The chiton Acanthopleura granulata uses aragonitic lenses embedded in its shell to focus light onto photoreceptors. Because aragonite is biaxially birefringent, the microstructure of the lens greatly ...impacts the optical performance. In addition, the chiton lives in the intertidal, so lenses experience two environments with different refractive indices: air and water. Using EBSD, we find that the lens is polycrystalline and contains curved grain boundaries. A combination of large, twinned grains and nanotwins ensure that the aragonitic axis is consistent across the lens. However, the orientation of the axis relative to the shell varies between lenses. Ray tracing simulations predict the optical performance of lenses of various microstructures in wet and dry environments. Though twinning helps to limit birefringence-induced aberrations, variations in the orientation of the axis between lenses lead to variations in focal lengths between lenses and cause image doubling in some lenses. As such, the birefringence of aragonite does not help the lens to transmit focused images in both air and water.
The ionization state of aspartate 26 in Lactobacillus casei dihydrofolate reductase has been investigated by selectively labeling the enzyme with 13Cgamma aspartic acid and measuring the 13C chemical ...shifts in the apo, folate-enzyme, and dihydrofolate-enzyme complexes. Our results indicate that no aspartate residue has a pKa greater than approximately 4.8 in any of the three complexes studied. The resonance of aspartate 26 in the dihydrofolate-enzyme complex has been assigned by site-directed mutagenesis; aspartate 26 is found to have a pKa value of less than 4 in this complex. Such a low pKa value makes it most unlikely that the ionization of this residue is responsible for the observed pH profile of hydride ion transfer apparent pKa = 6.0; Andrews, J., Fierke, C. A., Birdsall, B., Ostler, G., Feeney, J., Roberts, G. C. K., and Benkovic, S. J. (1989) Biochemistry 28, 5743-5750. Furthermore, the downfield chemical shift of the Asp 26 (13)Cgamma resonance in the dihydrofolate-enzyme complex provides experimental evidence that the pteridine ring of dihydrofolate is polarized when bound to the enzyme. We propose that this polarization of dihydrofolate acts as the driving force for protonation of the electron-rich O4 atom which occurs in the presence of NADPH. After this protonation of the substrate, a network of hydrogen bonds between O4, N5 and a bound water molecule facilitates transfer of the proton to N5 and transfer of a hydride ion from NADPH to the C6 atom to complete the reduction process.
Machine learning (ML) techniques are enjoying rapidly increasing adoption. However, designing and implementing the systems that support ML models in real-world deployments remains a significant ...obstacle, in large part due to the radically different development and deployment profile of modern ML methods, and the range of practical concerns that come with broader adoption. We propose to foster a new systems machine learning research community at the intersection of the traditional systems and ML communities, focused on topics such as hardware systems for ML, software systems for ML, and ML optimized for metrics beyond predictive accuracy. To do this, we describe a new conference, MLSys, that explicitly targets research at the intersection of systems and machine learning with a program committee split evenly between experts in systems and ML, and an explicit focus on topics at the intersection of the two.
The FMN-binding domain of human NADPH-cytochrome P450 reductase,corresponding to exons 3-;7, has been expressed at high level in anactive form and labelled with ^sup 13^C and ^sup 15^N. Mostof the ...backbone and aliphatic side-chain ^sup 1^H, ^sup 15^Nand ^sup 13^C resonances have been assigned using heteronucleardouble- and triple-resonance methods, together with a semiautomaticassignment strategy. The secondary structure as estimated from the chemicalshift index and NOE connectivities consists of six α-helices and fiveβ-strands. The global fold was deduced from the long-range NOEsunambiguously assigned in a 4D ^sup 13^C-resolved HMQC-NOESY-HMQCspectrum. The fold is of the alternating α/β type, with the fiveβ-strands arranged into a parallel β-sheet. The secondarystructure and global fold are very similar to those of the bacterialflavodoxins, but the FMN-binding domain has an extra short helix in place ofa loop, and an extra helix at the N-terminus (leading to the membrane anchordomain in the intact P450 reductase). The experimental constraints werecombined with homology modelling to obtain a structure of the FMN-bindingdomain satisfying the observed NOE constraints. Chemical shift comparisonsshowed that the effects of FMN binding and of FMN reduction are largelylocalised at the binding site.PUBLICATION ABSTRACT
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