Dissertations / Theses on the topic 'And Correlations: BasicConcepts and Methods'

It is well known that very few models of interacting systems particularly those in dimension higher than two, can be solved exactly. The mean-field treatment is the first step in approximate calculations for such models. Although mean-field approximation leads to sufficiently accurate results of the thermodynamic properties of these systems away from critical points, most often it fails miserably close to the critical points. In this thesis, we propose to study direct methods (not based on any mean-field type approximations) for proving the exponential decay of the two point-correlation functions and the analyticity of the pressure (free energy per unit volume) for models of Kac type. The methods are based on the Helffer-Sjöstrand formula for the covariance in terms of Witten's Laplacians.

Correlation effects in the one-dimensional Hubbard model are studied by application of the L-resolvent method. The calculations are well beyond one-particle mean field approximation. All correlations involving two neighboring sites are included exactly and higher order correlations are approximated. The effects of varying temperature, band filling, Coulomb repulsion and external magnetic field are investigated. Two-site correlations for non-half-filled band fillings are calculated for the first time. Some exact relations between correlation functions are derived by electron-hole symmetry. Results indicate that short-range spin correlations always favor antiferromagnetic order. Large Coulomb repulsion induces a gap in the excitation spectrum and a metal-insulator transition is predicted as the Coulomb repulsion parameter is changed.
Ph. D.

