Meeting report of the European mouse complex genetics network SYSGENET.

The second scientific meeting of the European systems genetics network for the study of complex genetic human disease using genetic reference populations (SYSGENET) took place at the Center for Cooperative Research in Biosciences in Bilbao, Spain, December 10-12, 2012. SYSGENET is funded by the European Cooperation in the Field of Scientific and Technological Research (COST) and represents a network of scientists in Europe that use mouse genetic reference populations (GRPs) to identify complex genetic factors influencing disease phenotypes (Schughart, Mamm Genome 21:331-336, 2010). About 50 researchers working in the field of systems genetics attended the meeting, which consisted of 27 oral presentations, a poster session, and a management committee meeting. Participants exchanged results, set up future collaborations, and shared phenotyping and data analysis methodologies. This meeting was particularly instrumental for conveying the current status of the US, Israeli, and Australian Collaborative Cross (CC) mouse GRP. The CC is an open source project initiated nearly a decade ago by members of the Complex Trait Consortium to aid the mapping of multigenetic traits (Threadgill, Mamm Genome 13:175-178, 2002). In addition, representatives of the International Mouse Phenotyping Consortium were invited to exchange ongoing activities between the knockout and complex genetics communities and to discuss and explore potential fields for future interactions.

Digital printing delivering value to the value network: CASE: STORA ENSO OYJ

Tutkielman tavoitteena oli tutkia, millaista arvoa digitaalinen painatusmenetelmä tuo yrityksen arvoverkostoon. Teoriaosassa tavoite oli rakentaa digitaalipainatuksen arvoverkostoa tutkien kirjallisuutta liittyen arvoketju- ja arvoverkostoajatteluun. Myös aiemmat tutkimukset ja kirjallisuus liittyen digitaalipainatukseen rakensivat osaltaan teoreettisen viitekehyksen muodostumista. Aiemmat tutkimukset digitaalisen painomenetelmän mahdollisuuksista ovat hyvin tekniikkapainotteisia, siksi tämä tutkimus liittyy enemmän kaupallisiin mahdollisuuksiin. Empiirinen osio tutkimuksesta tehtiin kvalitatiivisena case -tutkimuksena, johon sisältyi yksi alayksikkö. Eli tutkittiin yhtä casea, jossa oli kaksi osapuolta. Tutkielma liittyy kiinteästi Stora Enson ja Valion väliseen digipainatus-projektiin, joka käynnistettiin helmikuussa 2001. Tutkielman teemahaastatteluihin valittiin henkilöt tästä projektiryhmästä. Projektiryhmän mielipiteitä ja havaintoja hyödyntäen pyrittiin löytämään tukea ja eroavaisuuksia teoriaosan muodostamaan viitekehykseen ja informaatioon. Empiirinen osuus tuki teoriaosassa esittämiä väittämiä hyvin, mutta myös muutamia uusia havaintoja esiintyi. Tutkimusongelmaan löydettiin monia vastauksia: digitaalipainatus luo arvoa yrityksen jakeluketjuun vähentämällä varastoja ja nopeuttamalla toimituksia. Jäätelöpakkausten markkinointi on aivan uuden haasteen edessä, koska mahdollisuudet kasvavat digitaalipainatuksen myötä huomattavasti. Kartongin valmistajalle arvo tulee parempien tuotteiden kautta, joista saa myös paremman tuoton. Digitaalipainatuksen arvoverkostossa tulee tapahtumaan muutoksia jatkossa, eri osapuolten roolit saattavat muuttua radikaalisti. Kuka hoitaa painatusta ja miten?

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke.

Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether poststroke connectivity remodeling depends on axonal and/or myelin changes. Diffusion-spectrum imaging and magnetization transfer MRI at 3T were performed in 10 patients in acute phase, at 1 and 6 months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender-matched healthy volunteers were scanned 1 month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to magnetic resonance imaging (MRI). In the contralesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR were performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation, and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke.

Maintenance process development for remote administration of network servers

Maintenance is a part of system development and it is possible to develop operation models for accomplishing maintenance tasks. These models can be applied to individual maintenance tasks, maintenance projects and version management. Beneficial operation models makes maintenance more effective and they assist in managing various changes. The purpose of this thesis was to develop a maintenance process which can be used to remote administer network servers. This consisted of defining those operation models and technical specifications which enable to set up, manage changes, maintain and monitor resources of information systems that are located in several different sites. At first in this thesis the needs of the process were determined and requirements were defined based on those needs. The meaning of processes in maintenance of information systems, maintenance workflows and challenges were studied. Then current practical problems and disadvantages of maintenance work were analyzed in order to focus the development to proper issues. Because available operation models did not cover all the recent needs, new maintenance process which fulfilled the requirements was developed.

