Variational Neural-Network Ansatz for Continuum Quantum Field Theory.

Physicists dating back to Feynman have lamented the difficulties of applying the variational principle to quantum field theories. In nonrelativistic quantum field theories, the challenge is to parametrize and optimize over the infinitely many n-particle wave functions comprising the state's Fock-space representation. Here we approach this problem by introducing neural-network quantum field states, a deep learning ansatz that enables application of the variational principle to nonrelativistic quantum field theories in the continuum. Our ansatz uses the Deep Sets neural network architecture to simultaneously parametrize all of the n-particle wave functions comprising a quantum field state. We employ our ansatz to approximate ground states of various field theories, including an inhomogeneous system and a system with long-range interactions, thus demonstrating a powerful new tool for probing quantum field theories.

Efficient fully-coherent quantum signal processing algorithms for real-time dynamics simulation.

Simulating the unitary dynamics of a quantum system is a fundamental problem of quantum mechanics, in which quantum computers are believed to have significant advantage over their classical counterparts. One prominent such instance is the simulation of electronic dynamics, which plays an essential role in chemical reactions, non-equilibrium dynamics, and material design. These systems are time-dependent, which requires that the corresponding simulation algorithm can be successfully concatenated with itself over different time intervals to reproduce the overall coherent quantum dynamics of the system. In this paper, we quantify such simulation algorithms by the property of being fully-coherent: the algorithm succeeds with arbitrarily high success probability 1 - δ while only requiring a single copy of the initial state. We subsequently develop fully-coherent simulation algorithms based on quantum signal processing (QSP), including a novel algorithm that circumvents the use of amplitude amplification while also achieving a query complexity additive in time t, ln(1/δ), and ln(1/ϵ) for error tolerance ϵ: Θ‖H‖|t|+ln(1/ϵ)+ln(1/δ). Furthermore, we numerically analyze these algorithms by applying them to the simulation of the spin dynamics of the Heisenberg model and the correlated electronic dynamics of an H2 molecule. Since any electronic Hamiltonian can be mapped to a spin Hamiltonian, our algorithm can efficiently simulate time-dependent ab initio electronic dynamics in the circuit model of quantum computation. Accordingly, it is also our hope that the present work serves as a bridge between QSP-based quantum algorithms and chemical dynamics, stimulating a cross-fertilization between these exciting fields.

Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype.

The actin cytoskeleton has been reported to restrict signalling in resting immune cells. Beta2-integrins, which mediate adhesion and cytoskeletal organization, are emerging as negative regulators of myeloid cell-mediated immune responses, but the molecular mechanisms involved are poorly understood. Here, we show that loss of the interaction between beta2-integrins and kindlin-3 abolishes the actin-linkage of integrins and the GM-CSF receptor in dendritic cells. This leads to increased GM-CSF receptor/Syk signalling, and to the induction of a transcriptional programme characteristic of mature, migratory dendritic cells, accumulation of migratory dendritic cells in lymphoid organs, and increased Th1 immune responses in vivo. We observe increased GM-CSF responses and increased survival in neutrophils where the interaction between integrin and the cytoskeleton is disrupted. Thus, ligand-reinforced beta2-integrin tail interactions restrict cytokine receptor signalling, survival, maturation and migration in myeloid cells and thereby contribute to immune homeostasis in vivo.

Effect of sand versus grass training surfaces during an 8-week pre-season conditioning programme in team sport athletes.

This study compared the use of sand and grass training surfaces throughout an 8-week conditioning programme in well-trained female team sport athletes (n = 24). Performance testing was conducted pre- and post-training and included measures of leg strength and balance, vertical jump, agility, 20 m speed, repeat speed (8 × 20 m every 20 s), as well as running economy and maximal oxygen consumption (VO2max). Heart rate (HR), training load (rating of perceived exertion (RPE) × duration), movement patterns and perceptual measures were monitored throughout each training session. Participants completed 2 × 1 h conditioning sessions per week on sand (SAND) or grass (GRASS) surfaces, incorporating interval training, sprint and agility drills, and small-sided games. Results showed a significantly higher (P < 0.05) HR and training load in the SAND versus GRASS group throughout each week of training, plus some moderate effect sizes to suggest lower perceptual ratings of soreness and fatigue on SAND. Significantly greater (P < 0.05) improvements in VO2max were measured for SAND compared to GRASS. These results suggest that substituting sand for grass training surfaces throughout an 8-week conditioning programme can significantly increase the relative exercise intensity and training load, subsequently leading to superior improvements in aerobic fitness.

Sand training: a review of current research and practical applications.

