Fast paths in large-scale dynamic road networks

Efficiently computing fast paths in large-scale dynamic road networks (where dynamic traffic information is known over a part of the network) is a practical problem faced by traffic information service providers who wish to offer a realistic fast path computation to GPS terminal enabled vehicles. The heuristic solution method we propose is based on a highway hierarchy-based shortest path algorithm for static large-scale networks; we maintain a static highway hierarchy and perform each query on the dynamically evaluated network, using a simple algorithm to propagate available dynamic traffic information over a larger part of the road network. We provide computational results that show the efficacy of our approach.     

Solid phase synthesis of aromatic oligoamides: application to helical water-soluble foldamers

Synthetic helical aromatic amide foldamers and in particular those based on quinolines have recently attracted much interest due to their capacity to adopt bioinspired folded conformations that are highly stable and predictable. Additionally, the introduction of water-solubilizing side chains has allowed to evidence promising biological activities. It has also created the need for methods that may allow the parallel synthesis and screening of oligomers. Here, we describe the application of solid phase synthesis to speed up oligomer preparation and allow the introduction of various side chains. The synthesis of quinoline-based monomers bearing protected side chains is described along with conditions for activation, coupling, and deprotection on solid phase, followed by resin cleavage, side-chain deprotection, and HPLC purification. Oligomers having up to 8 units were thus synthesized. We found that solid phase synthesis is notably improved upon reducing resin loading and by applying microwave irradiation. We also demonstrate that the introduction of monomers bearing benzylic amines such as 6-aminomethyl-2-pyridinecarboxylic acid within the sequences of oligoquinolines make it possible to achieve couplings using a standard peptide coupling agent and constitute an interesting alternative to the use of acid chloride activation required by quinoline residues. The synthesis of a tetradecameric sequence was thus smoothly carried out. NMR solution structural studies show that these alternate aminomethyl-pyridine residues do not perturb the canonical helix folding of quinoline monomers in protic solvents, contrary to what was previously observed in nonprotic solvents.     

A note on scheduling identical coupled tasks in logarithmic time

The coupled tasks problem consists in scheduling n jobs on a single machine. Each job i is made of two operations with processing times a_i and b_i and a fixed required delay L_i between them. Operations cannot overlap in time but operations of different jobs can be interleaved. The objective is to minimize the makespan of the schedule. In this note we show that the problem with identical jobs (∀i,a_i=a,b_i=b,L_i=L) can be solved in O(logn) time when a,b,L are fixed. This problem is motivated by radar scheduling applications where tasks corresponding to transmitting radiowaves and listening to potential echoes are coupled.     

Impact of Genomics and in Silico Related Technologies in the Drug Discovery Process

In order to evaluate to what extent will genomics and in silico related technologies improve overall drug discovery process, we analyzed three studies comping cost, time and attrition rate at each step of the drug discovery process, between standard pharmaceutical and genomics based approaches.     

Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry

Chemical biology and drug discovery are two scientific activities that pursue different goals but complement each other. The former is an interventional science that aims at understanding living systems through the modulation of its molecular components with compounds designed for this purpose. The latter is the art of designing drug candidates, i.e., molecules that act on selected molecular components of human beings and display, as a candidate treatment, the best reachable risk benefit ratio. In chemical biology, the compound is the means to understand biology, whereas in drug discovery, the compound is the goal. The toolbox they share includes biological and chemical analytic technologies, cell and whole-body imaging, and exploring the chemical space through state-of-the-art design and synthesis tools. In this article, we examine several tools shared by drug discovery and chemical biology through selected examples taken from research projects conducted in our institute in the last decade. These examples illustrate the design of chemical probes and tools to identify and validate new targets, to quantify target engagement in vitro and in vivo, to discover hits and to optimize pharmacokinetic properties with the control of compound concentration both spatially and temporally in the various biophases of a biological system.     

Time-resolved polymer deformation using polarized planar array infrared spectroscopy

Polarized planar array infrared (PA-IR) spectroscopy is shown for the first time to be a powerful approach to study the mechanical deformation of polymers. A dual-beam PA-IR spectrometer was built to enable the simultaneous recording of parallel- and perpendicular-polarized spectra at the same sample spot. The technique provides orientation and structural information during and after fast irreversible deformations with a low-ms (or sub-ms) time resolution and a low data scatter. In proof-of-concept experiments, the possibilities of polarized PA-IR spectroscopy are illustrated by studying the deformation of poly(ethylene terephthalate) thin films.     

Preemptive scheduling of equal-length jobs to maximize weighted throughput

We study the problem of computing a preemptive schedule of equal-length jobs with given release times, deadlines and weights. Our goal is to maximize the weighted throughput. In Graham's notation this problem is described as . We provide an O(n⁴)-time algorithm, improving the previous bound of O(n¹⁰).     

12/14/14‐Helix Formation in 2:1 α/β‐Hybrid Peptides Containing Bicyclo[2.2.2]octane Ring Constraints

The highly constrained β‐amino acid ABOC induces different types of helices in β urea and 1:1 α/β amide oligomers. The latter can adopt 11/9‐ and 18/16‐helical folds depending on the chain length in solution. Short peptides alternating proteinogenic α‐amino acids and ABOC in a 2:1 α/β repeat pattern adopted an unprecedented and stable 12/14/14‐helix. The structure was established through extensive NMR, molecular dynamics, and IR studies. While the 1:1 α‐AA/ABOC helices diverged from the canonical α‐helix, the helix formed by the 9‐mer 2:1 α/β‐peptide allowed the projection of the α‐amino acid side chains in a spatial arrangement according to the α‐helix. Such a finding constitutes an important step toward the conception of functional tools that use the ABOC residue as a potent helix inducer for biological applications.