In this paper we compare the behaviour of adverbs of frequency (de Swart 1993) like usually with the behaviour of adverbs of quantity like for the most part in sentences that contain plural definites. We show that sentences containing the former type of Q-adverb evidence that Quantificational Variability Effects (Berman 1991) come about as an indirect effect of quantification over situations: in order for quantificational variability readings to arise, these sentences have to obey two newly observed constraints that clearly set them apart from sentences containing corresponding quantificational DPs, and that can plausibly be explained under the assumption that quantification over (the atomic parts of) complex situations is involved. Concerning sentences with the latter type of Q-adverb, on the other hand, such evidence is lacking: with respect to the constraints just mentioned, they behave like sentences that contain corresponding quantificational DPs. We take this as evidence that Q-adverbs like for the most part do not quantify over the atomic parts of sum eventualities in the cases under discussion (as claimed by Nakanishi and Romero (2004)), but rather over the atomic parts of the respective sum individuals.

Fungi are present everywhere in indoor and outdoor environments. Many fungi are toxigenic or pathogenic that may cause various public health concerns. Rapid detection, quantification and characterization of fungi in living and working environments are essential for exposure risk assessment to safe guard public health. Rapid and accurate detection and identification of fungi using molecular method require specific markers. In this thesis, partial mt SSU and LSU rDNA were amplified and sequenced from 31 fungal species of 16 genera. Sequence alignments showed that fungal mt SSU and LSU rDNA contained sufficient amount of variation for the development of markers that can discriminate even among closely related species. Forty-eight probes were designed and were verified as highly specific to 25 fungal species commonly detected in living and working environments. These specific probes would have potential applications in clinical diagnosis and public health-related environmental monitoring. Nested PCR is a highly sensitive and specific method. Based on the nuclear 18S rDNA sequence variation pattern, three nested PCR systems were developed to detect the conifer tree pathogen Gremmeniella abietina, an ascomycete fungus that causes stem canker and shoot dieback in many conifer species. The three nested PCR systems showed high specificity and sensitivity. These methods could have broad applications in forest protection and disease management programs. Quantitative real-time PCR offers the ability of simultaneous detection and quantification of DNA of a specific microbe in one reaction. Based on the 18S rDNA sequence, two real-time PCR assays were developed to detect and quantify Wallemia sebi, a deuteromycete fungus commonly found in agricultural environments and is suspected to be a causative agent of farmer’s lung disease. Both PCR systems proved to be highly specific and sensitive for W. sebi detection even in a high background of other fungal DNAs. Application of the real-time PCR methods in the quantification of W. sebi in the aerosols of a farm revealed a high concentration of W. sebi spores (107/m3). The study indicates that W. sebi is a dominant fungus in agriculture environments. Cladosporium spores are important aeroallergens, and prolonged exposure to elevated spore concentrations can provoke chronic allergy and asthma. A TaqMan probe and a SYBR Green I based real-time PCR assay were developed to detect and quantify Cladosporium in aerosols. The two real-time PCR systems proved to be highly specific and sensitive for Cladosporium. These methods were employed to quantify Cladosporium in aerosols of five different indoor environments. High spore concentration of Cladosporium (107/m3) was observed in a cow barn. Cladosporium spore concentration in paper and pulp factory and countryside house also exceeded threshold value for clinical significance. Prolonged exposure in these environments could impose certain health risk. Thus, monitoring Cladosporium spore concentration in indoor environments is important for indoor air quality control.

