Дисертації з теми "Phenotying"
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1
Zhou, Felix. "Phenotyping cellular motion." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:9fb6a57d-2e16-43c9-92e6-895330353e51.
Повний текст джерелаАнотація:
In the development of multicellular organisms, tissue development and homeostasis require coordinated cellular motion. For example, in conditions such as wound healing, immune and epithelial cells need to proliferate and migrate. Deregulation of key signalling pathways in pathological conditions causes alterations in cellular motion properties that are critical for disease development and progression, in cancer it leads to invasion and metastasis. Consequently there is strong interest in identifying factors, including drugs that affect the motion and interactions of cells in disease using experimental models suitable for high-content screening. There are two main modes of cell migration; individual and collective migration. Currently analysis tools for robust, sensitive and comprehensive motion characterisation in varying experimental conditions for large extended timelapse acquisitions that jointly considers both modes are limited. We have developed a systematic motion analysis framework, Motion Sensing Superpixels (MOSES) to quantitatively capture cellular motion in timelapse microscopy videos suitable for high-content screening. MOSES builds upon established computer vision approaches to deliver a minimal parameter, robust algorithm that can i) extract reliable phenomena-relevant motion metrics, ii) discover spatiotemporal salient motion patterns and iii) facilitate unbiased analysis with little prior knowledge through unique motion 'signatures'. The framework was validated by application to numerous datasets including YouTube videos, zebrafish immunosurveillance and Drosophila embryo development. We demonstrate two extended applications; the analysis of interactions between two epithelial populations in 2D culture using cell lines of the squamous and columnar epithelia from human normal esophagus, Barrett's esophagus and esophageal adenocarcinoma and the automatic monitoring of 3D organoid culture growth captured through label-free phase contrast microscopy. MOSES found unique boundary formation between squamous and columnar cells and could measure subtle changes in boundary formation due to external stimuli. MOSES automatically segments the motion and shape of multiple organoids even if present in the same field of view. Automated analysis of intestinal organoid branching following treatment agrees with independent RNA-seq results.
2
Ericksen, Daniel S. (Daniel Southwick) 1977. "High-throughput genomic phenotyping." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28527.
Повний текст джерелаАнотація:
Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.Includes bibliographical references (p. 63-65).
In the wake of the development of technology to sequence the complete genome of an organism, it has become expedient to generate methodologies to elucidate and characterize the function of all genes constituting the complete genetic makeup of an organism, whereby the knowledge of the genetic code may be for scientific and intellectual profit. This work consists of an investigation into two possible methods for determining the role of genes involved in the DNA and cellular damage response, though the methods are generally applicable to investigating a wide variety of biological pathways and responses. A library of approximately 4,800 yeast (Saccharomyces cerevisiae) deletion strains produced by the Saccharomyces Genome Deletion Project and consisting essentially of all possible mutants having one non-essential gene deleted (and replaced with unique identification tags called "bar codes") from the genome are employed in this endeavor. The methods focus on gathering phenotype data in a high-throughput manner and in response to the alkylating agent methyl methanesulfonate (MMS). The first method makes use of a new technology called the Living ChipTM, which can hold libraries of compounds or cell cultures in an array of 50-nl channels and which could ideally accommodate all deletion strains on a single array. The second method involves pooling all strains together in a single culture and allowing them to grow competitively to determine their relative fitness based on a specific treatment.
by Daniel S. Ericksen.
S.M.
3
Singh, Shantanu. "Quantitative Phenotyping in Tissue Microenvironments." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306940222.
Повний текст джерела
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Tikhomirova, Victoria E., Olga A. Kost, Olga V. Kryukova, Elena Z. Golukhova, Naida I. Bulaeva, Aigerim Z. Zholbaeva, Leo A. Bokeria, Joe G. N. Garcia, and Sergei M. Danilov. "ACE phenotyping in human heart." PUBLIC LIBRARY SCIENCE, 2017. http://hdl.handle.net/10150/625490.
Повний текст джерелаАнотація:
Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.
5
Wang, Xin. "Inferring cellular networks from phenotyping screens." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648275.
Повний текст джерела
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Edelman, Nicholas (Nicholas A. ). "Automated phenotyping of mouse social behavior." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/76810.
Повний текст джерелаАнотація:
Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 66-68).
Inspired by the connections between social behavior and intelligence, I have developed a trainable system to phenotype mouse social behavior. This system is of immediate interest to researchers studying mouse models of social disorders such as depression or autism. Mice studies provide a controlled environment to begin exploring the questions of how to best quantify social behavior. For the purposes of evaluating this system and to encourage further research, I introduce a new video dataset annotated with five social behaviors: nose-to-nose sniffing, nose-to-head sniffing, nose-to-anogenital sniffing, crawl under / crawl over, and upright head contact. These four behaviors are of particular importance to researchers characterizing mouse social avoidance [9]. To effectively phenotype mouse social behavior, the system incorporates a novel mice tracker, and modules to represent and to classify social behavior. The mice tracker addresses the challenging computer vision problem of tracking two identical, highly deformable mice through complex occlusions. The tracker maintains an ellipse model of both mice and leverages motion cues and shape priors to maintain tracks during occlusions. Using these tracks, the classification system represents behavior with 14 spatial features characterizing relative position, relative motion, and shape. A regularized least squares (RLS) classifier, trained over representative instances of each behavior, classifies the behavior present in each frame. This system demonstrates the enormous potential for building automated systems to quantitatively study mouse social behavior.
by Nicholas Edelman.
M.Eng.
7
Ghadieh, Rachelle. "Phenotyping and heritability of constitutional thinness." Thesis, Lyon, 2021. https://tel.archives-ouvertes.fr/tel-03789601.
Повний текст джерелаАнотація:
Cette thèse est divisée en deux parties l'une consiste une revue de la littérature et la deuxième comprend quatre manuscrits. Peu d'études sur la MC ont été réalisées en Europe, aucune donnée n'est actuellement disponible sur les aspects cliniques et biologiques de la MC au Liban ou dans la région du Moyen-Orient. La pathologie MC reste mal recherchée et mal comprise. Cette première étude évaluant l'héritabilité du MC est menée dans deux cohortes de familles françaises et libanaises de MC a démontré que MC est un caractère héritable. La transmission génétique de ce caractère semble le plus souvent être autosomique récessive.La deuxième étude visée a caractériser plusieurs caractéristiques métaboliques et nutritionnelles dans une cohorte libanaise de sujets MC. L'étude est la première du genre dans la région du Moyen-Orient et peut être considérée comme une base pour une comparaison multinationale de cet état de sous-poids. Il a démontre pour la première fois que les libanaises n'ont pas de signes de déficit et confirme les principales caractéristiques nutritionnelles décrites précédemment dans les cohortes françaises. Les petites différences décrites doivent être confirmées par des cohortes plus grandes.La troisième étude était la première étude validant la forme arabe du DEBQ. Ce n'est pas un simple travail de validation, les facteurs associés au DEBQ ont également été étudiés. DEBQ est un outil pratique pour catégoriser les facteurs comportementaux liés aux habitudes alimentaires individuelles, y compris ceux impliqués dans les troubles de l'alimentation. Le manuscrit de la revue de la littérature a été construit et structuré comme complément au manuscrit évaluant l'héritage de la MC. Finalement, la MC est un nouveau sujet et la plupart des études ont été menées sur les jeunes femmes CT à Saint-Etienne, France. Il est de grande importance de conduire plus de recherches sur la MC pour comprendre les mécanismes et l'héritabilité de l'extrême minceur et trouver l'explication de ce phénomène pourrait être une étape dans le traitement de l'obésité et pour répondre à la demande de la MC et satisfaire leur désir de prendre du poidsThis thesis is divided into two parts one consisting of a review of the literature and the second one involves four manuscripts. few studies on CT were done in Europe, no data is currently available on clinical and biological aspects of constitutional thinness in Lebanon or the middle east region. CT pathology remains poorly researched and understood. This first study evaluating the heritability of CT and conducted in two cohorts of french and lebanese CT families demonstrated that CT runs in families and is a heritable trait. The genetic transmission of this trait seem to be most often autosomal recessive. The second study aimed to characterize several metabolic and nutritional features in a lebanese cohort of CT subjects. the study is the first of its kind in the middle east region and can be considered as a base for a multinational comparison of this underweight state. It demonstrated for the first time that lebanese CT persons have no signs of deficits and confirmed the major nutrition features previously described in french cohorts. Small differences described for the first time need to be confirmed by larger cohorts. The third study was the first study validating the arabic form of DEBQ. It’s not just a simple validation work, factors associated with DEBQ were also studied. DEBQ is a convenient tool to categorize behavioral factors related to individual eating patterns, including those implicated in eating disorders.The literature review manuscript was constructed and structured as a complement to the manuscript evaluating the inheritability in constitutional thinness. Overall, CT is a new topic and most studies were conducted on CT young women in Saint-Etienne - France. It is of high importance to conduct more research on CT to understand the mechanisms and heritability of extreme thinness and finding the explanation behind this phenomenon might be a step in the treatment of obesity and to meet the ct's demand and satisfy their desire to gain weight
8
Barker, Jared W. III. "Development of a field-based high-throughput mobile phenotyping platform." Thesis, Kansas State University, 2014. http://hdl.handle.net/2097/17543.
Повний текст джерелаАнотація:
Master of ScienceDepartment of Biological and Agricultural Engineering
Naiqian Zhang
In order to meet food, fiber, and bio-fuel needs of a growing world population, crop-breeding methods must be improved and new technologies must be developed. One area under focus is the decoding of the genetic basis of complex traits, such as yield and drought stress tolerance, and predicting these traits from genetic composition of lines or cultivars. In the last three decades, significant advances in genotyping methods have resulted in a wealth of genomic information; however, little improvement has occurred for methods of collecting corresponding plant trait data, especially for agronomic crops. This study developed a mobile, field-based, high-throughput sensor platform for rapid and repeated measurement of plant characteristics. The platform consisted of three sets of sensors mounted on a high-clearance vehicle. Each set of sensors contained two infrared thermometers (IRT), one ultrasonic sensor, one Crop Circle, and one GreenSeeker. Each sensor set measured canopy temperature, crop height, and spectral reflectance. In addition to the sensors, the platform was equipped with an RTK-GPS system that provided precise, accurate position data for georeferencing sensor measurements. Software for collecting, georeferencing, and logging sensor data was developed using National Instruments LabVIEW and deployed on a laptop computer. Two verification tests were conducted to evaluate the phenotyping system. In the first test, data timestamps were analyzed to determine if the system could collect data at the required rate of 10 Hz and 5 Hz for sensor data and position data, respectively. The determination was made that, on average, IRT, ultrasonic, and Crop Circle data are received in intervals of 100 ms (SD = 10 ms), GreenSeeker data are received in intervals of 122 ms(SD=10 ms), and position data are received in intervals of 200 ms (SD = 32 ms). The second test determined that a statistically significant relationship exists between sensor readings and ambient light intensity and ambient temperatures. Whether the relationship is significant from a practical stand point should be determined based on specific application of the sensors.
