Flexible strategies for association analysis with genomic phenotypes

Thesis (Ph.D.)--University of Washington, 2016-08

Theatrical Latency: Walking Katrina Palmer’s The Loss Adjusters

In this article I introduce the term ‘theatrical latency’ as a pleasurable effect experienced when listening to sound in relation to visual perception. Latency refers to both the phenomena of audio delay (in feedback from analogue to digital conversion and the momentary lapses experienced when playing live with recorded music) and a theatrical sensation that comes from the reanimation of visual environments through aural framing. In this configuration, the notion of latency takes on a double meaning as both a recorded phenomenon and the retrieval of something dormant within physical objects, sites or materials. These ideas will be introduced through my experience of walking Katrina Palmer’s site-specific audio work The Loss Adjusters (2015) on the island of Portland (UK). The audio tracks create an extended meditation on Portland, interweaving specific locations and histories with fictional characters and ghosts of the island.

Walking as physical exercise in Fibromyalgia: an elicitation study from the Theory of Planned Behavior

Este estudio corresponde a la primera fase de investigación formativa recomendada en la teoría de la Acción Planeada para desarrollar una intervención. Nuestros objetivos son identificar las creencias modales sobre la realización de una pauta de ejercicio en personas con fibromialgia, probar los ítems para la evaluación directa de los constructos predictivos y explorar sus relaciones con la conducta. Evaluamos a 46 mujeres con fibromialgia. El análisis de contenido mostró un mayor número de consecuencias positivas que negativas asociadas a la ejecución de la pauta de ejercicio (creencias comportamentales); la familia y los amigos son los referentes importantes (creencias normativas) y se detectaron factores facilitadores e inhibidores de la ejecución de la conducta de ejercicio, relacionados con aspectos de la fibromialgia (creencias de control) como el dolor, la fatiga y el estado de ánimo. El índice de consistencia interna más bajo fue el de la escala de norma subjetiva (α= .78). Los resultados confirman el sedentarismo de la muestra (conducta previa: Media=3.67; rango=1-7) aunque también sugieren que estas personas tienen intención de realizar la conducta (Media= 5.67). Las relaciones obtenidas entre los constructos son las esperadas desde la teoría, apoyando la pertinencia de aplicarla en la conducta y población seleccionada.

Has the time come for genomic tests to guide the use of adjuvant chemotherapy in node-positive breast cancer?

SCOPUS: ed.j

I cried to dream again: discovery and meaning-making in walking simulators

Paper presented at the 1st International Joint Conference of DiGRA and FDG Dundee, August 1-6, 2016.

Uskonto, yksilö ja yhteisö moraalin määrittäjänä - The Walking Dead -sarjan henkilöhahmojen moraaliongelmissa

Tässä tutkielmassa tarkastelen sitä, miten moraaliongelmien ratkaisuiden resurssina käytetään uskontoa, yksilöä tai yhteisöä televisiosarja The Walking Deadin henkilöhahmojen moraaliongelmissa. Tutkimuksessani lähden ensimmäiseksi kysymään, mitä moraaliongelmia sarja ylipäätään esittelee. Kiinnostukseni kohdistuu tämän jälkeen siihen, minkälaisen pohjan yhteisö luo moraaliratkaisujen tekemiseen ja siihen, miten yksilölliset tarpeet vaikuttavat päätösten perusteluihin. Tämän jälkeen mielenkiintoni keskittyy siihen, minkälaisia uskonnollisia resursseja henkilöhahmot käyttävät ongelmien ratkaisuun vai käyttävätkö lainkaan. Näiden jälkeen suhteutan moraaliongelmien ratkaisuihin käytetyt resurssit samalle viivalle ja pohdin, mitä henkilöhahmot eniten käyttävät moraaliongelmien ratkaisujen perusteena. Tutkimusaineistona toimii televisiosarja The Walking Dead, jonka henkilöhahmojen moraaliongelmia tutkin. Tutkimukseni analyysimenetelmäksi valikoitui laadullinen aineistolähtöinen sisällönanalyysi, jonka avulla olen rajannut tutkimusongelmani sekä lähdeaineistoni. Tämän jälkeen olen ryhmitellyt aineistoni valitsemieni aihepiirien mukaisesti ja lopuksi olen muodostanut tekemästäni havainnoista yhteenvedon. Sisällönanalyysin lisäksi tutkimukseni on osa fiktiivisen elämänmuodon tutkimusta. Tässä olen hyödyntänyt sisällönanalyysin menetelmiä: havainnointia, erittelyä ja vertailua. Tutkimuksessani päädyin siihen tulokseen, että moraaliongelmien resursseina voidaan sanoa käytettävän kaikkia eri mainitsemiani vaihtoehtoja: päätöksiä tehdään niin yksilöllisen tarpeen, yhteisöllisen tarpeen kuin uskonnollisuuden ja uskonnonkin kautta. Merkittävää on kuitenkin se, että suurin osa moraaliongelmien ratkaisuista pohjautuu kuitenkin yhteisön hyvinvoinnin ja elonjäämisen perusteista.

