Multi-input CRISPR/Cas genetic circuits that interface host regulatory networks

Genetic circuits require many regulatory parts in order to implement signal processing or execute algorithms in cells. A potentially scalable approach is to use dCas9, which employs small guide RNAs (sgRNAs) to repress genetic loci via the programmability of RNA:DNA base pairing. To this end, we use dCas9 and designed sgRNAs to build transcriptional logic gates and connect them to perform computation in living cells. We constructed a set of NOT gates by designing five synthetic Escherichia coli σ[subscript 70] promoters that are repressed by corresponding sgRNAs, and these interactions do not exhibit crosstalk between each other. These sgRNAs exhibit high on‐target repression (56‐ to 440‐fold) and negligible off‐target interactions (< 1.3‐fold). These gates were connected to build larger circuits, including the Boolean‐complete NOR gate and a 3‐gate circuit consisting of four layered sgRNAs. The synthetic circuits were connected to the native E. coli regulatory network by designing output sgRNAs to target an E. coli transcription factor (malT). This converts the output of a synthetic circuit to a switch in cellular phenotype (sugar utilization, chemotaxis, phage resistance).United States. Defense Advanced Research Projects Agency (CLIO N66001‐12‐C‐4016)National Institutes of Health (U.S.) (GM095765)National Institute of General Medical Sciences (U.S.) (Grant P50 GMO98792)Synthetic Biology Engineering Research Center (EEC0540879)United States. Defense Advanced Research Projects Agency (Ginkgo BioWorks. CLIO N66001‐12‐C‐4018)United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N00014‐13‐1‐0074)United States. Office of Naval Research. Multidisciplinary University Research Initiative (Boston University. Award 4500000552)United States. Air Force Office of Scientific Research (FA9550‐11‐C‐0028)American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship (32 CFR 168a

Realisation of a programmable two-qubit quantum processor

The universal quantum computer is a device capable of simulating any physical system and represents a major goal for the field of quantum information science. Algorithms performed on such a device are predicted to offer significant gains for some important computational tasks. In the context of quantum information, "universal" refers to the ability to perform arbitrary unitary transformations in the system's computational space. The combination of arbitrary single-quantum-bit (qubit) gates with an entangling two-qubit gate is a gate set capable of achieving universal control of any number of qubits, provided that these gates can be performed repeatedly and between arbitrary pairs of qubits. Although gate sets have been demonstrated in several technologies, they have as yet been tailored toward specific tasks, forming a small subset of all unitary operators. Here we demonstrate a programmable quantum processor that realises arbitrary unitary transformations on two qubits, which are stored in trapped atomic ions. Using quantum state and process tomography, we characterise the fidelity of our implementation for 160 randomly chosen operations. This universal control is equivalent to simulating any pairwise interaction between spin-1/2 systems. A programmable multi-qubit register could form a core component of a large-scale quantum processor, and the methods used here are suitable for such a device.Comment: 7 pages, 4 figure

Evidence for Efimov quantum states in an ultracold gas of cesium atoms

Systems of three interacting particles are notorious for their complex physical behavior. A landmark theoretical result in few-body quantum physics is Efimov's prediction of a universal set of bound trimer states appearing for three identical bosons with a resonant two-body interaction. Counterintuitively, these states even exist in the absence of a corresponding two-body bound state. Since the formulation of Efimov's problem in the context of nuclear physics 35 years ago, it has attracted great interest in many areas of physics. However, the observation of Efimov quantum states has remained an elusive goal. Here we report the observation of an Efimov resonance in an ultracold gas of cesium atoms. The resonance occurs in the range of large negative two-body scattering lengths, arising from the coupling of three free atoms to an Efimov trimer. Experimentally, we observe its signature as a giant three-body recombination loss when the strength of the two-body interaction is varied. We also detect a minimum in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point with which to explore the universal properties of resonantly interacting few-body systems. While Feshbach resonances have provided the key to control quantum-mechanical interactions on the two-body level, Efimov resonances connect ultracold matter to the world of few-body quantum phenomena.Comment: 18 pages, 3 figure

Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation

Topological Schr\"odinger cats: Non-local quantum superpositions of topological defects

Topological defects (such as monopoles, vortex lines, or domain walls) mark locations where disparate choices of a broken symmetry vacuum elsewhere in the system lead to irreconcilable differences. They are energetically costly (the energy density in their core reaches that of the prior symmetric vacuum) but topologically stable (the whole manifold would have to be rearranged to get rid of the defect). We show how, in a paradigmatic model of a quantum phase transition, a topological defect can be put in a non-local superposition, so that - in a region large compared to the size of its core - the order parameter of the system is "undecided" by being in a quantum superposition of conflicting choices of the broken symmetry. We demonstrate how to exhibit such a "Schr\"odinger kink" by devising a version of a double-slit experiment suitable for topological defects. Coherence detectable in such experiments will be suppressed as a consequence of interaction with the environment. We analyze environment-induced decoherence and discuss its role in symmetry breaking.Comment: 7 pages, 4 figure

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account

Observation of an Efimov spectrum in an atomic system

In 1970 V. Efimov predicted a puzzling quantum-mechanical effect that is still of great interest today. He found that three particles subjected to a resonant pairwise interaction can join into an infinite number of loosely bound states even though each particle pair cannot bind. Interestingly, the properties of these aggregates, such as the peculiar geometric scaling of their energy spectrum, are universal, i.e. independent of the microscopic details of their components. Despite an extensive search in many different physical systems, including atoms, molecules and nuclei, the characteristic spectrum of Efimov trimer states still eludes observation. Here we report on the discovery of two bound trimer states of potassium atoms very close to the Efimov scenario, which we reveal by studying three-particle collisions in an ultracold gas. Our observation provides the first evidence of an Efimov spectrum and allows a direct test of its scaling behaviour, shedding new light onto the physics of few-body systems.Comment: 10 pages, 3 figures, 1 tabl