Caratterizzazione di sequenze di DNA mediante catene di Markov

Questa tesi si inserisce nell’ambito di studio dei modelli stocastici applicati alle sequenze di DNA. I random walk e le catene di Markov sono tra i processi aleatori che hanno trovato maggiore diffusione in ambito applicativo grazie alla loro capacità di cogliere le caratteristiche salienti di molti sistemi complessi, pur mantenendo semplice la descrizione di questi. Nello specifico, la trattazione si concentra sull’applicazione di questi nel contesto dell’analisi statistica delle sequenze genomiche. Il DNA può essere rappresentato in prima approssimazione da una sequenza di nucleotidi che risulta ben riprodotta dal modello a catena di Markov; ciò rappresenta il punto di partenza per andare a studiare le proprietà statistiche delle catene di DNA. Si approfondisce questo discorso andando ad analizzare uno studio che si ripropone di caratterizzare le sequenze di DNA tramite le distribuzioni delle distanze inter-dinucleotidiche. Se ne commentano i risultati, al fine di mostrare le potenzialità di questi modelli nel fare emergere caratteristiche rilevanti in altri ambiti, in questo caso quello biologico.

Markov Process Modeling of A System Under WIPLOAD Control

This paper analyzes a proposed release controlmethodology, WIPLOAD Control (WIPLCtrl), using a transfer line case modeled by Markov process modeling methodology. The performance of WIPLCtrl is compared with that of CONWIP under 13 system configurations in terms of throughput, average inventory level, as well as average cycle time. As a supplement to the analytical model, a simulation model of the transfer line is used to observe the performance of the release control methodologies on the standard deviation of cycle time. From the analysis, we identify the system configurations in which the advantages of WIPLCtrl could be observed.

Catene di Markov nascoste e giochi stocastici.

In questa trattazione si introduce il concetto di catena di Markov nascosta: una coppia di processi stocastici (X,O), dove X è una catena di Markov non osservabile direttamente e O è il processo stocastico delle osservazioni, dipendente istante per istante solo dallo stato corrente della catena X. In prima istanza si illustrano i metodi per la soluzione di tre problemi classici, dato un modello di Markov nascosto e una sequenza di segnali osservati: valutare la probabilità della osservazione nel modello, trovare la sequenza nascosta di stati più probabile e aggiornare il modello per rendere più probabile l'osservazione. In secondo luogo si applica il modello ai giochi stocastici, nel caso in cui solo uno dei giocatori non è a conoscenza del gioco in ogni turno, ma può cercare di ottenere informazioni utili osservando le mosse dell'avversario informato. In particolare si cercano strategie basate sul concetto di catena di Markov nascoste e si analizzano i risultati ottenuti per valutare l'efficienza dell'approccio.

Catene di Markov reversibili e applicazioni al metodo Montecarlo basato sulle catene di Markov

Gli argomenti trattati in questa tesi sono le catene di Markov reversibili e alcune applicazioni al metodo Montecarlo basato sulle catene di Markov. Inizialmente vengono descritte alcune delle proprietà fondamentali delle catene di Markov e in particolare delle catene di Markov reversibili. In seguito viene descritto il metodo Montecarlo basato sulle catene di Markov, il quale attraverso la simulazione di catene di Markov cerca di stimare la distribuzione di una variabile casuale o di un vettore di variabili casuali con una certa distribuzione di probabilità. La parte finale è dedicata ad un esempio in cui utilizzando Matlab sono evidenziati alcuni aspetti studiati nel corso della tesi.

Syntheses of Cross-Linking Agents, Molecular Modeling of Oligonucleotides and Polypeptide-Ion Complexes

Each section of this thesis will be subdivided into three parts encompassing all of the research in which I have been involved during the past three years. These will be referred to under the headings "Syntheses:' "Molecular Modeling," and "Cross-linking Efficiencies." Each of these subdivisions may have divisions within them when necessary in order to fully detail the research.

Factors affecting nucleolytic efficiency of some ternary metal complexes with DNA binding and recognition domains. Crystal and molecular structure of Zn(phen)(edda)

The binding selectivity of the M(phen)(edda) (M = Cu, Co, Ni, Zn; phen = 1,10-phenanthroline, edda = ethylenediaminediacetic acid) complexes towards ds(CG)(6), ds(AT)(6) and ds(CGCGAATTCGCG) B-form oligonucleotide duplexes were studied by CD spectroscopy and molecular modeling. The binding mode is intercalation and there is selectivity towards AT-sequence and stacking preference for A/A parallel or diagonal adjacent base steps in their intercalation. The nucleolytic properties of these complexes were investigated and the factors affecting the extent of cleavage were determined to be: concentration of complex, the nature of metal(11) ion, type of buffer, pH of buffer, incubation time, incubation temperature, and the presence of hydrogen peroxide or ascorbic acid as exogenous reagents. The fluorescence property of these complexes and its origin were also investigated. The crystal structure of the Zn(phen)(edda) complex is reported in which the zinc atom displays a distorted trans-N4O2 octahedral geometry; the crystal packing features double layers of complex molecules held together by extensive hydrogen bonding that inter-digitate with adjacent double layers via pi...pi interactions between 1,10-phenanthroline residues. The structure is compared with that of the recently described copper(II) analogue and, with the latter, included in molecular modeling. (C) 2008 Elsevier B.V. All rights reserved.

