product categories for their target marketing efforts, such as segment-specific rewards in loyalty programs, cross-merchandising activities, targeted direct mailings, customized supplements in catalogues, or customized promotions. The proposed methodology requires cus- tomers' multi-category purchase histories as input data and proceeds in a stepwise manner. It combines various data compression techniques and integrates an opti- mization approach which suggests candidate product categories for segment-specific targeted marketing such that cross-category spillover effects for non-promoted categories are maximized. To demonstrate the empirical performance of our pro- posed procedure, we examine the transactions from a real-world loyalty program of a major grocery retailer. A simple scenario-based analysis using promotion responsiveness reported in previous empirical studies and prior experience by domain experts suggests that targeted promotions might boost profitability between 15 % and 128 % relative to an undifferentiated standard campaign.

This dissertation investigates data reduction strategies from a signal processing perspective in centralized detection and estimation applications. First, it considers a deterministic source observed by a network of sensors and develops an analytical strategy for ranking sensor transmissions based on the magnitude of their test statistics. The benefit of the proposed strategy is that the decision to transmit or not to transmit observations to the fusion center can be made at the sensor level resulting in significant savings in transmission costs. A sensor network based on target tracking application is simulated to demonstrate the benefits of the proposed strategy over the unconstrained energy approach. Second, it considers the detection of random signals in noisy measurements and evaluates the performance of eigenvalue-based signal detectors. Due to their computational simplicity, robustness and performance, these detectors have recently received a lot of attention. When the observed random signal is correlated, several researchers claim that the performance of eigenvalue-based detectors exceeds that of the classical energy detector. However, such claims fail to consider the fact that when the signal is correlated, the optimal detector is the estimator-correlator and not the energy detector. In this dissertation, through theoretical analyses and Monte Carlo simulations, eigenvalue-based detectors are shown to be suboptimal when compared to the energy detector and the estimator-correlator.