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Pari, Marco. "Image Analysis Methods for Sugar Beet Phenotyping." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/10533/.
Повний текст джерелаАнотація:
In un mondo che richiede sempre maggiormente un'automazione delle attività della catena produttiva industriale, la computer vision rappresenta uno strumento fondamentale perciò che viene già riconosciuta internazionalmente come la Quarta Rivoluzione Industriale o Industry 4.0. Avvalendomi di questo strumento ho intrapreso presso l'azienda Syngenta lo studio della problematica della conta automatica del numero di foglie di una pianta. Il problema è stato affrontato utilizzando due differenti approcci, ispirandosi alla letteratura. All'interno dell'elaborato è presente anche la descrizione progettuale di un ulteriore metodo, ad oggi non presente in letteratura. Le metodologie saranno spiegate in dettaglio ed i risultati ottenuti saranno confrontati utilizzando i primi due approcci. Nel capitolo finale si trarranno le conclusioni sulle basi dei risultati ottenuti e dall'analisi degli stessi.
10
Thomas, Shery. "Phenotyping and genotyping of idiopathic infantile nystagmus." Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/7973.
Повний текст джерелаАнотація:
Background: Nystagmus can be a manifestation of ocular or systemic disorders. However, it may represent a separate disease entity by itself as in idiopathic infantile nystagmus (IIN). In 2004, Kerrison et al. localised the gene causing X-linked IIN to Xq26-27 (NYS1); however, the gene/genes causing IIN had not been identified. Aims and Objectives: The aims of this study were threefold. 1. To ascertain families and singletons (sporadic subjects) with IIN. 2. To further refine the locus NYS1 and to identify the gene causing X-linked IIN 3. To describe and compare the phenotype of subjects with IIN Methods: 39 families and 78 singletons with nystagmus were recruited and phenotyped. Genotyping with microsatellite markers were performed in the X-linked families to refine the genetic interval at Xq26-27. Gene sequencing was carried out by our collaborators (not by the author) at the Sanger Institute. The clinical features and eye movement recordings of 90 subjects with mutations in the FRMD7 gene were compared to 48 subjects with IIN not associated with mutations in this gene (non-FRMD7 group). Results: I: 149 familial subjects and 78 sporadic subjects with IIN were phenotyped. 121 subjects from 30 families were diagnosed to have X-linked IIN while 28 subjects from 9 families had other diagnosis such as albinism and aniridia. II: Genetic mapping in 16 families with X-linked IIN, refined the critical interval at Locus NYS1 (Xq26-17) to a 9mB region between markers DXS8072 and DXS8094 which contained about 80 genes. High throughput DNA sequencing was carried out at the Sanger Institute which led to the discovery of FRMD7, mutations in which is associated with X-linked IIN. III: The median visual acuity in subjects with a FRMD7 mutation was log MAR 0.301. The number of subjects with good stereopsis (Lang positive) was higher in the FRMD7 group (93.4%) compared to subjects in the non- FRMD7 group (78.4%). None of the subjects in the FRMD7 group had severe (>15˚) anomalous head posture (AHP) while 27% of subjects in the non-FRMD7 group had AHP more than 15˚. 52.17% of obligate female carriers of a FRMD7 mutation were clinically affected. Discussion: This study identified the first gene causing idiopathic infantile nystagmus. The phenotypic characteristics of these subjects will help in clinically identifying subjects with IIN due to mutations in FRMD7. In addition it has generated a stage for further research into the mechanisms behind ocular motor control.
11
Wolfer, Arnaud. "Time-dependent metabolic phenotyping of inflammatory dysregulation." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/58241.
Повний текст джерелаАнотація:
A rich and functional description of a patient health status is the fundamental basis for the personalisation of treatment and the targeting of interventions. The function of inflammation in the healing process as well as its involvement in most major diseases is well established, yet the specific mechanism by which it contributes to the pathogenesis is still not fully understood. If conditions arising from a dysregulation of the inflammatory process are to be treated before they become irreversible, a novel understanding of these pathologies must be achieved and a stratification of patients based on their inflammatory status undertaken. The work presented in this thesis aims to deliver new analytical and statistical approaches to support the investigation of the time-dependent dysregulation of inflammation. Lipid mediators have been described as exerting a major role in the initiation and regulation of the inflammatory response, yet analytical platforms for their large-scale characterisation in human biofluids are lacking. This thesis reports the validation of an assay for the simultaneous quantification of pro- and anti-inflammatory signalling molecules in multiple human biofluids. The coverage of the assay in each biofluid is subsequently established, characterising inflammatory signalling across biological compartments. A second study explores the assay’s applicability in a clinical context; investigating the relationship between lipid mediators, current clinical markers of inflammation and post-operative complications. Characterising the interplay between signalling and regulatory networks is key to understanding a living system’s response to perturbations, yet few statistical approaches are suited for the detection of time-dependent patterns in short and irregularly sampled longitudinal datasets. This thesis reports the development of a statistical approach to support the identification of altered time-trajectories in such studies. The method’s wide applicability is subsequently demonstrated on two investigations covering the diversity of metabolic phenotyping data generation platforms. This thesis is a proof of concept for the characterisation of patient-specific inflammatory status in a clinical context and the identification of altered time-dependent patterns. Both analytical and statistical developments have been motivated by the needs of real world applications and provide a template for the characterisation and analysis of the molecular basis for treatment.
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Thomas, Rhys Huw. "Phenotyping paroxysmal conditions to empower genetic research." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/44849/.
Повний текст джерелаАнотація:
I describe the process of preparing cohorts of individuals with two paediatric onset paroxysmal disorders – hyperekplexia and juvenile myoclonic epilepsy – for second generation sequencing. This involves: i) listening to the individual; ii) identifying subgroups; iii) using non-‐core features to create subgroups; iv) and assessing the importance of copy number variation. Using focus groups and an interpretative phenomenological approach clinicians and people with epilepsy produced 398 questions focused on epilepsy treatment. The most important themes for the professionals were – teatment pogrammes or non-‐epileptic attack disorder and concerns about side effectsinutero.For patients cognitive drug side effects and managing the consequences of drug side effects were most important. Studying ninety-‐seven individuals with hyperekplexia confirmed that all gene-‐positive cases present in the neonatal period and that clonazepam is the treatment of choice (95% found it efficacious). Patients with SLC6A5 and GLRB mutations were more likely to have developmental delay (RR1.5 p<0.01; RR1.9 p<0.03) than those with GLRA1 mutations; 92% of GLRB cases reported a mild to severe delay in speech acquisition. Juvenile myoclonic epilepsy is challenging to subdivide based on seizure and EEG features. The neuropsychological profile of limited number of patients 39) as examined in great detail including tests Q WAIS), emory TYM,WMS),executive function (BADS, DKEFS), affect (HADS). TYM was as sensitive as a full WMS for identifying cognitive errors and the zoo map and key search tests were performed particularly poorly. Personality profiling (EPQ-‐BV) identifies the cohort as having high levels of neurotic and introvert traits. Three atypical ‘hyperekplexia’ cases had alternative diagnoses suggested by copy number analysis. The juvenile myoclonic epilepsy patients had an 8% frequency of recognised pathogenic CNVs– but no recurrent variants were identified.A number of non-‐epilepsy related findings were identified including a potentially preventable cause of SUDEP.
13
Atkinson, Jonathan A. "Phenotyping root architecture in diverse wheat germplasm." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/30478/.
Повний текст джерелаАнотація:
Wheat is a crop of global importance accounting for 20% of global calorie consumption and a similar percentage of the daily protein for 2.5 billion people in less developed countries. To meet the food production demands of a predicted global population of 9 billion people by 2050, wheat yields need to increase by 1.7% per annum, whilst facing the added pressures of reduced fertilizer inputs and potentially reduced land availability. Plant root systems are key for efficient water and nutrient uptake and thus have a direct impact on yield, and yet there has been competitively little research into root system improvement. A high-throughput root phenotyping pipeline for wheat seedlings was designed consisting of a germination paper-based growth system combined with image segmentation and analysis software. A number of lines from the A.E. Watkins landrace population were characterised to test the final pipeline design. The pipeline was then utilized to phenotype a population of 94 lines from a doubled haploid population for quantitative trait loci (QTL) discovery. In total, 29 root QTL were discovered, with 2 loci co-localising with QTL for grain yield and nitrogen uptake efficiency discovered in field trials. Modern wheat varieties may have limited genetic diversity, due to changes in ploidy throughout evolution and subsequent domestication. With this in mind, thirty five ancient wheat relatives and eighteen amphidiploid hybrids were phenotyped for seedling root architectural traits, to determine the amount of phenotypic variation within ancient wheat species, and whether this variation can be transferred to modern varieties. The utilization of seedling root trait phenotyping is discussed and future research directions are identified.
14
Kiang, Tony (Kuo-Liang). "Valproic acid : mechanisms of hepatotoxicity and reaction phenotyping." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/16684.
Повний текст джерелаАнотація:
Valproic acid (VPA) therapy is associated with a rare but severe hepatotoxicity. The relationships between the various pathophysiological findings of VPA-induced hepatotoxicity and the role of VPA biotransformation in the induction of hepatotoxicity have not been systematically investigated. The present thesis compared the effects of VPA, synthesized VPA metabolites, and alpha-F-VPA on markers of mitochondrial dysfunction (WST-1), cytotoxicity (LDH), oxidative stress (DCF), and glutathione (GSH) depletion in a novel model of sandwich-cultured rat hepatocytes (SCRH). The contribution of the CYP- and UGT-mediated biotransformation of VPA in VPA-induced toxicity was also examined. Time-dependent effects of VPA on GSH depletion were characterized in relation to the effects of VPA on the WST-1, LDH, and DCF markers. The effects of glutathione supplementation on the attenuation of the markers for VPA-induced toxicities were investigated. Urine samples from children on VPA therapy were assayed to correlate levels of VPA metabolites with the lipid peroxidation marker, 15-F2t-isoprostane. Lastly, the contributions of hepatic CYP-enzymes in the oxidative metabolism of VPA were characterized in human liver microsomes.
Our findings in SCRH indicated that (E)-2,4-diene-VPA was the only exogenously administered metabolite tested that was consistently more toxic than VPA. Consistent with this finding, alpha-F-VPA, which is resistant to bioactivation by several biotransformation pathways, was nontoxic. Chemical inhibition experiments indicated that the CYP- and UGT-mediated metabolism of VPA or the in situ generated VPA metabolites were unlikely involved in the observed VPA-induced toxicities in SCRH. Furthermore, VPA-associated GSH depletion appeared not to be a factor in the mitochondrial dysfunction, but may play a partial role in VPA-induced cytotoxicity. GSH may serve a protective role against VPA-induced oxidative stress in SCRH. In human subjects, the VPA-glucuronide or N-acetylcysteine metabolites were extremely weak but statistically significant predictors of lipid peroxidation in the urine of children receiving VPA. From the reaction phenotyping experiments, CYP2C9 was the major catalyst for the formation of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA in human liver microsomes, whereas CYP2A6 contributed partially to 3-OH-VPA formation. Overall, these findings add significant knowledge to the role of VPA and its metabolites in the induction of hepatotoxicity and how VPA is metabolized in humans.
