"Going back to our roots": second generation biocomputing

Researchers in the field of biocomputing have, for many years, successfully "harvested and exploited" the natural world for inspiration in developing systems that are robust, adaptable and capable of generating novel and even "creative" solutions to human-defined problems. However, in this position paper we argue that the time has now come for a reassessment of how we exploit biology to generate new computational systems. Previous solutions (the "first generation" of biocomputing techniques), whilst reasonably effective, are crude analogues of actual biological systems. We believe that a new, inherently inter-disciplinary approach is needed for the development of the emerging "second generation" of bio-inspired methods. This new modus operandi will require much closer interaction between the engineering and life sciences communities, as well as a bidirectional flow of concepts, applications and expertise. We support our argument by examining, in this new light, three existing areas of biocomputing (genetic programming, artificial immune systems and evolvable hardware), as well as an emerging area (natural genetic engineering) which may provide useful pointers as to the way forward.Comment: Submitted to the International Journal of Unconventional Computin

Maximal Pivots on Graphs with an Application to Gene Assembly

We consider principal pivot transform (pivot) on graphs. We define a natural variant of this operation, called dual pivot, and show that both the kernel and the set of maximally applicable pivots of a graph are invariant under this operation. The result is motivated by and applicable to the theory of gene assembly in ciliates.Comment: modest revision (including different latex style) w.r.t. v2, 16 pages, 5 figure

Applications of Evolutionary Algorithms in Formal Languages

Starting from the model proposed by means of Grammatical Evolution, we extend the applicability of the parallel and cooperative searching processes of Evolutionary Algorithms to a new topic: Tree Adjoining Grammar parsing. We evolved derived trees using a string-tree-representation.We also used a linear matching function to compare the yield of a derived tree with a given input. The running tests presented several encouraging results. A post running analysis allowed us to propose several research directions for extending the currently known computational mechanisms in the mildly context sensitive class of languages

Models of natural computation : gene assembly and membrane systems

This thesis is concerned with two research areas in natural computing: the computational nature of gene assembly and membrane computing. Gene assembly is a process occurring in unicellular organisms called ciliates. During this process genes are transformed through cut-and-paste operations. We study this process from a theoretical point of view. More specifically, we relate the theory of gene assembly to sorting by reversal, which is another well-known theory of DNA transformation. In this way we obtain a novel graph-theoretical representation that provides new insights into the nature of gene assembly. Membrane computing is a computational model inspired by the functioning of membranes in cells. Membrane systems compute in a parallel fashion by moving objects, through membranes, between compartments. We study the computational power of various classes of membrane systems, and also relate them to other well-known models of computation.Netherlands Organisation for Scientific Research (NWO), Institute for Programming research and Algorithmics (IPA)UBL - phd migration 201

Dissecting cellular signaling in Phytophthora

Many oomycetes are economically important pathogens, causing enormous yield losses in crop plants. Others threaten natural vegetation, while some species can cause harmful diseases in animals. Oomycetes, also known as water molds, are morphologically similar to fungi and also occupy similar environmental niches, but during evolution the two groups evolved independently (Chapter l). They show many differences, in particular at the subcellular level, and this often has consequences for the efficacy of chemical control agents and hence, the efficient control of oomycete disesases. The research described in this thesis is aimed at enhancing our basic knowledge of plant pathogenic oomycetes in the genus Phytophthora and to gain more insight in their remarkable biology. It focusses on two processes, cellular signaling and cytoskeleton dynamics. Uncovering mechanisms that govern these processes may help in designing novel, oomycete-specific control strategies. Cellular signaling is crucial for every living organism. It controls important processes, allows for communication, and enables organisms to respond to environmental cues. Two important eukaryotic signal transduction pathways that are usually interconnected through intermediate signaling components, are G-protein signaling and phospholipid signaling. Oomycetes, however, possess a unique class of G-protein coupled receptors (GPCRs) that have a phosphatidylinositol kinase (PIPK) as an accessory domain pointing to a more direct connection between the two major signaling pathways. When first discov- ered, these so-called GPCR-PIPKs were thought to be restricted to oomycetes. In Chapter 2, we show the sporadic occurrence of these so-called GPCR-PIPKs in a diverse but limited group of unicellular microorganisms, divided over nearly all eukaryotic supergroups. Our analyses revealed that nearly all GPCR-PIPKs contain a unique, conserved motif located in between the GPCR domain and the PIPK domain. GPCR-PIPKs are likely ancestral to eukaryotes and significantly expanded in the last common ancestor of oomycetes. We further identified five hitherto unknown classes of GPCRs with accessory domains, GPCR- bigrams. All classes of GPCR-bigrams are shared by oomycetes, and except for three, some classes are sparsely present in organisms from other taxa. Most accessory domains of GPCR-bigrams are universal players in signal transduction. Our findings point to an an- cestral signaling system in eukaryotic microorganisms where GPCR-mediated sensing is directly linked to downstream responses. In classical G-protein signaling, a GPCR senses extracellular signals and changes confor- mation upon ligand binding, thereby activating the associated heterotrimeric G-protein complex, consisting of a G-protein α (Gα), β (Gβ), and γ (Gγ) subunit. In turn, the acti- vated G-protein complex dissociates from the receptor and its subunits stimulate down- stream effector proteins. In Chapter 3, we investigated the function of the Gγ subunit of Phytophthora infestans. The overall similarity of this Gγ subunit with non-oomycete Gγ subunits is low, but the similarity with its homologs in other oomycetes is high. The Gγ- encoding gene, Pigpg1, is expressed in all life stages and peaks in spores. To elucidate the function of the P. infestans Gγ subunit, we generated Pigpg1-silenced and overexpression transformants and analyzed their phenotypes. However, many transformed lines had severe growth defects and were not viable. The few that could be maintained produced less sporangia, that were malformed. These findings demonstrate that the Gγ subunit has an important role in P. infestans. It is crucial for proper sporangia development, and likely forms a dimer with the P. infestans Gβ subunit, thereby mediating signaling. The microtubule (MT) cytoskeleton is a system of intracellular filaments, that is able to quickly adapt different configurations. This process is regulated by microtubular dynam- ics and MT-associated proteins (MAPs). The MT cytoskeleton has a myriad of roles, for example in processes that provide structural rigidity to cells or allow for polarized cell growth and cell movement. Chapter 4 focuses on the MT cytoskeleton in Phytophthora. Live cell imaging of transgenic Phytophthora palmivora lines carrying an ectopically inte- grated GFP-α-tubulin fusion gene provided insight in the spatio-temporal organization of the MT cytoskeleton in Phytophthora. In addition, we provide an inventory of putative MT-associated proteins in P. infestans. Unique types of the motor proteins dynein and kinesin were found, including some members with accessory domains not found else- where in combination with a motor protein domain. This study provides a basis for future research on MTs and MAPs in Phytophthora and a first glimpse of the dynamics of the MT cytoskeleton in an oomycete. The low rate of homologous recombination in oomycetes makes that transgenes are integrated randomly and until recently genome editing was unattainable. The implemen- tation of a CRISPR/Cas9 system in Phytophthora sojae is a significant asset for the molecular toolbox of oomycetes. So far, genome editing using CRISPR/Cas9 has been successfully applied in only a few Pyhytophthora species. In Chapter 5 we explore the effectuation of CRISPR/Cas9 for targeted genome editing in P. infestans. With the original constructs that were developed for P. sojae, we did not obtain any transformants in which the target gene was mutagenized. In an effort to pinpoint the reason for failure, we tailored the constructs for P. infestans and implemented several modifications in the CRISPR/Cas9 system but without success. We also explored the delivery of pre-assembled ribonucleoprotein com- plexes. We describe an extensive effort in optimization of the system and outline possible causes for failure. In Chapter 6, the main results of this thesis are integrated and discussed. Remarkable features of oomycetes and their cellular signaling systems are outlined. Possible modes of action of GPCR-bigrams are proposed as well as future directions for research on cellular signaling in Phytophthora. More knowledge on the elementary processes addressed in this thesis will expose new strategies for the design of novel, oomycete-specific control agents to mitigate damage caused by these devastating pathogens.</p

