Reconstructing multisets over commutative groupoids and affine functions over nonassociative semirings

A reconstruction problem is formulated for multisets over commutative groupoids. The cards of a multiset are obtained by replacing a pair of its elements by their sum. Necessary and sufficient conditions for the reconstructibility of multisets are determined. These results find an application in a different kind of reconstruction problem for functions of several arguments and identification minors: classes of linear or affine functions over nonassociative semirings are shown to be weakly reconstructible. Moreover, affine functions of sufficiently large arity over finite fields are reconstructible.Comment: 18 pages. Int. J. Algebra Comput. (2014

Rational engineering of microRNA-regulated viruses for cancer gene therapy

MicroRNAs (miRNAs) are small noncoding RNA molecules that have important regulatory roles in a wide range of biological processes. miRNAs are often expressed in a tissue- and/or differentiation state-specific patterns, and it is estimated that miRNAs can regulate the expression of more than 50% of all human genes. We have exploited these tissue-specific miRNA expression patterns in the modification of viral replicative tropism. In order to engineer the replicative tropism of oncolytic adenoviruses, we developed a recombinant adenovirus that in the 3 UTR of the critical E1A gene contains sequences complementary to the liver-specific miRNA miR122. This allowed us to generate a novel recombinant adenovirus that was severely attenuated in human liver, but replicated to high titres in colorectal cancer. Systemic injection of miR122-targeted adenovirus into mice did not induce liver toxicity. In a human lung cancer xenograft mouse model this miR122-targeted adenovirus showed potent antitumour activity. We also studied the possibility to exploit neuron-specific miRNA expression patterns in the modification of tissue tropism of an alphavirus Semliki Forest virus (SFV). We engineered SFV genome to contain sequences complementary to the neuron-specific miRNA miR124. In vitro characterization of this novel virus showed that the modification of the SFV genome per se did not affect polyprotein processing or oncolytic potency. Intraperitoneally administered miR124-targeted SFV displayed an attenuated spread into the central nervous system (CNS) and increased survival of infected mice. Also, mice pre-infected with miR124-targeted SFV elicited strong protective immunity against otherwise lethal challenge with a highly virulent wild-type SFV strain. In conclusion, these results show that miRNA-targeting is a potent new strategy to engineer viral tropism in development of safer and more efficient reagents for virotherapy applications.MikroRNA:t (miRNA) ovat pieniä ei-koodaavia RNA molekyylejä joilla on tärkeä tehtävä useiden erilaisten biologisten prosessien säätelyssä. MiRNA:t ekpressoituvat usein kudos- ja/tai kehitysvaihespesifisesti sekä säätelevät jopa yli 50 prosenttia kaikista ihmisen geeneistä. Tässä väitöskirjatutkimuksessa pyrimme käyttämään hyväksi miRNA:iden kudosspesifistä ekpressiota virusten kudostropismin muokkaamisessa vähentääksemme virusvektoreiden haitallista kudostoksisuutta. Muokataksemme adenovirusvektoreiden kudostropismia, kehitimme uudentyyppisen adenoviruksen jonka E1A-geenin 3 ei-koodaavalle alueelle lisäsimme ihmisen maksaspesifisen miRNA miR122:n tunnistussekvenssejä. Tunnistussekvenssien lisäyksellä saimme aikaan adenoviruksen (miR122-targetoitu adenovirus) jonka replikaatiokyky oli huomattavasti heikentynyt ihmisen maksassa, mutta pystyi replikoitumaan voimakkaasti perä- ja paksusuolisyöpäkudoksessa. Hiireen systeemisesti injisoitu miR122-targetoitu adenovirus ei aiheuttanut maksatoksisuutta. Ihmisen keuhkosyöpähiirimallissa miR122-targetoitu virus tappoi tehokkaasti syöpäsoluja. Tässä väitöskirjatutkimuksessa tutkimme myös hermosoluspesifisen miRNA miR124:n hyväksikäyttöä Semliki Forest-viruksen (SFV) kudostropismin muokkauksessa. Kehitimme SFV:n jonka genomiin oli sisällytetty miR124:n tunnistussekvenssejä. In vitro-kokeilla osoitimme tämän miR124-targetoidun SFV:n proteiinien prosessoituvan normaalisti sekä onkolyyttisen tehon säilyneen villityypin viruksen kaltaisena. Vatsaonteloon injisoitu miR124-targetoitu SFV levisi hyvin heikosti keskushermostossa joka johti vähentyneeseen neurotoksisuuteen. Osoitimme myös miR124-targetoidun viruksen toimivan tehokkaana rokotteena erittäin patogeeniselle L10 SFV-kannalle. Tässä väitöskirjatutkimuksessa pystyimme osoittamaan miRNA-targetoinnin olevan tehokas uusi tapa muokata virusten kudostropismia ja parantaa virusvektoreiden turvallisuutta

A note on minors determined by clones of semilattices

The C-minor partial orders determined by the clones generated by a semilattice operation (and possibly the constant operations corresponding to its identity or zero elements) are shown to satisfy the descending chain condition.Comment: 6 pages, proofs improved, introduction and references adde

Graph quasivarieties

Introduced by C. R. Shallon in 1979, graph algebras establish a useful connection between graph theory and universal algebra. This makes it possible to investigate graph varieties and graph quasivarieties, i.e., classes of graphs described by identities or quasi-identities. In this paper, graph quasivarieties are characterized as classes of graphs closed under directed unions of isomorphic copies of finite strong pointed subproducts.Comment: 15 page

The arity gap of polynomial functions over bounded distributive lattices

Let A and B be arbitrary sets with at least two elements. The arity gap of a function f: A^n \to B is the minimum decrease in its essential arity when essential arguments of f are identified. In this paper we study the arity gap of polynomial functions over bounded distributive lattices and present a complete classification of such functions in terms of their arity gap. To this extent, we present a characterization of the essential arguments of polynomial functions, which we then use to show that almost all lattice polynomial functions have arity gap 1, with the exception of truncated median functions, whose arity gap is 2.Comment: 7 page

Galois connection for sets of operations closed under permutation, cylindrification and composition

We consider sets of operations on a set A that are closed under permutation of variables, addition of dummy variables and composition. We describe these closed sets in terms of a Galois connection between operations and systems of pointed multisets, and we also describe the closed sets of the dual objects by means of necessary and sufficient closure conditions. Moreover, we show that the corresponding closure systems are uncountable for every A with at least two elements.Comment: 22 pages; Section 4 adde