Abstract Background: According to the World Health Organization, 39 million people is completely blind. Between the genetic disorders causing visual impairment, by affecting 1 person to 3000-4000, Inherited Retinal Dystrophies, Occult Macular Dystrophy and Age-related Macular Degeneration are the most diffuse. Inherited Retinal Disorders (IRD) are retinal degenerations caused by mutations in at least 280 genes and more loci. IRD can be both syndromic or not-syndromic, inherited or sporadic, and all the inheritance patterns are possible. In fact, in addition to the autosomal dominant, autosomal recessive and the X-linked forms, sporadic, digenic and mitochondrial ones are possible. One of the most significant characteristics is their great genetic heterogeneity, due to the high number of genes and possible mutations involved. These genes transduce proteins involved in phototransduction and visual cycle processes, expressed in retinal pigmented epithelium or photoreceptors cells. The diseases are progressive and characterized by difficulties in night vision, loss of peripheral vision and photophobia, until complete blindness. Besides the genetic heterogeneity, these pathologies are characterized by allelic and clinical heterogeneity, which make the clinical diagnosis and the genotype-phenotype correlations complex, whenever the genetic cause is known. If genetic heterogeneity is determined by the presence of different mutations that induce the same clinical manifestation, clinical (or allelic) heterogeneity occurs in the presence of mutations on the same gene that cause different phenotypes. While Occult Macular Dystrophy (OMD) is an inherited macular dystrophy caused by mutation in RP1L1 gene with an autosomal dominant pattern of inheritance, Age-related Macular Degeneration (AMD) is a complex disorder caused by an association of genetic, environmental and advanced age susceptibility. Currently no diagnostic tests or definitive treatment for these disorders are available. Aim of the study: The objective of this project is the development of diagnostic tests valid for the genetic characterization of patients affected by IRD or OMD. For this purpose, 620 patients and affected family members were clinically characterized, and a genetic biobank was created from the collection of their DNA, available for possible genetic testing. Based on the pathology they are affected, diagnostic tests were performed using Sanger sequencing or Next Generation Sequencing (NGS), following which correlations between the genotype and the phenotype were made. Materials and methods: IRD patients were recruited and DNA extracted from blood samples. Retinal tissue and biopsies were collected too, in accordance with the current legal regulations. Genetic screening of 190 patients was realized using NGS targeted technology by MiSeq Illumina and identified mutations were then confirmed using Sanger sequencing. Genotype-phenotype correlations were elaborated, and risk factors determination was performed in 118 patients by means TaqMan PCR for 7 polymorphisms. OMD patients were screened for RP1L1 gene and 60 proband suspected to be affected by X-linked retinitis pigmentosa for RP2 and RPGR genes using Sanger sequencing. After a clinical anamnesis and in-depth visual examination, the patients were subjected to blood sampling from which the DNA was extracted and stored in the biobank. In parallel, a retinal biobank was generated from the collection of donors' retinas, collected according to the regulations in force. Genetic screening was performed on 190 patients affected by different autosomal recessive or dominant forms of IRD, using the targeted NGS technology, with panels of 25 genes. After selecting the variants or mutations identified by the analysis, Sanger sequencing was performed to confirm them. The correct attribution of the results to the analyzed individuals was achieved by comparing the genetic profiles obtained from the biobank DNA and the residual one from the NGS analysis. Genetic screening of patients with X-linked forms of IRD (n = 60) or OMD (n = 5) was obtained by means of Sanger sequencing of RPGR and RP2 (IRD) or RP1L1 (OMD) genes. A genetic susceptibility tool was developed and applied to 118 patients (39 of whom previously screened with NGS), using real time PCR, to evaluate the expression of 7 polymorphisms associated with AMD in subjects affected by IRD. Results: With NGS screening 256 variants/mutations were identified in 126 patients. Among these, 49% is represented by novel alterations. The most mutated genes are USH2A (15%) and ABCA4 (14%), while no alteration was found in the BEST1, CRX, LRAT and RLBP1 genes. 27% of cases were completely resolved, while 39% only partially, due to the identification of only one recessive mutation or of variants of uncertain significance. Missense variants cover 80% of the total, followed by nonsense mutations (9%), frameshift insertions/deletions (8%), in-frame insertions/deletions (2%) and splicing alterations (1%). The correlation of the identified genotype with the diagnosed phenotype was possible in about half of genetically characterized patients. From the comparison it was possible to identify triallelic forms, often with the missense G1961E mutation of ABCA4 as an aggravating allele, and a new gene-disease association for the PRPF31 gene that in three patients causes Usher's syndrome. The analysis of the probands with X-linked forms of Retinitis Pigmentosa allowed the identification of a frameshift insertion in the ORF15 of the RPGR gene, a nonsense mutation in RPGR gene and an already known missense mutation in RP2, in three distinct families. Among the patients with OMD, the missense S1199F mutation in RP1L1 was identified for two of them. The susceptibility test for the 7 SNPs showed a high genetic high of AMD in 38 subjects, medium high in 16, medium in 36, and low in 28. Conclusions: NGS technology has proved to be a useful diagnostic tool for the autosomal dominant or autosomal recessive forms of retinal dystrophies, allowing massive and parallel sequencing of many genes and patients. The percentage of genetically characterized patients is consistent with the data in the literature. The use of a panel of genes turns out to be an acceptable compromise between the results obtained and the criticality related to the large amount of output data, compared to whole genome or whole exome sequencing. Much of the genetic data has been correlated with the clinical manifestations of the patients. Sanger technology, gold standard of sequencing, is optimal for the identification of the genetic cause in all pathologies where one or a few genes are involved, such as the X-linked forms of IRD or the OMD. The expression of risk factors, predisposing to macular degeneration, while not correlating with the severity of the confirmed mutations, could provide important relationships with the pathologies of which the subjects are affected. The identification of the genetic causes of these pathologies will bring a new thrust to the development of gene and cell therapies, fundamental for the treatment of hereditary retinal diseases.
