Paramyxovirus V proteins interact with the RNA helicase LGP2 to inhibit RIG-I-dependent interferon induction

This work was supported by the Wellcome Trust (grant AL087751/B)RIG-I and mda-5 are activated by viral RNA and stimulate type I interferon production. Laboratory of genetics and physiology 2 (LGP2) shares homology with RIG-I and mda-5 but lacks the CARD domains required for signaling. The V proteins of paramyxoviruses limit interferon induction by binding mda-5 and preventing its activation; however, they do not bind RIG-I and have not been considered inhibitors of RIG-I signaling. Here we uncover a novel mechanism of RIG-I inhibition in which the V protein of parainfluenzavirus type 5 (PIV5; formerly known as simian virus type 5 [SV5]) interacts with LGP2 and cooperatively inhibits induction by RIG-I ligands. A complex between RIG-I and LGP2 is observed in the presence of PIV5-V, and we propose that this complex is refractory to activation by RIG-I ligands. The V proteins from other paramyxoviruses also bind LGP2 and demonstrate LGP2-dependent inhibition of RIG-I signaling. This is significant, because it demonstrates a general mechanism for the targeting of the RIG-I pathway by paramyxoviruses.Publisher PDFPeer reviewe

Dominant role of many-body effects on the carrier distribution function of quantum dot lasers

The effects of free-carrier-induced shift and broadening on the carrier distribution function are studied considering different extreme cases for carrier statistics (Fermi–Dirac and random carrier distributions) as well as quantum dot (QD) ensemble inhomogeneity and state separation using a Monte Carlo model. Using this model, we show that the dominant factor determining the carrier distribution function is the free carrier effects and not the choice of carrier statistics. By using empirical values of the free-carrier-induced shift and broadening, good agreement is obtained with experimental data of QD materials obtained under electrical injection for both extreme cases of carrier statistics

Discrete-query quantum algorithm for NAND trees

Recently, Farhi, Goldstone, and Gutmann gave a quantum algorithm for evaluating NAND trees that runs in time O(sqrt(N log N)) in the Hamiltonian query model. In this note, we point out that their algorithm can be converted into an algorithm using O(N^{1/2 + epsilon}) queries in the conventional quantum query model, for any fixed epsilon > 0.Comment: 2 pages. v2: updated name of one autho

Discrete-Query Quantum Algorithm for NAND Trees

This is a comment on the article “A Quantum Algorithm for the Hamiltonian NAND Tree” by Edward Farhi, Jeffrey Goldstone, and Sam Gutmann, Theory of Computing 4 (2008) 169--190. That paper gave a quantum algorithm for evaluating NAND trees with running time O(√N) in the Hamiltonian query model. In this note, we point out that their algorithm can be converted into an algorithm using N^[1/2 + o(1)] queries in the conventional (discrete) quantum query model

Exponential improvement in precision for simulating sparse Hamiltonians

We provide a quantum algorithm for simulating the dynamics of sparse Hamiltonians with complexity sublogarithmic in the inverse error, an exponential improvement over previous methods. Specifically, we show that a $d$-sparse Hamiltonian $H$ acting on $n$ qubits can be simulated for time $t$ with precision $\epsilon$ using $O\big(\tau \frac{\log(\tau/\epsilon)}{\log\log(\tau/\epsilon)}\big)$ queries and $O\big(\tau \frac{\log^2(\tau/\epsilon)}{\log\log(\tau/\epsilon)}n\big)$ additional 2-qubit gates, where $\tau = d^2 \|{H}\|_{\max} t$. Unlike previous approaches based on product formulas, the query complexity is independent of the number of qubits acted on, and for time-varying Hamiltonians, the gate complexity is logarithmic in the norm of the derivative of the Hamiltonian. Our algorithm is based on a significantly improved simulation of the continuous- and fractional-query models using discrete quantum queries, showing that the former models are not much more powerful than the discrete model even for very small error. We also simplify the analysis of this conversion, avoiding the need for a complex fault correction procedure. Our simplification relies on a new form of "oblivious amplitude amplification" that can be applied even though the reflection about the input state is unavailable. Finally, we prove new lower bounds showing that our algorithms are optimal as a function of the error.Comment: v1: 27 pages; Subsumes and improves upon results in arXiv:1308.5424. v2: 28 pages, minor change