Platform Architectures for Policy-Based Network Access Control

Tämä diplomityö käsittelee sääntöpohjaisen verkkoon pääsyn hallinnan (NAC) ratkaisuja arkkitehtonisesta näkökulmasta. Työssä käydään läpi Trusted Computing Groupin, Microsoft Corporationin, Juniper Networksin sekä Cisco Systemsin NAC-ratkaisuja. NAC koostuu joukosta uusia sekä jo olemassa olevia teknologioita, jotka auttavat ennalta määriteltyyn sääntökantaan perustuen hallitsemaan suojattuun verkkoon pyrkivien laitteiden tietoliikenneyhteyksiä. Käyttäjän tunnistamisen lisäksi NAC pystyy rajoittamaan verkkoon pääsyä laitekohtaisten ominaisuuksien perusteella, esimerkiksi virustunnisteisiin ja käyttöjärjestelmäpäivityksiin liittyen ja paikkaamaan tietyin rajoituksin näissä esiintyviä puutteita verkkoon pääsyn sallimiseksi. NAC on verraten uusi käsite, jolta puuttuu tarkka määritelmä. Tästä johtuen nykymarkkinoilla myydään ominaisuuksiltaan puutteellisia tuotteita NAC-nimikkeellä. Standardointi eri valmistajien NAC-komponenttien yhteentoimivuuden takaamiseksi on meneillään, minkä perusteella ratkaisut voidaan jakaa joko avoimia standardeja tai valmistajakohtaisia standardeja noudattaviksi. Esitellyt NAC-ratkaisut noudattavat standardeja joko rajoitetusti tai eivät lainkaan. Mikään läpikäydyistä ratkaisuista ei ole täydellinen NAC, mutta Juniper Networksin ratkaisu nousee niistä potentiaalisimmaksi jatkokehityksen ja -tutkimuksen kohteeksi TietoEnator Processing & Networks Oy:lle. Eräs keskeinen ongelma NAC-konseptissa on työaseman tietoverkolle toimittama mahdollisesti valheellinen tietoturvatarkistuksen tulos, minkä perusteella pääsyä osittain hallitaan. Muun muassa tähän ongelmaan ratkaisuna voisi olla jo nykytietokoneista löytyvä TPM-siru, mikä takaa tiedon oikeellisuuden ja koskemattomuuden.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Soft tissue artifact distribution on lower limbs during treadmill gait: Influence of skin markers' location on cluster design.

Segment poses and joint kinematics estimated from skin markers are highly affected by soft tissue artifact (STA) and its rigid motion component (STARM). While four marker-clusters could decrease the STA non-rigid motion during gait activity, other data, such as marker location or STARM patterns, would be crucial to compensate for STA in clinical gait analysis. The present study proposed 1) to devise a comprehensive average map illustrating the spatial distribution of STA for the lower limb during treadmill gait and 2) to analyze STARM from four marker-clusters assigned to areas extracted from spatial distribution. All experiments were realized using a stereophotogrammetric system to track the skin markers and a bi-plane fluoroscopic system to track the knee prosthesis. Computation of the spatial distribution of STA was realized on 19 subjects using 80 markers apposed on the lower limb. Three different areas were extracted from the distribution map of the thigh. The marker displacement reached a maximum of 24.9mm and 15.3mm in the proximal areas of thigh and shank, respectively. STARM was larger on thigh than the shank with RMS error in cluster orientations between 1.2° and 8.1°. The translation RMS errors were also large (3.0mm to 16.2mm). No marker-cluster correctly compensated for STARM. However, the coefficient of multiple correlations exhibited excellent scores between skin and bone kinematics, as well as for STARM between subjects. These correlations highlight dependencies between STARM and the kinematic components. This study provides new insights for modeling STARM for gait activity.

Synaptic depression and slow oscillatory activity in a biophysical network model of the cerebral cortex

Short-term synaptic depression (STD) is a form of synaptic plasticity that has a large impact on network computations. Experimental results suggest that STD is modulated by cortical activity, decreasing with activity in the network and increasing during silent states. Here, we explored different activity-modulation protocols in a biophysical network model for which the model displayed less STD when the network was active than when it was silent, in agreement with experimental results. Furthermore, we studied how trains of synaptic potentials had lesser decay during periods of activity (UP states) than during silent periods (DOWN states), providing new experimental predictions. We next tackled the inverse question of what is the impact of modifying STD parameters on the emergent activity of the network, a question difficult to answer experimentally. We found that synaptic depression of cortical connections had a critical role to determine the regime of rhythmic cortical activity. While low STD resulted in an emergent rhythmic activity with short UP states and long DOWN states, increasing STD resulted in longer and more frequent UP states interleaved with short silent periods. A still higher synaptic depression set the network into a non-oscillatory firing regime where DOWN states no longer occurred. The speed of propagation of UP states along the network was not found to be modulated by STD during the oscillatory regime; it remained relatively stable over a range of values of STD. Overall, we found that the mutual interactions between synaptic depression and ongoing network activity are critical to determine the mechanisms that modulate cortical emergent patterns.