Processi di semi-Markov a tempo discreto

Studio della teoria dei processi di semi-Markov nella modellizzazione a tempo discreto. Introduzione delle catene di rinnovo di Markov, del nucleo di semi-Markov e delle catene di semi-Markov, risultati ad essi relativi. Analisi delle equazioni di rinnovo di Markov, caratterizzazione degli stati di una catena di semi-Markov, teorema di esistenza e unicità dell'equazione di rinnovo di Markov. Un esempio concreto.

Urban land use change analysis and modelling: a case study of Setubal-Sesimbra, Portugal

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

A longitudinal study on delirium in nursing homes.

OBJECTIVE: To investigate the evolution of delirium of nursing home (NH) residents and their possible predictors. DESIGN: Post-hoc analysis of a prospective cohort assessment. SETTING: Ninety NHs in Switzerland. PARTICIPANTS: Included 14,771 NH residents. MEASUREMENTS: The Resident Assessment Instrument Minimum Data Set and the Nursing Home Confusion Assessment Method were used to determine follow-up of subsyndromal or full delirium in NH residents using discrete Markov chain modeling to describe long-term trajectories and multiple logistic regression analyses to determine predictors of the trajectories. RESULTS: We identified four major types of delirium time courses in NH. Increasing severity of cognitive impairment and of depressive symptoms at the initial assessment predicted the different delirium time courses. CONCLUSION: More pronounced cognitive impairment and depressive symptoms at the initial assessment are associated with different subsequent evolutions of delirium. The presence and evolution of delirium in the first year after NH admission predicted the subsequent course of delirium until death.

Algoritmos genéticos canônico e elitista: uma abordagem comparativa

Universidade Federal do Rio Grande do Norte

Low energy elastic and electronically inelastic electron scattering from biomolecules.

Reactions initiated by collisions with low-energy secondary electrons has been found to be the prominent mechanism toward the radiation damage on living tissues through DNA strand breaks. Now it is widely accepted that during the interaction with these secondary species the selective breaking of chemical bonds is triggered by dissociative electron attachment (DEA), that is, the capture of the incident electron and the formation of temporary negative ion states [1,2,3]. One of the approaches largely used toward a deeper understanding of the radiation damage to DNA is through modeling of DEA with its basic constituents (nucleotide bases, sugar and other subunits). We have tried to simplify this approach and attempt to make it comprehensible at a more fundamental level by looking at even simple molecules. Studies involving organic systems such as carboxylic acids, alcohols and simple ¯ve-membered heterocyclic compounds are taken as starting points for these understanding. In the present study we investigate the role played by elastic scattering and electronic excitation of molecules on electron-driven chemical processes. Special attention is focused on the analysis of the in°uence of polarization and multichannel coupling e®ects on the magnitude of elastic and electronically inelastic cross-sections. Our aim is also to investigate the existence of resonances in the elastic and electronically inelastic channels as well as to characterize them with respect to its type (shape, core-excited or Feshbach), symmetry and position. The relevance of these issues is evaluated within the context of possible applications for the modeling of discharge environments and implications in the understanding of mutagenic rupture of DNA chains. The scattering calculations were carried out with the Schwinger multichannel method (SMC) [4] and its implementation with pseudopotentials (SMCPP) [5] at di®erent levels of approximation for impact energies ranging from 0.5 eV to 30 eV. References [1] B. Boudai®a, P. Cloutier, D. Hunting, M. A. Huels and L. Sanche, Science 287, 1658 (2000). [2] X. Pan, P. Cloutier, D. Hunting and L. Sanche, Phys. Rev. Lett. 90, 208102 (2003). [3] F. Martin, P. D. Burrow, Z. Cai, P. Cloutier, D. Hunting and L. Sanche, Phys. Rev. Lett. 93, 068101 (2004). [4] K. Takatsuka and V. McKoy, Phys. Rev. A 24, 2437 (1981); ibid. Phys. Rev. A 30, 1734 (1984). [5] M. H. F. Bettega, L. G. Ferreira and M. A. P. Lima, Phys. Rev. A 47, 1111 (1993).