15
Cheang, Mun Hong. "Comprehensive cardiovascular phenotyping of children with renal disease." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10059369/.
Повний текст джерелаАнотація:
Children with chronic kidney disease (CKD) have significantly increased cardiovascular mortality. The reasons for this remain unclear, as the pathological effects of renal disease have not been well characterised. This is because current methods of assessment like echocardiography have significant limitations. Cardiovascular magnetic resonance imaging (CMR) is the reference standard method for cardiovascular assessment. Therefore, the aim of this thesis is to investigate the utility of CMR for the cardiovascular assessment of children with renal disease. Three separate studies were carried out to comprehensively characterise the cardiovascular phenotype in the following groups: pre-dialysis CKD, dialysis dependent CKD and renovascular hypertension. They were compared with a control group of healthy and essential hypertension children. All subjects underwent a CMR study with non-invasive blood pressure measurements. The protocol included novel sequences that assessed diastolic function and myocardial velocity, in addition to conventional measures. Between group ANOVA comparisons were performed as described; mild, moderate and severe pre-dialysis CKD (n=100) versus healthy children (n=20), Haemodialysis (n=9), peritoneal dialysis (n=8), pre-dialysis CKD stage 5 (n=10) versus healthy children (n=10), and renovascular hypertension (n=15), essential hypertension (n=15) versus healthy children (n=15).Blood pressure and systemic vascular resistance (SVR) were elevated while total arterial compliance was normal in all renal patients. There was also evidence of left ventricular remodelling without hypertrophy in pre-dialysis and renovascular children. Diastolic dysfunction was present in all renal patients. Systolic myocardial velocity was impaired only in CKD but not in renovascular hypertension. In conclusion, CMR offers valuable insight into the cardiovascular characteristics of renal disease. Hypertension in renal disease is predominantly secondary to elevated SVR. Diastolic impairment preceded left ventricular hypertrophy. Sub-clinical systolic dysfunction was also present in renal dysfunction. Further studies are warranted to investigate the future role of CMR for cardiovascular risk assessment in paediatric renal disease.
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Jackson, Frances. "Metabolic phenotyping and metagenomic analysis of developing infants." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/58184.
Повний текст джерелаАнотація:
Early life experiences, including mode of delivery and nutrition during the neonatal period, have been proven to have an impact on health in later life. Studying human metabolic development has major implications for understanding the aetiology and risk of disease, including metabolic syndrome. Initially, a sample preparation protocol was developed and optimised using metabonomic procedures for studying urine and faeces from infants, to accommodate for limited sample volume and to take into account the compositional differences between adult and infant biofluids. This primarily indicated that age is an important variable that contributes to the metabolic profile of biofluids. Faecal metabonomics is fast becoming a useful tool for defining interactions among host, microbial communities and nutritional interventions. Infant development trajectory was assessed through analysis of faecal metabolic profiling by 1H NMR. A large non-clinical cohort longitudinal study was obtained; 1802 faecal samples from 524 infants at 6 time points from 4 days to 730 days postpartum. Furthermore, 1H NMR, UPLC-MS and metagenomic phenotyping techniques was performed on urine (n=278) and faecal (n=308) samples from 150 infants born term or preterm (< 37 wks gestational age). This multi-omics approach provided further demonstration of contribution of microbial co-metabolites to infant metabolism early in life and therefore the potential impact on overall health. This PhD project was able to identify certain metabolic pathways which were shown to be different in relation to gestation age as well as postnatal age, mode of delivery, BMI status and nutrition. In particular, choline and methylamine derivatives (e.g. betaine, trimethylamine), short chain fatty acids (SCFA) and amino acids related to nutrition and the gut microbiome functionality as well as metabolites indicating infant renal development from birth (e.g. myo-inositol, 1-N-methylnicotinamide). Overall, these investigations have shown that an understanding of the sources of variation in biofluid metabolite profiles are essential for interpretation of data acquired during normal infant development.
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Wang, Qianru Ph D. Massachusetts Institute of Technology. "Electrical-phenotyping of the bacterial envelope using microfluidics." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120197.
Повний текст джерелаАнотація:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 109-118).
The bacterial cell envelope is a complex multi-layered covering, crucial for cell viability and physiological capabilities. Phenotypic analysis of bacterial envelopes is challenging due to the small size and low cultivability of microbes. The emerging microfluidic techniques enable quantitative and nondestructive probing of cell envelopes by measuring their physical properties. This thesis demonstrates that phenotypic variations on bacterial envelopes change their surface polarizability-an intrinsic dielectric property-in a manner that can be distinguished by microfluidic dielectrophoresis (DEP). The three-dimensional insulator-based dielectrophoresis (3DiDEP), a microfluidic technique previously reported by our group, was optimized to explore the diverse surface phenotypes of bacterial electrochemical activity and lipopolysaccharide (LPS) biosynthesis. Electrochemically active bacteria transport electrons directly from their interior to external insoluble electron accepters, e.g. metal oxides or electrodes in electrochemical systems, via a process known as extracellular electron transfer (EET), holding an exciting promise in energy conversion and bioremediation. Using 3DiDEP, we demonstrate for the first time the strong correlation between microbial EET and cell surface polarizability, generalizable to three bacterial species with variant electrochemical activities, including Geobacter sulfurreducens, Shewanella oneidensis, and Escherichia coli heterologously expressing Shewanella EET pathways. We also applied 3DiDEP to achieve rapid quantification of LPS, the major component and virulence determinant in Gram-negative bacterial outer membrane. We examined E. coli mutant strains with various LPS components truncated, and show that structural diversity in LPS affects the trapping voltages required for 3DiDEP cell immobilization. Last but not least, we studied the interplay of electrothermal and induced charge electroosmosis (ICEO) flows, which can interfere DEP operations but are often overlooked in the design of iDEP systems. The effects of fluidic ionic strength, applied electric field, and insulating channel geometry on temperature rise and fluid velocities were investigated from a theoretical and experimental viewpoint. Taken together, this thesis introduces surface polarizability as a novel physical property for assessing microbial EET and LPS composition. Dielectrophoretic screening of bacterial envelope polarizability may unlock a vast repertoire of EET- and LPS- related biochemical applications, and will be useful as guidance for further DEP-based phenotypic analysis of a diverse array of cells and organisms.
by Qianru Wang.
Ph. D.
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Sawiak, Stephen John. "Computational methods for mouse brain phenotyping using MRI." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611550.
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Cleary, J. O. S. "High-throughput transgenic mouse phenotyping using microscopic-MRI." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1347518/.
Повний текст джерелаАнотація:
With the completion of the human genome sequence in 2003, efforts have shifted towards elucidating gene function. Such phenotypic investigations are aided by advances in techniques for genetic modification of mice, with whom we share ~99% of genes. Mice are key models for both examination of basic gene function and translational study of human conditions. Furthering these efforts, ambitious programmes are underway to produce knockout mice for the ~25,000 mouse genes. In the coming years, methods to rapidly phenotype mouse morphology will be in great demand. This thesis demonstrates the development of non-invasive microscopic magnetic resonance imaging (\muMRI) methods for high-resolution ex-vivo phenotyping of mouse embryo and mouse brain morphology. It then goes on to show the application of computational atlasing techniques to these datasets, enabling automated analysis of phenotype. First, the issue of image quality in high-throughput embryo MRI was addressed. After investigating preparation and imaging parameters, substantial gains in signal- and contrast-to-noise were achieved. This protocol was applied to a study of Chd7+/- mice (a model of CHARGE syndrome), identifying cardiac defects. Combining this protocol with automated segmentation-propagation techniques, phenotypic differences were shown between three groups of mice in a volumetric analysis involving a number of organ systems. Focussing on the mouse brain, the optimal preparation and imaging parameters to maximise image quality and structural contrast were investigated, producing a high-resolution in-skull imaging protocol. Enhanced delineation of hippocampal and cerebellar structures was observed, correlating well to detailed histological comparisons. Subsequently this protocol was applied to a phenotypic investigation of the Tc1 model of Down syndrome. Using both visual inspection and automated, tensor based morphometry, novel phenotypic findings were identified in brain and inner ear structures. It is hoped that a combination of \muMRI with computational analysis techniques, as presented in this work, may help ease the burden of current phenotyping efforts.
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Christenson, Brent Scott. "Characterization of soybean seed yield using optimized phenotyping." Thesis, Kansas State University, 2013. http://hdl.handle.net/2097/16030.
Повний текст джерелаАнотація:
Master of ScienceDepartment of Agronomy
William T. Schapaugh Jr
Crops research moving forward faces many challenges to improve crop performance. In breeding programs, phenotyping has time and economic constraints requiring new phenotyping techniques to be developed to improve selection efficiency and increase germplasm entering the pipeline. The objectives of these studies were to examine the changes in spectral reflectance with soybean breeding from 1923 to 2010, evaluate band regions most significantly contributing to yield estimation, evaluate spectral reflectance data for yield estimation modeling across environments and growth stages and to evaluate the usefulness of spectral data as an optimized phenotyping technique in breeding programs. Twenty maturity group III (MGIII) and twenty maturity group IV (MGIV) soybeans, arranged in a randomized complete block design, were grown in Manhattan, KS in 2011 and 2012. Spectral reflectance data were collected over the growing season in a total of six irrigated and water- stressed environments. Partial least squares and multiple linear regression were used for spectral variable selection and yield estimation model building. Significant differences were found between genotypes for yield and spectral reflectance data, with the visible (VI) having greater differences between genotypes than the near-infrared (NIR). This study found significant correlations with year of release (YOR) in the VI and NIR portions of the spectra, with newer released cultivars tending to have lower reflectance in the VI and high reflectance in the NIR. Spectral reflectance data accounted for a large portion of variability for seed yield between genotypes using the red edge and NIR portions of the spectra. Irrigated environments tended to explain a larger portion of seed yield variability than water-stressed environments. Growth stages most useful for yield estimation was highly dependent upon the environment as well as maturity group. This study found that spectral reflectance data is a good candidate for exploration into optimized phenotyping techniques and with further research and validation datasets, may be a suitable indirect selection technique for breeding programs.
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Dandekar, Samantha Sujata. "Detailed clinical phenotyping in Age-related Macular Degeneration." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444668/.
Повний текст джерелаАнотація:
Age-related Macular Degeneration (AMD) is a degenerative disorder that accounts for about 50% of blindness in England and Wales. At present there is no effective treatment. It occurs in genetically susceptible individuals exposed to environmental factors such as smoking but so far specific factors remain to be identified. For this descriptive study, 879 patients with Age-Related Maculopathy (ARM) and AMD and 44 spouses with normal maculae, to act as a comparison group, were recruited from a tertiary referral centre. The clinical phenotypes were analysed from fundus photographs, fluorescein angiography and autofluorescence (AF) images. Fundus features were characterised as they are thought to reflect the genes conferring risk in an individual and may allow greater understanding of disease mechanisms. These data demonstrated (1) A revised grading system shown to be reproducible for use with digital images (2) A moderate concordance rate for phenotype between eyes with end- stage AMD (kappa statistic=0.48 95% CI = 0.38-0.57, p0.001). (3) Distinct characteristics, including a larger area and higher counts of soft drusen with focal areas of increased AF, in fellow eyes of those with unilateral visual loss due to geographic atrophy (GA). (4) An increased susceptibility of the inferotemporal macula to GA. (5) Preserved integrity of the retinal pigment epithelium (RPE) in the initial stages of CNV development as identified from AF images. (6) Loss of scotopic rather than photopic function over areas of increased AF, as determined by fine matrix mapping, indicating the preferential vulnerability of rods. (7) No difference in smoking history between those with neovascular compared to non-neovascular AMD. Although AMD has been extensively investigated, this study extends our knowledge of retinal AF, the relative susceptibility of rods compared to cones at the macula and suggests both eyes of an individual are more discordant for late stages of AMD compared to drusen.
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Norris, F. C. "Mouse embryo phenotyping using high-resolution 3D imaging." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1418468/.
Повний текст джерелаАнотація:
The immense challenge of annotating the entire mouse genome has stimulated development of cutting-edge imaging technologies in a drive for novel information. These techniques promise to improve our understanding of the genes involved in embryo development, at least one third of which have been shown to be essential. Aligning advanced imaging technologies with biological needs will be fundamental to maximising the number of phenotypes discovered in the coming years. International efforts are underway to meet this challenge through an integrated and sophisticated approach to embryo phenotyping, which will include advanced imaging tools. This thesis investigates advanced imaging methodologies and computational image analysis techniques for mouse embryo phenotyping using magnetic resonance imaging (MRI). Additionally, the novel application of an emerging method called photoacoustic imaging is demonstrated for imaging mouse embryos in utero. First, the lack of tissue staining capabilities that currently limits embryo MR imaging was addressed by investigating the MRI staining properties of two readily available contrast agents and their underlying contrast enhancement mechanisms. A methodological framework was developed for high-throughput screening of embryos using diffusion MRI and implemented to study the splotch mouse model of human neural tube defects. A validation study was carried out to comprehensively assess the accuracy of volumetric measurements generated using a computational image analysis method called segmentation propagation. Finally, an all-optical photoacoustic scanner and novel time-reversal image reconstruction algorithm were developed, enabling photoacoustic imaging of whole embryos in utero. Overall, this thesis presents advanced imaging methodologies and computational image analysis techniques that may form an essential part of the toolkit available for annotating the mouse genome and facilitate identification of novel phenotypes in the coming years.
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McGill, Laura-Ann. "Novel cardiovascular magnetic resonance phenotyping of the myocardium." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/49247.
Повний текст джерелаАнотація:
INTRODUCTION: Left ventricular (LV) microstructure is unique, composed of a winding helical pattern of myocytes and rotating aggregations of myocytes called sheetlets. Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease characterised by left ventricular hypertrophy (LVH), however the link between LVH and underlying microstructural aberration is poorly understood. In vivo cardiovascular diffusion tensor imaging (cDTI) is a novel cardiovascular MRI (CMR) technique, capable of characterising LV microstructural dynamics non-invasively. In vivo cDTI may therefore improve our understanding microstructural-functional relationships in health and disease. METHODS AND RESULTS: The monopolar diffusion weighted stimulated echo acquisition mode (DW-STEAM) sequence was evaluated for in vivo cDTI acquisitions at 3Tesla, in healthy volunteers (HV), patients with hypertensive LVH, and HCM patients. Results were contextualised in relation to extensively explored technical limitations. cDTI parameters demonstrated good intra-centre reproducibility in HCM, and good inter-centre reproducibility in HV. In all subjects, cDTI was able to depict the winding helical pattern of myocyte orientation known from histology, and the transmural rate of change in myocyte orientation was dependent on LV size and thickness. In HV, comparison of cDTI parameters between systole and diastole revealed an increase in transmural gradient, combined with a significant re-orientation of sheetlet angle. In contrast, in HCM, myocyte gradient increased between phases, however sheetlet angulation retained a systolic-like orientation in both phases. Combined analysis with hypertensive patients revealed a proportional decrease in sheetlet mobility with increasing LVH. CONCLUSION: In vivo DW-STEAM cDTI can characterise LV microstructural dynamics non-invasively. The transmural rate of change in myocyte angulation is dependent on LV size and wall thickness, however inter phase changes in myocyte orientation are unaffected by LVH. In contrast, sheetlet dynamics demonstrate increasing dysfunction, in proportion to the degree of LVH. Resolving technical limitations is key to advancing this technique, and improving the understanding of the role of microstructural abnormalities in cardiovascular disease expression.
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Babahosseini, Hesam. "Single Cell Biomechanical Phenotyping using Microfluidics and Nanotechnology." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/64502.
Повний текст джерелаАнотація:
Cancer progression is accompanied with alterations in the cell biomechanical phenotype, including changes in cell structure, morphology, and responses to microenvironmental stress. These alterations result in an increased deformability of transformed cells and reduced resistance to mechanical stimuli, enabling motility and invasion. Therefore, single cell biomechanical properties could be served as a powerful label-free biomarker for effective characterization and early detection of single cancer cells. Advances and innovations in microsystems and nanotechnology have facilitated interrogation of the biomechanical properties of single cells to predict their tumorigenicity, metastatic potential, and health state.
This dissertation utilized Atomic Force Microscopy (AFM) for the cell biomechanical phenotyping for cancer diagnosis and early detection, efficacy screening of potential chemotherapeutic agents, and also cancer stem-like/tumor initiating cells (CSC/TICs) characterization as the critical topics received intensive attention in the search for effective cancer treatment. Our findings demonstrated the capability of exogenous sphingosine to revert the aberrant biomechanics of aggressive cells and showed a unique, mechanically homogeneous, and extremely soft characteristic of CSC/TICs, suitable for their targeted isolation. To make full use of cell biomechanical cues, this dissertation also considered the application of nonlinear viscoelastic models such as Fractional Zener and Generalized Maxwell models for the naturally complex, heterogeneous, and nonlinear structure of living cells.
The emerging need for a high-throughput clinically relevant alternative for evaluating biomechanics of individual cells led us to the development of a microfluidic system. Therefore, a high-throughput, label-free, automated microfluidic chip was developed to investigate the biophysical (biomechanical-bioelectrical) markers of normal and malignant cells.
Most importantly, this dissertation also explored the biomechanical response of cells upon a dynamic loading instead of a typical transient stress. Notably, metastatic and non-metastatic cells subjected to a pulsed stress regimen exerted by AFM exhibited distinct biomechanical responses. While non-metastatic cells showed an increase in their resistance against deformation and resulted in strain-stiffening behavior, metastatic cells responded by losing their resistance and yielded slight strain-softening. Ultimately, a second generation microfluidic chip called an iterative mechanical characteristics (iMECH) analyzer consisting of a series of constriction channels for simulating the dynamic stress paradigm was developed which could reproduce the same stiffening/softening trends of non-metastatic and metastatic cells, respectively. Therefore, for the first time, the use of dynamic loading paradigm to evaluate cell biomechanical responses was used as a new signature to predict malignancy or normalcy at a single-cell level with a high (~95%) confidence level.Ph. D.
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Dammannagari, Gangadhara Shravan. "Mobile high-throughput phenotyping using watershed segmentation algorithm." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/35387.
Повний текст джерелаАнотація:
Master of ScienceDepartment of Computing and Information Sciences
Mitchell L. Neilsen
This research is a part of BREAD PHENO, a PhenoApps BREAD project at K-State which combines contemporary advances in image processing and machine vision to deliver transformative mobile applications through established breeder networks. In this platform, novel image analysis segmentation algorithms are being developed to model and extract plant phenotypes. As a part of this research, the traditional Watershed segmentation algorithm has been extended and the primary goal is to accurately count and characterize the seeds in an image. The new approach can be used to characterize a wide variety of crops. Further, this algorithm is migrated into Android making use of the Android APIs and the first ever user-friendly Android application implementing the extended Watershed algorithm has been developed for Mobile field-based high-throughput phenotyping (HTP).
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Weindl, Karin. "Cognitive phenotyping of wildtype and mutant mouse lines." kostenfrei, 2008. http://mediatum2.ub.tum.de/doc/644688/644688.pdf.
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Coxon, Thomas Liam. "2D and 3D phenotyping murine models of Amelogenesis imperfecta." Thesis, University of Liverpool, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539608.
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Boyd, Joseph. "Deep learning for computational phenotyping in cell-based assays." Thesis, Université Paris sciences et lettres, 2020. https://pastel.archives-ouvertes.fr/tel-02928984.
Повний текст джерелаАнотація:
Le phénotypage computationnel est un ensemble de technologies émergentes permettant d’étudier systématiquement le rôle du génome dans l’obtention de phénotypes, les caractéristiques observables d’un organisme et de ses sous- systèmes. En particulier, les essais cellulaires permettent de cribler des panels de petites molécules ou de moduler l’expression des gènes, et de quantifier les effets sur les caractéristiques phénotypiques allant de la viabilité à la morphologie cellulaire. Le criblage à haut contenu étend les méthodologies des criblages cellulaires à une lecture à haut contenu basée sur des images, en particulier les canaux multiplexés de la microscopie à fluorescence. Les cribles basés sur de multiples lignées cellulaires sont aptes à différencier les phénotypes de différents sous-types d’une maladie, représentant l’hétérogénéité moléculaire concernée dans la conception de thérapies médicales de précision. Ces modèles biologiques plus riches sous-tendent une approche plus ciblée pour le traitement de maladies mortelles telles que le cancer. Un défi permanent pour le criblage à haut contenu est donc la synthèse des lectures hétérogènes dans les cribles à multiples lignées cellulaires. Parallèlement, l’état de l’art établi en matière d’applications d’analyse d’images et de vision par ordinateur est l’apprentissage profond. Cependant, son rôle dans le criblage à haut contenu ne fait que commencer à être réalisé. Cette thèse aborde deux problématiques de l’analyse à haut contenu des lignées cellulaires cancéreuses. Les contributions sont les suivantes : (i) une démonstration du potentiel d’apprentissage profond et de modèles générateurs dans le criblage à haut contenu ; (ii) une solution basée sur l’apprentissage profond au problème de l’hétérogénéité dans un criblage de médicaments sur plusieurs lignées cellulaires ; et (iii) de nouvelles applications de modèles de traduction d’image à image comme alternative à la microscopie à fluorescence coûteuse actuellement nécessaire pour le criblage à haut contenuComputational phenotyping is an emergent set of technologies for systematically studying the role of the genome in eliciting phenotypes, the observable characteristics of an organism and its subsystems. In particular, cell-based assays screen panels of small compound drugs or otherwise modulations of gene expression, and quantify the effects on phenotypic characteristics ranging from viability to cell morphology. High content screening extends the methodologies of cell-based screens to a high content readout based on images, in particular the multiplexed channels of fluorescence microscopy. Screens based on multiple cell lines are apt to differentiating phenotypes across different subtypes of a disease, representing the molecular heterogeneity concerned in the design of precision medicine therapies. These richer biological models underpin a more targeted approach for treating deadly diseases such as cancer. An ongoing challenge for high content screening is therefore the synthesis of the heterogeneous readouts in multi-cell-line screens. Concurrently, deep learning is the established state-of-the-art image analysis and computer vision applications. However, its role in high content screening is only beginning to be realised. This dissertation spans two problem settings in the high content analysis of cancer cell lines. The contributions are the following: (i) a demonstration of the potential for deep learning and generative models in high content screening; (ii) a deep learning-based solution to the problem of heterogeneity in a multi-cell-line drug screen; and (iii) novel applications of image-to-image translation models as an alternative to the expensive fluorescence microscopy currently required for high content screening
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Johnson, David Herbert. "Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1250086728.
