Das Harnblasenkarzinom ist eines der häufigsten urogenitalen Karzinome. In den letzten Jahren wurden zunehmend neue molekulare Marker entwickelt, um Karzinome nicht-invasiv detektieren zu können, darunter die chromosomale Fluoreszenz-in-situ-Hybridisierung. In der vorliegenden Studie sollte die Durchführbarkeit der Methode an bereits zytologisch aufbereiteten (gefärbten) Präparaten untersucht, bereits erhobene zytologische Untersuchungsergebnisse mit den FISH-Resultaten verglichen, zytologisch zweifelhafte Befunde geklärt und retrospektiv festgestellt werden, ob eine im Verlauf beobachtete Karzinomentwicklung (positives follow-up) zu einem früheren Zeitpunkt bei noch negativen zytologischen Resultaten durch die FISH-Methode nachweisbar gewesen wäre. In die vorliegende Studie gingen 79 zytologische Präparate ein, darunter HE- und Papanicolaou-gefärbte Präparate. Alle Präparate wurden nach mehreren Waschschritten in einer Proteaselösung inkubiert und danach mit der Sondenmischung des UroVysion™ Bladder Cancer Recurrence Kits inkubiert, die mit zentromerspezifischen Chromosomensonden und einer Lokus-spezifischen Sonde die Chromosomen 3, 7, 17 und den Lokus 9p21 fluoreszenzmarkiert. Anschließend erfolgte die Hybridisierung und das Gegenfärben. Bei der Befundung nach Vysis™-Kriterien musste das Präparat für eine positive (maligne) Befundung vier oder mehr der 25 Zellkerne mit einer Zunahme der Signale der Chromosomen 3, 7 oder 17 oder 12 oder mehr Zellkerne mit einem oder keinem Signal für 9p21 aufweisen. Nach den Kriterien der Basler Arbeitsgruppe galt ein Präparat mit 2 oder mehr Zellkernen mit Signalzunahme bei Chromosom 3, 7 und 17 oder bei Verlust eines oder beider 9p2-Signale als maligne. Im Hinblick auf die erbrachten Ergebnisse war FISH nach Vysis-Schema deutlich sensitiver als die Zytologie (79,2 % vs. 54,2 %). Die Auswertung nach Basel war gleich sensitiv, jedoch mit 76,4 % deutlich weniger spezifisch (Vysis-Verfahren 92,7 %, Zytologie 98,2 %). Zytologie und FISH waren bei höher-gradigen Karzinomen gleich sensitiv (je 100 %). Die Sensitivität nahm mit dem Grad der Zellaberrationen ab. 91 % betrug die Sensitivität der FISH bei G2-Karzinomen gegenüber 72,7 % der Zytologie. Daneben kann von einer prognostischen Aussagekraft aktuell falsch-positiver Vysis-Ergebnisse ausgegangen werden. Ungefärbte Präparate und HE-gefärbte Präparate zeigten sich unabhängig von der Gewinnungsmethode des Zellmaterials als uneingeschränkt zugänglich für eine FISH-Auswertung. Papanicolaou-gefärbte Routinepräparate waren in der Auswertung unbefriedigend mit falsch-negativen Resultaten. Die Klärung zytologisch zweifelhafter Befunde gelang auch mit FISH nur unbefriedigend. Beide Verfahren hatten im schwierig diagnostizierbaren Bereich der niedriggradigen Karzinome Sensitivitätseinbußen und kamen bei den G1-Karzinomen auf eine Sensitivität von je 60 %. Höhergradige Karzinome (G3) wurden von beiden Verfahren sicher detektiert. Retrospektiv konnte festgestellt werden, dass FISH in vielen Fällen eine im Verlauf beobachtete Karzinomentwicklung (positives follow-up) zum Zeitpunkt der negativen zytologischen Beurteilung hat nachweisen können. Zusammenfassend erwies sich FISH als ein Untersuchungsverfahren mit guter diagnostischer und prognostischer Aussagekraft.

