Simulating chemistry efficiently on fault-tolerant quantum computers

Quantum computers can in principle simulate quantum physics exponentially faster than their classical counterparts, but some technical hurdles remain. Here we consider methods to make proposed chemical simulation algorithms computationally fast on fault-tolerant quantum computers in the circuit model. Fault tolerance constrains the choice of available gates, so that arbitrary gates required for a simulation algorithm must be constructed from sequences of fundamental operations. We examine techniques for constructing arbitrary gates which perform substantially faster than circuits based on the conventional Solovay-Kitaev algorithm [C.M. Dawson and M.A. Nielsen, \emph{Quantum Inf. Comput.}, \textbf{6}:81, 2006]. For a given approximation error $\epsilon$, arbitrary single-qubit gates can be produced fault-tolerantly and using a limited set of gates in time which is $O(\log \epsilon)$ or $O(\log \log \epsilon)$; with sufficient parallel preparation of ancillas, constant average depth is possible using a method we call programmable ancilla rotations. Moreover, we construct and analyze efficient implementations of first- and second-quantized simulation algorithms using the fault-tolerant arbitrary gates and other techniques, such as implementing various subroutines in constant time. A specific example we analyze is the ground-state energy calculation for Lithium hydride.Comment: 33 pages, 18 figure

Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2−/−/Crb1Rd8/RD8, Cx3cr1−/−/Crb1Rd8/RD8 and CCl2−/−/Cx3cr1−/−/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

A compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast

A significant number of patients receiving breast-conserving surgery (BCS) for invasive carcinoma and ductal carcinoma in situ (DCIS) may need reoperation following tumor-positive margins from final histopathology tests. All current intraoperative margin assessment modalities have specific limitations. As a first step towards the development of a compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast, we prove that the system\u27s dimensions can be reduced without affecting imaging performance. We analysed the variation in noise and contrast to noise ratio (CNR) with decreasing system length using the edge illumination x-ray phase contrast imaging setup. Two-(planar) and three-(computed tomography (CT)) dimensional imaging acquisitions of custom phantoms and a breast tissue specimen were made. Dedicated phase retrieval algorithms were used to separate refraction and absorption signals. A \u27single-shot\u27 retrieval method was also used, to retrieve thickness map images, due to its simple acquisition procedure and reduced acquisition times. Experimental results were compared to numerical simulations where appropriate. The relative contribution of dark noise signal in integrating detectors is significant for low photon count statistics acquisitions. Under constant exposure factors and magnification, a more compact system provides an increase in CNR. Superior CNR results were obtained for refraction and thickness map images when compared to absorption images. Results indicate that the \u27single-shot\u27 acquisition method is preferable for a compact CT intraoperative specimen scanner; it allows for shorter acquisition times and its combination of the absorption and refraction signals ultimately leads to a higher contrast. The first CT images of a breast specimen acquired with the compact system provided promising results when compared to those of the longer length system

The Primarily Undergraduate Nanomaterials Cooperative: A New Model for Supporting Collaborative Research at Small Institutions on a National Scale

The Primarily Undergraduate Nanomaterials Cooperative (PUNC) is an organization for research-active faculty studying nanomaterials at Primarily Undergraduate Institutions (PUIs), where undergraduate teaching and research go hand-in-hand. In this perspective, we outline the differences in maintaining an active research group at a PUI compared to an R1 institution. We also discuss the work of PUNC, which focuses on community building, instrument sharing, and facilitating new collaborations. Currently consisting of 37 members from across the United States, PUNC has created an online community consisting of its Web site (nanocooperative.org), a weekly online summer group meeting program for faculty and students, and a Discord server for informal conversations. Additionally, in-person symposia at ACS conferences and PUNC-specific conferences are planned for the future. It is our hope that in the years to come PUNC will be seen as a model organization for community building and research support at primarily undergraduate institutions

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8+ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (P<0.001; HR=1.94 (1.44–2.61)) and loss of CD8+ TILs (P=0.006; HR=0.63 (0.45–0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM+/TIL− patients was 30% (95% CI 21–40%) compared to 76% (95% CI: 66–84%) for RHAMM−/TIL+ patients (P<0.001). The 5-year cancer-specific survival of T1/T2/RHAMM+/TIL− patients was 48% (20–72%) and significantly worse compared to T3/T4/RHAMM−/TIL+ patients (71% 95% CI 56–82%); P=0.039). Stratifying by nodal status, only N+/RHAMM+/TIL− patients demonstrated a significantly worse prognosis than N0/RHAMM+/TIL− patients (P=0.005). Loss of CD8+ TILs was predictive of local recurrence in RHAMM+ tumours (P=0.009) only. RHAMM and CD8+ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy

Effects of Marine Reserves versus Nursery Habitat Availability on Structure of Reef Fish Communities

No-take marine fishery reserves sustain commercial stocks by acting as buffers against overexploitation and enhancing fishery catches in adjacent areas through spillover. Likewise, nursery habitats such as mangroves enhance populations of some species in adjacent habitats. However, there is lack of understanding of the magnitude of stock enhancement and the effects on community structure when both protection from fishing and access to nurseries concurrently act as drivers of fish population dynamics. In this study we test the separate as well as interactive effects of marine reserves and nursery habitat proximity on structure and abundance of coral reef fish communities. Reserves had no effect on fish community composition, while proximity to nursery habitat only had a significant effect on community structure of species that use mangroves or seagrass beds as nurseries. In terms of reef fish biomass, proximity to nursery habitat by far outweighed (biomass 249% higher than that in areas with no nursery access) the effects of protection from fishing in reserves (biomass 21% lower than non-reserve areas) for small nursery fish (≤25 cm total length). For large-bodied individuals of nursery species (>25 cm total length), an additive effect was present for these two factors, although fish benefited more from fishing protection (203% higher biomass) than from proximity to nurseries (139% higher). The magnitude of elevated biomass for small fish on coral reefs due to proximity to nurseries was such that nursery habitats seem able to overrule the usually positive effects on fish biomass by reef reserves. As a result, conservation of nursery habitats gains importance and more consideration should be given to the ecological processes that occur along nursery-reef boundaries that connect neighboring ecosystems