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Johnson, David Herbert. "Phenotyping rodents models of obesity using magnetic resonance imaging." Cleveland, Ohio : Case Western Reserve University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1250086728.
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Spratt, Christopher. "Development of behavioural tasks for phenotyping of transgenic mice." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/23201.
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Decalmer, Samantha Clare. "Phenotyping patients with chronic cough presenting to a specialist clinic." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494302.
Повний текст джерелаАнотація:
Introduction: Chronic cough is a common complaint, accounting for one third of all referrals to chest physicians. National and international guidelines exist for treatment and investigation, despite this, in upto 42% of patients, no cause for cough is found. Whether this represents undiagnosed pathology, inadequate treatment or 'idiopathic cough' is unclear. Gastro-oesophageal reflux is reported as a common cause of chronic cough but the exact mechanism by which this occurs is unclear. Both direct cough receptor stimulation (microaspiration and LPR), and indirect stimulation (an oesophago-tracheo-bronchial reflex) have been proposed. Methods: 100 chronic cough patients have been comprehensively investigated, incorporating routine bronchoscopy and oesophageal impedance/pH into the diagnostic algorithm. Cough has been evaluated, both before and after treatment, by subjective assessment and objective cough sound monitoring. Results: Subjective assessment of cough was found to be affected by patient anxiety and depression and related only moderately to cough frequency.
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Wang, Yan [Verfasser]. "Phenotyping of circulating monocytes in coronary artery diseases / Yan Wang." Ulm : Universität Ulm. Medizinische Fakultät, 2015. http://d-nb.info/1073216349/34.
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Taylor, James Michael. "Validation of a new method for platelet HPA-1 phenotyping." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1133736.
Повний текст джерелаАнотація:
Polymorphisms of platelet glycoproteins (GPs) are frequently targets for anti-platelet antibodies. At least 19 antigenic polymorphisms have been identified on platelet GPs. Antibodies against the HPA-lb polymorphism (a Leu to Pro switch at amino acid residue 33 of the IIIa sub-unit of GP IIb/Illa) have been attributed to as much as 90% of all cases of neonatal alloimmune thrombocytopenic purpura and posttransfusion purpura in caucasians. The HPA-lb polymorphism has also been equivocally associated with coronary artery disease, particularly early onset (<60 years of age) myocardial infarction. Current technology for identifying individuals with the HPA-lb phenotype is limited to the labor-intensive, highly technical and expensive process of DNA amplification by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) analysis.This study proposes an alternative method for phenotyping individuals for the HPA-1 polymorphism using the Biocytex Platelet HPA-1 kit. The kit identifies the HPA-1 polymorphism utilizing two monoclonal CD61 (platelet glycoprotein IIb/IIIa) antibodies, one of which has a lowered affinity for GP llb/Illa possessing the HPA-lb polymorphism. Fluorescent labeling of bound antibody allows for flow cytometric quantitation of antibody binding capacity (ABC) for both monoclonal antibodies, and ratios derived from the ABC can be used to phenotype previously unknown samples.The Biocytex HPA-1 kit identified 73 of 74 (98.6%) individuals possessing the HPA1 a/HPA-1 a phenotype, 22 of 22 (100%) HPA-1 a/HPA-1 b individuals and 4 of 4 (100%) HPAIb/HPA-Ib individuals. All HPA-lb phenotypes were confirmed by PCR/RFLP. Total accuracy of the test system was 99%.Department of Biology
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Payne, Thomas. "Novel biomarkers of renal transplant failure/dysfunction via spectroscopic phenotyping." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/61777.
Повний текст джерелаАнотація:
Successful renal transplantation not only improves patients’ quality and duration of life, but also confers a substantial economic healthcare cost saving. With the growing burden of end-stage renal disease and the requirement for renal replacement therapy, strategies to augment transplant success and subsequent graft survival become more vital than ever. Herein, an objective means of characterising renal function across the transplant journey, and appropriately stratifying in accordance to individual contingencies/factors (including the early detection of renal dysfunction), based on metabolism is explored. Patient pairs, recipients and donors, were metabolically phenotyped prior to (24 h) and post (days 1–5) transplantation using a multi-platform analytical approach (i.e., Nuclear Magnetic Resonance Spectroscopy (NMR) and Mass Spectrometry (MS)) of urine and plasma (n = 50). Using advanced statistics, the resulting metabolic profiles were subsequently modelled, and related to multiple clinical phenotypes (and outcomes), to increase the understanding of molecular changes/signatures across transplantation, capturing valuable information pertinent to transplant type, cause, co-morbidity, modality, immunology and complication (p-value < 0.05) – over donors as well as recipients. An attempt to then develop predictive algorithms for the early detection of renal dysfunction was preliminary defined within the confines of the study design, where integrated NMR and MS metabolic data improved patient stratification for complications over clinical measures (receiver operator characteristic area under curve over 0.900) and potentially replace current measures. While prospective/multicentre studies are imperative for subsequent real-world adoption (qualification/validation), the work conducted herein encompassed much of the first stage of marker development – discovery – where metabolic phenotyping renal transplantation has provided a deeper characterisation of patient journeys with new insights into multiple contingencies/factors (including complication). Such findings infer the value of metabolic phenotyping to augment and potentially replace current measures and methods to better inform decision making in the clinic on the individual/precision level.
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An, Nan. "Plant high-throughput phenotyping using photogrammetry and 3D modeling techniques." Diss., Kansas State University, 2015. http://hdl.handle.net/2097/20493.
Повний текст джерелаАнотація:
Doctor of PhilosophyAgronomy
Kevin Price
Stephen M. Welch
Plant phenotyping has been studied for decades for understanding the relationship between plant genotype, phenotype, and the surrounding environment. Improved accuracy and efficiency in plant phenotyping is a critical factor in expediting plant breeding and the selection process. In the past, plant phenotypic traits were extracted using invasive and destructive sampling methods and manual measurements, which were time-consuming, labor-intensive, and cost-inefficient. More importantly, the accuracy and consistency of manual methods can be highly variable. In recent years, however, photogrammetry and 3D modeling techniques have been introduced to extract plant phenotypic traits, but no cost-efficient methods using these two techniques have yet been developed for large-scale plant phenotyping studies. High-throughput 3D modeling techniques in plant biology and agriculture are still in the developmental stages, but it is believed that the temporal and spatial resolutions of these systems are well matched to many plant phenotyping needs. Such technology can be used to help rapid phenotypic trait extraction aid crop genotype selection, leading to improvements in crop yield. In this study, we introduce an automated high-throughput phenotyping pipeline using affordable imaging systems, image processing, and 3D reconstruction algorithms to build 2D mosaicked orthophotos and 3D plant models. Chamber-based and ground-level field implementations can be used to measure phenotypic traits such as leaf length, rosette area in 2D and 3D, plant nastic movement, and diurnal cycles. Our automated pipeline has cross-platform capabilities and a degree of instrument independence, making it suitable for various situations.
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Yu, Haipeng. "Designing and modeling high-throughput phenotyping data in quantitative genetics." Diss., Virginia Tech, 2020. http://hdl.handle.net/10919/97579.
Повний текст джерелаАнотація:
Quantitative genetics aims to bridge the genome to phenome gap. The advent of high-throughput genotyping technologies has accelerated the progress of genome to phenome mapping, but a challenge remains in phenotyping. Various high-throughput phenotyping (HTP) platforms have been developed recently to obtain economically important phenotypes in an automated fashion with less human labor and reduced costs. However, the effective way of designing HTP has not been investigated thoroughly. In addition, high-dimensional HTP data bring up a big challenge for statistical analysis by increasing computational demands. A new strategy for modeling high-dimensional HTP data and elucidating the interrelationships among these phenotypes are needed. Previous studies used pedigree-based connectetdness statistics to study the design of phenotyping. The availability of genetic markers provides a new opportunity to evaluate connectedness based on genomic data, which can serve as a means to design HTP. This dissertation first discusses the utility of connectedness spanning in three studies. In the first study, I introduced genomic connectedness and compared it with traditional pedigree-based connectedness. The relationship between genomic connectedness and prediction accuracy based on cross-validation was investigated in the second study. The third study introduced a user-friendly connectedness R package, which provides a suite of functions to evaluate the extent of connectedness. In the last study, I proposed a new statistical approach to model high-dimensional HTP data by leveraging the combination of confirmatory factor analysis and Bayesian network. Collectively, the results from the first three studies suggested the potential usefulness of applying genomic connectedness to design HTP. The statistical approach I introduced in the last study provides a new avenue to model high-dimensional HTP data holistically to further help us understand the interrelationships among phenotypes derived from HTP.Doctor of Philosophy
Quantitative genetics aims to bridge the genome to phenome gap. With the advent of genotyping technologies, the genomic information of individuals can be included in a quantitative genetic model. A new challenge is to obtain sufficient and accurate phenotypes in an automated fashion with less human labor and reduced costs. The high-throughput phenotyping (HTP) technologies have emerged recently, opening a new opportunity to address this challenge. However, there is a paucity of research in phenotyping design and modeling high-dimensional HTP data. The main themes of this dissertation are 1) genomic connectedness that could potentially be used as a means to design a phenotyping experiment and 2) a novel statistical approach that aims to handle high-dimensional HTP data. In the first three studies, I first compared genomic connectedness with pedigree-based connectedness. This was followed by investigating the relationship between genomic connectedness and prediction accuracy derived from cross-validation. Additionally, I developed a connectedness R package that implements a variety of connectedness measures. The fourth study investigated a novel statistical approach by leveraging the combination of dimension reduction and graphical models to understand the interrelationships among high-dimensional HTP data.
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Webster, Kevin A. Ph D. "Behavioral Phenotyping of VMAT1 Knockout Mice: Relevance to Neuropsychiatric Disorders." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4190.