A longitudinal study on delirium in nursing homes

OBJECTIVE To investigate the evolution of delirium of nursing home (NH) residents and their possible predictors. DESIGN Post-hoc analysis of a prospective cohort assessment. SETTING Ninety NHs in Switzerland. PARTICIPANTS Included 14,771 NH residents. MEASUREMENTS The Resident Assessment Instrument Minimum Data Set and the Nursing Home Confusion Assessment Method were used to determine follow-up of subsyndromal or full delirium in NH residents using discrete Markov chain modeling to describe long-term trajectories and multiple logistic regression analyses to determine predictors of the trajectories. RESULTS We identified four major types of delirium time courses in NH. Increasing severity of cognitive impairment and of depressive symptoms at the initial assessment predicted the different delirium time courses. CONCLUSION More pronounced cognitive impairment and depressive symptoms at the initial assessment are associated with different subsequent evolutions of delirium. The presence and evolution of delirium in the first year after NH admission predicted the subsequent course of delirium until death.

Learning Data-Driven Models of Non-Verbal Behaviors for Building Rapport Using an Intelligent Virtual Agent

There is a growing societal need to address the increasing prevalence of behavioral health issues, such as obesity, alcohol or drug use, and general lack of treatment adherence for a variety of health problems. The statistics, worldwide and in the USA, are daunting. Excessive alcohol use is the third leading preventable cause of death in the United States (with 79,000 deaths annually), and is responsible for a wide range of health and social problems. On the positive side though, these behavioral health issues (and associated possible diseases) can often be prevented with relatively simple lifestyle changes, such as losing weight with a diet and/or physical exercise, or learning how to reduce alcohol consumption. Medicine has therefore started to move toward finding ways of preventively promoting wellness, rather than solely treating already established illness. Evidence-based patient-centered Brief Motivational Interviewing (BMI) interven- tions have been found particularly effective in helping people find intrinsic motivation to change problem behaviors after short counseling sessions, and to maintain healthy lifestyles over the long-term. Lack of locally available personnel well-trained in BMI, however, often limits access to successful interventions for people in need. To fill this accessibility gap, Computer-Based Interventions (CBIs) have started to emerge. Success of the CBIs, however, critically relies on insuring engagement and retention of CBI users so that they remain motivated to use these systems and come back to use them over the long term as necessary. Because of their text-only interfaces, current CBIs can therefore only express limited empathy and rapport, which are the most important factors of health interventions. Fortunately, in the last decade, computer science research has progressed in the design of simulated human characters with anthropomorphic communicative abilities. Virtual characters interact using humans’ innate communication modalities, such as facial expressions, body language, speech, and natural language understanding. By advancing research in Artificial Intelligence (AI), we can improve the ability of artificial agents to help us solve CBI problems. To facilitate successful communication and social interaction between artificial agents and human partners, it is essential that aspects of human social behavior, especially empathy and rapport, be considered when designing human-computer interfaces. Hence, the goal of the present dissertation is to provide a computational model of rapport to enhance an artificial agent’s social behavior, and to provide an experimental tool for the psychological theories shaping the model. Parts of this thesis were already published in [LYL+12, AYL12, AL13, ALYR13, LAYR13, YALR13, ALY14].

Modeling sequencing errors by combining Hidden Markov models.

Among the largest resources for biological sequence data is the large amount of expressed sequence tags (ESTs) available in public and proprietary databases. ESTs provide information on transcripts but for technical reasons they often contain sequencing errors. Therefore, when analyzing EST sequences computationally, such errors must be taken into account. Earlier attempts to model error prone coding regions have shown good performance in detecting and predicting these while correcting sequencing errors using codon usage frequencies. In the research presented here, we improve the detection of translation start and stop sites by integrating a more complex mRNA model with codon usage bias based error correction into one hidden Markov model (HMM), thus generalizing this error correction approach to more complex HMMs. We show that our method maintains the performance in detecting coding sequences.

MAMOT: hidden Markov modeling tool.

Hidden Markov models (HMMs) are probabilistic models that are well adapted to many tasks in bioinformatics, for example, for predicting the occurrence of specific motifs in biological sequences. MAMOT is a command-line program for Unix-like operating systems, including MacOS X, that we developed to allow scientists to apply HMMs more easily in their research. One can define the architecture and initial parameters of the model in a text file and then use MAMOT for parameter optimization on example data, decoding (like predicting motif occurrence in sequences) and the production of stochastic sequences generated according to the probabilistic model. Two examples for which models are provided are coiled-coil domains in protein sequences and protein binding sites in DNA. A wealth of useful features include the use of pseudocounts, state tying and fixing of selected parameters in learning, and the inclusion of prior probabilities in decoding. AVAILABILITY: MAMOT is implemented in C++, and is distributed under the GNU General Public Licence (GPL). The software, documentation, and example model files can be found at http://bcf.isb-sib.ch/mamot