Sand surfaces can offer a higher energy cost (EC) and lower impact training stimulus compared with firmer and more traditional team sport training venues such as grass. This review aims to summarise the existing research on sand training, with a specific focus on its application as a team sports training venue. Compared with grass, significant physiological and biomechanical differences are associated with sand exercise. However, evidence also exists to suggest that training adaptations unique to sand can positively influence firm-ground performance. Furthermore, the lower impact forces experienced on sand can limit muscle damage, muscle soreness, and decrements in performance capacity relative to exercise intensity. Therefore, using a sand training surface in team sports may allow greater training adaptations to be achieved, while reducing performance decrements and injuries that may arise from heavy training. Nevertheless, further research should investigate the effect of sand surfaces over a greater range of training types and performance outcomes, to increase the application of sand training for team sports.

Crystal structures of novel allosteric peptide inhibitors of HIV integrase identify new interactions at the LEDGF binding site.

An optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95, that have not previously been described as being accessible within the binding site. We show that the peptides inhibit the interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN strand transfer. The interactions identified represent a potential framework for the development of new HIV-IN inhibitors.

Analysis of Orders for QTc-Prolonging Medication for Intensive and Cardiac Care Unit Patients with Pre-existing QTc Prolongation (QTIPPP Study).

BACKGROUND: A prolonged QTc interval on electrocardiography is often used as a surrogate marker for ventricular arrhythmia. Medications that can prolong the QTc interval may increase the risk of cardiac complications, although the exact incidence is unknown. It is reasonable to assume that administration of QTc-prolonging medications to patients with pre-existing QTc prolongation will further increase the risk of cardiac consequences. This study was designed to examine the frequency of prescription of QTc-prolonging medications in such patients and to explore the potential for clinical pharmacists to minimize the associated risks. OBJECTIVES: The primary objective was to identify the number of patients with pre-existing prolonged QTc interval for whom QTc-prolonging medications were prescribed, from among all patients with orders for QTc-prolonging medications. The secondary objectives were to determine patterns of intervention by clinical pharmacists in these cases and to document any further QTc prolongation and occurrence of cardiac events. METHODS: A prospective, observational, quality assessment study was conducted over 4.5 months. Adult patients admitted to beds with cardiac monitoring by telemetry for whom one or more QTc-prolonging medications were ordered were eligible for inclusion. Patients were included if the QTc interval was longer than 450 ms on the most recent 12-lead electrocardiogram before the QTc-prolonging medication was ordered. These patients were followed to identify outcomes of interest after administration of QTc-prolonging medication. RESULTS: Overall, a QTc-prolonging medication was prescribed for 207 patients. Of these, 53 patients (26%) had pre-existing prolongation of the QTc interval. Clinical pharmacists made recommendations related to 28 medication orders; of these, 16 (57%) were accepted by the physician. Fifty-one (96%) of the 53 patients received at least one dose of QTc-prolonging medication and were monitored daily for complications. Nine (18%) of the 51 patients who underwent daily monitoring experienced at least one cardiac event. CONCLUSIONS: A substantial proportion (26%) of patients for whom QTc-prolonging medications were prescribed had pre-existing prolongation of the QTc interval. Clinical pharmacists may have a role in reducing the risk of subsequent complications.

Surface display of IgG Fc on baculovirus vectors enhances binding to antigen-presenting cells and cell lines expressing Fc receptors.

Recombinant baculoviruses (recBV) were constructed with dual cassettes for constitutive expression of human IgG Fc following infection of insect cells and the structural proteins of hepatitis C virus (core, E1 and E2) following transduction of mammalian cells. The IgG Fc was expressed in insect cells as a fusion protein with the signal sequence and transmembrane region of either the native baculovirus envelope protein gp64 or the human transferrin receptor as a type I or type II integral membrane protein, respectively. The IgG Fc fusion proteins formed functional homodimers on the surface of recBV-infected insect cells and were incorporated into the envelope of recBV particles during egress from the infected cell. Both pseudotyped recBV bound specifically to recombinant soluble FcgammaRIIalpha receptor and to cell lines and antigen-presenting cells expressing Fc receptors (FcRs). These novel baculoviral vectors, which target cells of the immune system that express FcRs, have potential applications for vaccination or gene therapy.

Differential effects on the hepatitis C virus (HCV) internal ribosome entry site by vitamin B12 and the HCV core protein.

To investigate the role of the hepatitis C virus internal ribosome entry site (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES elements were constructed to contain the reciprocal domain IV in the otherwise HCV and classical swine fever virus IRES elements. This permitted an examination of the role of domain IV in the control of HCV translation. A specific inhibitor of the HCV IRES, vitamin B(12), was shown to inhibit translation directed by all IRES elements which contained domain IV from the HCV and the GB virus B IRES elements, whereas the HCV core protein could only suppress translation from the wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin B(12) and the core protein differ, and they target different regions of the IRES.