Riassunto Presupposti dello studio: Secondo l’organizzazione mondiale della sanità, 39 milioni di persone sono ciechi. Tra principali cause genetiche che inducono compromissione visiva, con una prevalenza di 1:2500-4000, le Distrofie Retiniche Ereditarie (i.e. Inherited Retinal Dystrophy - IRD), la Distrofia Maculare Occulta (OMD) e la Degenerazione Maculare legate all’Età (AMD) sono le più diffuse. Le prime sono un gruppo di patologie che inducono degenerazioni retiniche indotte da mutazione in almeno 280 geni e molti loci. Le forme di IRD possono essere sindromiche o non sindromiche, sporadiche o ereditarie, con tutti i pattern di eredità possibili. Infatti, oltre alle forme autosomiche dominati e recessive e le forme legate al cromosoma X, sono possibili forme sporadiche, digeniche e mitocondriali. Una delle principali caratteristiche di queste patologie è la loro elevata eterogeneità, legata all’elevato numero di geni e di mutazioni coinvolti. Questi geni, infatti, codificano proteine coinvolte nei processi di foto-trasduzione e del ciclo visivo, espressi principalmente nelle cellule dell’epitelio pigmentato retinico o nei fotorecettori. Queste malattie hanno un andamento progressivo che inizia, generalmente, con difficoltà nella visione notturna, perdita della visione periferica e fotofobia, fino alla cecità assoluta. Oltre alla eterogeneità genetica, queste patologie sono caratterizzate da eterogeneità allelica e clinica, che rendono complessa la diagnosi clinica ed anche le correlazioni genotipo-fenotipo, qualora si conosca la causa genetica del paziente. Se l‘eterogeneità genetica è determinata dalla presenza di differenti mutazioni che inducono la stessa manifestazione clinica, l’eterogeneità clinica (o allelica) si ha in presenza di mutazioni sullo stesso gene che causano fenotipi differenti. Mentre la Degenerazione Maculare Occulta è una distrofia maculare ereditaria causata da mutazioni nel gene RP1L1, con una trasmissione autosomica dominate, la Degenerazione Maculare legata all’Età è una patologia complessa causata dall’associazione di fattori genetici, ambientali e dall’età avanzata. Attualmente per queste patologie non sono disponibili né test diagnostici né cure. Scopo dello studio: L’obiettivo di questo progetto è lo sviluppo di test diagnostici validi per la caratterizzazione genetica dei pazienti affetti da IRD o OMD. Per tale scopo, 620 pazienti e familiari affetti sono stati clinicamente caratterizzati e dalla collezione dei loro DNA è stata creata una biobanca genetica disponibile per eventuali test genetici. In base alla patologia di cui sono affetti, i test diagnostici sono stati eseguiti mediante utilizzo di Sanger sequencing o Next Generation Sequencing (NGS) al seguito del quale sono stati realizzate delle correlazioni tra il genotipo e il fenotipo. Materiali e metodi: Dopo anamnesi clinica e approfondito esame visivo, i pazienti sono stati sottoposti a prelievo di sangue da cui è stato estratto il DNA stoccato all’interno della biobanca. In parallelo una biobanca retinica è stata generata dalla collezione di retine di domatori, raccolte in accordo alle normative vigenti. Lo screening genetico è stato eseguito su 190 pazienti affetti da differenti forme autosomiche recessive o dominanti di IRD, mediante la tecnologia targeted NGS, con pannelli di 25 geni. Dopo la selezione delle varianti o mutazioni identificate dall’analisi, è stato eseguito il sequenziamento Sanger per la loro conferma. La corretta attribuzione dei risultati agli individui analizzati è stata realizzata grazie alla comparazione di profili genetici ottenuti dal DNA della biobanca e quello residuo dall’analisi NGS. Lo screening genetico, dei pazienti affetti da forme X-linked di IRD (n=60) o da OMD (n=5) è stato ottenuto da sequenziamento Sanger dei geni RPGR e RP2 (IRD) o RP1L1 (OMD). Un test di suscettibilità genetica è stato sviluppato e applicato a 118 pazienti (39 dei quali precedentemente screenati con NGS), mediante real time PCR, per valutare l’espressione di 7 polimorfismi associati all’AMD nei soggetti affetti da IRD. Risultati: Con lo screening NGS 256 varianti/mutazioni sono state identificate in 126 pazienti. Tra queste il 49% è rappresentato da alterazioni non note in letteratura. I geni maggiormente mutati sono USH2A (15%) e ABCA4 (14%), mentre nessuna alterazione è stata riscontrata nei geni BEST1, CRX, LRAT and RLBP1. Il 27% dei casi è stato completamente risolto, mentre il 39% solo parzialmente, a causa dell’identificazioni di una sola mutazione recessiva o di varianti di significato incerto. Le varianti missenso coprono l'80% del totale, seguite dalle mutazioni nonsenso (9%), dalle inserzioni/delezioni frameshift (8%), dalle inserzioni/delezioni in-frame (2%) e dalle alterazioni di splicing (1%). La correlazione del genotipo identificato con il fenotipo diagnosticato è stata possibile in quasi la metà dei pazienti geneticamente caratterizzati. Dalla comparazione è stato possibile identificare forme trialleliche, con la mutazione missenso G1961E di ABCA4 come allele aggravante, e una nuova associazione gene-malattia per il gene PRPF31 che in tre pazienti causa la sindrome di Usher. L’analisi dei probandi affetti da forme X-linked di Retinite Pigmentosa ha permesso l’identificazione di un’inserzione framshift nell’ORF15 del gene RPGR, una mutazione nonsenso in RPGR gene e una mutazione missenso nota in RP2, in tre famiglie distinte. Tra i pazienti affetti da OMD, è stata identificato per due di essi la mutazione missenso S1199F in RP1L1. Il test di suscettibilità per i 7 SNP ha evidenziato un elevato alto genetico di AMD in 38 soggetti, medio alto in 16, medio in 36, e basso in 28. Conclusioni: La tecnologia NGS si è rivelata un utile strumento diagnostico per le forme autosomiche dominanti o recessive di distrofie retiniche, permettendo il sequenziamento massivo e parallelo di molti geni e pazienti. La percentuale di pazienti geneticamente caratterizzati è coerente con i dati presenti in letteratura. L’uso di un pannello di geni risulta essere un accettabile compromesso tra la i risultati ottenuti e le criticità legate alla grande quantità di dati output, rispetto alle analisi di whole genome o whole exome sequencing. Buona parte dei dati genetici sono stati correlati alle manifestazioni cliniche dei pazienti. La tecnologia Sanger, gold standard del sequenziamento, è ottimale per l’identificazione della causa genetica in tutte le patologie ove uno o pochi geni sono coinvolti, come le forme X-linked di IRD o la OMD. L’espressione di fattori di rischio, predisponenti alla degenerazione maculare, pur non correlando con la severità delle mutazioni confermate, potrebbe fornire importanti relazioni con le patologie di cui i soggetti sono affetti. L'identificazione delle cause genetiche di queste patologie porterà una nuova spinta nello sviluppo di nuove terapie geniche e cellulari, fondamentali per il trattamento delle patologie retiniche ereditarie.