Oman pelikokemuksensa herra? Pelaajan valta, toimijuus ja vallan illuusio The Walking Dead -videopelissä

Tutkielma tarkastelee zombiteemaisessa The Walking Dead -videopelissä (Telltale Games 2012) ilmeneviä pelaajan toimijuuden ja vallan ulottuvuuksia sekä niiden merkitystä pelikokemuksille pelianalyysin avulla. Keskiössä ovat pelikokemuksen aikana syntyvät kuvitteellisen vallan tuntemukset. Tutkielman tarkoituksena on selvittää, mikä merkitys pelissä tehdyillä valinnoilla ja niiden seurauksilla voi pelikokemukselle olla sekä lisäksi pohtia erilaisia konkreettisen vaikuttamisen keinoja. Tutkielma tarkastelee lisäksi niitä tapoja, joilla peli itse osallistuu rakentamaan ja vahvistamaan pelaajan tuntemuksia pelitarinan ja -kokemuksen hallinnasta. Tutkielman aineistona toimivat videopeli sekä Telltale Community -verkkokeskustelupalstalta kerätyt kommentit, jotka avartavat käsiteltyjä näkökulmia sekä tuovat esille pelaajien kokemuksia. Kommenttien perusteella tehty analyysi on laadullista, eikä pyri kattavaan otantaan. Videopeli on aina jossain määrin ennalta rakennettu kokonaisuus, mutta sen tuottamia kokemuksia ei voida koskaan täysin säädellä ennalta. Vaikka pelin valinta- ja etenemismahdollisuudet ovat tarkoin rajattuja, voi peli synnyttää pelaajissa vahvoja vallassa olemisen tunteita sekä uniikkeja pelikokemuksia, joihin muilla pelaajilla ei ole pääsyä. Huomio ei kohdistu yksittäisen pelaajan kokemuksiin vaan nimenomaan siihen, millä kaikilla mahdollisilla tavoilla peli voidaan kokea. Pelissä koetuista valtatuntemuksista tulee kuvitteellisia vasta silloin, jos pelaaja tulee tietoiseksi toimijuutensa rajallisuudesta tai vaikutusvaltansa pinnallisuudesta. Illuusion rikkoutuminen vähentää tunnetta vaikutusvallasta, muttei poista pelikokemuksen ainutlaatuisuutta. Pelaajalla on vapaus päättää pelaamisestaan, tekemistään tulkinnoista sekä siitä, mitkä pelin tapahtumat ovat hänelle tärkeitä. Pelaaja on oman pelikokemuksensa herra, koska hän voi antaa pelin tapahtumille haluamansa merkitykset.

How much walking should be advocated for good health in adolescent girls?

