Designing algorithms to aid discovery by chemical robots

Recently, automated robotic systems have become very efficient, thanks to improved coupling between sensor systems and algorithms, of which the latter have been gaining significance thanks to the increase in computing power over the past few decades. However, intelligent automated chemistry platforms for discovery orientated tasks need to be able to cope with the unknown, which is a profoundly hard problem. In this Outlook, we describe how recent advances in the design and application of algorithms, coupled with the increased amount of chemical data available, and automation and control systems may allow more productive chemical research and the development of chemical robots able to target discovery. This is shown through examples of workflow and data processing with automation and control, and through the use of both well-used and cutting-edge algorithms illustrated using recent studies in chemistry. Finally, several algorithms are presented in relation to chemical robots and chemical intelligence for knowledge discovery

Accurate prediction of gene feedback circuit behavior from component properties

A basic assumption underlying synthetic biology is that analysis of genetic circuit elements, such as regulatory proteins and promoters, can be used to understand and predict the behavior of circuits containing those elements. To test this assumption, we used time‐lapse fluorescence microscopy to quantitatively analyze two autoregulatory negative feedback circuits. By measuring the gene regulation functions of the corresponding repressor–promoter interactions, we accurately predicted the expression level of the autoregulatory feedback loops, in molecular units. This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology

Enhanced many-body effects in the excitation spectrum of a weakly-interacting rotating Bose-Einstein condensate

The excitation spectrum of a highly-condensed two-dimensional trapped Bose-Einstein condensate (BEC) is investigated within the rotating frame of reference. The rotation is used to transfer high-lying excited states to the low-energy spectrum of the BEC. We employ many-body linear-response theory and show that, once the rotation leads to a quantized vortex in the ground state, already the low-energy part of the excitation spectrum shows substantial many-body effects beyond the realm of mean-field theory. We demonstrate numerically that the many-body effects grow with the vorticity of the ground state, meaning that the rotation enhances them even for very weak repulsion. Furthermore, we explore the impact of the number of bosons $N$ in the condensate on a low-lying single-particle excitation, which is describable within mean-field theory. Our analysis shows deviations between the many-body and mean-field results which clearly persist when $N$ is increased up to the experimentally relevant regime, typically ranging from several thousand up to a million bosons in size. Implications are briefly discussed

Linear Boolean classification, coding and "the critical problem"

The problem of constructing a minimal rank matrix over GF(2) whose kernel does not intersect a given set S is considered. In the case where S is a Hamming ball centered at 0, this is equivalent to finding linear codes of largest dimension. For a general set, this is an instance of "the critical problem" posed by Crapo and Rota in 1970. This work focuses on the case where S is an annulus. As opposed to balls, it is shown that an optimal kernel is composed not only of dense but also of sparse vectors, and the optimal mixture is identified in various cases. These findings corroborate a proposed conjecture that for annulus of inner and outer radius nq and np respectively, the optimal relative rank is given by (1-q)H(p/(1-q)), an extension of the Gilbert-Varshamov bound H(p) conjectured for Hamming balls of radius np

Time-dependent multi-orbital mean-field for fragmented Bose-Einstein condensates

The evolution of Bose-Einstein condensates is usually described by the famous time-dependent Gross-Pitaevskii equation, which assumes all bosons to reside in a single time-dependent orbital. In the present work we address the evolution of fragmented condensates, for which two (or more) orbitals are occupied, and derive a corresponding time-dependent multi-orbital mean-field theory. We call our theory TDMF($n$), where $n$ stands for the number of evolving fragments. Working equations for a general two-body interaction between the bosons are explicitly presented along with an illustrative numerical example.Comment: 16 pages, 1 figur

Zoo of quantum phases and excitations of cold bosonic atoms in optical lattices

Quantum phases and phase transitions of weakly- to strongly-interacting bosonic atoms in deep to shallow optical lattices are described by a {\it single multi-orbital mean-field approach in real space}. For weakly-interacting bosons in 1D, the critical value of the superfluid to Mott insulator (MI) transition found is in excellent agreement with {\it many-body} treatments of the Bose-Hubbard model. For strongly-interacting bosons, (i) additional MI phases appear, for which two (or more) atoms residing in {\it each site} undergo a Tonks-Girardeau-like transition and localize and (ii) on-site excitation becomes the excitation lowest in energy. Experimental implications are discussed.Comment: 12 pages, 3 figure

L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

Build-up of coherence between initially-independent subsystems: The case of Bose-Einstein condensates

When initially-independent subsystems are made to contact, {\it coherence} can develop due to interaction between them. We exemplify and demonstrate this paradigm through several scenarios of two initially-independent Bose-Einstein condensates which are allowed to collide. The build-up of coherence depends strongly on time, interaction strength and other parameters of each condensate. Implications are discussed.Comment: 11 pages, 3 figure