Exploring constrained quantum control landscapes

The broad success of optimally controlling quantum systems with external fields has been attributed to the favorable topology of the underlying control landscape, where the landscape is the physical observable as a function of the controls. The control landscape can be shown to contain no suboptimal trapping extrema upon satisfaction of reasonable physical assumptions, but this topological analysis does not hold when significant constraints are placed on the control resources. This work employs simulations to explore the topology and features of the control landscape for pure-state population transfer with a constrained class of control fields. The fields are parameterized in terms of a set of uniformly spaced spectral frequencies, with the associated phases acting as the controls. Optimization results reveal that the minimum number of phase controls necessary to assure a high yield in the target state has a special dependence on the number of accessible energy levels in the quantum system, revealed from an analysis of the first- and second-order variation of the yield with respect to the controls. When an insufficient number of controls and/or a weak control fluence are employed, trapping extrema and saddle points are observed on the landscape. When the control resources are sufficiently flexible, solutions producing the globally maximal yield are found to form connected `level sets' of continuously variable control fields that preserve the yield. These optimal yield level sets are found to shrink to isolated points on the top of the landscape as the control field fluence is decreased, and further reduction of the fluence turns these points into suboptimal trapping extrema on the landscape. Although constrained control fields can come in many forms beyond the cases explored here, the behavior found in this paper is illustrative of the impacts that constraints can introduce.Comment: 10 figure

Search complexity and resource scaling for the quantum optimal control of unitary transformations

The optimal control of unitary transformations is a fundamental problem in quantum control theory and quantum information processing. The feasibility of performing such optimizations is determined by the computational and control resources required, particularly for systems with large Hilbert spaces. Prior work on unitary transformation control indicates that (i) for controllable systems, local extrema in the search landscape for optimal control of quantum gates have null measure, facilitating the convergence of local search algorithms; but (ii) the required time for convergence to optimal controls can scale exponentially with Hilbert space dimension. Depending on the control system Hamiltonian, the landscape structure and scaling may vary. This work introduces methods for quantifying Hamiltonian-dependent and kinematic effects on control optimization dynamics in order to classify quantum systems according to the search effort and control resources required to implement arbitrary unitary transformations

Exploring the trade-off between fidelity- and time-optimal control of quantum unitary transformations

Generating a unitary transformation in the shortest possible time is of practical importance to quantum information processing because it helps to reduce decoherence effects and improve robustness to additive control field noise. Many analytical and numerical studies have identified the minimum time necessary to implement a variety of quantum gates on coupled-spin qubit systems. This work focuses on exploring the Pareto front that quantifies the trade-off between the competitive objectives of maximizing the gate fidelity $\mathcal{F}$ and minimizing the control time $T$. In order to identify the critical time $T^{\ast}$, below which the target transformation is not reachable, as well as to determine the associated Pareto front, we introduce a numerical method of Pareto front tracking (PFT). We consider closed two- and multi-qubit systems with constant inter-qubit coupling strengths and each individual qubit controlled by a separate time-dependent external field. Our analysis demonstrates that unit fidelity (to a desired numerical accuracy) can be achieved at any $T \geq T^{\ast}$ in most cases. However, the optimization search effort rises superexponentially as $T$ decreases and approaches $T^{\ast}$. Furthermore, a small decrease in control time incurs a significant penalty in fidelity for $T < T^{\ast}$, indicating that it is generally undesirable to operate below the critical time. We investigate the dependence of the critical time $T^{\ast}$ on the coupling strength between qubits and the target gate transformation. Practical consequences of these findings for laboratory implementation of quantum gates are discussed.Comment: 23 pages, 11 figure

Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth

Determining the nanoflare heating frequency of an X-ray Bright Point observed by MaGIXS