Background: It is currently not known how much walking should be advocated for good health in adolescent girls. The aim of this study was therefore to recommend health referenced standards for step defined physical activity relating to appropriate health criterion/indicators in a group of adolescent girls. Method: Two hundred and thirty adolescent girls aged between 12-15years volunteered to take part in the study. Each participant undertook measurements (BMI, waist circumference, % body fat and blood pressure) to define health status. Activity data were collected by pedometer and used to assess daily step counts and accumulated daily activity time over seven consecutive days. Results: Individuals classified as ‘healthy’ did not take significantly more steps·day−1 nor spend more time in moderate intensity activity than individuals classified as at health risk or with poor health profiles. Conclusion: ‘Healthy’ adolescent girls do not walk significantly more in term of steps·day−1 or time spent in activity than girls classified as ‘unhealthy’. This could suggest that adolescent girls may not walk enough to stratify health and health related outcomes and as a result the data could not be used to inform an appropriate step guideline for this population.

Engineering the zinc finger recombinase for use in targeted genomic editing

No abstract available.

Genomic and biochemical investigation of soybean antioxidant metabolism in response to growth at elevated carbon dioxide and elevated ozone

Metabolism in an environment containing of 21% oxygen has a high risk of oxidative damage due to the formation of reactive oxygen species. Therefore, plants have evolved an antioxidant system consisting of metabolites and enzymes that either directly scavenge ROS or recycle the antioxidant metabolites. Ozone is a temporally dynamic molecule that is both naturally occurring as well as an environmental pollutant that is predicted to increase in concentration in the future as anthropogenic precursor emissions rise. It has been hypothesized that any elevation in ozone concentration will cause increased oxidative stress in plants and therefore enhanced subsequent antioxidant metabolism, but evidence for this response is variable. Along with increasing atmospheric ozone concentrations, atmospheric carbon dioxide concentration is also rising and is predicted to continue rising in the future. The effect of elevated carbon dioxide concentrations on antioxidant metabolism varies among different studies in the literature. Therefore, the question of how antioxidant metabolism will be affected in the most realistic future atmosphere, with increased carbon dioxide concentration and increased ozone concentration, has yet to be answered, and is the subject of my thesis research. First, in order to capture as much of the variability in the antioxidant system as possible, I developed a suite of high-throughput quantitative assays for a variety of antioxidant metabolites and enzymes. I optimized these assays for Glycine max (soybean), one of the most important food crops in the world. These assays provide accurate, rapid and high-throughput measures of both the general and specific antioxidant action of plant tissue extracts. Second, I investigated how growth at either elevated carbon dioxide concentration or chronic elevated ozone concentration altered antioxidant metabolism, and the ability of soybean to respond to an acute oxidative stress in a controlled environment study. I found that growth at chronic elevated ozone concentration increased the antioxidant capacity of leaves, but was unchanged or only slightly increased following an acute oxidative stress, suggesting that growth at chronic elevated ozone concentration primed the antioxidant system. Growth at high carbon dioxide concentration decreased the antioxidant capacity of leaves, increased the response of the existing antioxidant enzymes to an acute oxidative stress, but dampened and delayed the transcriptional response, suggesting an entirely different regulation of the antioxidant system. Third, I tested the findings from the controlled environment study in a field setting by investigating the response of the soybean antioxidant system to growth at elevated carbon dioxide concentration, chronic elevated ozone concentration and the combination of elevated carbon dioxide concentration and elevated ozone concentration. In this study, I confirmed that growth at elevated carbon dioxide concentration decreased specific components of antioxidant metabolism in the field. I also verified that increasing ozone concentration is highly correlated with increases in the metabolic and genomic components of antioxidant metabolism, regardless of carbon dioxide concentration environment, but that the response to increasing ozone concentration was dampened at elevated carbon dioxide concentration. In addition, I found evidence suggesting an up regulation of respiratory metabolism at higher ozone concentration, which would supply energy and carbon for detoxification and repair of cellular damage. These results consistently support the conclusion that growth at elevated carbon dioxide concentration decreases antioxidant metabolism while growth at elevated ozone concentration increases antioxidant metabolism.