Making SENSE - Sustained Effort Network for treatment of Status Epilepticus as a multicenter prospective registry.

BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725.

Innovation process management of complex consumer products and services in new innovation paradigm – case location based business

Innovation is the word of this decade. According to innovation definitions, without positive sales impact and meaningful market share the company’s product or service has not been an innovation. Research problem of this master thesis is to find out what is the innovation process of complex new consumer products and services in new innovation paradigm. The objective is to get answers to two research questions: 1) What are the critical success factors what company should do when it is implementing the paradigm change in mass markets consumer business with complex products and services? 2) What is the process or framework one firm could follow? The research problem is looked from one company’s innovation creation process, networking and organization change management challenges point of views. Special focus is to look the research problem from an existing company perspective which is entering new business area. Innovation process management framework of complex new consumer products and services in new innovation paradigm has been created with support of several existing innovation theories. The new process framework includes the critical innovation process elements companies should take into consideration in their daily activities when they are in their new business innovation implementing process. Case company location based business implementation activities are studied via the new innovation process framework. This case study showed how important it is to manage the process, look how the target market and the competition in it is developing during company’s own innovation process, make decisions at right time and from beginning plan and implement the organization change management as one activity in the innovation process. In the end this master thesis showed that all companies need to create their own innovation process master plan with milestones and activities. One plan does not fit all, but all companies can start their planning from the new innovation process what was introduced in this master thesis.

Building an Access Network for Triple-Play Services

This final project was made for the Broadband department of TeliaSonera. This project gives an overview on how internet service provider might build an access network so that they can offer triple-play services. It also gives information on what equipment is needed and what is required from the access, aggregation and edge networks. The project starts by describing the triple-play service. Then it moves on to optical fiber cables, the network technology and network architecture. At the end of the project there is an example of the process and construction of the access network. It will give an overview of the total process and problems that a network planner might face during the planning phase of the project. It will give some indication on how one area is built from the start to finish. The conclusion of the project presents some points that must be taken into consideration when building an access network. The building of an access network has to be divided to a time span of eight to ten years, where one year is one phase in the project. One phase is divided into three parts; Selecting the areas and targets, Planning the areas and targets, and Documentation. The example area gives indication on the planning of an area. It is almost impossible to connect all targets at the same time. This means that the service provider has to complete the construction in two or three parts. The area is considered to be complete when more than 80% of the real estates have fiber.

Optimizing Mobile Java Location-Based Services in Symbian OS

This thesis evaluates methods for obtaining high performance in applications running on the mobile Java platform. Based on the evaluated methods, an optimization was done to a Java extension API running on top the Symbian operating system. The API provides location-based services for mobile Java applications. As a part of this thesis, the JNI implementation in Symbian OS was also benchmarked. A benchmarking tool was implemented in the analysis phase in order to implement extensive performance test set. Based on the benchmark results, it was noted that the landmarks implementation of the API was performing very slowly with large amounts of data. The existing implementation proved to be very inconvenient for optimization because the early implementers did not take performance and design issues into consideration. A completely new architecture was implemented for the API in order to provide scalable landmark initialization and data extraction by using lazy initialization methods. Additionally, runtime memory consumption was also an important part of the optimization. The improvement proved to be very efficient based on the measurements after the optimization. Most of the common API use cases performed extremely well compared to the old implementation. Performance optimization is an important quality attribute of any piece of software especially in embedded mobile devices. Typically, projects get into trouble with performance because there are no clear performance targets and knowledge how to achieve them. Well-known guidelines and performance models help to achieve good overall performance in Java applications and programming interfaces.

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

Considering tourist perceptions and network configuration in destination management

The competitiveness of tourism destinations is a relevant issue for tourism studies, moreso, is a key element on the daily basis of tourism destinations. In this sense, the management of tourism destinations is essential to maintain competitive advantages. In this article tourism destination is considered as a relational network, where interaction and cooperation is needed among tourist agents, to achieve major levels of competitive advantage and a more effective destination management system. In addition, the perceptions of tourists are obtained from two main sources. The first one is the social construction of a tourism destination previous to the visit and the second one is obtained from the interaction between tourists and tourism destination agents during the visit. In this sense, the management of tourism destination to emit a homogenous and collective image is a factor that can reduce the gap if dissatisfaction from the previous and real tourist perception. The discussion is centered on the relationship within a destination, between the supply network and the targeted demand, considering these two approaches jointly, to benefit destination management. The main result is a conceptual model that shows how tourism agents and tourists in the tourism destination interact to improve the destination competitiveness