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

New absolute magnitude calibrations for W Ursa Majoris type binaries

Parallaxes of W UMa stars in the Hipparcos catalogue have been analyzed. 31 W UMa stars, which have the most accurate parallaxes ($\sigma_{\pi}/\pi<0.15$) which are neither associated with a photometric tertiary nor with evidence of a visual companion, were selected for re-calibrating the Period--Luminosity--Color (PLC) relation of W UMa stars. Using the Lutz--Kelker (LK) bias corrected (most probable) parallaxes, periods ($0.26< P(day)< 0.87$), and colors (0.04<$(B-V)_{0}$<1.28) of the 31 selected W UMa, the PLC relation have been revised and re-calibrated. The difference between the old (revised but not bias corrected) and the new (LK bias corrected) relations are almost negligible in predicting the distances of W UMa stars up to about 100 parsecs. But, it increases and may become intolerable as distances of stars increase. Additionally, using $(J-H)_{0}$ and $(H-K_{s})_{0}$ colors from 2MASS (Two Micron All Sky Survey) data, a PLC relation working with infrared data was derived. It can be used with infrared colors in the range $-0.01<(J-H)_{0}<0.58$, and $-0.10<(H-K_{s})_{0}<0.18$. Despite {\em 2MASS} data are single epoch observations, which are not guaranteed at maximum brightness of the W UMa stars, the established relation has been found surprisingly consistent and reliable in predicting LK corrected distances of W UMa stars.Comment: 9 pages, 8 figures and 2 tables, accepted for publication in Astronomische Nachrichte

Entanglement Percolation in Quantum Networks

Quantum networks are composed of nodes which can send and receive quantum states by exchanging photons. Their goal is to facilitate quantum communication between any nodes, something which can be used to send secret messages in a secure way, and to communicate more efficiently than in classical networks. These goals can be achieved, for instance, via teleportation. Here we show that the design of efficient quantum communication protocols in quantum networks involves intriguing quantum phenomena, depending both on the way the nodes are displayed, and the entanglement between them. These phenomena can be employed to design protocols which overcome the exponential decrease of signals with the number of nodes. We relate the problem of establishing maximally entangled states between nodes to classical percolation in statistical mechanics, and demonstrate that quantum phase transitions can be used to optimize the operation of quantum networks.Comment: Accepted for publication in Nature Physics. This is the original submitted versio

Lack of cardioprotection from subcutaneously and preischemic administered Liraglutide in a closed chest porcine ischemia reperfusion model

<p>Abstract</p> <p>Background</p> <p>Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with Liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model.</p> <p>Methods</p> <p>Danish Landrace Pigs (70–80 kg) were randomly assigned to Liraglutide (10 μg/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate.</p> <p>Results</p> <p>The infarct size in relation to ischemic risk region in the control versus the Liraglutide group did not differ significantly: 0.46 ± 0.14 and 0.54 ± 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the Liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly.</p> <p>Conclusion</p> <p>Liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.</p

Quantum optical coherence can survive photon losses: a continuous-variable quantum erasure correcting code

A fundamental requirement for enabling fault-tolerant quantum information processing is an efficient quantum error-correcting code (QECC) that robustly protects the involved fragile quantum states from their environment. Just as classical error-correcting codes are indispensible in today's information technologies, it is believed that QECC will play a similarly crucial role in tomorrow's quantum information systems. Here, we report on the first experimental demonstration of a quantum erasure-correcting code that overcomes the devastating effect of photon losses. Whereas {\it errors} translate, in an information theoretic language, the noise affecting a transmission line, {\it erasures} correspond to the in-line probabilistic loss of photons. Our quantum code protects a four-mode entangled mesoscopic state of light against erasures, and its associated encoding and decoding operations only require linear optics and Gaussian resources. Since in-line attenuation is generally the strongest limitation to quantum communication, much more than noise, such an erasure-correcting code provides a new tool for establishing quantum optical coherence over longer distances. We investigate two approaches for circumventing in-line losses using this code, and demonstrate that both approaches exhibit transmission fidelities beyond what is possible by classical means.Comment: 5 pages, 4 figure

