Labradorinnoutajien uveaalimelanoomat

Koirien silmän suonikalvoston, eli uvean, melanooma (UM) on useimmiten tarkkarajainen ja tumma kohouma iiriksessä. Se kehittyy yleensä hitaasti ja lähettää etäpesäkkeitä harvemmin; vain alle kolmannes on pahanlaatuisia. Ihmispotilaista puolestaan tauti lopulta leviää noin puolella, usein aggressiivisena ja kohtalokkain seurauksin. Kasvava ymmärryksemme UM:n taustoista ja kehittymisestä koirissa voi auttaa ymmärtämään paremmin tämän monitahoisen sairauden syntyä ja kulkua myös ihmisissä. Spontaanisti UM:n sairastuvat lemmikkikoirat tarjoavat hyvän ja eettisen testikentän myös uusille hoitokeinoille. Ihmisillä UM esiintyy selkeästi enemmän tietyissä suvuissa. On havaittavissa eroja myös koirarotujen kesken: labradorinnoutaja näyttäisi olevan yliedustettuna. Tämä viittaa perinnölliseen altistumiseen. Ihmisiltä on löydetty useita uveaalimelanoomalle altistavia geenejä. Suomalaisista perheistä, joissa esiintyy periytyvää UM:ää, neljänneksellä on ituradan mutaatio BAP1 -geenissä. Itse kasvaimista tämä geeni puuttuu tai on toimimaton noin puolessa. BAP1 -mutaatiot on myös yhdistetty moniin muihin syöpiin. Ihmisten ja koirien BAP1 -geenit ovat hyvin samanlaisia; niiden tuottama mRNA on 80 %:sti samankaltaista ja niiden koodaamat proteiiniketjut ovat 98 %:n homologialla lähes identtisiä. Tässä työssä kartoitin seitsemän iiriksen melanoomaa tai melanosytoomaa sairastaneen labradorinnoutajan BAP1 -geenin koodaavan alueen mahdolliset sekvenssimuutokset niiden itusolulinjassa. Neljällä koirista ilmeni sama viiden eriperintäisen (heterotsygoottisen) emäsmuutoksen kaava: yksi synonyyminen variaatio eksonissa 17, g.37,363,076G>A, p.(Ser721Ser), sekä neljä varianttia intronialueilla lähellä eksoneita 4, 10, 11 ja 14. Lopuilla kolmella koiralla ei ollut lainkaan BAP1 sekvenssimuutoksia. Seuraavaksi tarvitaan vertailevaa tutkimusta terveiden labradorinnoutajien BAP1 -geenin sekvenssistä, jotta voidaan arvioida liittyvätkö havaitut variantit todellakin UM:n, vai onko kyseessä ainoastaan labradorinnoutajille ominaisista yhden nukleotidin polymorfismeista. Kasvaimen kehityksen kokonaiskuvan saamisesta olisi tutkimusta myös syytä jatkaa itse UM-kasvainten kudosnäytteiden kanssa: mahdolliset somaattiset variantit ovat yleisiä löydöksiä ja avaisivat UM:n alkuperää ja kehitystä laajemmin. Yli sadalla geenillä arvioidaan olevan yhteys tähän tautiin, joten tutkimuksen rajoittaminen vain yhden geenin tarkasteluun on kapea-alaista. Resurssien salliessa olisikin hedelmällisempää lähestyä ongelmaa tulevaisuudessa koko genomin sekvensointien kautta sekä ituradan, että kasvainsolujen osalta.Canine uveal melanoma (UM) usually manifests as a slowly developing, darker pigmented and well distinguishable mass in the iris. Less than a third of them are considered malignant, which is much less than with other melanocytic cancers. In contrast, in humans, 90% of UM occurs in the choroid and half of the patients eventually develop aggressive and often lethal metastases. Understanding the disease process and genetic background in dogs might also help us further the knowledge and improve the treatment options of humans. There is a hereditary component to the oncogenesis of the UM: the disease is more common in a Caucasian race and is also found in certain families. It is also more prevalent in certain dog breeds; Labrador Retrievers seem to be overrepresented. Several susceptibility genes have been identified in humans. One with the strongest association with UM is a tumor suppressor gene BAP1, which is dysfunctional or missing in nearly half of the human uveal melanomas. This gene is a so-called secondary driver of the UM and mutations in it spark the metastasizing process. There is a germline mutation of BAP1 in fourth of Finnish UM families and these mutations are also connected to various other cancers. Moreover, BAP1 shows over 98% protein product homology and almost 80% mRNA homology between dogs and humans, making it an appealing study target also for canines. Should a single variant account for high UM risk, a DNA test could be developed to be used in breeding and veterinary diagnostics. In this work, I mapped the BAP1 germline mutations of seven Labrador Retrievers with diagnosed uveal melanomas or melanocytomas. It was found that four dogs shared the same set of five heterozygous single nucleotide variants (SNV). One of the SNVs within exon 17 was synonymous, g.37,363,076G>A, p.(Ser721Ser), while the other four SNVs were intronic, residing close to exons 4, 10, 11 and 14. In the future, variant comparisons with healthy Labradors are needed to study the role of the identified variants for the development of UM, as the SNVs now found could also just be a part of a common variation in the Labrador Retriever gene pool. To grasp a bigger picture of the UM tumor development, the tumors themselves should also be analyzed for somatic mutations. Moreover, when we know that the disease is likely affected by over a hundred genes, studying just one gene is unnecessarily self-restricting. Modern full genome sequencing techniques should be used for catching all the predisposing genes simultaneously

