864 research outputs found

    Developing a Pilot Case and Modelling the Development of a Large European CO<sub>2</sub> Transport Infrastructure -The GATEWAY H2020 Project

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    The H2020 GATEWAY project aims to develop a comprehensive model Pilot Case which, intentionally, will pave the ground for CCS deployment in Europe. It will result from the assessment of, technical, commercial, judicial and societal issues related to a future CO2 transport infrastructure. The Pilot Case derived on this basis, will emphasize a gateway for CO2 transport in the North Sea Basin. Four potential pilot cases have been evaluated through a combination of techno-economic modelling of the individual cases and evaluation against more qualitative criteria. The chosen Pilot Case, Rotterdam Nucleus, will be refined and developed during the remaining period of the GATEWAY project. To maximise impact, the GATEWAY project adapts its work to lay the foundation for a future application to a European ‘Project of Common Interest’ (PCI). Continuous dialogue with the most relevant stakeholders is an important part of GATEWAY, as a Coordination and Support Action (CSA) H2020 project

    ALE Meta-Analysis Workflows Via the Brainmap Database: Progress Towards A Probabilistic Functional Brain Atlas

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    With the ever-increasing number of studies in human functional brain mapping, an abundance of data has been generated that is ready to be synthesized and modeled on a large scale. The BrainMap database archives peak coordinates from published neuroimaging studies, along with the corresponding metadata that summarize the experimental design. BrainMap was designed to facilitate quantitative meta-analysis of neuroimaging results reported in the literature and supports the use of the activation likelihood estimation (ALE) method. In this paper, we present a discussion of the potential analyses that are possible using the BrainMap database and coordinate-based ALE meta-analyses, along with some examples of how these tools can be applied to create a probabilistic atlas and ontological system of describing function–structure correspondences

    Orbital angular momentum superposition states in transmission electron microscopy and bichromatic multiphoton ionization

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    The coherent control of electron beams and ultrafast electron wave packets dynamics have attracted significant attention in electron microscopy as well as in atomic physics. In order to unify the conceptual pictures developed in both fields, we demonstrate the generation and manipulation of tailored electron orbital angular momentum (OAM) superposition states either by employing customized holographic diffraction masks in a transmission electron microscope or by atomic multiphoton ionization utilizing pulse-shaper generated carrier-envelope phase stable bichromatic ultrashort laser pulses. Both techniques follow similar physical mechanisms based on Fourier synthesis of quantum mechanical superposition states allowing the preparation of a broad set of electron states with uncommon symmetries. We describe both approaches in a unified picture based on an advanced spatial and spectral double slit and point out important analogies. In addition, we analyze the topological charge and discuss the control mechanisms of the free-electron OAM superposition states. Their generation and manipulation by phase tailoring in transmission electron microscopy and atomic multiphoton ionization is illustrated on a 7-fold rotationally symmetric electron density distribution.Comment: K. Eickhoff and C. Rathje contributed equally to this wor

    Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

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    Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels.Maps of fractional amplitude of low frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 female) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 female). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Further, we evaluated if the strength of co-localization is associated with the observed clinical symptoms.Patients displayed significantly reduced fALFF in fronto-temporal and fronto-parietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b, 5-HT2a), dopamine (D2), and γ-aminobutyric acid (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with D2 and NET was associated with cognitive symptoms and disease severity of bvFTD.Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD

    Genetic selection for bovine chromosome 18 haplotypes associated with divergent somatic cell score affects postpartum reproductive and metabolic performance

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    The susceptibility of animals to periparturient diseases has a great effect on the economic efficiency of dairy industries, on the frequency of antibiotic treatment, and on animal welfare. The use of selection for breeding cows with reduced susceptibility to diseases offers a sustainable tool to improve dairy cattle farming. Several studies have focused on the association of distinct bovine chromosome 18 genotypes or haplotypes with performance traits. The aim of this study was to test whether selection of Holstein Friesian heifers via SNP genotyping for alternative paternal chromosome 18 haplotypes associated with favorable (Q) or unfavorable (q) somatic cell scores influences postpartum reproductive and metabolic diseases. Thirty-six heifers (18 Q and 18 q) were monitored from 3 wk before calving until necropsy on d 39 (± 4 d) after calving. Health status and rectal temperature were measured daily, and body condition score and body weight were assessed once per week. Blood samples were drawn twice weekly, and levels of insulin, nonesterified fatty acids, insulin-like growth factor-I, growth hormone, and β-hydroxybutyrate were measured. Comparisons between the groups were performed using Fisher's exact test, chi-squared test, and the GLIMMIX procedure in SAS. Results showed that Q-heifers had reduced incidence of metritis compared with q-heifers and were less likely to develop fever. Serum concentrations of β-hydroxybutyrate were lower and insulin-like growth factor-I plasma concentrations were higher in Q- compared with q-heifers. However, the body condition score and withers height were comparable between haplotypes, but weight loss tended to be lower in Q-heifers compared with q-heifers. No differences between the groups were detected concerning retained fetal membranes, uterine involution, or onset of cyclicity. In conclusion, selection of chromosome 18 haplotypes associated with a reduced somatic cell score resulted in a decreased incidence of postpartum reproductive and metabolic diseases in this study. The presented data add to the existing knowledge aimed at avoiding negative consequences of genetic selection strategies in dairy cattle farming. The underlying causal mechanisms modulated by haplotypes in the targeted genomic region and immune competence necessitate further investigation

    The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data

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    <p>Abstract</p> <p>Background</p> <p>Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.</p> <p>Findings</p> <p>In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.</p> <p>Conclusions</p> <p>The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.</p

    Ice nucleating properties of the sea ice diatom <i>Fragilariopsis cylindrus</i> and its exudates

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    In this study, we investigated the ice nucleation activity of the Antarctic sea ice diatom Fragilariopsis cylindrus. Diatoms are the main primary producers of organic carbon in the Southern Ocean, and the Antarctic sea ice diatom F. cylindrus is one of the predominant species. This psychrophilic diatom is abundant in open waters and within sea ice. It has developed several mechanisms to cope with the extreme conditions of its environment, for example, the production of ice-binding proteins (IBPs) and extracellular polymeric substances known to alter the structure of ice. Here, we investigated the ice nucleation activity of F. cylindrus using a microfluidic device containing individual sub-nanolitre (∼90 µm) droplet samples. The experimental method and a newly implemented Poisson-statistics-based data evaluation procedure applicable to samples with low ice nucleating particle concentrations were validated by comparative ice nucleation experiments with well-investigated bacterial samples from Pseudomonas syringae (Snomax®). The experiments reveal an increase of up to 7.2 ∘C in the ice nucleation temperatures for seawater containing F. cylindrus diatoms when compared to pure seawater. Moreover, F. cylindrus fragments also show ice nucleation activity, while experiments with the F. cylindrus ice-binding protein (fcIBP) show no significant ice nucleation activity. A comparison with experimental results from other diatoms suggests a universal behaviour of polar sea ice diatoms, and we provide a diatom-mass-based parameterization of their ice nucleation activity for use in models.</p

    Genetic Studies of Sulfadiazine-resistant and Methionine-requiring \u3cem\u3eNeisseria\u3c/em\u3e Isolated From Clinical Material

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    Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species

    Stabilization of protein-protein interactions in drug discovery

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    Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p
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