The ice melting and lateral cavity formation caused by in situ burning (ISB) of liquid fuels in ice-infested waters was studied in order to improve predictions on the removal efficiency of this oil spill mitigation method. For this purpose, several experimental studies were conducted to increase the fundamental understanding of the mechanisms that lead to ice melting and lateral cavity formation. The findings of the experimental studies provided the required knowledge to mathematically formulate the ice melting problem. Mathematical scaling analysis of ice melting during burning of oils in the vicinity of ice was performed to create a tool to estimate the extent of melting that occurs during ISB in ice-infested waters. A series of lab-scale experiments were designed to systematically investigate the ice melting problem. The first set of experiments were conducted in cylindrical shaped ice cavities with a 5.7 cm diameter. Burning of n-octane from ignition to natural extinction and the subsequent geometry change of the ice, fuel thickness, and fuel temperature were measured. The preliminary experimental observations showed that the melting of the ice walls was higher in areas where the fuel layer was in contact with ice compared with places of flame exposure. Based on these observations, a hypothesis that suggested the convective flows in the liquid fuel (driven mainly by surface tension and buoyancy) were contributing in melting of the ice was proposed to explain the origins of the lateral cavity. To evaluate this hypothesis, two dimensionless numbers (Marangoni and Rayleigh) were calculated as the indicators of the mechanisms of convection in the fuel layer. The comparison between the melting speed and these dimensionless numbers indicated surface tension driven flow was dominant while the role of buoyancy was negligible. In another set of experiments, Particle Image Velocimetry (PIV) was used to study the flow structure within the liquid-phase of n-octane pool fire bound on one side by an ice wall. Experiments were conducted in a square glass tray (9.6 cm × 9.6 cm × 5 cm) with a 3 cm thick ice wall placed on one side of the tray. Burning rate, flame height, and melting front velocity were measured to analyze the effect of heat feedback on melting of the ice. The melting rate of the ice increased from 0.6 cm/min for the first 50 seconds after ignition to 1 cm/min for the rest of burning period. Meanwhile, the measurement of the burning rates and flame heights showed two distinctive behaviors; a growth period from self-sustained ignition to the peak mass loss rate (first 50 seconds after ignition) followed by a steady phase from the peak of mass loss rate until the manual extinguishment. Similarly, the flow field measurements by a 2-dimensional PIV system indicated the existence of two different flow regimes. In the moments before ignition of the fuel, coupling of surface tension and buoyancy forces led to a combined one roll structure in the fuel. This was when a single large vortex was observed in the flow field. After ignition the flow field began transitioning toward an unstable flow regime (separated) with an increase in number of vortices around the ice wall. As the burning rate/flame height increased the velocity and evolving flow patterns enhanced the melting rate of the ice wall. Experimentally determined temperature contours showed that a hot zone with thickness of approximately 3 mm was present below the free surface, corresponding to the multi-roll location. The change in the flow field behavior was found to relate to the melting front velocity of ice. To further study the lateral cavity phenomena, a parametric experimental study on melting of ice adjacent to liquids exposed from above to various heat fluxes was conducted in order to understand the role of liquid properties in formation of cavities in ice. Multiple liquids with wide variety and range of thermophysical properties were used in order to identify the key influential properties on melting. The melting rate of the ice and penetration speed of the liquid in a transparent glass tray (70 mm × 70 mm × 45 mm) with a 20 mm thick ice wall (70 mm × 50 mm × 20 mm) was measured. The melting front velocities obtained from experiments were then compared to surface flow velocities of liquids obtained through a scaling analysis of the surface flow to elucidate the influence of the various thermophysical properties of the liquids on ice melting. The surface velocity of the liquids correlated well to the melting front velocities of the ice which showed a clear relationship between the flow velocity and melting front velocity. As the final step of this work, to extend the findings of the experimental studies conducted herein to larger sizes comparable to realistic situations in the Arctic, an order of magnitude scaling analysis was performed to obtain the extent of ice melting. The scaling considered the heat feedback from the flame to fuel surface, the convective heat transfers toward the ice, and the melting energy continuity of ice. The existing experimental data on the size of lateral cavity were also collected and were correlated to the results of the scaling analysis using a nonlinear regression fitting technique. The mathematical correlation that was obtained by the scaling analysis can be used to predict the size of the lateral cavity for a given fuel, pool fire diameter, and burning time. This correlation will provide a predictive tool to estimate the size of a potential lateral cavity formed during ISB of a given spill scenario. In general, the ability to predict the ice melting caused by burning of spilled oil in ice-infested waters is of great practical importance for assessment of the response outcome. This would assist with quantifying the geometry change of the burning medium which in turn will define oil burning rate and extinction condition. Knowledge of burning behavior and extinction condition indicate the burned volume which can directly be used to define the removal effectiveness of ISB. Nevertheless, this analysis was conducted on a generic interaction of oil and ice and the specific details that are observed in actual application of ISB in ice-infested waters were neglected for simplicity. Extending the outcome of this study to more specific (scenario-based) oil-in-ice situation and improving the predictability of the melting correlation with large-scale experiments are the next steps to develop this work.

