Quantitative refinement of reaction-based biomodels

In the field of molecular biology, scientists adopted for decades a reductionist perspective in their inquiries, being predominantly concerned with the intricate mechanistic details of subcellular regulatory systems. However, integrative thinking was still applied at a smaller scale in molecular biology to understand the underlying processes of cellular behaviour for at least half a century. It was not until the genomic revolution at the end of the previous century that we required model building to account for systemic properties of cellular activity. Our system-level understanding of cellular function is to this day hindered by drastic limitations in our capability of predicting cellular behaviour to reflect system dynamics and system structures. To this end, systems biology aims for a system-level understanding of functional intraand inter-cellular activity. Modern biology brings about a high volume of data, whose comprehension we cannot even aim for in the absence of computational support. Computational modelling, hence, bridges modern biology to computer science, enabling a number of assets, which prove to be invaluable in the analysis of complex biological systems, such as: a rigorous characterization of the system structure, simulation techniques, perturbations analysis, etc. Computational biomodels augmented in size considerably in the past years, major contributions being made towards the simulation and analysis of large-scale models, starting with signalling pathways and culminating with whole-cell models, tissue-level models, organ models and full-scale patient models. The simulation and analysis of models of such complexity very often requires, in fact, the integration of various sub-models, entwined at different levels of resolution and whose organization spans over several levels of hierarchy. This thesis revolves around the concept of quantitative model refinement in relation to the process of model building in computational systems biology. The thesis proposes a sound computational framework for the stepwise augmentation of a biomodel. One starts with an abstract, high-level representation of a biological phenomenon, which is materialised into an initial model that is validated against a set of existing data. Consequently, the model is refined to include more details regarding its species and/or reactions. The framework is employed in the development of two models, one for the heat shock response in eukaryotes and the second for the ErbB signalling pathway. The thesis spans over several formalisms used in computational systems biology, inherently quantitative: reaction-network models, rule-based models and Petri net models, as well as a recent formalism intrinsically qualitative: reaction systems. The choice of modelling formalism is, however, determined by the nature of the question the modeler aims to answer. Quantitative model refinement turns out to be not only essential in the model development cycle, but also beneficial for the compilation of large-scale models, whose development requires the integration of several sub-models across various levels of resolution and underlying formal representations.

High prevalence of the GSTM3*A/B polymorphism in sub-Sarahan African populations

A 3-bp insertion/deletion polymorphism in intron 6 of GSTM3 (rs1799735, GSTM3*A/*B) affects the activity of the phase 2 xenobiotic metabolizing enzyme GSTM3 and has been associated with increased cancer risk. The GSTM3*B allele is rare or absent in Southeast Asians, occurs in 5-20% of Europeans but was detected in 80% of Bantu from South Africa. The wide genetic diversity among Africans led us to investigate whether the high frequency of GSTM3*B prevailed in other sub-Saharan African populations. In 168 healthy individuals from Angola, Mozambique and the São Tomé e Príncipe islands, the GSTM3*B allele was three times more frequent (0.74-0.78) than the GSTM3*A allele (0.22-0.26), with no significant differences in allele frequency across the three groups. We combined these data with previously published results to carry out a multidimensional scaling analysis, which provided a visualization of the worldwide population affinities based on the GSTM3 *A/*B polymorphism.

Summa rerum genera esse tantum duo: substantiam nimirum & accidens, ex suffragio ampliss. facult. philos. in florentissimo ad Auram Athenaeo, sub umbone ... dn. mag. Simonis Tålpo, met & log. professoris famigeratissimi, consistorii Acad. assessoris gravissimi nec non annexae Pijkensis pastoris longe fidelissimi. Summos in philosophia honores aditurus dissertatione philosophica ad sobrie philosophantium examen modeste delata statuere conabitur Jeremias Wallenius J. f. Tavastensis. Ad diem 21. Nov. anni redempti orbis M. DC. XC. IV. Horis pomeridianis in auditorio maximo

Invokaatio: A.J.

Positiones philosophicae ex fragrantissimo philosophiae viridario carptìm collectae. Quas ex consensu amplissimae [et] venerandae facultatis philosophicae in Regiâ Academiâ Aboënsi. Sub praesidio, ... dn. Michaelis Gyllenstålpes, Wexionii, j. u. & philos: doct: pereximii, ll:m polit: & hist: prof: publ: celeberrimi, p. t. rectoris magnifici, moecenatis, praecept. ac promotoris quovis obsequii & honoris genere plurimùm prosequendi. Liberalis exercitij gratia, publicae eruditorum disquisitioni modestè sistit Daniel B. Rosander Smolandus s. r. m.tis stipendiarius. In auditorio majori ad diem 22. Novemb. anno 1654. Horis ab 8. antemeridianis

Variantti A.

