Formulas as Programs

We provide here a computational interpretation of first-order logic based on a constructive interpretation of satisfiability w.r.t. a fixed but arbitrary interpretation. In this approach the formulas themselves are programs. This contrasts with the so-called formulas as types approach in which the proofs of the formulas are typed terms that can be taken as programs. This view of computing is inspired by logic programming and constraint logic programming but differs from them in a number of crucial aspects. Formulas as programs is argued to yield a realistic approach to programming that has been realized in the implemented programming language ALMA-0 (Apt et al.) that combines the advantages of imperative and logic programming. The work here reported can also be used to reason about the correctness of non-recursive ALMA-0 programs that do not include destructive assignment.Comment: 34 pages, appears in: The Logic Programming Paradigm: a 25 Years Perspective, K.R. Apt, V. Marek, M. Truszczynski and D.S. Warren (eds), Springer-Verlag, Artificial Intelligence Serie

Completeness of resolution revisited

AbstractBy a novel argument we prove the completeness of (ground) resolution. The argument allows us to give the completeness proofs for various strategies of resolution in a uniform way, thus contributing to the insight into these strategies. For example, our exposition shows how the more efficient strategies can be derived from an analysis of the redundancies in the completeness proofs. Moreover, by using Zorn's Lemma in dealing with infinite sets of ground clauses, we obtain completeness proofs which are completely independent of the cardinality of both the language and the set of clauses. We discuss the set theoretic status of these results

Extensionality of simply typed logic programs

We set up a framework for the study of extensionality in the context of higher-order logic programming. For simply typed logic programs we propose a novel declarative semantics, consisting of a model class with a semi-computable initial model, and a notion of extensionality. We show that the initial model of a simply typed logic program, in case the program is extensional, collapses into a simple, set-theoretic representation. Given the undecidability of extensionality in general, we develop a decidable, syntactic criterion which is sufficient for extensionality. Some typical examples of higher-order logic programs are shown to be extensional

Functionalization of Nanoparticles with Tyrosine Hydroxylase : Biotechnological and Therapeutic Implications

Tyrosine hydroxylase (TH) er et viktig enzym for nervesystemet, fordi det katalyserer det første steget i syntesen av dopamin, noradrenalin og adrenalin. Nivået på TH og dopamin synker hos Parkinsons pasienter pga. den gradvise celledøden i den hjernedelen som heter substantia nigra. Vanlig behandling går ut på å ta levodopa som er forløperen til dopamin, men effekten avtar etter hvert, og pasientene får alvorlige bivirkninger ved høye doser. Det trengs altså et bedre behandlingstilbud. En mulighet kan være å tilføre mer TH vha. en enzymerstatningsterapi som også vil gjenopprette dopaminnivået. Hovedformålet med denne avhandlingen er å finne ut hvordan TH kan bli brukt som biologisk medisin. Vi har derfor utviklet forskjellige nanopartikkel-baserte formuleringer som kan stabilisere og levere TH, og evaluert det terapeutiske potensiale til TH-lastede nanopartikler. Vi begynte med å produsere TH sammen med forskjellige fusjonspartnere og fikk et stabilt enzym som vi målte strukturen av. Så valgte vi porøst silisium og maltodekstrin nanopartikler som mulige bærere av TH. De første forsøkene med porøst silisium viste at det er en sammenheng mellom fotoluminescensen og frigjøringen av et modellprotein som kan være nyttig i sporing av legemiddelleveringen i kroppen. Videre fant vi at TH kunne bindes i nanopartikler av porøst silisium, men at dette førte til aggregering av TH. Maltodekstrin-nanopartikler kunne derimot absorbere store mengder TH samtidig som de forhindret eller forsinket TH aggregeringen. Vi observerte at disse nanopartiklene kunne levere TH til nerveceller og hjernevev og dermed økte den intracellulære TH aktiviteten. Alt i alt har denne avhandlingen gitt et godt innblikk i de strukturelle mekanismene og de funksjonelle forutsetningene som trengs for å kunne lage vellykkede nanopartikkel-baserte formuleringer av TH. TH-lastede nanopartikler har muligheten til å bli videreutviklet til enzymerstatningsterapi for sykdommer hvor det er for lite aktivt TH, som f.eks. ved Parkinsons sykdom.Tyrosine hydroxylase (TH) is important for neuronal function as it is the rate-limiting enzyme in the synthesis of dopamine, noradrenaline, and adrenaline. In Parkinson’s disease, the levels of TH and dopamine decrease, due to progressive loss of the dopaminergic neurons in a part of the midbrain called substantia nigra. Treatment is typically with the dopamine precursor, levodopa, but its pharmacological effect wears off, and the patients develop serious side effects, so there is a need for better treatment options. One alternative could be to replace the lacking TH with an enzyme replacement therapy and thereby restore the dopamine levels. The main goal of this thesis has been to investigate how TH can be pharmacologically developed into a potential biological drug. We have therefore studied different nanoparticle (NP)-based formulations to stabilize and deliver TH and evaluated the therapeutic potential of TH-loaded NPs. We started out by using fusion tags in the preparation of TH to obtain a stable enzyme of which we determined the full-length solution structure. Then we selected porous silicon and maltodextrin NPs as potential carriers of TH. Initial characterization revealed that the photoluminescent properties of porous silicon can be tuned to correlate with the release of a model protein, which can be useful in tracking of drug delivery. Furthermore, we found that TH loading in porous silicon NPs occurred through electrostatic interactions, but that it also induced TH aggregation. On the other hand, maltodextrin NPs absorbed large amounts of TH while preventing or delaying its aggregation. We observed functional delivery of TH by these NPs to neuronal cells and tissue, which significantly increased the intracellular TH activity. All in all, this thesis has given insights into the structural mechanisms and functional prerequisites necessary for successful formulations of TH with NPs, which shows the therapeutic potential of enzyme replacement therapy with TH-loaded NPs.Doktorgradsavhandlin

Loop-checking and the uniform word problem for join-semilattices with an inflationary endomorphism

We solve in polynomial time two decision problems that occur in type checking when typings depend on universe level constraints