Comparative genomic approaches for investigating evolution in the microbial and viral populations of the rumen

The rumen is home to a diverse population of microorganisms encompassing all three domains of life: Bacteria, Archaea, and Eukarya. Viruses have also been documented to be present in large numbers; however, little is currently known about their role in the dynamics of the rumen ecosystem. This research aimed to use a comparative genomics approach in order to assess the potential evolutionary mechanisms at work in the rumen environment. We proposed to do this by first assessing the diversity and potential for horizontal gene transfer (HGT) of multiple strains of the cellulolytic rumen bacterium, Ruminococcus flavefaciens, and then by conducting a survey of rumen viral metagenome (virome) and subsequent comparison of the virome and microbiome sequences to ascertain if there was genetic information shared between these populations. We hypothesize that the bacteriophages play an integral role in the community dynamics of the rumen, as well as driving the evolution of the rumen microbiome through HGT. In our analysis of the Ruminococcus flavefaciens genomes, there were several mobile elements and clustered regularly interspaced short palindromic repeat (CRISPR) sequences detected, both of which indicate interactions with bacteriophages. The rumen virome sequences revealed a great deal of diversity in the viral populations. Additionally, the microbial and viral populations appeared to be closely associated; the dominant viral types were those that infect the dominant microbial phyla. The correlation between the distribution of taxa in the microbiome and virome sequences as well as the presence of CRISPR loci in the R. flavefaciens genomes, suggested that there is a “kill-the-winner” community dynamic between the viral and microbial populations in the rumen. Additionally, upon comparison of the rumen microbiome and rumen virome sequences, we found that there are many sequence similarities between these populations indicating a potential for phage-mediated HGT. These results suggest that the phages represent a gene pool in the rumen that could potentially contain genes that are important for adaptation and survival in the rumen environment, as well as serving as a molecular ‘fingerprint’ of the rumen ecosystem.

Contrasting effects of historical contingency on phenotypic and genomic trajectories during a two-step evolution experiment with bacteria

Background The impact of historical contingency, i.e. the past evolutionary history of a population, on further adaptation is mostly unknown at both the phenotypic and genomic levels. We addressed this question using a two-step evolution experiment. First, replicate populations of Escherichia coli were propagated in four different environmental conditions for 1000 generations. Then, all replicate populations were transferred and propagated for further 1000 generations to a single new environment. Results Using this two-step experimental evolution strategy, we investigated, at both the phenotypic and genomic levels, whether and how adaptation in the initial historical environments impacted evolutionary trajectories in a new environment. We showed that both the growth rate and fitness of the evolved populations obtained after the second step of evolution were contingent upon past evolutionary history. In contrast however, the genes that were modified during the second step of evolution were independent from the previous history of the populations. Conclusions Our work suggests that historical contingency affects phenotypic adaptation to a new environment. This was however not reflected at the genomic level implying complex relationships between environmental factors and the genotype-to-phenotype map.

Development, characterization and use of genomic SSR markers for assessment of genetic diversity in some Saudi date palm ( Phoenix dactylifera L.) cultivars

Background: The present study was undertaken towards the development of SSR markers and assessing genetic relationships among 32 date palm ( Phoenix dactylifera L.) representing common cultivars grown in different geographical regions in Saudi Arabia. Results: Ninety-three novel simple sequence repeat markers were developed and screened for their ability to detect polymorphism in date palm. Around 71% of genomic SSRs were dinucleotide, 25% tri, 3% tetra and 1% penta nucleotide motives. Twenty-two primers generated a total of 91 alleles with a mean of 4.14 alleles per locus and 100% polymorphism percentage. A 0.595 average polymorphic information content and 0.662 primer discrimination power values were recorded. The expected and observed heterozygosities were 0.676 and 0.763 respectively. Pair-wise similarity values ranged from 0.06 to 0.89 and the overall cultivars averaged 0.41. The UPGMA cluster analysis recovered by principal coordinate analysis illustrated that cultivars tend to group according to their class of maturity, region of cultivation, and fruit color. Analysis of molecular variations (AMOVA) revealed that genetic variation among and within cultivars were 27% and 73%, respectively according to geographical distribution of cultivars. Conclusions: The developed microsatellite markers are additional values to date palm characterization tools that can be used by researchers in population genetics, cultivar identification as well as genetic resource exploration and management. The tested cultivars exhibited a significant amount of genetic diversity and could be suitable for successful breeding program. Genomic sequences generated from this study are available at the National Center for Biotechnology Information (NCBI), Sequence Read Archive (Accession numbers. LIBGSS_039019).

