Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and pareto filters

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.

Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling

Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation, whereas Wnt-3 enhanced SCNP proliferation transiently and increased neurogenesis through β-catenin signaling. Consistent with this, Wnt-3a and Wnt-3 differently regulate the expression of Cyclin-dependent kinase inhibitors. Furthermore, Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through ß-catenin and TCF4-dependent transcription. GSK-3ß inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.

Automatic target validation based on neuroscientific literature mining for tractography.

Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well-studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human). We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision), meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/.

Percolation of spatially constrained Erdos-R enyi networks with degree correlations

Motivated by experiments on activity in neuronal cultures [J. Soriano, M. Rodr ́ıguez Mart́ınez, T. Tlusty, and E. Moses, Proc. Natl. Acad. Sci. 105, 13758 (2008)], we investigate the percolation transition and critical exponents of spatially embedded Erd̋os-Ŕenyi networks with degree correlations. In our model networks, nodes are randomly distributed in a two-dimensional spatial domain, and the connection probability depends on Euclidian link length by a power law as well as on the degrees of linked nodes. Generally, spatial constraints lead to higher percolation thresholds in the sense that more links are needed to achieve global connectivity. However, degree correlations favor or do not favor percolation depending on the connectivity rules. We employ two construction methods to introduce degree correlations. In the first one, nodes stay homogeneously distributed and are connected via a distance- and degree-dependent probability. We observe that assortativity in the resulting network leads to a decrease of the percolation threshold. In the second construction methods, nodes are first spatially segregated depending on their degree and afterwards connected with a distance-dependent probability. In this segregated model, we find a threshold increase that accompanies the rising assortativity. Additionally, when the network is constructed in a disassortative way, we observe that this property has little effect on the percolation transition.

New TTCN interfaces for WCDMA base station testing

WCDMA tukiasema (Node B) on osa UMTS-järjestelmän radioverkkoa. Node B on tärkeä verkkoelementti, jonka tarkoituksena on yhdistää mobiilikäyttäjät verkkoon. Telecom –ohjelmisto (TCOM SW) on vastuussa suuresta osasta Node B:n toiminnallisuutta. TCOM SW:n testaukseen käytetään paljon resursseja, jotta ohjelmiston oikeasta toiminnasta ja laadusta voidaan varmistua. System component testing on testausvaihe, jossa järjestelmän (Node B) osa (system component, tässä diplomityössä TCOM SW) testataan ennen sen integroimista muuhun järjestelmään. Tähän tarvitaan testityökalu ja testitapausten toteutus. Node B TTCN Tester (testeri) on työkalu, jota käytetään Node B:n ohjelmiston testauksessa. Testitapaukset toteutetaan TTCN-testinotaatiota käyttäen ja testataan testerin avulla. TCOM SW:n system component –testausvaihetta varten testeriin lisättiin uudet rajapinnat, joiden avulla voidaan simuloita Node B:n ATM-ohjelmistoa sekä WPA- ja WTR-yksiköitä. Tässä diplomityössä toteuttiin TTCN testitapaukset uusille rajapinnoille. Testitapaukset tekivät TCOM SW system component –testausvaiheen riippumattomaksi Node B:n ATM-ohjelmistosta sekä WPA- ja WTR-yksiköistä. Lisäksi TCOM SW:n toiminnan testaus näissä rajapinnoissa voidaan tästä lähtien tehdä automaattisesti. Testitapauksien toiminta varmistettiin testeriä käyttäen. Tulokset olivat hyviä, uudet testitapaukset ja TTCN rajapinnat toimivat oikein lisäten testauksen tehokkuutta.

The synchronization of personal information between mobile devices and online services by using SyncML