Effect of non-random mating on genomic and BLUP selection schemes

<p>Abstract</p> <p>Background</p> <p>The risk of long-term unequal contribution of mating pairs to the gene pool is that deleterious recessive genes can be expressed. Such consequences could be alleviated by appropriately designing and optimizing breeding schemes i.e. by improving selection and mating procedures.</p> <p>Methods</p> <p>We studied the effect of mating designs, random, minimum coancestry and minimum covariance of ancestral contributions on rate of inbreeding and genetic gain for schemes with different information sources, i.e. sib test or own performance records, different genetic evaluation methods, i.e. BLUP or genomic selection, and different family structures, i.e. factorial or pair-wise.</p> <p>Results</p> <p>Results showed that substantial differences in rates of inbreeding due to mating design were present under schemes with a pair-wise family structure, for which minimum coancestry turned out to be more effective to generate lower rates of inbreeding. Specifically, substantial reductions in rates of inbreeding were observed in schemes using sib test records and BLUP evaluation. However, with a factorial family structure, differences in rates of inbreeding due mating designs were minor. Moreover, non-random mating had only a small effect in breeding schemes that used genomic evaluation, regardless of the information source.</p> <p>Conclusions</p> <p>It was concluded that minimum coancestry remains an efficient mating design when BLUP is used for genetic evaluation or when the size of the population is small, whereas the effect of non-random mating is smaller in schemes using genomic evaluation.</p

All Optical Implementation of Multi-Spin Entanglement in a Semiconductor Quantum Well

We use ultrafast optical pulses and coherent techniques to create spin entangled states of non-interacting electrons bound to donors (at least three) and at least two Mn2+ ions in a CdTe quantum well. Our method, relying on the exchange interaction between localized excitons and paramagnetic impurities, can in principle be applied to entangle a large number of spins.Comment: 17 pages, 3 figure

Anyons in a weakly interacting system

We describe a theoretical proposal for a system whose excitations are anyons with the exchange phase pi/4 and charge -e/2, but, remarkably, can be built by filling a set of single-particle states of essentially noninteracting electrons. The system consists of an artificially structured type-II superconducting film adjacent to a 2D electron gas in the integer quantum Hall regime with unit filling fraction. The proposal rests on the observation that a vacancy in an otherwise periodic vortex lattice in the superconductor creates a bound state in the 2DEG with total charge -e/2. A composite of this fractionally charged hole and the missing flux due to the vacancy behaves as an anyon. The proposed setup allows for manipulation of these anyons and could prove useful in various schemes for fault-tolerant topological quantum computation.Comment: 7 pages with 3 figures. For related work and info visit http://www.physics.ubc.ca/~fran

Isolated Distal Deep Vein Thrombosis: Perspectives from the GARFIELD-VTE Registry

Isolated distal deep vein thrombosis (IDDVT) represents up to half of all lower limb DVT. This study investigated treatment patterns and outcomes in 2,145 patients with IDDVT in comparison with those with proximal DVT (PDVT; n = 3,846) and pulmonary embolism (PE; n = 4,097) enrolled in the GARFIELD-VTE registry. IDDVT patients were more likely to have recently undergone surgery (14.6%) or experienced leg trauma (13.2%) than PDVT patients (11.0 and 8.7%, respectively) and PE patients (12.7 and 4.5%, respectively). Compared with IDDVT, patients with PDVT or PE were more likely to have active cancer (7.2% vs. 9.9% and 10.3%). However, influence of provoking factors on risk of recurrence in IDDVT remains controversial. Nearly all patients (IDDVT, PDVT, and PE) were given anticoagulant therapy. In IDDVT, PDVT, and PE groups the proportion of patients receiving anticoagulant therapy was 61.4, 73.9, and 81.1% at 6 months and 45.8, 54.7, and 61.9% at 12 months. Over 12 months, the incidence of all-cause mortality, cancer, and recurrence was significantly lower in IDDVT patients than PDVT patients (hazard ratio [HR], 0.61 [95% confidence interval [CI], 0.48-0.77]; sub-HR [sHR], 0.60 [95% CI, 0.39-0.93]; and sHR, 0.76 [95% CI, 0.60-0.97]). Likewise, risk of death and incident cancer was significantly (both p < 0.05) lower in patients with IDDVT compared with PE. This study reveals a global trend that most IDDVT patients as well as those with PDVT and PE are given anticoagulant therapy, in many cases for at least 12 months