Significant changes in GM metabolite concentrations were observed in AN possibly triggered by elevated excitotoxin Glu. Increased tCho may indicate modifications of membrane phospholipids due to increased catabolism in the parietal region. Since no significant changes in phosphorylated choline compounds were found for the frontal region, the tCho increase in this region may hint to fluidity changes.
Urban planning and intelligent transportation management are facing key challenges in today's ever more urbanized world. Providing the right tools to city planners is crucial to cope with these challenges. Data collected from citizens' mobile communication can be used as the foundation for such tools. These kinds of data can facilitate various analysis tasks, such as the extraction of human movement patterns or determining the urban dynamics of a city. City planners can closely monitor such patterns based on which strategic decisions can be taken to improve a city's infrastructure. In this paper, we introduce a novel visual analytics approach for pattern exploration and search in global system for mobile communications mobile networks. We define geospatial and matrix representations of data, which can be interactively navigated. The approach integrates data visualization with suitable data analysis algorithms, allowing to spatially and temporally compare mobile usage, identify regularities, as well as anomalies in daily mobility patterns across regions and user groups. As an extension to our visual analytics approach, we further introduce space-time prisms with uncertain markers to visually analyze the uncertainty of urban mobility patterns.
We report the first structures of an unusual 13/11-helix (alternating i,i+1 {NH--O=C} and i,i+3 {C=O--H—N} H-bonds) formed by a heteromeric 1:1 se-quence of alpha- and delta-amino acids, using both XRD and NMR. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation, we also observe an apolar interaction between the ethyl residue of one delta-amino acid and the cyclohexyl group of the next delta-residue in the sequence that seems to stabilize one type of helix over another. Using this structural information, we have inserted two ornithine residues within the helix to install bis-amine functionality. The resulting foldamer acts as a minimalistic aldolase mimic.
Apoptin is a small viral protein capable of inducing cell death selectively in cancer cells. Despite its potential as an anticancer agent, relatively little is known about its mechanism of toxicity and cancer-selectivity. Previous experiments suggest that cancer-selective phosphorylation modulates Apoptin toxicity, although a lack of chemical tools has hampered the dissection of underlying mechanisms. Here, we describe structure-function studies with site-specifically phosphorylated Apoptin (Apoptin-T108ph) in living cells which revealed that Thr108 phosphorylation is the selectivity switch for Apoptin toxicity. Mechanistic investigations link T108ph to actin binding, cytoskeletal disruption and downstream inhibition of anoikis-resistance as well as cancer cell invasion. These results establish Apoptin as a protein pro-drug, selectively activated in cancer cells by phosphorylation, which disrupts the cytoskeleton and promotes cell death. We anticipate that this mechanism provides a framework for the design of next generation anticancer proteins with enhanced selectivity and potency.
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