Quantum Separability and Entanglement Detection via Entanglement-Witness Search and Global Optimization

We focus on determining the separability of an unknown bipartite quantum state $\rho$ by invoking a sufficiently large subset of all possible entanglement witnesses given the expected value of each element of a set of mutually orthogonal observables. We review the concept of an entanglement witness from the geometrical point of view and use this geometry to show that the set of separable states is not a polytope and to characterize the class of entanglement witnesses (observables) that detect entangled states on opposite sides of the set of separable states. All this serves to motivate a classical algorithm which, given the expected values of a subset of an orthogonal basis of observables of an otherwise unknown quantum state, searches for an entanglement witness in the span of the subset of observables. The idea of such an algorithm, which is an efficient reduction of the quantum separability problem to a global optimization problem, was introduced in PRA 70 060303(R), where it was shown to be an improvement on the naive approach for the quantum separability problem (exhaustive search for a decomposition of the given state into a convex combination of separable states). The last section of the paper discusses in more generality such algorithms, which, in our case, assume a subroutine that computes the global maximum of a real function of several variables. Despite this, we anticipate that such algorithms will perform sufficiently well on small instances that they will render a feasible test for separability in some cases of interest (e.g. in 3-by-3 dimensional systems)

Characterization of Adherent Bacteroidales from Intestinal Biopsies of Children and Young Adults with Inflammatory Bowel Disease

There is extensive evidence implicating the intestinal microbiota in inflammatory bowel disease [IBD], but no microbial agent has been identified as a sole causative agent. Bacteroidales are numerically dominant intestinal organisms that associate with the mucosal surface and have properties that both positively and negatively affect the host. To determine precise numbers and species of Bacteroidales adherent to the mucosal surface in IBD patients, we performed a comprehensive culture based analysis of intestinal biopsies from pediatric Crohn's disease [CD], ulcerative colitis [UC], and control subjects. We obtained biopsies from 94 patients and used multiplex PCR or 16S rDNA sequencing of Bacteroidales isolates for species identification. Eighteen different Bacteroidales species were identified in the study group, with up to ten different species per biopsy, a number higher than demonstrated using 16S rRNA gene sequencing methods. Species diversity was decreased in IBD compared to controls and with increasingly inflamed tissue. There were significant differences in predominant Bacteroidales species between biopsies from the three groups and from inflamed and uninflamed sites. Parabacteroides distasonis significantly decreased in inflamed tissue. All 373 Bacteroidales isolates collected in this study grew with mucin as the only utilizable carbon source suggesting this is a non-pathogenic feature of this bacterial order. Bacteroides fragilis isolates with the enterotoxin gene [bft], previously associated with flares of colitis, were not found more often at inflamed colonic sites or within IBD subjects. B. fragilis isolates with the ability to synthesize the immunomodulatory polysaccharide A [PSA], previously shown to be protective in murine models of colitis, were not detected more often from healthy versus inflamed tissue

Assessing the relationship between human well-being and ecosystem services: a review of frameworks

Focusing on the most impoverished populations, we critically review and synthesise key themes from dominant frameworks for assessing the relationship between well-being and ecosystem services in developing countries. This requires a differentiated approach to conceptualising well-being that appropriately reflects the perspectives of the poorest-those most directly dependent on ecosystem services, and their vulnerability to external and policy-driven environmental change. The frameworks analysed draw upon environmental sciences, economics, psychology, sociology, and anthropology, and were selected on the basis of their demonstrated or potential ability to illustrate the relationship between environmental change and human well-being, as well as their prevalence in real world applications. Thus, the synthesis offered here is informed by the various theoretical, methodological, and hermeneutical contributions from each field to the notion of well-being. The review highlights several key dimensions that should be considered by those interested in understanding and assessing the impact of environmental change on the well-being of the world's poorest people: the importance of interdisciplinary consideration of well-being, the need for frameworks that integrate subjective and objective aspects of well-being, and the central importance of context and relational aspects of well-being. The review is of particular interest to those engaged in the post-2015 development agenda

Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity

N-Acyl indolines 4 are potent, non-covalent Notum inhibitors developed from a covalent virtual screening hit 2a. The lead compounds were simple to synthesise, achieved excellent potency in a biochemical Notum-OPTS assay and restored Wnt signalling in a cell-based TCF/LEF reporter assay. Multiple high resolution X-ray structures established a common binding mode of these inhibitors with the indoline bound centred in the palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent Notum inhibitors and so illustrates a complementary approach for hit generation and target inhibition

Updating Maryland\u27s Sea-level Rise Projections

With its 3,100 miles of tidal shoreline and low-lying rural and urban lands, The Free State is one of the most vulnerable to sea-level rise. Historically, Marylanders have long had to contend with rising water levels along its Chesapeake Bay and Atlantic Ocean and coastal bay shores. Shorelines eroded and low-relief lands and islands, some previously inhabited, were inundated. Prior to the 20th century, this was largely due to the slow sinking of the land since Earth’s crust is still adjusting to the melting of large masses of ice following the last glacial period. Over the 20th century, however, the rate of rise of the average level of tidal waters with respect to land, or relative sea-level rise, has increased, at least partially as a result of global warming. Moreover, the scientific evidence is compelling that Earth’s climate will continue to warm and its oceans will rise even more rapidly. Recognizing the scientific consensus around global climate change, the contribution of human activities to it, and the vulnerability of Maryland’s people, property, public investments, and natural resources, Governor Martin O’Malley established the Maryland Commission on Climate Change on April 20, 2007. The Commission produced a Plan of Action1 that included a comprehensive climate change impact assessment, a greenhouse gas reduction strategy, and strategies for reducing Maryland’s vulnerability to climate change. The Plan has led to landmark legislation to reduce the state’s greenhouse gas emissions and a variety of state policies designed to reduce energy consumption and promote adaptation to climate change

Structural Analysis and Development of Notum Fragment Screening Hits

The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer's disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallographic fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the analysis of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to >1000 μM. Analysis of the fragments' diverse binding modes, enzymatic inhibitory activities, and chemical properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1-phenyl-1,2,3-triazole 7, and its related cluster members, have shown promising lead-like properties. These became the focus of our fragment development activities, resulting in compound 7d with IC50 0.0067 μM. The large number of Notum fragment structures and their initial optimization provided an important basis for further Notum inhibitor development

Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit

Notum is a carboxylesterase that suppresses Wnt signaling through deacylation of an essential palmitoleate group on Wnt proteins. There is a growing understanding of the role Notum plays in human diseases such as colorectal cancer and Alzheimer's disease, supporting the need to discover improved inhibitors, especially for use in models of neurodegeneration. Here, we have described the discovery and profile of 8l (ARUK3001185) as a potent, selective, and brain-penetrant inhibitor of Notum activity suitable for oral dosing in rodent models of disease. Crystallographic fragment screening of the Diamond-SGC Poised Library for binding to Notum, supported by a biochemical enzyme assay to rank inhibition activity, identified 6a and 6b as a pair of outstanding hits. Fragment development of 6 delivered 8l that restored Wnt signaling in the presence of Notum in a cell-based reporter assay. Assessment in pharmacology screens showed 8l to be selective against serine hydrolases, kinases, and drug targets

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured