Intermolecular N-H...O=C hydrogen bonding in the crystal structure of 6-amino-1,3-dimethyluracil

The 6-amino- 1,3-dimethyluracil molecule [6-amino- 1,3- dimethyl-2,4(1H,3H)-pyrimidinedione], C6H9N302 (I), lies on a crystallographic mirror plane and participates in an extensive two-dimensional hydrogen-bonding network in the solid state. Each molecule is involved in N-- H...O=C hydrogen bonding involving the amino and carbonyl gr. oups, with O...N separations of 2.894 (3) and 2.904 (3) A

A Mixed-Integer Conic Program for the Moving-Target Traveling Salesman Problem based on a Graph of Convex Sets

This paper introduces a new formulation that finds the optimum for the Moving-Target Traveling Salesman Problem (MT-TSP), which seeks to find a shortest path for an agent, that starts at a depot, visits a set of moving targets exactly once within their assigned time-windows, and returns to the depot. The formulation relies on the key idea that when the targets move along lines, their trajectories become convex sets within the space-time coordinate system. The problem then reduces to finding the shortest path within a graph of convex sets, subject to some speed constraints. We compare our formulation with the current state-of-the-art Mixed Integer Conic Program (MICP) solver for the MT-TSP. The experimental results show that our formulation outperforms the MICP for instances with up to 20 targets, with up to two orders of magnitude reduction in runtime, and up to a 60\% tighter optimality gap. We also show that the solution cost from the convex relaxation of our formulation provides significantly tighter lower bounds for the MT-TSP than the ones from the MICP.Comment: 7 pages, 4 figure

Courteous Cars: Decentralized Multiagent Traffic Coordination

A major goal in robotics is to develop machines that perform useful tasks with minimal supervision. Instead of requiring each small detail to be specified, we would like to describe the task at a high level and have the system autonomously execute in a manner that satisfies that desired task. While the single robot case is difficult enough, moving to a multirobot behavior adds another layer of challenges. Having every robot achieve its specific goals while contributing to a global coordinated task requires each robot to react to information about other robots, for example, to avoid collisions. Furthermore, each robot must incorporate new information into its decision framework to react to environmental changes induced by other robots since this knowledge may effect its behavior

Expression capable library for studies of Neisseria gonorrhoeae, version 1.0

Background The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system. Results The clone set thus far includes 1672 of the 2250 predicted ORFs of the N. gonorrhoeae genome, of which 1393 (83%) are sequence-validated. Included in this set are 48 of the 61 ORFs of the gonococcal genetic island of strain MS11, not present in the sequenced genome of strain FA1090. L-arabinose-inducible glutathione-S-transferase (GST)-fusions were constructed from random clones and each was shown to express a fusion protein of the predicted size following induction, demonstrating the use of the recombination cloning system. PCR amplicons of each ORF used in the cloning reactions were spotted onto glass slides to produce DNA microarrays representing 2035 genes of the gonococcal genome. Pilot experiments indicate that these arrays are suitable for the analysis of global gene expression in gonococci. Conclusion This archived set of Gateway® entry clones will facilitate high-throughput genomic and proteomic studies of gonococcal genes using a variety of expression and analysis systems. In addition, the DNA arrays produced will allow us to generate gene expression profiles of gonococci grown in a wide variety of conditions. Together, the resources produced in this work will facilitate experiments to dissect the molecular mechanisms of gonococcal pathogenesis on a global scale, and ultimately lead to the determination of the functions of unknown genes in the genome

High Yielding Continuous-Flow Synthesis of Norketamine

A new continuous-flow process is presented for synthesis of the pharmaceutical intermediate norketamine (5). Our approach has been to take the well-established and industrially applied batch synthetic route to this promising antidepressant precursor and convert it to a telescoped multi-stage continuous-flow platform. This involves the α-bromination of a ketone, an imination/rearrangement sequence with liquid ammonia, and a thermally induced α-iminol rearrangement. Our approach is high yielding and provides several processing advantages including the reduction of many of the hazards conventionally associated with this route, particularly in the handling of liquid bromine, hydrogen bromide gas, and liquid ammonia. Each of these presents serious operational challenges in a batch process at scale

Dynamic but discordant alterations in zDHHC5 expression and palmitoylation of its substrates in cardiac pathologies

S-palmitoylation is an essential lipid modification catalysed by zDHHC-palmitoyl acyltransferases that regulates the localisation and activity of substrates in every class of protein and tissue investigated to date. In the heart, S-palmitoylation regulates sodium-calcium exchanger (NCX1) inactivation, phospholemman (PLM) inhibition of the Na+/K+ ATPase, Nav1.5 influence on membrane excitability and membrane localisation of heterotrimeric G-proteins. The cell surface localised enzyme zDHHC5 palmitoylates NCX1 and PLM and is implicated in injury during anoxia/reperfusion. Little is known about how palmitoylation remodels in cardiac diseases. We investigated expression of zDHHC5 in animal models of left ventricular hypertrophy (LVH) and heart failure (HF), along with HF tissue from humans. zDHHC5 expression increased rapidly during onset of LVH, whilst HF was associated with decreased zDHHC5 expression. Paradoxically, palmitoylation of the zDHHC5 substrate NCX1 was significantly reduced in LVH but increased in human HF, while palmitoylation of the zDHHC5 substrate PLM was unchanged in all settings. Overexpression of zDHHC5 in rabbit ventricular cardiomyocytes did not alter palmitoylation of its substrates or overall cardiomyocyte contractility, suggesting changes in zDHHC5 expression in disease may not be a primary driver of pathology. zDHHC5 itself is regulated by post-translational modifications, including palmitoylation in its C-terminal tail. We found that in HF palmitoylation of zDHHC5 changed in the same manner as palmitoylation of NCX1, suggesting additional regulatory mechanisms may be involved. This study provides novel evidence that palmitoylation of cardiac substrates is altered in the setting of HF, and that expression of zDHHC5 is dysregulated in both hypertrophy and HF