Combining multiple forecasts in order to generate a single, more accurate one is a well-known approach. A simple average of forecasts has been found to be robust despite theoretically better approaches, increasing availability in the number of expert forecasts, and improved computational capabilities. The dominance of a simple average is related to the small sample sizes and to the estimation errors associated with more complex methods. We study the role that expert correlation, multiple experts, and their relative forecasting accuracy have on the weight estimation error distribution. The distributions we find are used to identify the conditions when a decision maker can confidently estimate weights versus using a simple average. We also propose an improved expert weighting approach that is less sensitive to covariance estimation error while providing much of the benefit from a covariance optimal weight. These two improvements create a new heuristic for better forecast aggregation that is simple to use. This heuristic appears new to the literature and is shown to perform better than a simple average in a simulation study and by application to economic forecast data.

The purpose of the current study was to address the relationship between Body Mass Index (BMI) status and psychological distress within the adolescent population. Data was acquired from the California Health Interview Survey (CHIS) 2011-2012, a state-wide phone survey which addresses health issues among the resident population. The present study used data from 2,1 04 California adolescents, utilizing variables relating to demographics, general health condition, and mental health.

Results indicated a statistically significant relationship between BMI and psychological distress, with overweight adolescents experiencing more distress and depression than their underweight/healthy weight counterparts. Gender and perceived general health condition were both significantly related to distress, with females and those of poor perceived general health condition experiencing greater psychological distress, regardless of weight status. This study has implications for social work policy and practice, especially in work with youth and families.

Abstract Increasing environmental and economic awareness are driving the development of combustion technologies to efficient biomass use and clean burning. To accomplish these goals, quantitative information about combustion variables is needed. However, for small-scale combustion units the existing monitoring methods are often expensive or complex. This study aimed to quantify correlations between flue gas temperatures and combustion variables, namely typical emission components, heat output, and efficiency. For this, data acquired from four small-scale combustion units and a large circulating fluidised bed boiler was studied. The fuel range varied from wood logs, wood chips, and wood pellets to biomass residue. Original signals and a defined set of their mathematical transformations were applied to data analysis. In order to evaluate the strength of the correlations, a multivariate distance measure based on information theory was derived. The analysis further assessed time-varying signal correlations and relative time delays. Ranking of the analysis results was based on the distance measure. The uniformity of the correlations in the different data sets was studied by comparing the 10-quantiles of the measured signal. The method was validated with two benchmark data sets. The flue gas temperatures and the combustion variables measured carried similar information. The strongest correlations were mainly linear with the transformed signal combinations and explicable by the combustion theory. Remarkably, the results showed uniformity of the correlations across the data sets with several signal transformations. This was also indicated by simulations using a linear model with constant structure to monitor carbon dioxide in flue gas. Acceptable performance was observed according to three validation criteria used to quantify modelling error in each data set. In general, the findings demonstrate that the presented signal transformations enable real-time approximation of the studied combustion variables. The potentiality of flue gas temperatures to monitor the quality and efficiency of combustion allows development toward cost effective control systems. Moreover, the uniformity of the presented signal correlations could enable straightforward copies of such systems. This would cumulatively impact the reduction of emissions and fuel consumption in small-scale biomass combustion
Tiivistelmä Kasvava ympäristö- ja kustannustietoisuus ohjaa polttoteknologioiden kehitystä yhä tehokkaampaan biomassan hyödyntämiseen ja puhtaampaan palamiseen. Näiden tavoitteiden saavuttamiseen tarvitaan mittaustietoa palamismuuttujista. Nykyiset palamisen seurantaan tarkoitetut ratkaisut ovat kuitenkin pienpolttolaitteita ajatellen usein kalliita tai monimutkaisia. Tässä työssä tutkittiin mitattujen savukaasun lämpötilojen riippuvuussuhdetta tyypillisiin kaasukomponentteihin, lämpötehoon ja tehokkuuteen. Tätä varten analysoitiin mittausaineistot neljästä erityyppisestä pienpolttolaitteesta ja suuresta kiertoleijupeti-kattilasta. Puupolttoaineina olivat klapi, hake, pelletti ja hakkuujäte. Analyysi tehtiin alkuperäisillä mittaussignaaleilla ja niistä matemaattisesti muunnetuilla signaaleilla. Riippuvuussuhteiden selvittämiseksi johdettiin informaatioteoriaan perustuva monimuuttuja-etäisyysmitta, jonka lukuarvolla mitataan signaalien samankaltaisuutta. Esitetty analyysimenetelmä sisälsi myös riippuvuuksien ajallisen muutoksen ja suhteellisten aikaviiveiden arvioinnin. Tulosten arvojärjestys perustui etäisyysmitan arvoon. Riippuvuussuhteiden samankaltaisuutta mittausaineistojen välillä vertailtiin 10-kvantiileilla. Analyysimenetelmän toimivuus vahvistettiin kahdella tunnetulla koeaineistolla. Savukaasun lämpötilojen ja palamismuuttujien mittaussignaaleissa oli samankaltainen informaatiosisältö. Vahvimmat riippuvuudet olivat muunnettujen signaalien yhdistelmillä pääosin lineaarisia ja palamisteorian mukaisia. Merkittävää oli, että tietyillä signaalimuunnos- ja palamismuuttujapareilla oli sama riippuvuussuhde kaikissa mittausaineistossa. Tämä todettiin myös simuloinneilla arvioitaessa savukaasujen hiilidioksidipitoisuutta lineaarisella, kiinteällä mallirakenteella. Mallin tarkkuus oli riittävä kolmella erityyppisellä kriteerillä jokaisessa mittausaineistossa. Tulosten perusteella signaalimuunnoksilla voidaan arvioida palamismuuttujia reaaliaikaisesti. Savukaasujen lämpötilojen potentiaali palamisen laadun ja tehokkuuden seurannassa mahdollistaa kustannustehokkaiden säätöratkaisujen kehityksen. Löydettyjä yleistettäviä riippuvuussuhteita hyödyntämällä niiden käyttöönotto lukuisissa polttolaitteissa helpottuisi. Pienpolton päästöjen ja polttoaineen kulutuksen vähentyminen olisi tällöin kumulatiivista