There is a large need for accurate methods detecting cardiovascular diseases, since they are one of the leading causes of mortality in the world, accounting for 29.3% of all deaths. Due to the complexity of the cardiovascular system, it is very challenging to develop methods for quantification of its function in order to diagnose, prevent and treat cardiovascular diseases. Ultrasound is a technique allowing for inexpensive, noninvasive imaging, but requires an experienced echocardiographer. Nowadays, methods like Tissue Doppler imaging (TDI) and Speckle tracking imaging (STI), measuring motion and deformation in the myocardium and the vessel walls, are getting more common in routine clinical practice, but without a proper visualization of the data provided by these methods, they are time-consuming and difficult to interpret. Thus, the general aim of this thesis was to develop novel ultrasound-based methods for accurate quantification and easily interpretable visualization of cardiovascular function. Five methods based on TDI and STI were developed in the present studies. The first study comprised development of a method for generation of bull’s-eye plots providing a color-coded two-dimensional visualization of myocardial longitudinal velocities. The second study proposed the state diagram of the heart as a new circular visualization tool for cardiac mechanics, including segmental color-coding of cardiac time intervals. The third study included development of a method describing the rotation pattern of the left ventricle by calculating rotation axes at different levels of the left ventricle throughout the cardiac cycle. In the fourth study, deformation data from the artery wall were tested as input to wave intensity analysis providing information of the ventricular – arterial interaction. The fifth study included an in-silico feasibility study to test the assessment of both radial and longitudinal strain in a kinematic model of the carotid artery. The studies showed promising results indicating that the methods have potential for the detection of different cardiovascular diseases and are feasible for use in the clinical setting. However, further development of the methods and both quantitative comparison of user dependency, accuracy and ease of use with other established methods evaluating cardiovascular function, as well as additional testing of the clinical potential in larger study populations, are needed. / QC 20100727

Pain and disorders of the human skeletal muscles are one of the most common reasons for medical consultations in the western countries today and there is a great need to improve both the understanding and treatment of several different muscular conditions. Techniques describing the muscle function in vivo are often limited by either their invasiveness or lack of spatial resolution. Electromyography (EMG) is the most common approach to assess the skeletal muscle function in vivo, providing information on the neurological input. However, the spatial resolution is in general limited and there are difficulties reaching deep musculature without using invasive needles. Moreover, it does not provide any information about muscle structure or mechanical aspects. Quantitative ultrasound techniques have gained interest in the area of skeletal muscles and enables non-invasive and in-vivo insight to the intramuscular activity, through the mechanical response of the activation. However, these techniques are developed and evaluated for cardiovascular applications and there are important considerations to be made when applying these methods in the musculoskeletal field.  This thesis is based on the work from four papers with the main focus to investigate and describe some of these considerations in combination with the development of processing and analyzing methods that can be used to describe the physiological characteristics of active muscle tissue. In the first paper the accuracy of the Doppler based technique Tissue Velocity Imaging (TVI) was evaluated in a phantom study for very low tissue velocities and the effect of the pulse repetition frequency was considered. The second paper presents a biomechanical model to describe the TVI strain’s dependency on the muscle fiber pennation angle. In the third and fourth papers the intramuscular activity pattern was assessed through the regional tissue deformation by motion mode (M-mode) strain imaging. The activity patterns were analyzed during force regulation and for the effects of fatigue. The work of this thesis show promising results for the application of these methods on skeletal muscles and indicate high clinical potential where quantitative ultrasound may be a valuable tool to reach a more multifaceted and comprehensive insight in the musculoskeletal function. However, the methodological considerations are highly important for the optimized application and further evaluation and development of analyzing strategies are needed. / <p>QC 20130516</p>

Dans un premier temps, nous mettrons en valeur le contexte technologique matériel et surtout logiciel qui permet aujourd'hui le développement de systèmes de mise en page pour les métiers de l'édition(§ I.1). Dans cette perspective, apparaîtront d'eux mêmes, la motivation et l'intérêt pratique présentés par l'étude détaillée du détourage, opération fondamentale qui consiste à extraire d'une photographie l'image d'un objet y figurant (§ I.2). Nous aborderons, dans la suite de ce chapitre une présentation plus technique des difficultés soulevées par l'automatisation du détourage. Plus précisément, nous présenterons le problème comme relevant à la fois de la segmentation et de l'interprétation d'image (§ I.3).