Повний текст джерелаАнотація:
Schizophrenia is a debilitating mental disorder that causes a large economic burden and is prevalent across all cultures and countries around the world. Although both environmental factors and genetics are known to play an important role in the etiology of schizophrenia, the exact role of genetics and its interaction with environmental factors in an individual’s predisposition to develop schizophrenia is poorly understood. Schizophrenia is characterized by symptoms that include positive symptoms (e.g. delusions, hallucinations, disorganized thinking and speech), negative symptoms (e.g. avolition, anhedonia, depressive-like behavior), and cognitive dysfunctions (e.g. executive functioning deficits in learning and memory, attention, and vigilance). Genomic screening has identified polymorphisms of the vesicular monoamine transporter 1 (VMAT1) gene (SLC18A1) that are associated with schizophrenia and bipolar disorder. The current study represents the first extensive phenotyping of both young and aged mice in which the VMAT1 gene (SLC18A1) has been deleted. The results demonstrated behavioral effects of deleting the VMAT1 gene that may relate to aspects of schizophrenic-like behavioral changes in this model. Specifically, young VMAT1 knockout mice displayed significant deficits in sensorimotor gating in the prepulse inhibition (PPI) task and in the acquisition of operant learning in the autoshaping task. When exposed to a mild stressor (24 hours of food deprivation), young VMAT1 knockout mice displayed a significant reduction in locomotor activity that was not evident under free-feeding conditions. Thus, young VMAT1 knockout mice showed deficits in tasks that model positive symptoms and cognitive deficits seen in schizophrenia; however, they did not display differences in behaviors related to models of the negative symptoms of schizophrenia or deficits in tasks designed to measure motor skills. While less extensive phenotyping was conducted in aged VMAT1 knockout mice, there were no significant deficits evident in any of the assays conducted in older animals. These findings demonstrated that deletion of the VMAT1 gene has behavioral effects that appear to be mediated by changes in brain monoamine function and changes in response to stressors (i.e. food deprivation) that may reflect changes in adrenal gland monoamine function.
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McCarthy, John P. J. "Phenotyping the dysregulation between BMI and adiposity in adult subjects." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/12256.
Повний текст джерелаАнотація:
AIMS The purpose of this thesis was to fully quantify the dysregulation between body mass index (BMI) and body adiposity in 3 phenotypically different groups of adults for whom BMI may be particularly unreliable. The 3 groups were: 1. The ‘Thin Fat’ , 2. The ‘Fat Fit’ 3. South Asians. A secondary purpose of the thesis was to evaluate the accuracy of 2-C body composition devices and proxy measurements to accurately assess regional and whole body adiposity. METHODS In order to establish a cohort baseline, whole body and regional adiposity were quantified using MRI and MRS. Cohort = 500 healthy adults. Participant’s adiposity data obtained were: TAT, SAT, ASAT, NASAT, IAAT, IHCL, S-IMCL, S-IMCL. Anthropometric data included: height, weight, waist circumference, hip circumference (and skinfolds in some sub-groups). Study 1: (A). In 21 healthy non-obese, males; 4 different 2-C body composition techniques (UWW, BIA, SKF, ADP) were compared to MRI adiposity data. Study 1: (B). In 74 adult Caucasian (40 females and 34 males) abdominal adiposity was measured using an abdominal BIA device (Viscan) and compared to MRI adiposity. Study 2: In 477 participants (343 male & 234 female) an in-depth comparison of BMI was conducted to identify TOFI individuals by developing a clinical index from the abdominal internal fat: subcutaneous abdominal fat (IAAT/ASAT) ratio for a normal range. Study 3: 50 males, fitness tested using VO2 max and then categorized by their fitness (fit vs unfit), and fatness (fat vs slim) according to MRI adiposity data. Study 4: 260 participants (68 Asian & 192 Caucasian) – age and BMI matched. Proxy measures WHR, WC etc compared. Apply study 3, TOFI cut-off to Asians adiposity data. RESULTS From the baseline adiposity data I confirmed that there is a wide range of regional body fat distributions (internal abdominal adipose tissue, IAAT; and abdominal subcutaneous adipose tissue, ASAT) by BMI, and that individuals with similar BMI values can show great variation in IAAT and ASAT. Study 1. (A). When whole cohort data were compared to MRI adiposity data there was no significant difference between the measures derived. However when the cohort was divided by ethnicity (Asian vs Caucasian) differences were more apparent. Caucasian adiposity was overestimated by up to 3% and Asian adiposity was underestimated by up to 11%. BodPod would be best suited to measuring Asian adiposity and BIA devices would be best suited to measuring Caucasian adiposity. Study 1. (B). The abdominal adiposity device (Viscan) using BIA method was not able to accurately measure IAAT in obese males and females. It appeared better at measuring subcutaneous adiposity (ASAT). It also appeared to be influenced by organ volumes in some cases – particularly the liver. Study 2. The ‘Thin on the Outside – Fat on the Inside’ (TOFI) phenotype can be defined using the ratio of IAAT and ASAT (IAAT/ASAT). The resulting TOFI index provides a quantitative means of comparing intra-abdominal fat deposition and thereby identifying “at risk” individuals. In Caucasians, cut-off values of >1.0 in males and >0.45 in females are proposed for TOFI definition. Additionally, anthropometric measurements such as waist circumference (WC) and waist to height ratio (WHtR) are not appropriate for classifying the TOFI phenotype. This is because these surrogates generally correlated more with total and subcutaneous adipose tissue stores than internal or ectopic depots. Study 3. IAAT and liver fat are lower in men who are fat, fit and active than in men who are fat, unfit and inactive. These ‘metabolically healthy’ individuals have the capacity to store excess fat in insulin-sensitive abdominal subcutaneous adipose tissue (ASAT) and this may help explain why the risk of chronic disease is lower in the ‘fat-fit’ than the ‘fat-unfit’. As a consequence, aerobic activity and the pursuit of physical fitness may be more appropriate goals in the battle against chronic disease than weight loss. Study 4. Asian Indian males were found to be significantly ‘fatter’ with significantly higher subcutaneous fat depots compared to similar Caucasian males. Given the increased metabolic risks seen in the Asian population increased IAAT measures were not found to be significantly higher. Additionally, the TOFI classification was not useful in identifying ‘at risk’ individuals in the Asian group. Also, waist circumference measurements did not identify Asian males that had significantly elevated ASAT. However, elevated liver fat stores were seen in Asian males and females compared to Caucasians. Liver fat may therefore be a potential ‘at risk’ identifier in this ethnic group. CONCLUSION The results of this thesis confirm BMI may be an inexpensive, non-invasive measure of obesity for predicting the risk of related complications, but its accuracy is limited by its dysregulation with adiposity. While obesity means excess body fat, the current definition of obesity using BMI is based on body weight regardless of its composition. The studies in this thesis have highlighted that fact that there are several different sub-populations of individuals for whom BMI does not tell the whole story. The Fat-Fit, the TOFI and the Asian Indian are specific phenotypic examples of these sub-populations. This is evidence of the fact that BMI should not be considered as the only measure of obesity. The results of this thesis also confirm that some techniques to measure adiposity are suboptimal for measuring percent body fat. For this reason MRI and other high quality (and high cost) imaging methods are still the best method for health risk based research.
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Chu, Thi Ha. "Phenotyping of chronic respiratory diseases in the South of Vietnam." Doctoral thesis, Universite Libre de Bruxelles, 2019. https://dipot.ulb.ac.be/dspace/bitstream/2013/288355/4/coverpage.pdf.
Повний текст джерелаАнотація:
Chronic respiratory diseases (CRDs) include chronic diseases involving the airways and other structures of the lung. In the current circumstance of Vietnam, people are exposed to numerous risk factors of CRD, such as heavy smoking, high frequency of pulmonary tuberculosis, chronic helminthiasis, allergic factors, migration and urbanization (the last associated with traffic-related pollution). The phenotype diagnoses should take into account the risk factors of each individual besides the clinical features, while the differential diagnoses mostly depend on the available techniques in each healthcare center. Our aim was to improve the differential diagnoses of the 3 most frequent CRDs: chronic obstructive pulmonary disease (COPD), asthma and COPD – asthma overlap syndrome (ACOS), in Vietnam. In the first part, we evaluated the prevalence of the allergen sensitization among patients with CRD, in regard to the urban and rural area in the South of Vietnam. House dust mites and cockroach droppings were the most frequent sensitizer. Compared with participants born in the urban setting, those born in the rural environment were less frequently sensitized and this protective effect disappeared in the case of migration from rural to urban areas. In the second part, we evaluated skin prick test as a method to screen dust mite sensitization in CRD in southern Vietnam. The data suggested that, in the present circumstance, skin prick test can be used to screen mite sensitization. In the third part, we evaluated the risk of mite sensitization in the native and migrant population, in regard to several environmental factors. Consistently with the hygiene hypothesis, compared to urban, exposure to high endotoxin concentration in rural was a protective factor against allergic sensitization. We reported for the first time that this effect was reversible among the migrants from rural to urban setting in association with lower endotoxin exposure. In the fourth part, we have defined asthma, COPD and ACOS based on clinical symptoms, cumulative smoking and airway expiratory flow with reversibility, on one side, and the age-related of the different phenotypes, on the other side. We hypothesized that the cumulative exposure to noxious particles should increase the age-related prevalence of COPD, while due to the immunosenescence process, the prevalence of IgE-mediated asthma should decrease with age, and ACOS prevalence being not related to age due to the combined mechanisms. In conclusion, we showed in the South of Vietnam that:1) mites and cockroach allergens were the most frequent sensitizer in chronic respiratory diseases;2) the skin prick test to mite has been validated to screen mite sensitization;3) associated with a reduced level of endotoxin level, migration from rural to the urban setting was a risk factor of mite sensitization in chronic respiratory diseases;4) based on the clinical symptoms, spirometric values, and cumulative smoking, the diagnosis of asthma, COPD and ACOS have been made and their prevalence were 25, 42 and 33%, respectively.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
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Voide, Romain. "Functional phenotyping of bone : a hierarchical assessment of bone failure characteristics." Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17524.
Повний текст джерела
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Vergara, Díaz Omar. "High-throughput field phenotyping in cereals and implications in plant ecophysiology." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668314.
Повний текст джерелаАнотація:
Global climate change effects on agroecosystems together with increasing world population is already threatening food security and endangering ecosystem stability. Meet global food demand with crops production under climate change scenario is the core challenge in plant research nowadays. Thus, there is an urgent need to better understand the underpinning mechanisms of plant acclimation to stress conditions contributing to obtain resilient crops. Also, it is essential to develop new methods in plant research that permit to better characterize non-destructively plant traits of interest. In this sense, the advance in plant phenotyping research by high throughput systems is key to overcome these challenges, while its verification in the field may clear doubts on its feasibility. To this aim, this thesis focused on wheat and secondarily on maize as study species as they make up the major staple crops worldwide. A large panoply of phenotyping methods was employed in these works, ranging from RGB and hyperspectral sensing to metabolomic characterization, besides of other more conventional traits. All research was performed with trials grown in the field and diverse stressor conditions representative of major constrains for plant growth and production were studied: water stress, nitrogen deficiency and disease stress. Our results demonstrated the great potential of leave-to-canopy color traits captured by RGB sensors for in-field phenotyping, as they were accurate and robust indicators of grain yield in wheat and maize under disease and nitrogen deficiency conditions and of leaf nitrogen concentration in maize. On the other hand, the characterization of the metabolome of wheat tissues contributed to elucidate the metabolic mechanisms triggered by water stress and their relationship with high yielding performance, providing some potential biomarkers for higher yields and stress adaptation. Spectroscopic studies in wheat highlighted that leaf dorsoventrality may affect more than water stress on the reflected spectrum and consequently the performance of the multispectral/hyperspectral approaches to assess yield or any other relevant phenotypic trait. Anatomy, pigments and water changes were responsible of reflectance differences and the existence of leaf-side-specific responses were discussed. Finally, the use of spectroscopy for the estimation of the metabolite profiles of wheat organs showed promising for many metabolites which could pave the way for a new generation phenotyping. We concluded that future phenotyping may benefit from these findings in both the low-cost and straightforward methods and the more complex and frontier technologies.Els efectes del canvi climàtic sobre els agro-ecosistemes i l’increment de la població mundial posa en risc la seguretat alimentària i l’estabilitat dels ecosistemes. Actualment, satisfer les demandes de producció d’aliments sota l’escenari del canvi climàtic és el repte central a la Biologia Vegetal. Per això, és indispensable entendre els mecanismes subjacents de l’aclimatació a l’estrès que permeten obtenir cultius resilients. També és precís desenvolupar nou mètodes de recerca que permetin caracteritzar de manera no destructiva els trets d’interès. L’avenç del fenotipat vegetal amb sistemes d’alt rendiment és clau per abordar aquests reptes. La present tesi s’enfoca en el blat i secundàriament en el panís com a espècies d’estudi ja que constitueixen els cultius bàsics arreu del món. Un ampli ventall de mètodes de fenotipat s’han utilitzat, des sensors RGB a híper-espectrals fins a la caracterització metabolòmica. La recerca s’ha dut a terme en assajos de camp i s’han avaluat diversos tipus d’estrès representatius de les majors limitacions pel creixement i producció vegetal: estrès hídric i biòtic i deficiència de nitrogen. Els resultats demostraren el gran potencial dels trets del color RGB (des de la planta a la capçada) pel fenotipat de camp, ja que foren indicadors precisos del rendiment a blat i panís sota condicions de malaltia i deficiència de nitrogen i de la concentració de nitrogen foliar a panís. La caracterització metabolòmica de teixits de blat contribuí a esbrinar els processos metabòlics endegats per l’estrès hídric i la seva relació amb comportament genotípic, proporcionant bio-marcadors potencials per rendiments més alts i l’adaptació a l’estrès. Estudis espectroscòpics en blat van demostrar que la dorsoventralitat pot afectar més que l’estrès hídric sobre l’espectre de reflectància i consegüentment sobre el comportament de les aproximacions multi/híper-espectrals per avaluar el rendiment i d’altres trets fenotípics com anatòmics i contingut de pigments. Finalment, l’ús de l’espectroscòpia per l’estimació del contingut metabòlic als teixits de blat resulta prometedor per molts metabòlits, la qual cosa obre les portes per a un fenotipat de nova generació. El fenotipat pot beneficiar-se d’aquestes troballes, tant en els mètodes de baix cost com de les tecnologies més sofisticades i d’avantguarda.
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Khairallah, Ramzi. "Metabolic phenotyping of murine hearts overexpressing constitutively active soluble guanylate cyclase." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18805.
Повний текст джерелаАнотація:
Although enhanced cGMP signaling can prevent hypertrophy, mechanisms underlying this cardioprotective effect are not well understood. In this study, we assessed the potential involvement of alterations in myocardial energy substrate metabolism, a parameter known to be determinant in the development of hypertrophy. We used mice overexpressing a constitutively active soluble guanylate cyclase in a cardiomyocyte-specific manner (GC+/0) and ex vivo heart perfusion at physiological workload with 13C-labeled substrates. Compared to controls, hearts from GC+/0 mice displayed a 38±9% lower contribution of exogenous fatty acids to acetyl-CoA formation, while that of carbohydrates remained unchanged despite a two-fold increase in glycolysis. The lower contribution of exogenous fatty acids to energy production was not associated with changes in energy demand or supply (contractile function, oxygen consumption, tissue acetyl-CoA or CoA levels, citric acid cycle flux rate) or the regulation of ?-oxidation (acetyl-CoA carboxylase activity, tissue malonyl-CoA levels). However, GC+/0 hearts showed a two-fold increase in the incorporation of exogenous oleate into triglycerides. Furthermore, a concomitant increase in triglyceride hydrolysis is consistent with our findings of a greater abundance of hormone sensitive lipase (HSL) protein (46±6%) and mRNA (22±4%) as well as a 37±13% decrease in its phosphorylation level at Ser-565. The latter covalent modification inhibits HSL and is regulated by AMP-activated protein kinase (AMPK), whose phosphorylation at its activating site Thr-172 was also reduced by 37±13%. These changes in exogenous fatty acid trafficking in GC+/0 hearts appear to be functionally relevant, as demonstrated by their resistance to fasting-induced myocardial triglyceride accumulation. This raises the possibility that enhanced cGMP signaling in cardiomyocytes may protect the heart from fatty acid-induced toxic effects, either as part of its anti-hypertrophic efUne plus grande utilisation des glucides au dépend des acides gras (AG) pour la production d'énergie a été documentée dans le cœur hypertrophique, mais il n'est toujours pas clair si ces changements métaboliques sont adaptatifs ou maladaptatifs. Étant donné que la voie du cGMP a des propriétés anti-hypertrophiques, nous avons émis l'hypothèse que des changements dans la sélection de substrats énergétiques peuvent être à l'origine de l'effet cardioprotecteur de cette voie. Des cœurs de souris qui surexpriment la guanylate cyclase spécifiquement dans les cardiomyocytes (Tg) ont été perfusés ex vivo au travail avec des substrats marqués au carbone-13. L'activité des voies métaboliques impliquées dans la production d'énergie tel que le cycle de Krebs a été corrélée à des paramètres fonctionnels et physiologiques. Comparativement aux souris témoins, les cœurs Tg maintiennent mieux leur intégrité membranaire, tel qu'indiqué par la baisse de la quantité de lactate déshydrogénase relâché par le cœur, tout en maintenant leur travail cardiaque. Au niveau métabolique, les cœurs Tg ne montrent pas de différence dans la contribution des glucides à la formation de l'acétyl-CoA malgré un flux glycolytique augmenté de 127±21% (p<0.01), alors que l'utilisation des acides gras (AG) est diminuée de 40±4% (p<0.05). Selon les résultats obtenus, cette diminution n'est pas attribuable à des changements: (i) des niveaux tissulaires du malonyl-CoA et de l'acétyl-CoA ou (ii) de l'activité du cycle de Krebs, suggérant que le statut énergétique du cœur n'est pas altéré, ou (iii) de l'expression des gènes métaboliques. Plutôt, il semblerait que les cœurs de souris GC+/0 compensent pour la baisse de la contribution des AG par une utilisation accrue des acides gras endogènes provenant des triglycérides. En effet, la quantité totale de lipase hormone-sensible est augmentée de 46±6% et son ARNm de 22±4%. De plus, sa pho
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Wetzel, Franziska. "Biomechanical Phenotyping of Cells in Tissue and Determination of Impact Factors." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-144866.
Повний текст джерелаАнотація:
Diese Arbeit beinhaltet Ergebnisse der ersten klinischen Studie zur Charakterisierung der mechanischen Eigenschaften von Zellen in einem Tumor mit der dafür notwendigen Probengröße. Dies ermöglichte die Erstellung eines umfassenden Bildes von Subpopulationen innerhalb eines Tumors mit großem diagnostischem Potential. Die Änderung der Einzelzellmechanik von Tumorzellen wird durch Veränderung des Zytoskeletts, einem komplexes Polymernetzwerk in Zellen, hervorgerufen. Mit Hilfe von Zellgiften wurde das Zytoskelett gezielt manipuliert, um den Einfluss einzelner Faktoren auf die Biomechanik zu bestimmen.
Aus Gewebeproben von Brustkrebspatienten wurden Zellen mit Hilfe enzymatischer Aufspaltung des extrazellulären Kollagennetzwerkes isoliert. Als Kontrollsystem wurden Primärzellen aus Brustreduktionsgewebe und aus Fibroadenomen, gutartigen Gewebeneubildungen der Brustdrüse, verwendet. Unter Einsatz des Optischen Stretchers, einer Zweistrahl-Laserfalle, wurden suspendierte Zellen für zwei Sekunden einer konstanten Zugspannung ausgesetzt und das Deformations- wie auch das anschließende Relaxationsverhalten beobachtet.
Dabei ergaben sich wesentliche Unterschiede zwischen Tumor- und Kontrollproben. Neben Zellen mit ähnlichen Steifigkeiten, enthielten Tumorproben Subpopulationen sehr weicher Zellen, wie sie in Normalgewebe nicht zu finden sind. Desweiteren war das Relaxationsverhalten der Tumorzellen stärker elastisch dominiert. Einzelne Zellen kontrahierten sogar aktiv gegen die Zugspannung. Versuche, das Zytoskelett mittels Zellgiften künstlich in einem Zustand zu bringen, der in Krebszellen beobachtet wurde, ergaben zwar ebenfalls die Zunahme weicherer Zellen, jedoch war das Relaxationsverhalten eher viskos dominiert. Fluoreszenzaufnahmen des Aktin-Zytoskeletts sowie der fokalen Adhäsionen, die das Aktin-Netzwerk der Zelle mit dem Substrat verankern, zeigten Veränderungen bei Krebszellen im Vergleich zu Kontrollen.
Darüber hinaus wurden Einflussfaktoren auf die Zellmechanik untersucht. Neben Kulturbedingungen, beeinflussen auch Alter und Medikation das biomechanische Verhalten. Die Steifigkeit der Krebszellen scheint vom Ursprungsgewebe beeinflusst zu werden, sodass Zellen verschiedener Krebsarten Steifigkeiten in unterschiedlichen Regimes zeigen.
Die Ergebnisse dieser Arbeit liefern wichtige Informationen für unser Verständnis der Karzinogenese und bilden die Grundlage für eine neue diagnostische Methode zur Bestimmung der Tumoraggressivität. Eine gezielte Untersuchung der gefundenen Subpopulationen in einem Tumor könnte dabei helfen, neue Therapieansätze zu entwickeln und damit die hohen Rezidivraten aggressiver Tumore zu vermindern.
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Ibrahim, Baharudin. "Exhaled breath analysis for diagnosis and phenotyping in obstructive lung diseases." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/exhaled-breath-analysis-for-diagnosis-and-phenotyping-in-obstructive-lung-diseases(17a130d4-4c44-43af-a006-65939c7315f7).html.