Simulating Hamiltonian dynamics with a truncated Taylor series

We describe a simple, efficient method for simulating Hamiltonian dynamics on a quantum computer by approximating the truncated Taylor series of the evolution operator. Our method can simulate the time evolution of a wide variety of physical systems. As in another recent algorithm, the cost of our method depends only logarithmically on the inverse of the desired precision, which is optimal. However, we simplify the algorithm and its analysis by using a method for implementing linear combinations of unitary operations to directly apply the truncated Taylor series.Comment: 5 page

Torture-survivors' experiences of healthcare services for pain : a qualitative study

Background: Increasing numbers of torture-survivors are presenting to UK healthcare services with persistent pain. However, there is a paucity of evidence surrounding the management of persistent pain among torture-survivors and their experience of healthcare services for pain is currently unknown. This qualitative study explores their experiences of services for managing pain, to inform clinical practice and service provision. Methods: Thirteen participants were recruited from a specialist pain clinic for torture-survivors in the United Kingdom. Utilising an ethnographic approach, data were collected via clinic appointment observations, interviews and medical records and analysed using inductive thematic analysis. Results: Three themes emerged in relation to torture-survivors’ experiences of healthcare services for pain: the patient–clinician relationship; multiplicity of diagnoses and treatments; lack of service integration. Participants described limited engagement in decision-making processes regarding their care. Lack of recognition of torture experience when diagnosing and treating pain, alongside multiple unsuccessful treatments, led to confusion, frustration and hopelessness. These issues were exacerbated by the disconnect between physical and mental health services. Conclusion: This study provides new insight into the challenges faced by torture-survivors when accessing healthcare services for pain. Our findings suggest current service provision is not meeting their complex needs. Clinical implications include the need for integrated care systems and better recognition of the influence of torture experience on persistent pain. Strategies to engage and empower torture-survivors in the management of their pain are suggested

Exponential algorithmic speedup by quantum walk

We construct an oracular (i.e., black box) problem that can be solved exponentially faster on a quantum computer than on a classical computer. The quantum algorithm is based on a continuous time quantum walk, and thus employs a different technique from previous quantum algorithms based on quantum Fourier transforms. We show how to implement the quantum walk efficiently in our oracular setting. We then show how this quantum walk can be used to solve our problem by rapidly traversing a graph. Finally, we prove that no classical algorithm can solve this problem with high probability in subexponential time.Comment: 24 pages, 7 figures; minor corrections and clarification

Reduced Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation: Current Perspectives

AbstractAllogeneic HCT after myeloablative conditioning is an effective therapy for patients with hematologic malignancies. In an attempt to extend this therapy to older patients or those with comorbidities, reduced intensity or truly nonmyeloablative regimens have been developed over the past decade. The principle underlying reduced intensity regimens is to provide some tumor kill with lessened regimen-related morbidity and mortality and then rely on graft-versus-tumor (GVT) effects to eradicate remaining malignant cells, whereas nonmyeloablative regimens rely primarily on GVT effects. In this article, 3 representative approaches are described, demonstrating the clinical application for hematopoietic and nonhematopoietic malignancies. Current challenges include controlling GVHD while allowing GVT to occur. In the future, clinical trials using reduced intensity and nonmyeloablative conditioning will be compared with myeloablative conditioning in selected malignancies to extend the application to standard-risk patients

Gallium Nitride Super-Luminescent Light Emitting Diodes for Optical Coherence Tomography Applications

The role of biasing of absorber sections in multi-contact GaN ~400nm SLEDs is discussed. We go on to assess such devices for OCT applications. Analysis of the SLED emission spectrum allows an axial resolution of 6.0μm to be deduced in OCT applications