Parechoviruses belong to the genus Parechovirus within the family Picornaviridae and are non-enveloped icosahedral viruses with a single-stranded RNA genome. Parechoviruses include human and animal pathogens classified into six species. Those that infect humans belong to the Parechovirus A species and can cause infections ranging from mild gastrointestinal or respiratory illness to severe neonatal sepsis. There are no approved antivirals available to treat parechovirus (nor any other picornavirus) infections. In this parechovirus review, we focus on the cleaved protein products resulting from the polyprotein processing after translation comparing and contrasting their known or predicted structures and functions to those of other picornaviruses. The review also includes our original analysis from sequence and structure prediction. This review highlights significant structural differences between parechoviral and other picornaviral proteins, suggesting that parechovirus drug development should specifically be directed to parechoviral targets.

For decades, the concept of “structural reform” has been dominant in the economic policy discourse of the EU and most of its member states, from Greece to Finland. The term gets its meaning mainly from neoclassical economic theory, though there are also Schumpeterian and other elements. An analysis of the theoretical underpinnings of the concept (which emerged in the 1980s and was spread through the Bretton Woods institutions and the OECD) reveals conceptual and theoretical ambiguities and factual weaknesses. While many of these weaknesses are related to unrealistic assumptions, I argue further that the realisticness of particular assumptions is different from the realism of the approach and relevance of the problematic. Second, to explore the limitations of the concept in its current meaning, I outline a brief genealogy of the concept of structure in social sciences and then juxtapose the economistic concept of structure with that of realist social theory. Third, I explore the implications of this deeper ontological conception of structure to the meaning and nature of possible structural reforms. Fourth, I give a few examples of alternative structural reforms to make my points more concrete. The envisioned programme of structural changes would amount to reversing the current EU strategy for growth. In the end, I summarise the overall argument.

We have developed a software for homology modelling by satisfaction of distance restraints using MODELLER back-end. The protocols used extend exploration of distance restraints and conformational space. We drive the models in optimization cycle towards better structures as assessed by the used metrics on DOPE score, retrospective distance restraint realization and others. Hydrogen bond networks are optimized for their size and connectivity density. The performance of the method is evaluated for its ability to reconstruct GPCR structures and an extracellular loop 2. The software is written in object-oriented Python (v.2.7) and supports easy extension with additional modules. We built a relational PostgreSQL database for the restraints to allow for data-driven machine and deep learning applications. An important part of the work was the visualization of the distance restraints with custom PyMOL scripts for three-dimensional viewing. Additionally, we automatically generate a plethora of diagnostic plots for assessing the performance of the modelling protocols. The software utilizes parallelism and is computationally practical with compute requirements on an order of magnitude lower than those typically seen in molecular dynamics simulations. The main challenges left to be solved is the evaluation of restraint goodness, assigning secondary structures, restraint interconditioning, and water and ligand placement.

We present a machine learning framework to simulate realistic galaxies for the Euclid Survey, producing more complex and realistic galaxies than the analytical simulations currently used in Euclid. The proposed method combines a control on galaxy shape parameters offered by analytic models with realistic surface brightness distributions learned from real Hubble Space Telescope observations by deep generative models. We simulate a galaxy field of 0.4x2006;deg(2) as it will be seen by the Euclid visible imager VIS, and we show that galaxy structural parameters are recovered to an accuracy similar to that for pure analytic Sersic profiles. Based on these simulations, we estimate that the Euclid Wide Survey (EWS) will be able to resolve the internal morphological structure of galaxies down to a surface brightness of 22.5x2006;magx2006;arcsec(-2), and the Euclid Deep Survey (EDS) down to 24.9x2006;magx2006;arcsec(-2). This corresponds to approximately 250 million galaxies at the end of the mission and a 50% complete sample for stellar masses above 10(10.6)M(circle dot) (resp. 10(9.6)M(circle dot)) at a redshift zx2004;similar to 0.5 for the EWS (resp. EDS). The approach presented in this work can contribute to improving the preparation of future high-precision cosmological imaging surveys by allowing simulations to incorporate more realistic galaxies.

The purpose of this study was to investigate the structure of ice cream, especially the effects of temperature, sugar composition and stabilizer-emulsifier concentration on the melt down, hardness and moulding properties of ice cream. The aim was to produce a soft and easily mouldable ice cream that suits the intended purpose. A sensory evaluation was conducted to the ice creams with desired structural properties. The literature review deals with ice cream ingredients, manufacturing process and factors affecting ice cream structure. For the experimental study, 16 ice creams with different compositions were made. The ice creams contained 12 or 6 % fat, different types of sugar compositions (A, B, C, D, E, F) and different concentrations of two types of stabilizer and emulsifier blends (A, B). Ice creams were stored at different temperatures. The hardness of ice cream was measured with a Texture Analyser, the melting rate was determined and the moulding properties were analysed with a moulding test. The two ice creams with desired structure were compared to a commercial ice cream in a sensory evaluation. The results of the hardness measurements revealed, that temperature and sugar composition affected hardness the most. Stabilizer and emulsifier concentration and type did not have an effect. The softest ice creams were those stored at higher temperatures and those made with sugar composition C, D, E and F. The slowest melting ice creams were the ones containing greater amounts of stabilizers and emulsifiers. The ice cream made with sugar composition D melted the fastest. For the moulding test, the softer ice creams were the easiest to mould. The ice cream made with sugar composition D was found to be too soft, almost runny, and the ones made with sugar composition A and B were found to be too hard. The ice creams made with sugar composition C, E and F were found pleasing. The batches containing a greater amount of stabilizer and emulsifier were found to be a bit gummy. In the sensory evaluation there were only one difference in sweetness found between the study ice creams and the commercial one. There were no differences found in creaminess and over all liking. From this can be concluded that the study ice creams are accepted by the consumers as well.

The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryo-electron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc)4 lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.

The accompanying collective research report is the result of the research project in 1986­90 between The Finnish Academy and the former Soviet Academy of Sciences. The project was organized around common field work in Finland and in the former Soviet Union and theoretical analyses of tree growth determining processes. Based on theoretical analyses, dynamic stand growth models were made and their parameters were determined utilizing the field results. Annual cycle affects the tree growth. Our theoretical approach was based on adaptation to local climate conditions from Lapland to South Russia. The initiation of growth was described as a simple low and high temperature accumulation driven model. Linking the theoretical model with long term temperature data allowed us to analyze what type of temperature response produced favorable outcome in different climates. Initiation of growth consumes the carbohydrate reserves in plants. We measured the dynamics of insoluble and soluble sugars in the very northern and Karelian conditions. Clear cyclical pattern was observed but the differences between locations were surprisingly small. Analysis of field measurements of CO2 exchange showed that irradiance is the dominating factor causing variation in photosynthetic rate in natural conditions during summer. The effect of other factors is so small that they can be omitted without any considerable loss of accuracy. A special experiment carried out in Hyytiälä showed that the needle living space, defined as the ratio between the shoot cylindric volume and needle surface area, correlates with the shoot photosynthesis. The penetration of irradiance into Scots pine canopy is a complicated phenomenon because of the movement of the sun on the sky and the complicated structure of branches and needles. A moderately simple but balanced forest radiation regime submodel was constructed. It consists of the tree crown and forest structure, the gap probability calculation and the consideration of spatial and temporal variation of radiation inside the forest. The common field excursions in different geographical regions resulted in a lot of experimental data of regularities of woody structures. The water transport seems to be a good common factor to analyse these properties of tree structure. There are evident regressions between cross-sectional areas measured at different locations along the water pathway from fine roots to needles. The observed regressions have clear geographical trends. For example, the same cross-sectional area can support three times higher needle mass in South Russia than in Lapland. Geographical trends can also be seen in shoot and needle structure. Analysis of data published by several Russian authors show, that one ton of needles transpire 42 ton of water a year. This annual amount of transpiration seems to be independent of geographical location, year and site conditions. The produced theoretical and experimental material is utilised in the development of stand growth model that describes the growth and development of Scots pine stands in Finland and the former Soviet Union. The core of the model is carbon and nutrient balances. This means that carbon obtained in photosynthesis is consumed for growth and maintenance and nutrients are taken according to the metabolic needs. The annual photosynthetic production by trees in the stand is determined as a function of irradiance and shading during the active period. The utilisation of the annual photosynthetic production to the growth of different components of trees is based on structural regularities. Since the fundamental metabolic processes are the same in all locations the same growth model structure can be applied in the large range of Scots pine. The annual photosynthetic production and structural regularities determining the allocation of resources have geographical features. The common field measurements enable the application of the model to the analysis of growth and development of stands growing on the five locations of experiments. The model enables the analysis of geographical differences in the growth of Scots pine. For example, the annual photosynthetic production of a 100-year-old stand at Voronez is 3.5 times higher than in Lapland. The share consumed to needle growth (30 %) and to growth of branches (5 %) seems to be the same in all locations. In contrast, the share of fine roots is decreasing when moving from north to south. It is 20 % in Lapland, 15 % in Hyytiälä Central Finland and Kentjärvi Karelia and 15 % in Voronez South Russia. The stem masses (115­113 ton/ha) are rather similar in Hyytiälä, Kentjärvi and Voronez, but rather low (50 ton/ha) in Lapland. In Voronez the height of the trees reach 29 m being in Hyytiälä and Kentjärvi 22 m and in Lapland only 14 m. The present approach enables utilization of structural and functional knowledge, gained in places of intensive research, in the analysis of growth and development of any stand. This opens new possibilities for growth research and also for applications in forestry practice.

Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nn-ITN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)(4) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. IMPORTANCE The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nn-ITN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.

Viruses have impacted the biosphere in numerous ways since the dawn of life. However, the evolution, genetic, structural, and taxonomic diversity of viruses remain poorly understood, in part because sparse sampling of the virosphere has concentrated mostly on exploring the abundance and diversity of dsDNA viruses. Furthermore, viral genomes are highly diverse, and using only the current sequence-based methods for classifying viruses and studying their phylogeny is complicated. Here we describe a virus, FLiP (Flavobacterium-infecting, lipid-containing phage), with a circular ssDNA genome and an internal lipid membrane enclosed in the icosahedral capsid. The 9,174-nt-long genome showed limited sequence similarity to other known viruses. The genetic data imply that this virus might use replication mechanisms similar to those found in other ssDNA replicons. However, the structure of the viral major capsid protein, elucidated at near-atomic resolution using cryo-electron microscopy, is strikingly similar to that observed in dsDNA viruses of the PRD1-adenovirus lineage, characterized by a major capsid protein bearing two beta-barrels. The strong similarity between FLiP and another member of the structural lineage, bacteriophage PM2, extends to the capsid organization (pseudo T = 21 dextro) despite the difference in the genetic material packaged and the lack of significant sequence similarity.