Monet henkilökohtaiset mobiililaitteet tarjoavat mahdollisuuden tallentaa henkilötietoja ja mahdollisuuden lyhyen kantaman radiotekniikoiden hyödyntämiseen. Vastaavasti henkilötietoja käyttävien tai vaativien verkkopalveluiden määrä on kasvussa. Mobiililaitteisiin tallennetut henkilötiedot tarjoavat potentiaalisen keinon välttää samojen henkilötietojen toistuva käsinsyöttö erilaisiin verkkopalveluihin ja keskitettyyn ajantasallapitoon. Tässä työssä käydään läpi ratkaisumalli henkilökohtaisen mobiililaitteen ja verkkopalveluiden välillä tapahtuvaan henkilötietojen siirtoon ja synkronointiin. Malli pohjautuu selainlaajennukseen, joka voi pyytää sekä selaimessa auki olevalta verkkopalvelun sivulta että mobiililta päätelaitteelta senhetkiset henkilötiedot ja synkronoida ne. Jo olemassaolevia henkilötietojen hallintaa helpottavia ratkaisuja käydään läpi arvioiden käyttökelpoisuutta tämänkaltaisiin tarpeisiin. Ratkaisumallin kannalta olennaiset tekniikat ja standardit, erityisesti Bluetooth ja SyncML, esitellään. Ratkaisumallin arkkitehtuuri käydään korkealla tasolla läpi ja esitellään toteutuksen yksityiskohtia. Tuloksena on periaatteeltaan kelvollinen henkilökohtaisten tietojen synkronointijärjestelmä, jonka toteutusta nykyisten mobiilien päätelaitteiden toiminnallisuus jossain määrin hankaloittaa.

Transparent Network Interfaces to Mobile Peer-to-Peer Environment

The fact that most of new Personal Data Assistant (PDA) devices and smartphones have the ability to communicate via different wireless technologies has made several new applications possible. While traditional network model is based on the idea of static hosts, mobile devices can create decentralized, self-organizing ad-hoc networks and act as peers in the network. This kind of adapting network is suitable for mobile devices which can freely join and leave the networks. Because several different wireless communication technologies are involved, flexible changing of the networking technology must be handled in order to enable seamless communication between these networks. This thesis presents a transparent network interface to mobile Peer-to-Peer environment which is named as Virtual PeerHood. Different wireless technologies and aspects of providing a seamless connectivity between these technologies are explored. The result is a middleware platform for mobile Peer-to-Peer environment, capable of handling several networking technologies.

Uusien rajapintojen vaikutus Nokia TETRA –rajapintapalvelimen arkkitehtuuriin

Nokia TETRA –järjestelmä on digitaaliseen tekniikkaan pohjautuva radiopuhelinjärjestelmä, joka on tarkoitettu erityisvaatimuksia omaavien organisaatioiden ammattikäyttöön. Sen tyypillisiä käyttäjiä ovat erilaiset viranomaiset, kuten poliisi, palo- ja pelastuslaitos sekä rajavartiolaitos. Se perustuu avoimeen TETRA-standardiin, joka määrittelee tärkeimmät palvelut ja rajapinnat tiettyjen verkkoelementtien välillä. TETRA-järjestelmän käyttöpaikkatyöasemat ja palvelimet perustuvat kaikki samaan Nokia TETRA –rajapintapalvelimen arkkitehtuuriin. Käyttöpaikat tarjoavat tehokkaat toiminnot verkon operatiiviseen käyttöön ja hallintaan. Palvelimet puolestaan tarjoavat ohjelmointirajapintansa kautta kolmansille osapuolille mahdollisuuden luoda TETRA-järjestelmän palveluita käyttäviä sovelluksia. Työn tavoitteena oli tutkia uusien rajapintojen soveltuvuutta sekä selvittää niiden vaikutusta Nokia TETRA –rajapintapalvelimen arkkitehtuuriin. Ensin kartoitettiin nykyisen arkkitehtuurin ongelmat ja puutteet äänikommunikaatioon käytetyssä tiedonsiirrossa, ja äänikommunikaatiossa käyttäjään päin. Näiden ratkaisemiseksi tutkittiin uusia rajapinta-vaihtoehtoja. Parhaiten soveltuvista vaihtoehdoista muodostettiin ratkaisu, jonka vaikutus uuden sukupolven arkkitehtuuriin selvitettiin.

Business potential evaluation of wireless local area networks: Teleoperator’s view

The objective of the thesis was to evaluate business potential of wireless local area networks (WLAN, Wireless LAN). At first, the scope of business potential evaluation of technology was introduced. Next, a general framework of business potential evaluation of technology based on literature was presented. In addition, convergence of cellular networks and data networks was studied in order to get an insight of current situation of mobile telecommunications industry. Finally, wireless local area networks business potential was evaluated. A wireless local area network is a data communication system, which combines data connectivity with mobility and is implemented in unlicensed frequency bands, allowing new business opportunities to emerge. The main markets of WLAN are corporate networks, public area networks and access networks. At the moment the penetration of WLAN terminals is low which derives to low demand of wireless LAN services. In addition, unlicensed spectrum forces the teleoperators to set the service price relatively low. The business potential is in integrating wireless LANs to cellular networks and in offering value added services to end users. The future of wireless LAN is to be complementary network to cellular networks. In this vision cellular networks provide voice and low data services and broadband wireless networks enable multimedia services.

