A model checking approach to the parameter estimation of biochemical pathways

Model checking has historically been an important tool to verify models of a wide variety of systems. Typically a model has to exhibit certain properties to be classed ‘acceptable’. In this work we use model checking in a new setting; parameter estimation. We characterise the desired behaviour of a model in a temporal logic property and alter the model to make it conform to the property (determined through model checking). We have implemented a computational system called MC2(GA) which pairs a model checker with a genetic algorithm. To drive parameter estimation, the fitness of set of parameters in a model is the inverse of the distance between its actual behaviour and the desired behaviour. The model checker used is the simulation-based Monte Carlo Model Checker for Probabilistic Linear-time Temporal Logic with numerical constraints, MC2(PLTLc). Numerical constraints as well as the overall probability of the behaviour expressed in temporal logic are used to minimise the behavioural distance. We define the theory underlying our parameter estimation approach in both the stochastic and continuous worlds. We apply our approach to biochemical systems and present an illustrative example where we estimate the kinetic rate constants in a continuous model of a signalling pathway

Alternative marine fuels: Prospects based on multi-criteria decision analysis involving Swedish stakeholders

There is a need for alternative marine fuels in order to reduce the environmental and climate impacts of shipping, in the short and long term. This study assesses the prospects for seven alternative fuels for the shipping sector in 2030, including biofuels, by applying a multi-criteria decision analysis approach that is based on the estimated fuel performance and on input from a panel of maritime stakeholders and by considering, explicitly, the influence of stakeholder preferences. Seven alternative marine fuels—liquefied natural gas (LNG), liquefied biogas (LBG), methanol from natural gas, renewable methanol, hydrogen for fuel cells produced from (i) natural gas or (ii) electrolysis based on renewable electricity, and hydrotreated vegetable oil (HVO)—and heavy fuel oil (HFO) as benchmark are included and ranked by ten performance criteria and their relative importance. The criteria cover economic, environmental, technical, and social aspects. Stakeholder group preferences (i.e., the relative importance groups assign to the criteria) influence the ranking of these options. For ship-owners, fuel producers, and engine manufacturers, economic criteria, in particular the fuel price, are the most important. These groups rank LNG and HFO the highest, followed by fossil methanol, and then various biofuels (LBG, renewable methanol, and HVO). Meanwhile, representatives from Swedish government authorities prioritize environmental criteria, specifically GHG emissions, and social criteria, specifically the potential to meet regulations, ranking renewable hydrogen the highest, followed by renewable methanol, and then HVO. Policy initiatives are needed to promote the introduction of renewable marine fuels

Tracking the Small with the Smallest – Using Nanotechnology in Tracking Zooplankton

A major problem when studying behavior and migration of small organisms is that many of the questions addressed for larger animals are not possible to formulate due to constraints on tracking smaller animals. In aquatic ecosystems, this problem is particularly problematic for zoo- and phytoplankton, since tracking devices are too heavy to allow the organism to act naturally. However, recent advances in nanotechnology have made it possible to track individual animals and thereby to focus on important and urgent questions which previously have not been possible to address. Here we report on a novel approach to track movement and migratory behavior of millimeter sized aquatic animals, particularly Daphnia magna, using the commercially available nanometer sized fluorescent probes known as quantum dots. Experimental trials with and without quantum dots showed that they did not affect behavior, reproduction or mortality of the tested animals. Compared to previously used methods to label small animals, the nano-labeling method presented here offers considerable improvements including: 24 h fluorescence, studies in both light and darkness, much improved optical properties, potential to study large volumes and even track animals in semi-natural conditions. Hence, the suggested method, developed in close cooperation between biologists, chemists and physicists, offers new opportunities to routinely study zooplankton responses to light, food and predation, opening up advancements within research areas such as diel vertical/horizontal migration, partial migration and other differences in intra- and interspecific movements and migration

Sickness presenteeism determines job satisfaction via affective-motivational states

Research on the consequences of sickness presenteeism, or the phenomenon of attending work whilst ill, has focused predominantly on identifying its economic, health, and absenteeism outcomes, neglecting important attitudinal-motivational outcomes. A mediation model of sickness presenteeism as a determinant of job satisfaction via affective-motivational states (specifically engagement with work and addiction to work) is proposed. This model adds to the current literature, by focusing on (i) job satisfaction as an outcome of presenteeism, and (ii) the psychological processes associated with this. It posits presenteeism as psychological absence and work engagement and work addiction as motivational states that originate in that. An online survey was completed by 158 office workers on sickness presenteeism, work engagement, work addiction, and job satisfaction. The results of bootstrapped mediation analysis with observable variables supported the model. Sickness presenteeism was negatively associated with job satisfaction. This relationship was fully mediated by both engagement with work and addiction to work, explaining a total of 48.07% of the variance in job satisfaction. Despite the small sample, the data provide preliminary support for the model. Given that there is currently no available research on the attitudinal consequences of presenteeism, these findings offer promise for advancing theorising in this area

Polarized inclusive leptoproduction, ℓN→hX\ell N \to hX, and the hadron helicity density matrix, ρ(h)\rho(h): possible measurements and predictions

We discuss the production of hadrons in polarized lepton nucleon interactions and in the current jet fragmentation region; using the QCD hard scattering formalism we compute the helicity density matrix of the hadron and show how its elements, when measurable, can give information on the spin structure of the nucleon and the spin dependence of the quark fragmentation process. The cases of $\rho$ vector mesons and $\Lambda$ baryons are considered in more details and, within simplifying assumptions, some estimates are given.Comment: 17 pages + 4 figures, plain LATeX, figures appended as uuencoded, compressed postscript fil

Response of macroinvertebrates to experimental nutrient and fish additions in European localities at different latitudes