Sorting Permutations: Games, Genomes, and Cycles

Permutation sorting, one of the fundamental steps in pre-processing data for the efficient application of other algorithms, has a long history in mathematical research literature and has numerous applications. Two special-purpose sorting operations are considered in this paper: context directed swap, abbreviated cds, and context directed reversal, abbreviated cdr. These are special cases of sorting operations that were studied in prior work on permutation sorting. Moreover, cds and cdr have been postulated to model molecular sorting events that occur in the genome maintenance program of certain species of single-celled organisms called ciliates. This paper investigates mathematical aspects of these two sorting operations. The main result of this paper is a generalization of previously discovered characterizations of cds-sortability of a permutation. The combinatorial structure underlying this generalization suggests natural combinatorial two-player games. These games are the main mathematical innovation of this paper.Comment: to appear in Discrete Mathematics, Algorithms and Application

The role of planktonic ciliates in lake ecosystems

http://www.ester.ee/record=b4336574~S1*es

Effects of regular use of scalable, technology enhanced solution for primary mathematics education

Mathematics is one of the key subjects in any school curriculum and most teachers agree that mathematical skills are important for students to master. There is an abundance of research in learning mathematics and a consensus exists among researchers that technology can enhance the learning process. However, many factors need to be taken into consideration when introducing technology into teaching mathematics. Developing a more natural collaboration between learning technology experts, teachers, and students ensures all stakeholders are considered. Involving teachers early on helps develop enduring commitment to innovations and practical solutions. Moreover, creating a culture of collaboration between experts in the field and teachers brings to bear the best of what both worlds have to offer. This thesis synthesizes six papers and offers additional findings that focus on how technology experts can collaborate with elementary teachers to improve student learning outcomes. We focus on managing educational change in ways that improve the sustainability of innovations. We also explore how technical and teaching experts co-create effective lesson plans. In one of the six papers we collected and reported teachers’ responses to survey questions covering typical usage patterns on a platform. Teachers’ direct feedback was collected and incorporated to improve technical solutions. Moreover, one study was conducted abroad to measure the effect of culture on the teaching and learning process. Evidence of effectiveness of technologically enhanced lessons and corresponding homework was based on multiple studies in grades 1 - 3, covering 379 students. The effectiveness of educational technology was measured based on two variables: student performance in mathematics, based on the learning objectives specified in the curriculum, and arithmetic fluency measured by how rapidly and accurately students solved basic arithmetic operations. Statistically significant findings show that educational technology can improve two target variables when comparing students who did not use educational technology to students who did. An additional effect size analysis was conducted to verify and compare results with previous research. Based on these results, platform use produced the same or better effect than previous studies. Based on teacher feedback and user growth on the platform, we managed to integrate technology into the regular school classroom in meaningful and sustainable ways. We were clearly able to support teachers in their practice in a manner that resulted in noticeable student achievement gains. A survey revealed a need to emphasize new features that were introduced to the platform