146 research outputs found

    Editorial Notes

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    The Editorial Board notes the remarkable evolution of the American Presidency during the twentieth century

    Editorial Notes

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    The Editorial Board notes the remarkable evolution of the American Presidency during the twentieth century

    Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities

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    The ubiquitin system regulates countless physiological and disease-associated processes and has emerged as an attractive entryway for therapeutic efforts. With over 600 members in the human proteome, ubiquitin ligases are the most diverse class of ubiquitylation enzymes and pivotal in encoding specificity in ubiquitin signaling. Although considerable progress has been made in the identification of small molecules targeting RING ligases, relatively little is known about the “druggability” of HECT (homologous to E6AP C terminus) ligases, many of which are critically implicated in human pathologies. A major obstacle to optimizing the few available ligands is our incomplete understanding of their inhibitory mechanisms and the structural basis of catalysis in HECT ligases. Here, we survey recent approaches to manipulate the activities of HECT ligases with small molecules to showcase the particular challenges and opportunities these enzymes hold as therapeutic targets

    Unexpected softness of bilayer graphene and softening of A-A stacked graphene layers

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    Density functional theory has been used to investigate the behavior of the π electrons in bilayer graphene and graphite under compression along the c axis. We have studied both conventional Bernal (A-B) and A-A stackings of the graphene layers. In bilayer graphene, only about 0.5% of the π-electron density is squeezed through the sp2 network for a compression of 20%, regardless of the stacking order. However, this has a major effect, resulting in bilayer graphene being about six times softer than graphite along the c axis. Under compression along the c axis, the heavily deformed electron orbitals (mainly those of the π electrons) increase the interlayer interaction between the graphene layers as expected, but, surprisingly, to a similar extent for A-A and Bernal stackings. On the other hand, this compression shifts the in-plane phonon frequencies of A-A stacked graphene layers significantly and very differently from the Bernal stacked layers. We attribute these results to some sp2 electrons in A-A stacking escaping the graphene plane and filling lower charge-density regions when under compression, hence, resulting in a nonmonotonic change in the sp2-bond stiffness

    How are oxygen budgets influenced by dissolved iron and growth of oxygenic phototrophs in an iron-rich spring system? Initial results from the Espan Spring in FĂĽrth, Germany

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    At present most knowledge on the impact of iron on 18O / 16O ratios (i.e. δ18O) of dissolved oxygen (DO) under circum-neutral conditions stems from experiments carried out under controlled laboratory conditions. These showed that iron oxidation leads to an increase in δ18ODO values. Here we present the first study on effects of elevated Fe(II) concentrations on the δ18ODO in a natural, iron-rich, circum-neutral watercourse. Our results show that iron oxidation was the major factor for rising dissolved oxygen isotope compositions in the first 85 m of the system in the cold season (February) and for the first 15 m during the warm season (May). Further along the course of the stream, the δ18ODO decreased towards values known for atmospheric equilibration around +24.6 ‰ during both seasons. Possible drivers for these changes may be reduced iron oxidation, increased atmospheric exchange and DO production by oxygenic phototrophic algae mats. In the cold season, the δ18ODO values stabilized around atmospheric equilibrium, whereas in the warm season stronger influences by oxygenic photosynthesis caused values down to +21.8 ‰. In the warm season from 145 m downstream of the spring, the δ18ODO increased again until it reached atmospheric equilibrium. This trend can be explained by respiratory consumption of DO combined with a relative decrease in photosynthetic activity and increasing atmospheric influences. Our study shows that dissolved Fe(II) can exert strong effects on the δ18ODO of a natural circum-neutral spring system even under constant supply of atmospheric O2. However, in the presence of active photosynthesis, with supply of O2 to the system, direct effects of Fe oxidation on the δ18ODO value become masked. Nonetheless, critical Fe(II) concentrations may indirectly control DO budgets by enhancing photosynthesis, particularly if cyanobacteria are involved.</p

    A high-level 3D visualization API for Java and ImageJ

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    BACKGROUND: Current imaging methods such as Magnetic Resonance Imaging (MRI), Confocal microscopy, Electron Microscopy (EM) or Selective Plane Illumination Microscopy (SPIM) yield three-dimensional (3D) data sets in need of appropriate computational methods for their analysis. The reconstruction, segmentation and registration are best approached from the 3D representation of the data set. RESULTS: Here we present a platform-independent framework based on Java and Java 3D for accelerated rendering of biological images. Our framework is seamlessly integrated into ImageJ, a free image processing package with a vast collection of community-developed biological image analysis tools. Our framework enriches the ImageJ software libraries with methods that greatly reduce the complexity of developing image analysis tools in an interactive 3D visualization environment. In particular, we provide high-level access to volume rendering, volume editing, surface extraction, and image annotation. The ability to rely on a library that removes the low-level details enables concentrating software development efforts on the algorithm implementation parts. CONCLUSIONS: Our framework enables biomedical image software development to be built with 3D visualization capabilities with very little effort. We offer the source code and convenient binary packages along with extensive documentation at http://3dviewer.neurofly.de
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