The sedimentary and plant-associated macroinvertebrate communities have been examined in a series of mesocosm experiments carried out in five locations, in Finland, Sweden, UK, Northwest Spain and Mediterranean Spain (the International Mesocosm Experiment). The experiments were designed to investigate how shallow lake ecosystems respond to the addition of nutrients and planktivorous fish along a climate gradient. Nutrient additions increased sedimentary benthos densities and total biomass to a plateau at intermediate levels of nutrients. The effect was greater in the warmest localities. Beyond the saturation point a further increase in nutrient loading had different effects depending on locality. Only in the southernmost site (in Mediterranean Spain), did it induce a shift to a turbid phase and macrophyte disappearance. Thus there are breakpoints in the relationship with nutrients, leading to alternative sediment communities subsequent to the water alternative states. Presence of fish increased the densities and biomass of sediment macroinvertebrates, more clearly in the more southern locality, where the fish Gambusia did not prey in the bottom animals. A stabilising role of macrophytes was observed by cutting them, samples taken three weeks after cutting indicated a higher effect of fish on the sediment community when macrophytes were not present. Nutrients tended also to increase densities of plant associated macroinvertebrates at low levels with a flattening of response at intermediate levels and a decline at high levels. At high fish level the numbers and biomass of plant-associated macroinvertebrates were lowered in all cases, because of increased predation. However fish addition at low level in most cases had the opposite effect, because their predation pressure was not high and regeneration of nutrients through their activities might increase food availability and control invertebrate predators. Fish influenced especially community composition, because they prey selectively. Addition of fish at low densities increased macroinvertebrate diversity. A diel migratory cycle was observed in plant-associated macroinvertebrates, but only in the southerly locations. Latitudinal influences on the structure of the macroinvertebrate communities occur but that they operate indirectly. There was a prominent effect of nutrients on these communities so that starting trophy is very important. Fish effects are layered on these and depend to a large extent on the particular range of diet of the species involved.Se ha estudiado la comunidad de macroinvertebrados bentónicos del sedimento así como la de los asociados a los macrófitos en una serie de mesocosmos concebidos para un experimento múltiple simultáneo llevado a cabo en cinco localidades europeas: Finlandia, Suecia, Reino Unido (UK), Noroeste de España y Levante Español. El experimento fue diseñado para investigar como responden los ecosistemas de lagos someros a los aportes de nutrientes y a la abundancia de peces planctívoros a lo largo de un gradiente climático. La adición de nutrientes incrementó la densidad del bentos del sedimento y su biomasa hasta estabilizarse a niveles intermedios de nutrientes, siendo este efecto mayor en las latitudes más bajas y cálidas. Más allá del punto de saturación, un aumento adicional de la carga de nutrientes tuvo efectos diferentes dependiendo de la localidad y solo en el lugar de menor latitud, (en el Levante Español) indujo el cambio hacia una fase turbia, con desaparición de los macrófitos, esto es, hay puntos de ruptura relacionados con la carga de nutrientes que conducen a comunidades alternativas en el sedimento, subsiguientes a los mencionados estados alternativos en las aguas someras. La presencia de peces aumentó la densidad y biomasa de los macroinvertebrados del sedimento, ello también más claramente en la localidad situada más al Sur, ya que el pez planctívoro ensayado (Gambusia) por lo general no depreda en los animales del sedimento. Se observó también el papel estabilizador de los macrófitos comparando las muestras tomadas antes y después de que estos fueran cortados, por ejemplo se observó un efecto mayor de los peces en las comunidades del sedimento cuando los macrófitos no estaban presentes. Los nutrientes tendieron también a incrementar las densidades de los macroinvertebrados asociados a los macrófitos cuando se aportan a bajos niveles, con una estabilización de la respuesta para los valores intermedios y un declive para los valores más altos. Cuando se adicionaron densidades altas de peces, el número y biomasa de los macroinvertebrados asociados a los macrófitos descendieron en todos los casos, como resultado del aumento de la depredación. Sin embargo, las adiciones a baja densidad de peces, en la mayoría de los casos, tuvo el efecto contrario, ya que su presión de depredación no es alta y pueden contribuir a la regeneración de los nutrientes a través de la vía detrítica que incrementa la disponibilidad de alimento, así como al control de otros invertebrados depredadores. La presencia de peces influenció especialmente la composición de la comunidad, ya que su depredación es selectiva. La adición de peces en bajas densidades aumentó la diversidad de los macroinvertebrados. También fue observado que el ciclo diario de migración en los macroinvertebrados asociados a los macrófitos, es más importante en las localidades ubicadas en las latitudes de más al Sur. Las influencias latitudinales en la estructura de las comunidades de macroinvertebrados, si bien sucede, opera indirectamente. Hay un efecto dominante de los nutrientes en estas comunidades, y el nivel trófico de las condiciones iniciales es muy importante. Los efectos de los peces se subordinan al de los nutrientes y dependen en gran medida de la dieta de las especies involucradas

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Evaluation of a Previously Suggested Plasma Biomarker Panel to Identify Alzheimer's Disease

There is an urgent need for biomarkers in plasma to identify Alzheimer's disease (AD). It has previously been shown that a signature of 18 plasma proteins can identify AD during pre-dementia and dementia stages (Ray et al, Nature Medicine, 2007). We quantified the same 18 proteins in plasma from 174 controls, 142 patients with AD, and 88 patients with other dementias. Only three of these proteins (EGF, PDG-BB and MIP-1δ) differed significantly in plasma between controls and AD. The 18 proteins could classify patients with AD from controls with low diagnostic precision (area under the ROC curve was 63%). Moreover, they could not distinguish AD from other dementias. In conclusion, independent validation of results is important in explorative biomarker studies

Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge

<p>Abstract</p> <p>Background</p> <p>Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation.</p> <p>Methods</p> <p>Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay.</p> <p>Results</p> <p>C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2%, (p = 0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups.</p> <p>Conclusions</p> <p>Systemically activated eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.</p

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014 Swedish University of Agriculture Sciences (SLU Aqua) Lysekil, Sweden 08-12 September 2014The RCM NS&EA met in Lysekil (Sweden) between 8-12 September 2014. The main purpose of the RCM is coordinate the National Programmes (NP) of the Member States (MS) in the North Sea region for 2015