in teacher training programs. Teachers also reported having a positive attitude towards the platform and the initiative gained wide acceptance among their peers.Matematiikka on yksi tärkeimmistä kouluaineista pelkästään tuntimääräisesti mitattunakin. Matematiikan osaamista ja oppimista pidetään yleisesti tärkeänä ja arvostettuna taitona. Matematiikan oppimisesta on valtavasti tutkimusta ja tutkijoiden keskuudessa vallitsee yhteisymmärrys tietotekniikan positiivisista mahdollisuuksista edistää matematiikan oppimista. Tietotekniikan ja oppimisen vuorovaikutus on kuitenkin monisyinen vyyhti ja sen onnistunut hyödyntäminen vaatii tutkijoiden, opettajien ja oppilaiden välistä tiivistä ja vuorovaikutteista yhteistyötä. Uusien innovaatioiden ja kokeilujen onnistumiselle ja niihin sitoutumiselle luodaan vahva pohja, kun opettajat otetaan mukaan kehitystyöhön ensimetreiltä lähtien. Tällaisen tiiviin yhteistyökulttuurin vaaliminen mahdollistaa käytännön työn ja teorian vahvuuksien hyödyntämisen. Tämä väitöstyö koostuu kuudesta artikkelista. Artikkelit kuvaavat, kuinka tutkijat ja opettajat työskentelivät yhdessä parantaakseen oppilaiden matematiikan oppimista. Tavoitteenamme oli muuttaa koulun käytänteitä pitkäjänteisesti ja kestävällä tavalla. Tutkimme kuinka tutkijat ja opettajat pystyivät yhdessä luomaan onnistuneita ja tehokkaita oppimiskokonaisuuksia. Opettajat olivat koko ajan kehitystyön keskiössä. Yhdessä kuudesta artikkelista tutkittiin kyselytutkimuksen avulla opettajien kokemuksia ja käyttötottumuksia. Näitä vastauksia hyödynnettiin teknisessä kehitystyössä ja hyvien käytänteiden hiomisessa. Yksi väitöskirjan tutkimuksista tehtiin ulkomailla opetus- ja oppimiskulttuureista vaikutusten huomioimiseksi. Sähköisten oppituntien ja kotitehtävien vaikuttavuuden arviointi perustuu useisiin 1.-3. luokilla tehtyihin tutkimuksiin ja kaikkiaan 379 oppilaan vastauksiin. Sähköisten oppituntien vaikuttavuutta arvioitiin kahden eri mittarin perusteella. Ensin matematiikan taitojen perusteella, eli kuinka hyvin kunkin luokka-asteen oppimistavoitteet olivat täyttyneet ja myöhemmin myös laskusujuvuuden perusteella, eli kuinka nopeasti ja tarkasti oppilaat pystyivät laskemaan peruslaskutoimituksia. Tulokset osoittavat, että opetusteknologian avulla pystytään parantamaan oppilaiden suoriutumista edellä mainittujen osa-alueiden osalta verrattuna oppilaisiin, jotka eivät käyttäneet opetusteknologiaa. Tulokset olivat tilastollisesti merkitseviä. Näiden tulosten varmistamiseksi laskettiin vaikuttavuuden suuruus ja sitä verrattiin aiempiin alan tutkimuksiin. Tulosten perusteella sähköisillä oppitunneilla oli sama tai parempi vaikuttavuus kuin aiemmissa tutkimuksissa. Opettajien palautteiden ja kasvavan käyttäjämäärän perusteella voidaan sanoa, että onnistuimme tavoitteessamme integroida opetusteknologiaa mielekkäällä tavalla osaksi koulutyötä. Onnistuimme myös tukemaan ja auttamaan opettajia opetustyössään ja samalla merkittävästi parantamaan oppilaiden suoriutumista. Kyselytutkimuksen perusteella huomasimme, että uusien ominaisuuksien kouluttamiseen tulee kiinnittää enemmän huomiota. Samassa tutkimuksessa opettajat raportoivat olevansa tyytyväisiä alustaan ja sähköiset oppitunnit näyttävät saaneen vankan jalansijan suomalaisessa opettajakunnassa

Basidiomycetes Telomeres – A Bioinformatics Approach

The bioinformatics analysis described in this paper allowed us to establish the type and the number of the telomere repeat unit in the basidiomycetes analyzed, to suggest the putative linkage groups in fungi where linkage maps are not available, to uncover misassembled telomere regions, and to reveal the preference for some gene models to be located at the subtelomeric regions and to uncover synteny among the subtelomere regions in the basidiomycetes analyzed.This work has been supported by funds of the AGL2008-05608-C02-01 of the Spanish National Plan of Scientific Research, the Bioethanol Euroinnova project of the Goverment of Navarre (Spain), by additional institutional support from the Public University of Navarre