Повний текст джерелаАнотація:
Introduction: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with a wide range of clinical manifestations not adequately described within the current diagnostic criteria. Exhaled breath analysis may provide a novel method for diagnosing and phenotyping these diseases. Our aim was to ascertain patterns of breath volatile organic compounds (VOCs) and nuclear magnetic resonance (NMR) spectral regions identifying diseased patients and subgroups determined by treatment requirement, asthma control, exacerbation frequency and inflammatory phenotypes. The validity and reproducibility of the methodology and the outcome were also investigated. Methods: Three separate clinical studies (two involving exhaled gas and one involving breath condensate) were conducted, as well as validation studies. In exhaled gas analysis, the adaptive breath sampler developed by Basanta et al was modified; efficiency of air supply and air filter and the reproducibility and stability of VOCs in storage were determined by comparing breath chromatograms. Concentrated late-expiratory breath samples were collected from asthmatics, COPD subjects and healthy controls. In the asthmatic group, sputum induction with hypertonic saline, fraction exhaled nitric oxide (FeNO) measurement and asthma control questionnaire (ACQ) were performed. In COPD subjects, sputum induction and exacerbation frequency were collected. In the exhaled breath condensate (EBC) study, similar data were collected in asthmatics and healthy controls. Breath samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) while EBC was analysed using NMR spectroscopy. Discriminatory compounds or NMR spectral regions were identified by univariate logistic regression, followed by multivariate analysis: 1. principal component analysis (PCA); 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis. The reproducibility was assessed using intraclass correlation coefficient (ICC).Results: In the COPD exhaled breath study, 11 VOCs significantly discriminated the COPD and healthy controls with AUROC of 0.74. The AUROC for phenotype discrimination was 0.83, 0.90, 0.94, 0.96 and 0.97 for inhaled corticosteroid (ICS) use, sputum eosinophilia (1% and 2% cut-off), neutrophilia (median cut-off) and exacerbation frequency respectively. In the asthma study, 15 VOCs significantly discriminated the two groups with AUROC of 0.93. The AUROC for phenotype discrimination was 0.96, 0.98, 0.90 and 0.97 for ICS use, eosinophils (2% cut-off), neutrophils (40% cut-off) and asthma control respectively. In EBC analysis, AUROC for asthmatics vs controls comparison was 0.96. Phenotyping results in this study were less good: only ICS use and sputum neutrophilia (65% cut-off) were clearly classified with AUROC of 0.89 and 0.88 while eosinophilia (3% cut-off) and asthma control had poor discrimination; 0.69 and 0.62 respectively. Breath VOC reproducibility varied greatly depending on the class of compounds studied, while for the EBC analysis, reproducibility was moderate to very good (ICCs in the range of 0.42-0.99).Conclusions: We have demonstrated the ability of breath analysis in discriminating asthmatics and COPD subjects from controls. Exhaled breath analysis was also able to phenotype these patients based on steroid treatment, sputum inflammatory cells, exacerbation frequency and asthma control. This metabolomic approach could provide a novel, non-invasive method of diagnosing and phenotyping obstructive lung diseases in the future.
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Malt, Layla. "Comparative phenotyping of Salmonella serovars in the context of epithelial infection." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665154.
Повний текст джерелаАнотація:
Salmonella enterica remains a major source of human and animal infection worldwide. Despite the identification of over 2,500 Salmonella serovars, the majority of our knowledge on Salmonella pathogenicity and host response mechanisms has developed through studies on a limited number of strains from a few serovars. Strain variation within and between serovars has not been fully investigated. Here, 18 Salmonella strains representing six serovars frequently recovered from human cases of infection have been characterised. All strains exhibited similar growth and motility characteristics but significant variation was observed in their abilities to form biofilms and to invade epithelial cells. Strain heterogeneity was evident both within and between serovars. Furthermore, the overall invasion profiles observed were conserved between epithelial cell lines and did not alter with the application of mild centrifugation. GFP reporter constructs confirmed that the Salmonella Pathogenicity Island (SPI) 1 structural gene, prgH, was only expressed in a subpopulation of Salmonella and this bistable expression returned after populations were sorted based on GFP expression and then allowed to recover. GFP and LacZ reporter constructs revealed a close correlation between SPI-l prgH promoter transcription at")d invasion in MDCK I cells at late log phase in the majority of strains examined, with low invasion associated with low levels of prgH promoter activity. Strains which lacked the effector protein, Salmonella outer protein E1 (SopEl) induced slower and smaller membrane ruffles in comparison to SopEl positive strain (SopEl +) S. Tm SL1344. However some SopE1+ strains were observed inducing membrane ruffles with comparable induction kinetics and ruffle diameters as strains which lacked SopEl. The presence of SopEl, large membrane ruffles or the fast induction of membrane ruffles did not ,correlate with invasion. These data demonstrate that significant strain variation exists between strains and serovars which may have important implications for Salmonella and other microbial infection studies
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Halpern, Yonatan. "Semi-Supervised Learning for Electronic Phenotyping in Support of Precision Medicine." Thesis, New York University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10192124.
Повний текст джерелаАнотація:
Medical informatics plays an important role in precision medicine, delivering the right information to the right person, at the right time. With the introduction and widespread adoption of electronic medical records, in the United States and world-wide, there is now a tremendous amount of health data available for analysis.
Electronic record phenotyping refers to the task of determining, from an electronic medical record entry, a concise descriptor of the patient, comprising of their medical history, current problems, presentation, etc. In inferring such a phenotype descriptor from the record, a computer, in a sense, "understands'' the relevant parts of the record. These phenotypes can then be used in downstream applications such as cohort selection for retrospective studies, real-time clinical decision support, contextual displays, intelligent search, and precise alerting mechanisms.
We are faced with three main challenges:
First, the unstructured and incomplete nature of the data recorded in the electronic medical records requires special attention. Relevant information can be missing or written in an obscure way that the computer does not understand.
Second, the scale of the data makes it important to develop efficient methods at all steps of the machine learning pipeline, including data collection and labeling, model learning and inference.
Third, large parts of medicine are well understood by health professionals. How do we combine the expert knowledge of specialists with the statistical insights from the electronic medical record?
Probabilistic graphical models such as Bayesian networks provide a useful abstraction for quantifying uncertainty and describing complex dependencies in data. Although significant progress has been made over the last decade on approximate inference algorithms and structure learning from complete data, learning models with incomplete data remains one of machine learning’s most challenging problems. How can we model the effects of latent variables that are not directly observed?
The first part of the thesis presents two different structural conditions under which learning with latent variables is computationally tractable. The first is the "anchored'' condition, where every latent variable has at least one child that is not shared by any other parent. The second is the "singly-coupled'' condition, where every latent variable is connected to at least three children that satisfy conditional independence (possibly after transforming the data).
Variables that satisfy these conditions can be specified by an expert without requiring that the entire structure or its parameters be specified, allowing for effective use of human expertise and making room for statistical learning to do some of the heavy lifting. For both the anchored and singly-coupled conditions, practical algorithms are presented.
The second part of the thesis describes real-life applications using the anchored condition for electronic phenotyping. A human-in-the-loop learning system and a functioning emergency informatics system for real-time extraction of important clinical variables are described and evaluated.
The algorithms and discussion presented here were developed for the purpose of improving healthcare, but are much more widely applicable, dealing with the very basic questions of identifiability and learning models with latent variables - a problem that lies at the very heart of the natural and social sciences.
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Amaral, Andreia Vanessa Campos Pusich. "Micropropagation, phenotyping and genotyping of chestnut progenies obtained from controlled crosses." Master's thesis, ISA, 2020. http://hdl.handle.net/10400.5/21510.
Повний текст джерелаАнотація:
Mestrado em Biologia dos Recursos Vegetais / Instituto Superior de Agronomia / Faculdade de Ciências. Universidade de LisboaPhytophthora cinnamomi is an oomycete that infects the roots and can cause the death of trees belonging to the Fagaceae family, such as genus Castanea. Ink disease is currently considered the major threat to chestnut trees in Europe, causing a high decrease in nut production, which is the highest income of mountain regions of Trás-os-Montes. Thus, genetic improvement for resistance aiming to developing new chestnut varieties less susceptible to this pathogen is very important for the national economy. The European species, Castanea sativa Mill., is susceptible to Phytophthora cinnamomi, while Asian species are resistant due to coevolution with the pathogen. INIAV initiated in 2006 a breeding program based on controlled crosses, using Asian species, namely Castanea crenata Sieb. & Zucc. (Japanese) and Castanea mollissima Blume (Chinese) as donors of resistance, and the sensitive European species as female progenitor with the objective of obtaining segregating progenies for the resistance character. During this thesis, phenotyping and genotyping of progenies of crosses performed in 2016 was carried out in order to select the most resistant individuals and try to associate resistance with fragment analysis patterns. This phenotyping-genotyping analysis was performed with 16 microsatellites in 47 genotypes and the result was 4 alleles that may be related to resistance. Was also performed the micropropagation of the genotypes SM904, SC55, SC1202 and SC914, already selected with improved resistance during the project on course, where this thesis fits. Calculations for multiplication rate and rooting percentage were made, important for the characterization of the genotypes. Genotype SM904 showed the highest result for both analysis. My work also contributes to one of the objectives of the current research program, which is to obtain new genotypes with improved resistance to Phytophthora cinnamomi to be used as rootstocks compatible for grafting with the national chestnut varieties of nut production
N/A
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Bala, Divya Chandrakant. "Cell Phenotype Analyzer: Automated Techniques for Cell Phenotyping using Contactless Dielectrophoresis." Thesis, Virginia Tech, 2016. http://hdl.handle.net/10919/71428.
Повний текст джерелаАнотація:
Cancer is among the leading causes of death worldwide. In 2012, there were 14 million new cases and 8.2 million cancer-related deaths worldwide. The number of new cancer cases is expected rise to 22 million within the next two decades. Most chronic cancers cannot be cured. However, if the precise cancer cell type is diagnosed at an earlier, less aggressive stage then the chance of curing the disease increases with accurate drug delivery. This work is a humble contribution to the advancement of cancer research. This work delves into biological cell phenotyping under a dielectrophoresis setup using computer vision. Dielectrophoresis is a well-known phenomenon in which dielectric particles are subjected to a non-homogeneous electric field. This work is an analytical part of a larger proposed system replete with hardware, software and microfluidics integration to achieve cancer cell characterization, separation and enrichment using contactless dielectrophoresis. To analyze the cell morphology, various detection and tracking algorithms have been implemented and tested on a diverse dataset comprising cell-separation video sequences. Other related applications like cell-counting and cell-proximity detection have also been implemented. Performances were evaluated against ground truth using metrics like precision, recall and RMS cell-count error. A detection approach using difference of Gaussian and super-pixel algorithm gave the highest average F-measure of 0.745. A nearest neighbor tracker and Kalman tracking method gave the best overall tracking performance with an average F-measure of 0.95. This combination of detection and tracking methods proved to be best suited for this dataset. A graphical user interface to automate the experimentation process of the proposed system was also designed.Master of Science
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Pan, Cuiping. "Phosphoproteomics and proteomic phenotyping to assess signal transduction in cancer cells." Diss., kostenfrei, 2008. http://edoc.ub.uni-muenchen.de/9241/.
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