Epileptic seizure presents a formidable threat to the life of its sufferers, leaving them unconscious within seconds of its onset. Having a mortality rate that is at least twice that of the general population, it is a true cause for concern which has gained ample attention from various research communities. About 800 million people in the world will have at least one seizure experience in their lifespan. Injuries sustained during a seizure crisis are one of the leading causes of death in epilepsy. These can be prevented by an early detection of seizure accompanied by a timely intervention mechanism. The research presented in this dissertation explores Kriging methods to exploit spatial correlations of electroencephalogram (EEG) Signals from the brain, for fast and accurate seizure detection in the Internet of Medical Things (IoMT) using edge computing paradigms, by modeling the brain as a three-dimensional spatial object, similar to a geographical panorama. This dissertation proposes basic, hierarchical and distributed Kriging models, with a deep neural network (DNN) wrapper in some instances. Experimental results from the models are highly promising for real-time seizure detection, with excellent performance in seizure detection latency and training time, as well as accuracy, sensitivity and specificity which compare well with other notable seizure detection research projects.

In the first 3 years of the Obama Administration, 2009-2011, the number of warning letters issued to pharmaceutical firms for manufacturing and quality issues increased by 81% to 49 letters. Only 9 letters were issued in the last 3 years of the George W. Bush Administration. Shortfalls in compliance and product quality led to medicine shortages that affected patients' treatment and health. This quantitative study sought to learn to what extent, if any, the independent variables, management behaviors and financial indicators at pharmaceutical firms in the United States, correlated with, or predicted, the dependent variable, compliance with the FDA regulations. FDA's enforcement actions on the firms were the treatment event. A shift in the relationship between the variables occurred after the FDA interventions, which highlighted a new level of compliance. Of the 1144 SurveyMonkey invitations sent to the members of the International Society of Pharmaceutical Engineers, only 21 completed the survey's 133 questions. Three research questions were addressed using correlations and linear regressions. The theory of planned behavior was applied to correlate behavioral constructs with the compliance of the firms leading to the rejection of the null hypothesis. By establishing an inverse relation between financial indicators and the firms' level of compliance, the study offers awareness and insight to senior leaders regarding their behaviors and the decision-making process. Enhancing managers' decision-making processes in light of their beliefs, along with their control over financial indicators, could reinforce the presence of effective quality systems among pharmaceutical manufacturers minimizing medicine shortages.

One of the early steps in axial turbine design is the use of one-dimensional (1D) mean line calculations to predict the turbine performance and estimate the principal geometric parameters, such as radius and blade heights, that will be needed in further computational fluid dynamic (CFD) studies. This 1D analysis is based on the estimation of the aerodynamic losses expressed as a function of simple blade parameters and the velocity triangles. In this regard, there exist different loss correlations widely used in literature to estimate these losses but at the same time there is a lack of information regarding differentiation between them. Thereafter, the objective in this work was to judge and compare the behaviors of the Kacker- Okapuu, Craig-Cox and Denton loss correlations, all of them widely-used in turbine performance prediction. Present work shows the implementation of these different loss correlations on an existing 1D mean line numerical tool, LUAX-T. Subsequently, once implemented, the correlations were compared and analyzed by the use of a validation process and performing a parametric study. The results show that similar key parameters such as the flow turning, solidity and aspect ratio rule the different loss mechanisms in each correlation. On the other hand, the parametric study shows that the correlations are in agreement with the theory and give similar trends for performance prediction even though they all predict different values of efficiency for the same turbine stage. Moreover, the validation process show the correlations were found to be accurate enough when comparing against two different sets of experimental data. However, it was also proved that the models are only accurate if used within the range of applicability they were developed for, hence a complete knowledge of the limitations of each correlation should be known prior to using them. Finally, the extension of the one-dimensional mean line numerical tool LUAX-T will serve to perform further studies related to turbine design, as there are very few non-confidential turbomachinery design tools available for teaching or researching. Furthermore, a parametric study tool was also developed as part of the program. This last extension and the loss implementation codes are described in this work.

