In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.

Logging residues from regeneration fellings for biofuel production - a GIS-based availability and supply cost analysis

Finland has large forest fuel resources. However, the use of forest fuels for energy production has been low, except for small-scale use in heating. According to national action plans and programs related to wood energy promotion, the utilization of such resources will be multiplied over the next few years. The most significant part of this growth will be based on the utilization of forest fuels, produced from logging residues of regeneration fellings, in industrial and municipal power and heating plants. Availability of logging residues was analyzed by means of resource and demand approaches in order to identify the most suitable regions with focus on increasing the forest fuel usage. The analysis included availability and supply cost comparisons between power plant sites and resource allocation in a least cost manner, and between a predefined power plant structure under demand and supply constraints. Spatial analysis of worksite factors and regional geographies were carried out using the GIS-model environment via geoprocessing and cartographic modeling tools. According to the results of analyses, the cost competitiveness of forest fuel supply should be improved in order to achieve the designed objectives in the near future. Availability and supply costs of forest fuels varied spatially and were very sensitive to worksite factors and transport distances. According to the site-specific analysis the supply potential between differentlocations can be multifold. However, due to technical and economical reasons ofthe fuel supply and dense power plant infrastructure, the supply potential is limited at plant level. Therefore, the potential and supply cost calculations aredepending on site-specific matters, where regional characteristics of resourcesand infrastructure should be taken into consideration, for example by using a GIS-modeling approach constructed in this study.

Secure many-to-one communications in wireless sensor networks

Wireless Sensor Networks (WSN) are formed by nodes with limited computational and power resources. WSNs are finding an increasing number of applications, both civilian and military, most of which require security for the sensed data being collected by the base station from remote sensor nodes. In addition, when many sensor nodes transmit to the base station, the implosion problem arises. Providing security measures and implosion-resistance in a resource-limited environment is a real challenge. This article reviews the aggregation strategies proposed in the literature to handle the bandwidth and security problems related to many-to-one transmission in WSNs. Recent contributions to secure lossless many-to-one communication developed by the authors in the context of several Spanish-funded projects are surveyed. Ongoing work on the secure lossy many-to-one communication is also sketched.

Response of wheat to additional nitrogen fertilizer application after pig slurry on over-fertilized soils

Pig slurry is a valuable nutrient resource but constitutes a waste disposal problem in areas of high animal density. In the semiarid area of Pla d’Urgell, in the Ebro Valley, North-East Spain, irrigated crops receive large amounts of nutrients in the form of manure and mineral fertilizers. We studied the effect of pig slurry and additional side-dress mineral fertilizers on irrigated wheat, Triticum aestivum L., on a coarse loam soil, with high soil P and K levels. Yields increased by 62.3% when using pig slurry. The application of ammonium sulfate nitrate sidedress did not significantly increase wheat production. The average apparent recoveries were higher for potassium (88.7%) than for nitrogen (51.3%) and phosphorus (36.3%). Greater amounts of soil NO3-N were measured over the four growing seasons, which was consistent with the amount of N applied. Macronutrient and micronutrient uptake was significant higher for pig slurry treatments, but only small differences were found between the pig slurry and pig slurry plus ammonium sulfate nitrate treatments. The unfertilized treatment showed significantly lower soil P, K, Cu and Zn content than pig slurry treatments; 34%, 21%, 34%, and 26% respectively. These findings could be used to develop a nutrient management plan based on knowledge of soil test results and crop nutrient removal. This could help to improve the use of pig slurry and mineral fertilizers on limited available land areas and prevent the accumulation of potentially toxic elements in soils and the export of nutrients through agricultural drainage.

Can wild ungulate carcasses provide enough biomass to maintain avian scavenger populations? An empirical assessment using a bio-inspired computational model

Background: The reduction in the amount of food available for European avian scavengers as a consequence of restrictive public health policies is a concern for managers and conservationists. Since 2002, the application of several sanitary regulations has limited the availability of feeding resources provided by domestic carcasses, but theoretical studies assessing whether the availability of food resources provided by wild ungulates are enough to cover energetic requirements are lacking. Methodology/Findings: We assessed food provided by a wild ungulate population in two areas of NE Spain inhabited by three vulture species and developed a P System computational model to assess the effects of the carrion resources provided on their population dynamics. We compared the real population trend with to a hypothetical scenario in which only food provided by wild ungulates was available. Simulation testing of the model suggests that wild ungulates constitute an important food resource in the Pyrenees and the vulture population inhabiting this area could grow if only the food provided by wild ungulates would be available. On the contrary, in the Pre-Pyrenees there is insufficient food to cover the energy requirements of avian scavenger guilds, declining sharply if biomass from domestic animals would not be available. Conclusions/Significance: Our results suggest that public health legislation can modify scavenger population trends if a large number of domestic ungulate carcasses disappear from the mountains. In this case, food provided by wild ungulates could be not enough and supplementary feeding could be necessary if other alternative food resources are not available (i.e. the reintroduction of wild ungulates), preferably in European Mediterranean scenarios sharing similar and socio-economic conditions where there are low densities of wild ungulates. Managers should anticipate the conservation actions required by assessing food availability and the possible scenarios in order to make the most suitable decisions.

Research resource: the dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis.

Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.

Perusterveydenhuollon ja erikoissairaanhoidon käytön seuranta ja ennakointi kuntanäkökulmasta

Follow-up of utilisation and prediction of primary health care and hospital care from the municipality point of view. Planning, follow-up, and evaluation of primary health care within municipality entail comprehensive information about factors that influence health. In addition to populationbased research, various statistical data and registries serve as sources of information. The present study examined utilisation of primary health care and hospital care with the existing databases, registries, and categorization of Diagnosis Related Groups (DRGs) from the municipality (purchaser) point of view. Research involving the cases of Paimio, Sauvo, and Turku as examples of municipalities pointed out that, even in the small municipalities, it is possible to assess and predict health services to be offered to the inhabitants by following databases and registries. Health-related databases and registries include a plenty of possible uses that have not adequately been employed at the level of municipality. Descriptive futures research and community analysis formed the framework of the study. Descriptive futures research may be used to establish predictions based on past developmental traditions, and quantitative time trend analyses may be employed to make estimations about future events. Community analysis will assist in making conclusions about population- based health care needs, in assessing the functionality or effectiveness of the health care system, and in appropriately targeting limited resources. The aim of the present study was to describe the health service profile so that the arrangements and planning of health services as well as the contract negotiations of hospital care become easier within municipalities. Another aim was to assess the application of Hilmo (registry for posting hospital care periods), Aitta and Sotka (statistical databases) for the purposes of resource planning in the procurement of hospital care. A third aim was to evaluate how the system of the DRGs adapts in the prediction of retaining health services within short (1-year), intermediate (5-year) and long range (10-15-year) intervals. The findings indicated that the follow-up of primary health care utilisation combined with follow-up of hospital care utilisation allows municipalities to plan and predict health services when databases are applied. Information about the past contacts with the databases has indicated that the health care culture and incidence of disease change rather slowly in the area of investigation. For the purposes of health care research, it is recommended that methods of application used in making predictions about health care utilisation need to be further developed

The resource-based view of the firm - resources, capabilities and sustainable competitive advantage

The main objective of this research paper was to synthesize, integrate and analyze the theoretical foundation of the resource-based view of the firm on sustainable competitive advantage. Accordingly, this research was a literature research employing the methodology of interpretative study of concept and unobtrusive measures. The core and majority of the research data was gathered from the major online journal databases. Only peer-reviewed articles from highly-esteemed journals on the subject of competitive advantage were used. The theoretical core of the research paper was centred on resources, capabilities, and the sustainability dilemma of competitive advantage. Furthermore, other strategic management concepts relating to the resource-based view of the firm were used with reference to the research objectives. The resource-based view of the firm continues to be a controversial but important are of strategic management research on sustainable competitive advantage. Consequently, the theoretical foundation and the empirical testing of the framework needs further work. However, it is evident that internal organizational factors in the form of resources and capabilities are vital for the formation of sustainable competitive advantage. Resources and capabilities are not, however, valuable on their own - competitive advantage requires seamless interplay and complementarity between bundles of resources and capabilities.