Este trabalho pretende avaliar o efeito da salinomicina no consumo de feno coast cross e sal proteinado, na digestibilidade total, ruminal in situ e in vitro, taxas de produção de gases e taxas de fermentação. Para a avaliação da digestibilidade e degradabilidade in situ foram utilizados 4 novilhos Holandeses com peso médio de 350 kg ± 43 kg. O delineamento experimental utilizado foi o quadrado latino com 4x4. No ensaio in vitro foram utilizados 4 substratos *8 inóculos *2 corridas com delineamento em blocos e arranjo fatorial. Os tratamentos estudados foram: 0; 0,1; 0,2; 0,3 mg de salinomicina /kg de peso vivo. Não foram encontradas diferenças significativas (p>0,05) no consumo de MS(1,92; 1,73; 1,60; 1,63 %PV), digestibilidade aparente da MS (81,79; 80,32; 80,32 e 80,49), na degradação in situ da MS (52; 51,25; 49,20 e 51,38) e na degradação in vitro da MS (45,31; 45,64; 45,77; 45,03) entre os vários tratamentos. Os únicos parâmetros onde foram identificadas alterações significativas entre os tratamentos foram no volume final de gases in vitro e nas curvas de taxas de fermentação. Os valores encontrados de para o volume final de gases foi de 231,8; 204; 168 e 157,78 ml /g de MS para a dose de 0; 0,1; 0,2 e 0,3 mg de salinomicina/ kg de PV, respectivamente. O tratamento 3 foi o que teve menores perdas de energia. / This experiment was conducted to evaluate the effect of graded levels of salinomycin on feed intake, apparent di estibility, gas production and fermentation rate, degradability in situ and in vitro of cynodon hay supplemented with proteic salt with 0, 0.1, 0.2 and 0,3mg of salynomicin per kg LW. Intake , digestibility and degradabilty studies were analysed as a latine square design 4x4 and in vitro trials followed the block randomized design with a two factors (inocula and substrate). No differences (p>)0,05) were found between the treatments for DM intake (1.92, 1.73, 1.60, 1.63 per % LW), DM digestibility (81.79, 80.32, 80.32 and 80.49), DM in situ degradability (52, 51.25, 49.20 and 51.38) and in vitro DM degradability (45.31, 45.64, 45.77 and 51.38). Differences between treatments were found only for potencial gas production in vitro (231.8, 204, 168 and 157.78 ml/g DM) for 0, 0.1, 0.2 and 0,3 mg of salinomycin/kg LW. Therefore, wasting energy was minimized at treatment 3.

Orientador: José de Anchieta de Castro e Horta Junior / Coorientador: Jackson Cioni Bittencourt / Banca: Luiz Fernando Takase / Banca: Luciana Pinato / Resumo: O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas... / Abstract: The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ... / Mestre

"In situ polymerizing hydrogel systems play an important role in many tissue engineering applications. They have proven to be useful in biomedical applications that require conversion of liquid macromer solution to tissue compliant hydrogel under physiological conditions. A series of poly(ethylene glycol)-co-poly(lactate) diacrylate macromers were synthesized with variable PEG molecular weight and lactate content. The macromer compositions were confirmed by NMR spectroscopy and ion chromatography. These macromers were polymerized to form hydrogels by free radical polymerization using either redox or photochemical initiators. The current study focused on the optimization of polymerization conditions. Compressive modulus and residual acrylate analysis were used to evaluate polymerization efficiency. To characterize the network structure, the swelling ratio values were converted to the average molecular weight between crosslinks ( ) and mesh sizes (ξ) using Flory-Rehner theory. Current study suggested hydrophobic modification is desired to achieve high polymerization efficiency. Electrospinning is a developing technique to produce ultra fine fibrous structures from polymer solutions. Current research efforts have focused on understanding the effects of principal parameters such as molecular weight distribution (MWD) and polymer surfactant interactions on the morphology of the electrospun patterns. Fundamental understanding of the dilute solution rheology of the polydisperse polymer/solvent and polymer/solvent/surfactant systems was first established. Using viscometry, the on-set of entanglement concentrations could be obtained for various systems. Electrospinning was then carried out to evaluate the effects of polymer molecular weight, molecular weight distribution (MWD) and the polymer-surfactant interaction on the fiber formation and morphological features. The importance of increased chain entanglements due to high molecular weight component within the polydisperse system and the expansion of the coil dimension by binding the surfactant micelles have been recognized. The critical concentrations for incipient as well as stable fiber formation were determined. "