Celiac disease (CD) is a common heritable immune related disorder where chronic inflammationof the small intestine is induced by the ingestion of gluten. The immune response leads to theinflammation and flattening of intestinal mucosa due to the damaged villi and thus results indefects in the absorption of nutrients. This defect can affect any organ or body system and exposeto the risk of lifelong complications such as cancer, autoimmune diseases and other complexdiseases. Now a day, celiac disease is becoming one of the well-studied models of complexdisorders.The PI3K- FOX signaling pathway is activated by many regulators and growth factors and playsa key role in cell cycle. Two components of this pathway, INSR and FOX, play crucial roles indiverse aspects of embryogenesis from the initial tissue genesis up to organ formation. INSR andFOX take part in development, differentiation, proliferation, apoptosis and stress resistance aswell as metabolism. SNP´s could affect the expression of neighboring genes. These SNP´s areshown to be as eQTLs, genomic loci that regulate the expression of genes. The aim of this studywas to detect and quantitate the expression of INSR and certain FOX genes in celiac disease.Quantitative real time PCR (QPCR) was used to analyze the expression of INSR, FOXO1,FOXO4 and FOXD3 genes in 38 celiac cases and 50 control samples. Three reference genesACTB, EPCAM and PGK1 were tested for their expression stability and their average was used inthe normalization procedure. Gene expression results were analyzed using the ΔCt method. Theexpression of INSR, FOXO1, FOXO4 and FOXD3 were described as their fold change in CDcompared to normal non-celiac mucosa. Our results indicated that FOXO4 and INSR wereexpressed less by 0.60 fold and FOXO1 was expressed less by 0.23 fold in CD samples. Theresults are preliminary and further studies will be needed to confirm if these findings are a resultof the intestinal inflammation in CD or if these genes are partly driving the disease itself.

By integrating the simplicity of 18O-labeling and the low signal-to-noise of MS/MS spectra with supporting software and combining them with global shotgun protein identification, a robust quantitative pipeline has been created that avoids the disadvantages of other quantitative approaches. Test mixtures of labeled and unlabeled peptides were subjected to LC-MS/MS profiling experiments. Software programs were developed and applied to automatically determine protein ratios between two samples while applying a correction for incomplete labeling. The measurement of relative abundance at the product ion (MS/MS) level, instead of at the full scan (MS) level, is shown to provide excellent accuracy and sensitivity. Ratio distributions approached the expected means, allowing empirical derivation of confidence level cutoffs for determining statistically significant fold-changes in protein abundance. A set of stringent criteria for detecting spurious ratios based on consistency checking between unlabeled and labeled y-ion pairs was found to highlight putative false positive identifications.

Purpose: To validate and assess the feasibility of using an assay of oral neutrophils to measure periodontal inflammation in uncooperative patients with special needs. Methods: Periodontal examination and neutrophil counts derived from oral swabs were performed on patients with special needs having comprehensive dental treatment under general anaesthesia (GA). The conventional periodontal measurements were compared to neutrophil levels while patients were under GA, and later at their recall examination. Results: Forty-nine patients were assessed under GA and 30 (61%) returned for recall examination. Spearman’s correlation allowed for comparisons between periodontal parameters and oral neutrophil counts. Despite limited cooperation, it was possible to acquire neutrophils (using swabs) for all patients that presented for recall examination in the ambulatory dental clinic. Conclusions: Oral neutrophil levels correlated significantly with conventional parameters of gingival inflammation and may serve as a standardized method for clinical assessment of periodontal diseases in the special needs population.

By integrating the simplicity of 18O-labeling and the low signal-to-noise of MS/MS spectra with supporting software and combining them with global shotgun protein identification, a robust quantitative pipeline has been created that avoids the disadvantages of other quantitative approaches. Test mixtures of labeled and unlabeled peptides were subjected to LC-MS/MS profiling experiments. Software programs were developed and applied to automatically determine protein ratios between two samples while applying a correction for incomplete labeling. The measurement of relative abundance at the product ion (MS/MS) level, instead of at the full scan (MS) level, is shown to provide excellent accuracy and sensitivity. Ratio distributions approached the expected means, allowing empirical derivation of confidence level cutoffs for determining statistically significant fold-changes in protein abundance. A set of stringent criteria for detecting spurious ratios based on consistency checking between unlabeled and labeled y-ion pairs was found to highlight putative false positive identifications.

Purpose: To validate and assess the feasibility of using an assay of oral neutrophils to measure periodontal inflammation in uncooperative patients with special needs. Methods: Periodontal examination and neutrophil counts derived from oral swabs were performed on patients with special needs having comprehensive dental treatment under general anaesthesia (GA). The conventional periodontal measurements were compared to neutrophil levels while patients were under GA, and later at their recall examination. Results: Forty-nine patients were assessed under GA and 30 (61%) returned for recall examination. Spearman’s correlation allowed for comparisons between periodontal parameters and oral neutrophil counts. Despite limited cooperation, it was possible to acquire neutrophils (using swabs) for all patients that presented for recall examination in the ambulatory dental clinic. Conclusions: Oral neutrophil levels correlated significantly with conventional parameters of gingival inflammation and may serve as a standardized method for clinical assessment of periodontal diseases in the special needs population.