Effect of temperature on genomic and some biological indices during embryonic and larval development of Caspian trout Salmo trutta caspius Kessler, 1877

Since 1966 especially recent decade, Caspian trout (Salmo trutta caspius Kessler, 1877) considered as a strategic endemic species for Caspian Sea fisheries resources also coldwater aquaculture in Iran. Nowadays habitat condition effects on this subspecies during life stages, artificial breeding and incubation period noticed by research and execution sessions of fisheries in Iran. Incubation duration of Caspian trout from artificial fertilization followed by green egg and eyed egg, hatching and yolk sac absorption identified as most sensitive stages for fish and any pollution, stress and deviation by natural life conditions of embryo up to larvae could provide possible mortalities and observable or hidden alterations. Among all vital factors for Caspian trout welfare even in conservation plans and stocks rehabilitation programs or recent attempts for domestication of this fish for introduction to cold water aquaculture industry, water temperature as the most important physical factor which might conserve or induce stress to rearing environment condition is not considered yet. In hatcheries activities, the temperature for incubation and rearing Caspian trout eggs is determining by available water temperature and wide range of temperatures in governmental or private farms is using depend on the water resources availability. Also global climate change consideration and increase temperature trend accompany with group of physical and chemical factors provided by fish farm discharges and other source points entered to the migration pathway of Caspian trout in spawning season were not investigated before. Natural spawning migration pathway is upstream of Caspian tout south and south west rivers especially in Cheshmehkileh upstream in Tonekabon, Iran directed this research focus on the mentioned location. For simulation of natural spawning bed for Caspian trout, water supplied from the upstream of Daryasar branch as headwater of Cheshmehkileh River which provided REDD water condition for in vitro incubation. Green eggs treatments of wild and F1 cultured brooders both 3+ were incubated. Incubation implemented in dark, constant temperature (4, 8, 12 degree centigrade) and DO–pH–temperature digital monitoring in 3 recycling incubators ended to yolk sac absorption and entering larval stage. Hatching success, possible genome alterations by HSP70 gene expression and comet assay implemented as diagnostic tools in 3 life stages of eyed egg– Alevin and Larvae. Numbers and diameters of larvae white fiber muscles measured by histology experiment and Hematoxylin–eosine staining. Results stated significant effect of incubation temperature on hatching success, genome and white fiber muscles of wild and F1 samples. Hatching success measured as 31% and 38% for cultured and wild cold treatments, 79% and 91% for normal and 64% and 73% for warm cultured and wild treatments respectively. Considerable mortality occurred for cold treatment and 8 degree centigrade stated the best thermal condition in normal incubator according to hatching success in wild Caspian trout samples.

RestrictionDigest: A powerful Perl module for simulating genomic restriction digests

Background: Reduced-representation sequencing technology iswidely used in genotyping for its economical and efficient features. A popular way to construct the reduced-representation sequencing libraries is to digest the genomic DNA with restriction enzymes. A key factor of this method is to determine the restriction enzyme(s). But there are few computer programs which can evaluate the usability of restriction enzymes in reduced-representation sequencing. SimRAD is an R package which can simulate the digestion of DNA sequence by restriction enzymes and return enzyme loci number as well as fragment number. But for linkage mapping analysis, enzyme loci distribution is also an important factor to evaluate the enzyme. For phylogenetic studies, comparison of the enzyme performance across multiple genomes is important. It is strongly needed to develop a simulation tool to implement these functions. Results: Here, we introduce a Perl module named RestrictionDigest with more functions and improved performance. It can analyze multiple genomes at one run and generate concise comparison of enzyme performance across the genomes. It can simulate single-enzyme digestion, double-enzyme digestion and size selection process and generate comprehensive information of the simulation including enzyme loci number, fragment number, sequences of the fragments, positions of restriction sites on the genome, the coverage of digested fragments on different genome regions and detailed fragment length distribution. Conclusions: RestrictionDigest is an easy-to-use Perl module with flexible parameter settings.With the help of the information produced by the module, researchers can easily determine the most appropriate enzymes to construct the reduced-representation libraries to meet their experimental requirements.