Conventional ‘well-stirred’ extrapolation methodology using intrinsic metabolic clearance data from rat liver microsomes poorly predicts in vivo clearance for approximately half of drug discovery compounds. The aim of this present study was to gain a more detailed understanding of the hepatobiliary disposition pathways which influence drug clearance. A set of 77 new chemical entities (NCEs), demonstrating a range of physicochemical properties and in vitro-in vivo clearance correlations (IVIVC), were employed to explore relationships between hepatobiliary disposition pathways in rat and physicochemical, structural and molecular properties of the NCEs. Primary rat hepatocytes with >80% cell viability were successfully isolated from male Han Wistar rats and used to establish in vitro models of drug uptake and biliary efflux. Preliminary studies with cultured primary rat hepatocytes indicated that uptake of d8-taurocholic acid and pitavastatin was time, concentration and temperature dependent. Initial studies with sandwich cultured primary rat hepatocytes demonstrated that cellular accumulation and biliary efflux of [3H]-Taurocholic acid was time and concentration dependent. These in vitro rat hepatocyte models were then used to investigate drug uptake and biliary efflux for all NCEs. In general, NCEs with high (passive) permeability showed better IVIVC and a lower incidence of active uptake and biliary efflux compared to NCEs with lower permeability, suggesting permeability is a key property influencing hepatobiliary drug disposition in rat. Preliminary in silico models analysing structural and molecular descriptors of substrates of active transport in rat hepatocytes were developed and indicated modest potential to highlight clearance pathways beyond hepatic metabolism but further follow up work with larger, more diverse compound sets is warranted to gain confidence in these models. Extended clearance models were investigated to estimate the effect of hepatic transporters on clearance and to predict the overall hepatic clearance of the NCEs. None of these models resulted in a 1 to 1 correlation but in general, improvements in clearance predictions were made when drug transport processes were accounted for. In vivo excretion studies using bile duct cannulated rats demonstrated that NCEs with high permeability and good IVIVC were not directly eliminated in bile or urine as unchanged drug, whereas NCEs with lower permeability and poor IVIVC (> 3-fold under predicted) were all directly eliminated unchanged indicating key drivers of clearance beyond metabolism. In conclusion these investigations confirmed a role for hepatic transporters in clearance but the complex nature of active transport mechanisms and a lack of robust in vitro tools create challenges in the quantitative prediction of hepatobiliary clearance. However, one of the key findings from this research, which is highly applicable in early drug discovery, was to identify the existence of disposition permeability relationships. These can be anticipated by observing physicochemical parameters of NCEs in conjunction with conventional IVIVC, since NCEs that are not highly permeable, possess some hydrophobic characteristics, and which are poor substrates of cytochrome P450 enzymes are more likely to be good substrates of transporters and be directly eliminated in bile and/or urine. The present study focused on exploring hepatobiliary disposition pathways using rat as the investigative species. Whilst there is no guarantee that pathways relevant to rat will be similar to other preclinical species or even humans, an early diagnosis of dominant clearance pathways can guide a more efficient use of the ADME-PK toolbox.

The basic idea of this paper is to outline a cross-curricular approach between mathematics and science. The aim is to close the often perceived gap between formal maths and authentic experience and to increase the students’ versatility in the use of mathematical terms. Students are to experience maths as logical, interesting and relevant through extra-mathematical references. Concrete physical or biological correlations may initiate mathematical activities, and mathematical terms are to be understood in logical contexts. Examples: physical experiments can lead to a comprehensive understanding of the concept of functions and of the intersection of medians in triangles. Biological topics can lead to the concepts of similarity and proportion as well as to the construction of pie charts. In the European ScienceMath Project a variety of teaching modules was developed and tested in secondary schools.

Cette these retrace les etapes rencontrees lors du projet de recherche et developpement: mise au point d'un anemometre ultrasonore correlatif. Dans la premiere moitie du rapport sont presentes differents elements devant permettre de poser rigoureusement et precisemment le probleme: caracterisation d'un appareil repondant a un ensemble de besoins et de contraintes. Dans la deuxieme moitie du rapport sont presentees les experimentations et les etudes necessaires a la mise au point d'un anemometre prototype. Ces experiences sont relatives a la faisabilite de l'appareil aux methodes de traitement de l'information (correlation, statistiques, redondance), et aux problemes technologiques rencontres (lies surtout a l'utilisation des ultrasons dans l'air). Enfin, les resultats de tests de validation en soufflerie sont exposes

En raison de leur capacité de prise, les liants hydrauliques sont utilisés à des fins très variées (e.g., matériaux de construction, substituts osseux, ...). La réaction de prise est toujours initiée par le mélange d'une ou plusieurs poudres fines avec une solution aqueuse. La dissolution des poudres réactives initiales entraîne la formation d'une pâte visqueuse, dont les propriétés évoluent avec le temps pour former une céramique poreuse monolithique par la nucléation et la précipitation de phase(s) plus stable(s). Dans le cadre de cette thèse, le plâtre CaSO4·2H2O obtenu par la réaction d'hydratation du sulfate de calcium hémihydraté CaSO4·0,5H2O est étudié dans des conditions standards (e.g., rapport massique liquide/solide, température et pression), afin de développer des techniques de caractérisation multi-physiques et multi-échelles in-situ et ex-situ pour suivre l'évolution de:- la composition des phases (réaction de dissolution et de précipitation) à l'aide de mesures calorimétriques, de la de la diffractométrie des rayons X et de la spectrophotométrie infrarouge à transformée de Fourier;- la microstructure à l'aide de la microscopie électronique à balayage et de la microtomographie aux rayons X;- les propriétés mécaniques en utilisant la mesure de vitesse de propagation des ultrasons, l'analyse mécanique dynamique en cisaillement et en compression et le test de résistance en compression. Ce panel de techniques a permis de suivre et de corréler les différentes transitions physiques survenant au cours de la réaction de prise et ainsi de dresser un portrait global des phénomènes physiques mis en jeu
Because of their setting ability, hydraulic binders are used for a wide variety of applications (e.g., construction materials, bone substitutes, ...). The setting reaction is always initiated by mixing one or several fine powders with an aqueous solution. The dissolution of the initial reactive powders results in the formation of a viscous paste, whose properties evolve with time to form a porous monolithic ceramic through the nucleation and precipitation of more stable phase(s). In this thesis, gypsum plaster CaSO4·2H2O obtained by the hydration reaction of calcium sulfate hemihydrate CaSO4·0,5H2O is studied under standard conditions (e.g., liquid/solid mass ratio, temperature and pressure), in order to develop multi-physic and multi-scale characterization techniques in-situ and ex-situ to monitor the evolution of:- the phase composition (rate of dissolution and precipitation) using calorimetric measurements, X-ray diffraction and Fourier-transform infrared spectrophotometry techniques;- the microstructure using scanning electron microscopy and X-ray microtomography;- the mechanical properties using ultrasonic propagation velocity measurement, shear and compressive dynamic mechanical analysis and compressive strength testing. This panel of techniques enabled to monitor and to correlate the various physical transitions occurring during the setting reaction, and thus to draw a global picture of the on-going phenomena