The potential for oil exploration on the Arctic Outer Continental Shelf warrants determination of an efficient method to clean up an oil spill. Traditional spill response equipment may not be practical in an Arctic environment; the presence of ice which may prevent proper deployment of equipment. The remoteness of the areas proposed for oil exploration lack the infrastructure and support networks necessary to stage a response to a large oil spill. These difficulties make it necessary to explore alternative means of oil spill cleanup. In situ burning is one method that may be particularly well-suited for arctic and sub-arctic environments due to the minimal amount of equipment required to achieve an efficient burn, i.e. high mass loss. The Arctic and sub- Arctic environments add an additional level of complexity by introducing a spill medium (ice) that is highly unstable at elevated temperatures. Our experiments sought to calculate the mass loss rate of oil mixtures to determine the efficiency with which they burn within ice channels of varying widths. Since fuel layer thickness is a critical factor in determining the effectiveness of an in situ burn the spread rate of oil along an ice channel was studied. Burning of oil in an ice channel yields low efficiencies (10%) primarily due to the geometric changes of the melting ice channel. The spreading was modeled as a constant flux rectilinear buoyancy-inertia governed flow. The melting causes an increase in the surface area and results in the critical thickness of the oil to be reached sooner. Based on the current bench- scale testing, losses due to ice melting cause the efficiencies of the burning process to be excessively low and not viable to full scale clean up. The results warrant future research to understand how varying other parameters, including starting mass of fuel, influence efficiencies.

As HPC systems move towards exascale, the discrepancy between computational power and I/O transfer rate is only growing larger. Lossy in situ compression is a promising solution to address this gap, since it alleviates I/O constraints while still enabling traditional post hoc analysis. This dissertation explores the viability of such a solution with respect to a specific kind of compressor — wavelets. We especially examine three aspects of concern regarding the viability of wavelets: 1) information loss after compression, 2) its capability to fit within in situ constraints, and 3) the compressor’s capability to adapt to HPC architectural changes. Findings from this dissertation inform in situ use of wavelet compressors on HPC systems, demonstrate its viabilities, and argue that its viability will only increase as exascale computing becomes a reality.

Le problème de l’accès aux ressources génétiques des plantes pour la sélection variétale est au cœur de la Révolution Verte. A partir des années 1960, les sélectionneurs font de la disparition des variétés locales sous l’effet de la diffusion de nouvelles variétés génétiquement homogènes un problème public à l’échelle mondiale. Dans une perspective qui croise la recherche d’archives et l’enquête de terrain, cette thèse revient sur la formation de ce problème, sur sa trajectoire historique et ses enjeux actuels. Il s’agit d’analyser l’hétérogénéité des savoirs scientifiques et des approches qui sont développés sur le thème de la conservation des ressources génétiques dans les arènes internationales. L’étude des débats et des initiatives menés dans le cadre de la FAO permet de comprendre quels sont les savoirs légitimés, lesquels sont marginalisés et comment la nature et les contours du problème ont été négociés. La place que les ressources génétiques occupent au cours d’épisodes clés de la Révolution Verte est également au cœur de ce travail. Cette thèse analyse spécifiquement l’importance accordée aux variétés locales de maïs dans le programme agricole que la Fondation Rockefeller met en place au Mexique à partir de 1943. Alors que le maïs hybride est généralement présenté comme un vecteur de la modernisation agricole, cette thèse montre que les experts sont confrontés à l’échec du paradigme d’amélioration variétale qu’ils étaient censés exporter. Face à une innovation uniquement applicable à une échelle très limitée, les semences paysannes du maïs restent l’option variétale la plus utilisée au Mexique. Ce travail montre que ce sont bien les choix pragmatiques des agriculteurs qui constituent le fondement de la conservation, de facto, des ressources génétiques du maïs dans ce pays. / The issue of access to plant genetic resources for plant breeding is at the heart of the Green Revolution. Beginning in the 1960s, the disappearance of local varieties with the spread of new genetically homogeneous varieties evolved into a public problem on a global scale. Combining archival research and field investigations, this thesis explores the emergence of this problem, its historical trajectory, and its current forms. I analyze the heterogeneity of scientific knowledge and approaches to the conservation of genetic resources developed in international arenas. An exploration of debates and initiatives within the framework of the FAO sheds light on the issues of which knowledges are legitimated and which marginalized, and on how the nature and outlines of the problem have been negotiated. An examination of the role of genetic resources in key episodes in the Green Revolution is also central to the study. The thesis specifically analyzes the importance attributed to local maize varieties in the agricultural program that the Rockefeller Foundation implemented in Mexico beginning in 1943. While hybrid maize is generally presented as a vector of agricultural modernization, this thesis shows how experts were faced with the failure of the varietal improvement paradigm that they were supposed to export. As hybrid maize is an innovation that is only applicable on a very limited scale, farmers’ maize seeds still are the most widely used varietal option in Mexico. The study shows that it is indeed the pragmatic choices of farmers that form the basis for the de facto conservation of the country’s maize genetic resources.