EMMI - Electric Solar Wind Sail Facilitated Manned Mars Initiative

The novel propellantless electric solar wind sail concept promises efficient low thrust transportation in the Solar System outside Earth's magnetosphere. Combined with asteroid mining to provide water and synthetic cryogenic rocket fuel in orbits of Earth and Mars, possibilities for affordable continuous manned presence on Mars open up. Orbital fuel and water enable reusable bidirectional Earth-Mars vehicles for continuous manned presence on Mars and allow smaller fuel fraction of spacecraft than what is achievable by traditional means. Water can also be used as radiation shielding of the manned compartment, thus reducing the launch mass further. In addition, the presence of fuel in the orbit of Mars provides the option for an all-propulsive landing, thus potentially eliminating issues of heavy heat shields and augmenting the capability of pinpoint landing. With this E-sail enabled scheme, the recurrent cost of continuous bidirectional traffic between Earth and Mars might ultimately approach the recurrent cost of running the International Space Station, ISS.Comment: 17 pages, 3 figures, 1 table, revised version to Acta Astronautic

Fast E-sail Uranus entry probe mission

The electric solar wind sail is a novel propellantless space propulsion concept. According to numerical estimates, the electric solar wind sail can produce a large total impulse per propulsion system mass. Here we consider using a 0.5 N electric solar wind sail for boosting a 550 kg spacecraft to Uranus in less than 6 years. The spacecraft is a stack consisting of the electric solar wind sail module which is jettisoned roughly at Saturn distance, a carrier module and a probe for Uranus atmospheric entry. The carrier module has a chemical propulsion ability for orbital corrections and it uses its antenna for picking up the probe's data transmission and later relaying it to Earth. The scientific output of the mission is similar to what the Galileo Probe did at Jupiter. Measurements of the chemical and isotope composition of the Uranian atmosphere can give key constraints to different formation theories of the Solar System. A similar method could also be applied to other giant planets and Titan by using a fleet of more or less identical probes.Comment: 14 pages, 5 figures, Meudon Uranus workshop (Sept 16-18, 2013) special issue of Planetary and Space Scienc

Electric solar wind sail applications overview

We analyse the potential of the electric solar wind sail for solar system space missions. Applications studied include fly-by missions to terrestrial planets (Venus, Mars and Phobos, Mercury) and asteroids, missions based on non-Keplerian orbits (orbits that can be maintained only by applying continuous propulsive force), one-way boosting to outer solar system, off-Lagrange point space weather forecasting and low-cost impactor probes for added science value to other missions. We also discuss the generic idea of data clippers (returning large volumes of high resolution scientific data from distant targets packed in memory chips) and possible exploitation of asteroid resources. Possible orbits were estimated by orbit calculations assuming circular and coplanar orbits for planets. Some particular challenge areas requiring further research work and related to some more ambitious mission scenarios are also identified and discussed.Comment: 18 pages, 3 figures, accepted for publication in ESTCube-1 special issue of Proceedings of the Estonian Academy of Science

Aurinkoenergia Marsin pinnalla ja pölyisessä ilmakehässä

Marsiin laskeutuvilla avaruusaluksilla on merkittävänä ongelmana aurinkopaneelien pinnalle kerääntyneen pölyn aiheuttama sähkötehon väheneminen. Tässä työssä mallinnetaan sekä pölyhiukkasen käytöstä Marsin ilmakehässä että valon kulkeutumista Marsin ilmakehän ja kerääntyneen pölykerroksen lävitse. Hiukkasten käyttäytymiseen liittyvien teorioiden ja toteutuneiden Mars-missioiden perusteella on laadittu tietokonemalli. Mallinnuksen tuloksena saadaan odotettavissa oleva valon intensiteetti Marsin pinnalla. Tulosten perusteella todetaan pölyn kasaantuvan varsin nopeasti ehkäisten siten aurinkopaneelien valonsaannin. Pienikin pölyn poistuma muuttaa tilanteen merkittävästi valoisammaksi. Aurinkoenergia on tämän tutkimuksen perusteella jatkossakin kehityskelpoinen energiavaihtoehto myös pidempään Marsin pinnalla toimiville tutkimusaluksille

Electric Solar Wind Sail in tailwind

The Electric Solar Wind Sail (E-sail) is a novelpropulsion concept that enables faster space travel tomany solar system targets. E-sail uses charged solarwind particles as the source of its propulsion. This isachieved by deploying long, conducting and chargedtethers, which get pushed by the solar wind byCoulomb drag [1].E-sail technology is being developed to technicalreadiness level (TRL) 4-5 by the European Union’sSeventh Framework Programme for Research andTechnological Development, EU FP7, in a projectnamed ESAIL (http://www.electric-sailing.fi/fp7).Prototypes of the key parts are to be produced. Thedesign will be scalable so that a real solar winddemonstration mission could be scaled up from them.We review here the latest results of the constantlyevolving E-sail project

Electric Solar Wind Sail in tailwind

The Electric Solar Wind Sail (E-sail) is a novelpropulsion concept that enables faster space travel tomany solar system targets. E-sail uses charged solarwind particles as the source of its propulsion. This isachieved by deploying long, conducting and chargedtethers, which get pushed by the solar wind byCoulomb drag [1].E-sail technology is being developed to technicalreadiness level (TRL) 4-5 by the European Union’sSeventh Framework Programme for Research andTechnological Development, EU FP7, in a projectnamed ESAIL (http://www.electric-sailing.fi/fp7).Prototypes of the key parts are to be produced. Thedesign will be scalable so that a real solar winddemonstration mission could be scaled up from them.We review here the latest results of the constantlyevolving E-sail project