Thesis (M.A.) -- Central Connecticut State University, 2010.
Thesis advisor: Joshua King. "... in partial fulfillment of Master of Arts in Biology." Includes bibliographical references (leaves 23-25). Also available via the World Wide Web.

碩士
朝陽科技大學
營建工程系碩士班
100
Deteriorated bridges managed by the local authorities often lack sufficient resources for sophisticated long-term maintenance and monitoring programs. There is a great demand of low-cost and efficient monitoring techniques suitable for bridge management. Previous study has indicated that images recorded using consumer digital cameras and processed by digital image correlation methods (DICM) has the potential to fulfill such a need. Current research applies DICM to obtain the displacement data that can be further analyzed using frequency domain decomposition, or FDD. Two bridges with light traffic conditions have been investigated. The measured displacement data are in reasonable agreement with the simulated data using SAP2000. Modal analysis and FDD are also performed using the numerical model for the two bridges. The modal frequencies and damping ratio values are also obtained based on the field experiments but require further verifications with the numerical simulation.

Cheung, Yu Hin Ray.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 47-49).
Abstracts in English and Chinese.
Chapter CHAPTER ONE: --- INTRODUCTION --- p.1
Chapter CHAPTER TWO: --- A UNIFIED BOOTSTRAP PROCEDURE --- p.7
Chapter CHAPTER THREE: --- A SIMULATION STUDY --- p.10
Chapter CHAPTER FOUR: --- RESULTS --- p.18
Chapter CHAPTER FIVE: --- DISCUSSION --- p.33
Chapter CHAPTER SIX: --- CONCLUSION --- p.37
APPENDICES --- p.38
REFERENCES --- p.46

碩士
淡江大學
財務金融學系碩士在職專班
95
The analysis and investigation subject of this study is to discover correlation between the spot market price:「Taiwan stock index」and the derivatives price: 「Daily close index of Taiwan stock index futures」、「Daily settle index of Taiwan stock index call-options」and「Daily settle index of Taiwan stock index put-options」. The sampling time is form 2004/06/17 to 2006/06/21. We use the traditional linear research methods and the nonparametric nonlinear research methods to test the 4 sets of series data for unit-root and cointegration. The result is that the 4 sets of series data found with unit-root, and then exists stationary after first difference. Either the traditional linear Johansen cointegration test method or the nonparametric cointegration test method(Bierens, 1997 & Breitung, 2002 )with more testing power, the testing outcome is that there are no more than 3 cointegration vectors between the Taiwan spot market price and the derivatives price. The result of the traditional Granger-causality testing is the spot market price causes the derivatives price in Taiwan. And the testing result of nonlinear Granger-causality is that exist a reciprocal feedback relationship between the spot market price and the derivatives price in Taiwan. And then we utilize general linear impulse-response function and nonstructural impulse-response function to test the 4 sets of data, and we found that the response of the derivatives price to the impulse of the spot market price is violent. Finally, by way of the testing of the general linear variance-decomposition method and nonlinear variance-decomposition method, we found that the spot market price has the maximum explanation power for the derivatives, and in the meanwhile the index call-options price and index put-options price have the superior explanation power for variance on themselves.

Cheung Shu Fai.
"August 2000."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2000.
Includes bibliographical references (p. 117-123).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.

We apply anisotropic Banach space methods together with operator renewal theory to obtain polynomial rates of decay of correlations for a class of generalized baker's transformations. The polynomial rates were proved for a smaller class of observables in a 2013 paper of Bose and Murray by fundamentally different methods. Our approach provides a direct analysis of the Frobenius-Perron operator associated to a generalized baker's transformation in contrast to the paper of Bose and Murray where decay rates are obtained for a factor map and lifted to the full map.
Graduate

