Molecular diversity of sterol 14α-demethylase substrates in plants, fungi and humans

AbstractMetabolism of lanosterol (LAN), 24-methylene-24,25-dihydrolanosterol (24-methyleneDHL), dihydrolanosterol (DHL) and obtusifoliol (OBT) by purified human, plant (Sorghum bicolor) and fungal (Candida albicans) sterol 14α-demethylase (CYP51; P45014DM) reconstituted with NADPH cytochrome P450 reductases was studied in order to elucidate the substrate specificity and sterol stereo- and regio-structural requirements for optimal CYP51 activity. Both human and C. albicans CYP51 could catalyse 14α-demethylation of each substrate with varying levels of activity, but having slightly higher activity for their respective endogenous substrates in vivo, dihydrolanosterol for human CYP51 (Vmax=0.5 nmol/min/nmol CYP51) and 24-methylene-24,25-dihydrolanosterol for C. albicans CYP51 (Vmax=0.3 nmol/min/nmol CYP51). In contrast, S. bicolor CYP51 showed strict substrate specificity and selectivity towards its own endogenous substrate, obtusifoliol (Vmax=5.5 nmol/min/nmol CYP51) and was inactive towards 14α-demethylation of lanosterol, 24-methylene-24,25-dihydrolanosterol and dihydrolanosterol. These findings confirm that the presence of the 4β-methyl group in the sterol molecule renders the plant CYP51 incapable of 14α-demethylation thus revealing the strict active site conservation of plant CYP51 during evolution

Hypergeometric decomposition of symmetric K3 quartic pencils

We study the hypergeometric functions associated to five one-parameter deformations of Delsarte K3 quartic hypersurfaces in projective space. We compute all of their Picard--Fuchs differential equations; we count points using Gauss sums and rewrite this in terms of finite field hypergeometric sums; then we match up each differential equation to a factor of the zeta function, and we write this in terms of global L-functions. This computation gives a complete, explicit description of the motives for these pencils in terms of hypergeometric motives.Comment: 70 pages, minor revision, to appear in Research in the Mathematical Science

Pulmonary arterial remodeling revealed by microfocal x-ray tomography

Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This \u27self-consistency\u27 property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns

Micro-CT Image-Derived Metrics Quantify Arterial Wall Distensibility Reduction in a Rat Model of Pulmonary Hypertension

We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension

Learned Camera Gain and Exposure Control for Improved Visual Feature Detection and Matching

Successful visual navigation depends upon capturing images that contain sufficient useful information. In this paper, we explore a data-driven approach to account for environmental lighting changes, improving the quality of images for use in visual odometry (VO) or visual simultaneous localization and mapping (SLAM). We train a deep convolutional neural network model to predictively adjust camera gain and exposure time parameters such that consecutive images contain a maximal number of matchable features. The training process is fully self-supervised: our training signal is derived from an underlying VO or SLAM pipeline and, as a result, the model is optimized to perform well with that specific pipeline. We demonstrate through extensive real-world experiments that our network can anticipate and compensate for dramatic lighting changes (e.g., transitions into and out of road tunnels), maintaining a substantially higher number of inlier feature matches than competing camera parameter control algorithms.Comment: Accepted to IEEE Robotics and Automation Letters and to the IEEE International Conference on Robotics and Automation (ICRA) 202

The modest professor:Interpretive charity and interpretive humility in John Rawls's lectures on the history of political philosophy

Governmen

Micromanipulation of InP lasers with optoelectronic tweezers for integration on a photonic platform

The integration of light sources on a photonic platform is a key aspect of the fabrication of self-contained photonic circuits with a small footprint that does not have a definitive solution yet. Several approaches are being actively researched for this purpose. In this work we propose optoelectronic tweezers for the manipulation and integration of light sources on a photonic platform and report the positional and angular accuracy of the micromanipulation of standard Fabry-Pérot InP semiconductor laser die. These lasers are over three orders of magnitude bigger in volume than any previously assembled with optofluidic techniques and the fact that they are industry standard lasers makes them significantly more useful than previously assembled microdisk lasers. We measure the accuracy to be 2.5 ± 1.4 µm and 1.4 ± 0.4° and conclude that optoelectronic tweezers are a promising technique for the micromanipulation and integration of optoelectronic components in general and semiconductor lasers in particular