Spontaneous Emergence of Chirality in the Limited Enantioselectivity Model: Autocatalytic Cycle Driven by an External Reagent

The emergence of chirality in enantioselective autocatalysis for compounds unable to transform according to the Frank-like reaction network is discussed with respect to the controversial limited enantioselectivity (LES) model composed of coupled enantioselective and non-enantioselective autocatalyses. The LES model cannot lead to spontaneous mirror symmetry breaking (SMSB) either in closed systems with a homogeneous temperature distribution or in closed systems with a stationary non-uniform temperature distribution. However, simulations of chemical kinetics in a two-compartment model demonstrate that SMSB may occur if both autocatalytic reactions are spatially separated at different temperatures in different compartments but coupled under the action of a continuous internal flow. In such conditions, the system can evolve, for certain reaction and system parameters, toward a chiral stationary state; that is, the system is able to reach a bifurcation point leading to SMSB. Numerical simulations in which reasonable chemical parameters have been used suggest that an adequate scenario for such a SMSB would be that of abyssal hydrothermal vents, by virtue of the typical temperature gradients found there and the role of inorganic solids mediating chemical reactions in an enzyme-like role.

Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood.

When a bloodstream infection (BSI) is suspected, most of the laboratory results-biochemical and haematologic-are available within the first hours after hospital admission of the patient. This is not the case for diagnostic microbiology, which generally takes a longer time because blood culture, which is to date the reference standard for the documentation of the BSI microbial agents, relies on bacterial or fungal growth. The microbial diagnosis of BSI directly from blood has been proposed to speed the determination of the etiological agent but was limited by the very low number of circulating microbes during these paucibacterial infections. Thanks to recent advances in molecular biology, including the improvement of nucleic acid extraction and amplification, several PCR-based methods for the diagnosis of BSI directly from whole blood have emerged. In the present review, we discuss the advantages and limitations of these new molecular approaches, which at best complement the culture-based diagnosis of BSI.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

NlmCategory="UNASSIGNED">This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

Universities as an Insourcing Resource in R&D Operations

Tutkimuksen tavoitteena on arvioida ja analysoida yliopistojen ja yritysten välistä yhteistyötä tutkimus- ja kehitystoiminnassa. Teoriapohjan ja kohdeyrityksen case esimerkin avulla on tarkoitus selvittää kriittiset tekijät yhteistyössä sekä rakentaa tulosten perusteella viitekehys näiden kahden osapuolen yhteistyön onnistumiseksi. Teoriatausta käsittelee osapuolten tärkeimpiä strategioita yhteistyön kannalta, yhteistyön yleisiä ominaisuuksia, vuorovaikutussuhteita niin ympäristöön, toimintoihin kuin osapuoliinkin. Teoriaosuus tukee empiiristä tutkimusta, jossa perehdytään yhteen kansalliseen 3G projektiin Soneran ja Jyväskylän yliopiston välillä. Yrityksen ja yliopiston välinen yhteistyö on hyvin yleistä Suomessa. Motivoivia tekijöitä ovat muun muassa Tekesin kannustava rahoitus ja yhteistyön edullisuus, osapuolten keskittyminen omaan ydinosaamiseensa, tiedon tuotteistuksen ja uusien teorioiden luomisen mahdollisuus, positiiviset vaikutukset markkina-arvoon, imagolliset tekijät sekä varautuminen tulevaisuuden trendeihin.

Radio Resource Management across UMTS Radio Network Subsystems

UMTS (Universal Mobile Telecommunication System), esimerkkinä kolmannen sukupolven matkapuhelinjärjestelmästä pyrkii toistamaan GSM:n (Global System for Mobile Communications) menestyksen. UMTS:n kaupallinen toiminta on parhaillaan alkamassa ja ensimmäinen kaupallinen verkko on jo aloittanut toimintansa Japanissa. Tämä diplomityö antaa yleiskuvan UMTS:stä keskittyen radioverkkojärjestelmän (UMTS Terrestrial Radio Access Network,UTRAN) radioresurssien hallintaan (Radio Resource Management, RRM). Työssä kuvataan radiorajapintojen toimintaa, mutta diplomityön pääaiheena on kuitenkin radioresurssien hallinta UMTS radioaliverkkojärjestelmien ylitse. Radioresurssien hallinta pitää sisällään joukon proseduureja, jotka vaikuttavat koko UTRAN:in rakenteen lävitse. On hyvin tärkeää saavuttaa oikea toiminnallisuus hajautettujen radioresurssien hallintaan jotta voitaisiin saavuttaa paras yhteyden laatu loppukäyttäjälle. Työssä käydään yksityiskohtaisesti lävitse radioresurssien hallinnan perusperiaatteet ja joukko proseduureja. RNSAP (Radio Network Subsystem Application Part) protokollaa tarkastellaan työssä esimerkkinä protokollasta joka osallistuu radioresurssien hallintaprosessiin.