abstract: Rapid advancements in genomic technologies have increased our understanding of rare human disease. Generation of multiple types of biological data including genetic variation from genome or exome, expression from transcriptome, methylation patterns from epigenome, protein complexity from proteome and metabolite information from metabolome is feasible. "Omics" tools provide comprehensive view into biological mechanisms that impact disease trait and risk. In spite of available data types and ability to collect them simultaneously from patients, researchers still rely on their independent analysis. Combining information from multiple biological data can reduce missing information, increase confidence in single data findings, and provide a more complete view of genotype-phenotype correlations. Although rare disease genetics has been greatly improved by exome sequencing, a substantial portion of clinical patients remain undiagnosed. Multiple frameworks for integrative analysis of genomic and transcriptomic data are presented with focus on identifying functional genetic variations in patients with undiagnosed, rare childhood conditions. Direct quantitation of X inactivation ratio was developed from genomic and transcriptomic data using allele specific expression and segregation analysis to determine magnitude and inheritance mode of X inactivation. This approach was applied in two families revealing non-random X inactivation in female patients. Expression based analysis of X inactivation showed high correlation with standard clinical assay. These findings improved understanding of molecular mechanisms underlying X-linked disorders. In addition multivariate outlier analysis of gene and exon level data from RNA-seq using Mahalanobis distance, and its integration of distance scores with genomic data found genotype-phenotype correlations in variant prioritization process in 25 families. Mahalanobis distance scores revealed variants with large transcriptional impact in patients. In this dataset, frameshift variants were more likely result in outlier expression signatures than other types of functional variants. Integration of outlier estimates with genetic variants corroborated previously identified, presumed causal variants and highlighted new candidate in previously un-diagnosed case. Integrative genomic approaches in easily attainable tissue will facilitate the search for biomarkers that impact disease trait, uncover pharmacogenomics targets, provide novel insight into molecular underpinnings of un-characterized conditions, and help improve analytical approaches that use large datasets.
Dissertation/Thesis
Doctoral Dissertation Molecular and Cellular Biology 2015

In this dissertation it is presented an empirical study that focus the period from 3 January 2007 to 1 October 2018, about the interactions between stock markets of Europe, United States of America (USA) and Asia, by implementing a generalized vector autoregressive (VAR) model and a dynamic conditional correlation (DCC) model. For this purpose, three different stock market indices (Euro Stoxx 50 - Europe, S&P 500 – USA, and Nikkei 225 – Asia) were chosen to be representative of each geography they concern, in order to inquire if the indices are related between each other or not. In general, the empirical results allow to conclude that returns of S&P 500 and Euro Stoxx 50 returns depend on their own past returns. Additionally, Euro Stoxx 50 returns are influenced by past returns of S&P 500 and there is no evidence of causality relationship from Nikkei 225 returns to any of the other indices returns. Moreover, the conditional analysis of the pairwise correlations reveals that these are positive. The results presented by the DCC model indicate that it provides an accurate description of the dynamics of the correlations between the time series analysed for the purpose of this dissertation.
No presente trabalho, é apresentado um estudo empírico com base no período entre 3 de Janeiro de 2007 e 1 de Outubro de 2018, acerca das interações entre os mercados de capitais da Europa, Estados Unidos da América (EUA) e Ásia, através da estimação do modelo VAR e do modelo DCC. Para este propósito, foram escolhidos três índices de ações representativos da geografia a que dizem respeito (Euro Stoxx 50 – Europa, S&P 500 – EUA e Nikkei 225 – Ásia) de modo averiguar se os índices estão relacionados entre si ou não. Em termos gerais, os resultados obtidos permitiram concluir que as taxas de rendibilidade dos índices S&P 500 e Euro Stoxx 50 dependem das suas rendibilidades passadas, as rendibilidades do Euro Stoxx 50 são influenciados pelas rendibilidades passadas do S&P 500 e não há evidências de causalidade nem do S&P 500 nem do Nikkei 225 para as rendibilidades dos restantes índices. Adicionalmente, a análise das correlações condicionais a pares revela que estas são positivas. Os resultados produzidos pelo modelo DCC revelam que este é um modelo apropriado para descrever as dinâmicas correlacionais entre as várias séries temporais em questão.

The present dissertation develops an invariant framework for 3D gesture comparison studies. 3D gesture comparison without Lagrangian models is challenging not only because of the lack of prediction provided by physics, but also because of a dual geometry representation, spatial dimensionality and non-linearity associated to 3D-kinematics. In 3D spaces, it is difficult to compare curves without an alignment operator since it is likely that discrete curves are not synchronized and do not share a common point in space. One has to assume that each and every single trajectory in the space is unique. The common answer is to assert the similitude between two or more trajectories as estimating an average distance error from the aligned curves, provided that the alignment operator is found. In order to avoid the alignment problem, the method uses differential geometry for position and orientation curves. Differential geometry not only reduces the spatial dimensionality but also achieves view invariance. However, the nonlinear signatures may be unbounded or singular. Yet, it is shown that pattern recognition between intrinsic signatures using correlations is robust for position and orientation alike. A new mapping for orientation sequences is introduced in order to treat quaternion and Euclidean intrinsic signatures alike. The new mapping projects a 4D-hyper-sphere for orientations onto a 3D-Euclidean volume. The projection uses the quaternion invariant distance to map rotation sequences into 3D-Euclidean curves. However, quaternion spaces are sectional discrete spaces. The significance is that continuous rotation functions can be only approximated for small angles. Rotation sequences with large angle variations can only be interpolated in discrete sections. The current dissertation introduces two multi-scale approaches that improve numerical stability and bound the signal energy content of the intrinsic signatures. The first is a multilevel least squares curve fitting method similar to Haar wavelet. The second is a geodesic distance anisotropic kernel filter. The methodology testing is carried out on 3D-gestures for obstetrics training. The study quantitatively assess the process of skill acquisition and transfer of manipulating obstetric forceps gestures. The results show that the multi-scale correlations with intrinsic signatures track and evaluate gesture differences between experts and trainees.