De Sveo-Gothis; qui vixerunt sub periodo Erici I.mi. ad Ericum 2.dum: memorans quomodo restituti sunt primum ab Erico, mox tamen ac multos annos ab incertis ducibus vexati, at nunquam vera religione destituti

Variantti B.

De Sveo-Gothis; qui vixerunt sub periodo Erici I.mi. ad Ericum 2.dum: memorans quomodo restituti sunt primum ab Erico, mox tamen ac multos annos ab incertis ducibus vexati, at nunquam vera religione destituti

Variantti A.

De Sveo-Gothis, qui vixerunt sub finem Testamenti Veteris, post praemissa nonnulla de Biarmorum Jumala, expendens quomodo hic verus Deus et Sathanam tunc strinxit circa religionis curam apud paganos, et sibi quosdam alios servavit pios adminiculis variis auctos

Variantti B.

Linea omnes dati generis determinato sub angulo secans in spatio trium dimensionum investigans

Dedikaatio: Fredrika Wilhelmina Stjernvall född Charpentier [ruots.].

Observationes nonnullae super naturam phrenoshematum [!]. Qvas consentiente ampliss: facultate philosophica in Regia Academia Aboënsi, sub praesidio, ... dn. Torst. Rudeen, poës. profess. ord. h. t. facult. phil. decani spectabilis, publici speciminis loco bonis examinandas modestè exhibet Jonas Emzeen, Wermel: ad d. 30 Aprilis anni 1697 loco [et] horis adsuetis

Variantti B.

Nova ratione determinantur loca telluris, ab effectibus parallaxis in transitu planetarum sub sole, dependentia

Arkit: A-B4.

De lingvis sub imperio Sveo-Gothico usitatioribus

Invokaatio: Favente Jehovâ.

Modelling Energy Consumption of a Switch using Fuzzy-Rule Classifier

The energy consumption of IT equipments is becoming an issue of increasing importance. In particular, network equipments such as routers and switches are major contributors to the energy consumption of internet. Therefore it is important to understand how the relationship between input parameters such as bandwidth, number of active ports, traffic-load, hibernation-mode and their impact on energy consumption of a switch. In this paper, the energy consumption of a switch is analyzed in extensive experiments. A fuzzy rule-based model of energy consumption of a switch is proposed based on the result of experiments. The model can be used to predict the energy saving when deploying new switches by controlling the parameters to achieve desired energy consumption and subsequent performance. Furthermore, the model can also be used for further researches on energy saving techniques such as energy-efficient routing protocol, dynamic link shutdown, etc.

Catalogus librorum & instrumentorum chirurgicorum b. m. viri Josephi Pippingsköld, m. d. profess. chirurg. [et] art. obstetr. ad Imp. Acad. Aboëns. nec non imp. coll. med. assessoris, sub hasta d. Oct. XXX & sqq. a. MDCCCXVI

Julkaisuvuosi nimekkeestä.

Crescimento econômico e liquidez externa no Brasil após 1970

Economic growth and foreign liquidity in Brazil after 1970. This paper assesses the relationship between the capital account and the Brazilian economic growth according to balance-of-payments constraint approach. The Thirlwall (1979)'s simple rule is extended to take into consideration capital account and several empirical evidence using time series analysis are shown. Conversely to the simple rule when fitted rates of balance-of-payment equilibrium economic growth average bellow the observed ones, fitted rates of growth using the rule extended to international liquidity are consistently greater than the observed ones. It is fair to conclude that, first, the Brazilian economy grows better during abundant international liquidity and, second, the economy sub utilizes such advantage growing far less than it could grow.

Corruption, income, and rule of law: empirical evidence from developing and developed economies

This article presents an empirical analysis based on cross-country data concerned with two points regarding corruption: (i) its effects on income; and (ii) how to mitigate corruption. The findings can be highlighted in two points. Firstly the idea that corruption is intrinsically connected with income is confirmed. Secondly, the traditional argument that an increase in rule of law represents a good strategy in the fight against corruption is valid for developing countries. Furthermore, this study reveals that the search for increasing the human development index represents a rule of thumb for high levels of income and to control corruption.