Ice-atmosphere interactions and sea ice predictability at multiple resolutions in the Community Earth System Model

Thesis (Master's)--University of Washington, 2016-06

Reconstructing Past Climate by Using Proxy Data and a Linear Climate Model

Thesis (Master's)--University of Washington, 2016-06

Seismically-Induced Rock-Slope Failure: Numerical Investigation using the Bonded Particle Model

Thesis (Ph.D.)--University of Washington, 2016-06

Salivary Gland and Tooth Abnormalities Massively Increase Caries Susceptibility in A Mouse Model of Cleft Lip/Palate

Thesis (Ph.D.)--University of Washington, 2016-04

New Thinking for Intervention: Towards a Culturally Responsive Model of Understanding Indigenous Suicide

Thesis (Ed.D.)--University of Washington, 2016-06

Examining the Differential Effects of a Universal SEL Curriculum on Student Functioning on a Dual Continua Model of Mental Health

Thesis (Ph.D.)--University of Washington, 2016-06

Toxicokinetics of domoic acid in a nonhuman primate model (Macaca fascicularis)

Thesis (Master's)--University of Washington, 2016-06

An Electromechanical Coupled Model of the Probe of a Scanning Fiber Imaging System

Thesis (Master's)--University of Washington, 2016-06

Formic acid mixing ratio (CIMS) and 3D wind data, plus SOSAA model runs -- Hyytiälä, Finland, Apr-Jun 2014

These are data of eddy covariance flux measurements of formic acid (HCOOH), performed by a chemical ionization mass spectrometer (CIMS) over a boreal forest canopy in Hyytiälä, Finland, in spring/summer 2014. Results from the 1-D chemical transport model runs using SOSAA (Simulate Organic vapours, Sulphuric Acid and Aerosols) are included as well. The data accompany a submission of a manuscript to Geophysical Research Letters for consideration for publication (Schobesberger et al.).

S. cerevisiae as a model for studying mutations in the human gene OPA1 associated with dominant optic atrophy and for drug discovery

L’atrofia ottica dominante (ADOA) è una malattia mitocondriale caratterizzata da difetti visivi, che si manifestano durante l’infanzia, causati da progressiva degenerazione delle cellule gangliari della retina (RGC). ADOA è una malattia genetica associata, nella maggior parte dei casi, a mutazioni nel gene OPA1 che codifica per la GTPasi mitocondriale OPA1, appartenente alla famiglia delle dinamine, principalmente coinvolta nel processo di fusione mitocondriale e nel mantenimento del mtDNA. Finora sono state identificate più di 300 mutazioni patologiche nel gene OPA1. Circa il 50% di queste sono mutazioni missenso, localizzate nel dominio GTPasico, che si pensa agiscano come dominanti negative. Questa classe di mutazioni è associata ad una sindrome più grave nota come “ADOA-plus”. Nel lievito Saccharomyces cerevisiae MGM1 è l’ortologo del gene OPA1: nonostante i due geni abbiano domini funzionali identici le sequenze amminoacidiche sono scarsamente conservate. Questo costituisce una limitazione all’uso del lievito per lo studio e la validazione di mutazioni patologiche nel gene OPA1, infatti solo poche sostituzioni possono essere introdotte e studiate nelle corrispettive posizioni del gene di lievito. Per superare questo ostacolo è stato pertanto costruito un nuovo modello di S. cerevisiae, contenente il gene chimerico MGM1/OPA1, in grado di complementare i difetti OXPHOS del mutante mgm1Δ. Questo gene di fusione contiene una larga parte di sequenza corrispondente al gene OPA1, nella quale è stato inserito un set di nuove mutazioni trovate in pazienti affetti da ADOA e ADOA-plus. La patogenicità di queste mutazioni è stata validata sia caratterizzando i difetti fenotipici associati agli alleli mutati, sia la loro dominanza/recessività nel modello di lievito. A tutt’oggi non è stato identificato alcun trattamento farmacologico per la cura di ADOA e ADOA-plus. Per questa ragione abbiamo utilizzato il nostro modello di lievito per la ricerca di molecole che agiscono come soppressori chimici, ossia composti in grado di ripristinare i difetti fenotipici indotti da mutazioni nel gene OPA1. Attraverso uno screening fenotipico high throughput sono state testate due differenti librerie di composti chimici. Questo approccio, noto con il nome di drug discovery, ha permesso l’identificazione di 23 potenziali molecole attive.

Monitoring inflammation and airway remodeling by FMT in a chronic asthma model

Asthma is a multifactorial disease for which a variety of mouse models have been developed. A major drawback of these models is represented by the transient nature of the airway pathology peaking 24 to 72 hours after challenge and resolving in 1 to 2 weeks. The objective of this study is to characterize the temporal evolution of pulmonary inflammation and remodeling in a recently described mouse model of chronic asthma (8 week treatment with 3 allergens relevant for the human pathology: Dust mite, Ragweed, and Aspergillus; DRA). We studied the DRA model taking advantage of fluorescence molecular tomography (FMT) imaging using near-infrared probes to non-invasively evaluate lung inflammation and airway remodeling. At 4, 6, 8 or 11 weeks, cathepsin- and metalloproteinase-dependent fluorescence was evaluated in vivo. A subgroup of animals, after 4 weeks of DRA, was treated with Budesonide (100 µg/kg intranasally) daily for 4 weeks. Cathepsin-dependent fluorescence in DRA-sensitized mice resulted significantly increased at 6 and 8 weeks, and was markedly inhibited by budesonide. This fluorescent signal well correlated with ex vivo analysis such as bronchoalveolar lavage eosinophils and alveolar cell infiltration. Metalloproteinase-dependent fluorescence was significantly increased at 8 and 11 weeks, nicely correlated with collagen deposition, as evaluated histologically by Masson’s Trichrome staining, and airway epithelium hypertrophy, and was also partly inhibited by budesonide. In conclusion, FMT proved suitable for longitudinal study to evaluate asthma progression, both in terms of inflammatory cell infiltration and airway remodeling, allowing the determination of treatment efficacy in a chronic asthma model in mice.

Model Mining and Efficient Verification of Software Product Lines

Software product line modeling aims at capturing a set of software products in an economic yet meaningful way. We introduce a class of variability models that capture the sharing between the software artifacts forming the products of a software product line (SPL) in a hierarchical fashion, in terms of commonalities and orthogonalities. Such models are useful when analyzing and verifying all products of an SPL, since they provide a scheme for divide-and-conquer-style decomposition of the analysis or verification problem at hand. We define an abstract class of SPLs for which variability models can be constructed that are optimal w.r.t. the chosen representation of sharing. We show how the constructed models can be fed into a previously developed algorithmic technique for compositional verification of control-flow temporal safety properties, so that the properties to be verified are iteratively decomposed into simpler ones over orthogonal parts of the SPL, and are not re-verified over the shared parts. We provide tool support for our technique, and evaluate our tool on a small but realistic SPL of cash desks.

Classification of Texts' Authorship Using a Regression Model on Compressed Data

2010 Mathematics Subject Classification: 68T50,62H30,62J05.

Group Comparisons on Cognitive Attributes Using the Least Squares Distance Model of Cognitive Diagnosis

2010 Mathematics Subject Classification: 62P15.

Implementation of the EM Algorithm for Maximum Likelihood Estimation of a Random Effects Model for One Longitudinal Ordinal Outcome

2010 Mathematics Subject Classification: 62J99.