Nanoflares are thought to be one of the prime candidates that can heat the solar corona to its multi-million kelvin temperature. Individual nanoflares are difficult to detect with the present generation instruments, however their presence can be inferred by comparing simulated nanoflare-heated plasma emissions with the observed emission. Using HYDRAD coronal loop simulations, we model the emission from an X-ray bright point (XBP) observed by the Marshall Grazing Incidence X-ray Spectrometer (MaGIXS), along with nearest-available observations from the Atmospheric Imaging Assembly (AIA) onboard Solar Dynamics Observatory (SDO) and X-Ray Telescope (XRT) onboard Hinode observatory. The length and magnetic field strength of the coronal loops are derived from the linear-force-free extrapolation of the observed photospheric magnetogram by Helioseismic and Magnetic Imager (HMI) onboard SDO. Each loop is assumed to be heated by random nanoflares, whose magnitude and frequency are determined by the loop length and magnetic field strength. The simulation results are then compared and matched against the measured intensity from AIA, XRT, and MaGIXS. Our model results indicate the observed emissions from the XBP under study could be well matched by a distribution of nanoflares with average delay times 1500 s to 3000 s, which suggest that the heating is dominated by high-frequency events. Further, we demonstrate the high sensitivity of MaGIXS and XRT to diagnose the heating frequency using this method, while AIA passbands are found to be the least sensitive.Comment: Accepted for publication in the Astrophysical Journal (ApJ

Designing stakeholder learning dialogues for effective global governance

A growing scholarship on multistakeholder learning dialogues suggests the importance of closely managing learning processes to help stakeholders anticipate which policies are likely to be effective. Much less work has focused on how to manage effective transnational multistakeholder learning dialogues, many of which aim to help address critical global environmental and social problems such as climate change or biodiversity loss. They face three central challenges. First, they rarely shape policies and behaviors directly, but work to ‘nudge’ or ‘tip the scales’ in domestic settings. Second, they run the risk of generating ‘compromise’ approaches incapable of ameliorating the original problem definition for which the dialogue was created. Third, they run the risk of being overly influenced, or captured, by powerful interests whose rationale for participating is to shift problem definitions or narrow instrument choices to those innocuous to their organizational or individual interests. Drawing on policy learning scholarship, we identify a six-stage learning process for anticipating effectiveness designed to minimize these risks while simultaneously fostering innovative approaches for meaningful and longlasting problem solving: Problem definition assessments; Problem framing; Developing coalition membership; Causal framework development; Scoping exercises; Knowledge institutionalization. We also identify six management techniques within each process for engaging transnational dialogues around problem solving. We show that doing so almost always requires anticipating multiple-step causal pathways through which influence of transnational and/or international actors and institutions might occur

Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer

BACKGROUND: Most women with a clinical presentation consistent with ovarian cancer have benign conditions. Therefore methods to distinguish women with ovarian cancer from those with benign conditions would be beneficial. We describe the development and preliminary evaluation of a serum-based multivariate assay for ovarian cancer. This hypothesis-driven study examined whether an informative pattern could be detected in stage I disease that persists through later stages. METHODOLOGY/PRINCIPAL FINDINGS: Sera, collected under uniform protocols from multiple institutions, representing 176 cases and 187 controls from women presenting for surgery were examined using high-throughput, multiplexed immunoassays. All stages and common subtypes of epithelial ovarian cancer, and the most common benign ovarian conditions were represented. A panel of 104 antigens, 44 autoimmune and 56 infectious disease markers were assayed and informative combinations identified. Using a training set of 91 stage I data sets, representing 61 individual samples, and an equivalent number of controls, an 11-analyte profile, composed of CA-125, CA 19-9, EGF-R, C-reactive protein, myoglobin, apolipoprotein A1, apolipoprotein CIII, MIP-1alpha, IL-6, IL-18 and tenascin C was identified and appears informative for all stages and common subtypes of ovarian cancer. Using a testing set of 245 samples, approximately twice the size of the model building set, the classifier had 91.3% sensitivity and 88.5% specificity. While these preliminary results are promising, further refinement and extensive validation of the classifier in a clinical trial is necessary to determine if the test has clinical value. CONCLUSIONS/SIGNIFICANCE: We describe a blood-based assay using 11 analytes that can distinguish women with ovarian cancer from those with benign conditions. Preliminary evaluation of the classifier suggests it has the potential to offer approximately 90% sensitivity and 90% specificity. While promising, the performance needs to be assessed in a blinded clinical validation study

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary