The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development.

Schistosomiasis affects millions of people in developing countries and is responsible for more than 200,000 deaths annually. Because of toxicity and limited spectrum of activity of alternatives, there is effectively only one drug, praziquantel, available for its treatment. Recent data suggest that drug resistance could soon be a problem. There is therefore the need to identify new drug targets and develop drugs for the treatment of schistosomiasis. Analysis of the Schistosoma mansoni genome sequence for proteins involved in detoxification processes found that it encodes a single cytochrome P450 (CYP450) gene. Here we report that the 1452 bp open reading frame has a characteristic heme-binding region in its catalytic domain with a conserved heme ligating cysteine, a hydrophobic leader sequence present as the membrane interacting region, and overall structural conservation. The highest sequence identity to human CYP450s is 22%. Double stranded RNA (dsRNA) silencing of S. mansoni (Sm)CYP450 in schistosomula results in worm death. Treating larval or adult worms with antifungal azole CYP450 inhibitors results in worm death at low micromolar concentrations. In addition, combinations of SmCYP450-specific dsRNA and miconazole show additive schistosomicidal effects supporting the hypothesis that SmCYP450 is the target of miconazole. Treatment of developing S. mansoni eggs with miconazole results in a dose dependent arrest in embryonic development. Our results indicate that SmCYP450 is essential for worm survival and egg development and validates it as a novel drug target. Preliminary structure-activity relationship suggests that the 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol moiety of miconazole is necessary for activity and that miconazole activity and selectivity could be improved by rational drug design

Topological change of the Fermi surface in ternary iron-pnictides with reduced c/a ratio: A dHvA study of CaFe2P2

We report a de Haas-van Alphen effect study of the Fermi surface of CaFe2P2 using low temperature torque magnetometry up to 45 T. This system is a close structural analogue of the collapsed tetragonal non-magnetic phase of CaFe2As2. We find the Fermi surface of CaFe2P2 to differ from other related ternary phosphides in that its topology is highly dispersive in the c-axis, being three-dimensional in character and with identical mass enhancement on both electron and hole pockets (~1.5). The dramatic change in topology of the Fermi surface suggests that in a state with reduced (c/a) ratio, when bonding between pnictogen layers becomes important, the Fermi surface sheets are unlikely to be nested

Criterion-related Validity of Forced-Choice Personality Measures: A Cautionary Note Regarding Thurstonian IRT versus Classical Test Theory Scoring

This study examined criterion-related validity for job-related composites of forced-choice personality scores against job performance using both Thurstonian Item Response Theory (TIRT) and Classical Test Theory (CTT) scoring methods. Correlations were computed across 11 different samples that differed in job or role within a job. A meta-analysis of the correlations (k = 11 and N = 613) found a higher average corrected correlation for CTT (mean ρ = .38) than for TIRT (mean ρ = .00). Implications and directions for future research are discussed

Unconventional Josephson Effect in Hybrid Superconductor-Topological Insulator Devices

We report on transport properties of Josephson junctions in hybrid superconducting-topological insulator devices, which show two striking departures from the common Josephson junction behavior: a characteristic energy that scales inversely with the width of the junction, and a low characteristic magnetic field for suppressing supercurrent. To explain these effects, we propose a phenomenological model which expands on the existing theory for topological insulator Josephson junctions

Separation-dependent localization in a two-impurity spin-boson model

Using a variational approach we investigate the delocalized to localized crossover in the ground state of an Ohmic two-impurity spin-boson model, describing two otherwise non-interacting spins coupled to a common bosonic environment. We show that a competition between an environment-induced Ising spin interaction and externally applied fields leads to variations in the system-bath coupling strength, $\alpha_c$, at which the delocalized-localized crossover occurs. Specifically, the crossover regime lies between $\alpha_c=0.5$ and $\alpha_c=1$ depending upon the spin separation and the strength of the transverse tunneling field. This is in contrast to the analogous single spin case, for which the crossover occurs (in the scaling limit) at fixed $\alpha_c\approx1$. We also discuss links between the two-impurity spin-boson model and a dissipative two-spin transverse Ising model, showing that the latter possesses the same qualitative features as the Ising strength is varied. Finally, we show that signatures of the crossover may be observed in single impurity observables, as well as in the behaviour of the system-environment entanglement.Comment: 12 pages, 9 figures. Published version. Expanded discussion of the distance dependence between the impurities, and added a related figur

Benchmarking treewidth as a practical component of tensor-network--based quantum simulation

Tensor networks are powerful factorization techniques which reduce resource requirements for numerically simulating principal quantum many-body systems and algorithms. The computational complexity of a tensor network simulation depends on the tensor ranks and the order in which they are contracted. Unfortunately, computing optimal contraction sequences (orderings) in general is known to be a computationally difficult (NP-complete) task. In 2005, Markov and Shi showed that optimal contraction sequences correspond to optimal (minimum width) tree decompositions of a tensor network's line graph, relating the contraction sequence problem to a rich literature in structural graph theory. While treewidth-based methods have largely been ignored in favor of dataset-specific algorithms in the prior tensor networks literature, we demonstrate their practical relevance for problems arising from two distinct methods used in quantum simulation: multi-scale entanglement renormalization ansatz (MERA) datasets and quantum circuits generated by the quantum approximate optimization algorithm (QAOA). We exhibit multiple regimes where treewidth-based algorithms outperform domain-specific algorithms, while demonstrating that the optimal choice of algorithm has a complex dependence on the network density, expected contraction complexity, and user run time requirements. We further provide an open source software framework designed with an emphasis on accessibility and extendability, enabling replicable experimental evaluations and future exploration of competing methods by practitioners.Comment: Open source code availabl

A systematic review of factors influencing habitat connectivity and biodiversity along road and rail routes in temperate zones

This systematic review, part funded by Network Rail Ltd (UK), considers the role of transportation corridors in habitat connectivity within temperate climates, through verge habitat, surrounding matrix, movement along and across the corridor, the wider landscape context and management practices. PICO terms were developed for the bibliographic search on 15/11/22 using Web of Science (all databases), yielding 168 studies for review. The risk of bias was minimised by excluding non-peer reviewed papers. Large and exotic taxa were excluded due to a focus on temperate zones, as were studies on invasive species and climate change where the primary focus was not ecological connectivity. Emergent themes were used to structure the paper. Results indicate that transportation corridors have significant potential for habitat connectivity, especially for generalist and open-specialist species, which favour early to mid-successional habitats. However, physiology is a key determinant in dispersal ability. Vegetation management should consider representative communities rather than individual species. Gaps exist in the range of taxa studied, understanding of seasonal variations and lifecycle stages supported in verges, survival factors such as predation and disease and changes to community structure. Rail environments are under-represented and there is limited knowledge on the relative impacts of vegetation management regimes