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

Handling of TDM Connections with Cello Media Gateway

UMTS is a 3rd generation telecommunication system, which introduces new network architecture. The change in the network architecture introduces new logical network nodes and changes the role of existing nodes in the network. This architecture changes the current vertically specialized network into a horizontally layered structure. In practice, the layering means that different levels in network hierarchy are separated, and they communicate over well-specified interfaces. The Connectivity Layer, at the bottom of the UMTS network architecture, contains Media Gateways (MGW). The GSM radio access network and UMTS access network are connected to the connectivity network via a MGW. External networks, e.g. ISDN networks, are accessed via other MGWs. The user plane is transported across the connectivity network between/via MGWs. ATM network is used as the backbone in Ericsson’s UMTS core network release 2.0. The main goal of this thesis is to study how the MGW is used to bridge ATM and TDM networks. The Circuit Emulation Service (CES) for ATM is studied, as the conversion from TDM to ATM is made according it. The transportation is made using AAL2 and the issues that it has with voice traffic are studied. The implementation and usage of TDM switching service in MGW are described in detail.

Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

Positioning Wireless Mobile Terminal Devices

Positioning techniques enable the positioning of mobile transportation vehicles. Location information can be used in transport planning as well as in vehicles. Information can also be transferred between vehicles and transport planning. For example, pickup and delivery information and route instructions can be exchanged wirelessly. In this thesis, techniques suitable for positioning vehicles are studied, as well as techniques enabling wireless connectivity of the vehicles to the transport planning system. A prototype based on one positioning and connectivity technique is implemented. As a result, a system capable of positioning vehicles is created. The vehicles can be located almost in real-time. The accuracy in positioning is sufficient to visualise the locations on a good quality 1:20000 city map.

JAVA APIS FOR BLUETOOTH WIRELESS TECHNOLOGY

Bluetooth™ Teknologia - Bluetooth Wireless Technology - on lyhyen kantaman langaton kommunikointiteknologia. Vaikka se onkin ensisijaisesti suunniteltu kaapelin korvaajaksi laitteiden omaan toimintaan liittyvässä liikenteessä, voidaan sitä myös käyttää alustana monen käyttäjien peleissä ja muissa vastaavissa sovelluksissa. Tassa diplomityössä esitellään Bluetooth teknologia sovellusohjelmoijan näkökulmasta. Työssä esitellään teollisuuskonsortion määrittelemä Java-ohjelmointirajapinta Bluetooth teknologiaan. Tämän rajapinnan avulla voidaan kehittää kannettavia sovelluksia jotka kommunikoivat Bluetooth yhteyden yli. Rajapinta pohjautuu "Java™ 2 Microedition" alustaan ja on siten toteutettavissa myös pienissä laitteissa kuten matkapuhelimissa. Työssä esitellään lyhyesti rajapinnan keskeiset osat sekä annetaan esimerkki rajapinnan käytöstä. Työn konstruktiivisessa osassa rajapinnan keskeiset on toteutettu kahdelle eri alustalle: Sambian™ ja Microsoft® Windows® käyttöjärjestelmille. Talla tavalla on saatu arvokasta tietoa siitä, miten kyseinen rajapinta tulisi toteuttaa ja myös siitä miten sovellukset sitä käyttäisivät. Keskeiset suunnitteluratkaisut ja saadut kokemukset on raportoitu työn kirjallisessa osassa. Vaikka työn konstruktiivinen osuus onkin luonteeltaan esitutkimus eikä tähdännyt tuotteeseen, on tuloksena syntynyttä rajapintaa tarkoitus käyttää useassa Nokian sisäisessä tutkimus-ja kehityshankkeessa.

Integrating Socket Server to the Workstation Environment of Series 40 Platform

Shortening development times of mobile phones are also accelerating the development times of mobile phone software. New features and software components should be partially implemented and tested before the actual hardware is ready. This brings challenges to software development and testing environments, especially on the user interface side. New features should be able to be tested in an environment, which has a look and feel like a real phone. Simulation environments are used to model real mobile phones. This makes possible to execute software in a mobile phone that does not yet exist. The purpose of this thesis is to integrate Socket Server software component to Series 40 simulation environments on Linux and Windows platforms. Socket Server provides TCP/IP connectivity for applications. All other software and hardware components below Socket Server do not exist in simulation environments. The scope of this work is to clarify how that can be done without connectivity problems, including design, implementation and testing phases.