<div>The rate effect of fiber-matrix interfacial debonding behavior of SC-15 epoxy and various fiber reinforcements was studied via in-situ visualization of the debonding event. Special focus has been placed on the dynamic transverse debonding of single fiber reinforced polymer composites. In this study, the debonding force history, debonding initiation, debonding crack velocity, and crack geometry were characterized using a quasi-static load frame and a modified tension Kolsky bar at loading velocities of 0.25 mm/s and 2.5 m/s. Cruciform-shaped specimens were used for interfacial transverse debonding between SC-15 epoxy matrix and various fiber reinforcements including S-2 glass, Kevlar® KM2, and tungsten fiber materials. The load history and high-speed images of the debonding event were simultaneously recorded. A major increase was observed for the average peak debonding force and a minor increase was observed for the average crack velocity with increasing loading velocity. The crack geometry of the cruciform specimens under both loading velocities was also tracked. Scanning electron microscopy of the recovered specimens revealed the debonding direction along the fiber-matrix interface through angled patterns on the failure surface.</div><div><br></div><div>The dynamic shear debonding of single fiber reinforced plastic composites were also studied via the real-time visualization with the fiber pull-out method. The interfacial shear debonding was studied between SC-15 epoxy and fiber reinforcements including S-2 glass, tungsten, steel, and carbon composite Z-pin fiber materials at 2.5 m/s and 5.0 m/s. Both S-2 glass fiber and Z-pin experienced catastrophic interfacial debonding whereas tungsten and steel wire experienced both catastrophic debonding and stick-slip behavior. Scanning electron microscope imaging of recovered epoxy beads revealed a snap-back behavior around the meniscus region of the bead for S-2 glass, tungsten, and steel fiber materials at 5.0 m/s whereas those at 2.5 m/s exhibited no snap-back behavior.</div>

Dyslexia is a neurodevelopmental disorder that affects between 5% and 12% of school-aged children. Individuals with dyslexia have difficulties in learning to read despite normal IQ levels and adequate socio-economical and educational opportunities. Dyslexia has a strong genetic component, but only a few candidate genes have been characterized to date. The KIAA0319 gene is a strong dyslexia candidate found to be associated with dyslexia in independent studies. The KIAA0319 genetic variants associated with dyslexia reside in a regulatory region. Studies in rat suggested that this gene is required for neuronal migration during early cortex formation. The KIAA0319-like (KIAA0319L) is a KIAA0319 homolog in structure and has recently been shown to play a role in dyslexia. I used zebrafish as a model organism both to study the effects of non-coding variants and to characterise kiaa0319 gene function. I used Gateway Tol2 technology to study the role of regulatory sequences. While these experiments led to inconclusive results, they highlighted some of the challenges but also the feasibility of using zebrafish as model organism to study genetic associations. In parallel, I studied the kiaa0319 function with knockout and knockdown experiments. Additionally, I conducted a detailed gene expression analysis with different in situ hybridisation protocols showing kiaa0319 ubiquitous expression in the whole embryo before 12 hours post fertilisation, with later specification to the eyes, brain, otic vesicle and notochord. Additionally, I have tested for the expression of kiaa0319l and showed similar expression pattern to the kiaa0319, but with significantly lower expression of kiaa0319l in zebrafish notochord. My data show, for the first time, that kiaa0319 has stage-specific expression in the brain and notochord during zebrafish early development, suggesting kiaa0319 specific role in the development of these structures. These results are in line with recent mouse studies. With this project I support the idea of kiaa0319 role being extended beyond the brain function and propose a role for kiaa03019 in the visual system and in the notochord.