Self-homodyne tomography of a twin-beam state

A self-homodyne detection scheme is proposed to perform two-mode tomography on a twin-beam state at the output of a nondegenerate optical parametric amplifier. This scheme has been devised to improve the matching between the local oscillator and the signal modes, which is the main limitation to the overall quantum efficiency in conventional homodyning. The feasibility of the measurement is analyzed on the basis of Monte-Carlo simulations, studying the effect of non-unit quantum efficiency on detection of the correlation and the total photon-number oscillations of the twin-beam state.Comment: 13 pages (two-column ReVTeX) including 21 postscript figures; to appear on Phys. Rev.

Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration

YesPolysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers.Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarshi

Systematic literature review of determinants of sedentary behaviour in older adults:a DEDIPAC study

BACKGROUND: Older adults are the most sedentary segment of society and high sedentary time is associated with poor health and wellbeing outcomes in this population. Identifying determinants of sedentary behaviour is a necessary step to develop interventions to reduce sedentary time. METHODS: A systematic literature review was conducted to identify factors associated with sedentary behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between 2000 and May 2014. The search strategy was based on four key elements: (a) sedentary behaviour and its synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of determinants (e.g. environmental, behavioural). Articles were included in the review if specific information about sedentary behaviour in older adults was reported. Studies on samples identified by disease were excluded. Study quality was rated by means of QUALSYST. The full review protocol is available from PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio-ecological model framework. RESULTS: Twenty-two original studies were identified out of 4472 returned by the systematic search. These included 19 cross-sectional, 2 longitudinal and 1 qualitative studies, all published after 2011. Half of the studies were European. The study quality was generally high with a median of 82 % (IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently investigated with consistent positive association for age, negative for retirement, obesity and health status. Only four studies considered environmental determinants suggesting possible association with mode of transport, type of housing, cultural opportunities and neighbourhood safety and availability of places to rest. Only two studies investigated mediating factors. Very limited information was available on contexts and sub-domains of sedentary behaviours. CONCLUSION: Few studies have investigated determinants of sedentary behaviour in older adults and these have to date mostly focussed on personal factors, and qualitative studies were mostly lacking. More longitudinal studies are needed as well as inclusion of a broader range of personal and contextual potential determinants towards a systems-based approach, and future studies should be more informed by qualitative work

Frustration in fuzzy protein complexes leads to interaction versatility

Disordered proteins frequently serve as interaction hubs involving a constrained variety of partners. Complexes with different partners frequently exhibit distinct binding modes, involving regions that remain disordered in the bound state. While the conformational properties of disordered proteins are well-characterized in their free states, less is known about the molecular mechanisms by which specificity can be achieved not with one but with multiple partners. Using the energy landscape theory concept of protein frustration, we demonstrate that complexes of disordered proteins exhibit a high degree of local frustration, especically at the binding interface. These suboptimal interactions lead to the possibility of multiple bound substates, each displaying distinct frustration patterns, which are differently populated in complexes with different partners. These results explain how specificity of disordered proteins can be achieved without a single common bound conformation and how the confliict between different interactions can be used to control the binding to multiple partners

A comprehensive fracture prevention strategy in older adults : The European union geriatric medicine society (EUGMS) statement

Published also in Aging Clinical and Experimental Research, Vol.28, No.4, WOS: 000379034800030Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. (C) 2016 Published by Elsevier Masson SAS.Peer reviewe

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes : Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.Peer reviewe

Student abstracts of selected articles

Vowel Nasality in Sudanese by Ron Trail, abstracted from Robins, R. H. 1957. Vowel Nasality in Sudanese, A Phonological and Grammatical Study. Studies in Linguistic Analysis, J.R. Firth ed. London: The Philological Society, 87-103. Style in Huichol by Nancy Freiberger, abstracted from Grimes, Joseph E. 1955. Style in Huichol Structure, Language 31.31-35. Trique Tone by Richard Bergman, abstracted from Longacre, Robert E. 1952. Five Phonemic Pitch Levels in Trique, Acta Linguistica 7.62-82. Tonme Representation in Mazatec Orthography by Ron Trail, abstracted from Gudschinsky, Sarah. 1959. Toneme Representation in Mazatec Orthography, Word, 15.446-52. Totonac Verb Inflection by Kenneth D. Smith, abstracted from Aschmann, Herman, and Wonderly, William L. 1952. Affixes and Implicit Categories in Totonac Verb Inflections, IJAL 18.130-45. Have as a Function Word by Jean Haggar, abstracted from Fries, Charles C. 1948. Have as a Function Word, Language Learning, 1.3,4-8. Bella Coola Phonology by Margie Griffin, abstracted from Newman, Stanley, 1947. Bella Coola I: Phonology, IJAL 13.129-34. Old High German Umlaut by Elwood Jacobson, abstracted from Twaddell, W. Freeman. 1938. A Note on Old High German Umlaut, Monatshefte für deutschen Unterricht, 30:177-81. Reprinted in Readings in Linguistics, edited by Martin Joos, 1958. Washington: American Council of Learned Societies, 85-87. The Phonemic Principle by Nancy Freiberger, abstracted from Swadesh, Morris, 1934. The Phonemic Principle, Language 10.117-29. Reprinted in Readings in Linguistics, edited by Martin Joos. 1958. Washington: American Council of Learned Societies, 1957, 32-37. Meaning and Dictionary Making by Nancy Freiberger, abstracted from Nida, Eugene A. 1958. Analysis of Meaning and Dictionary Making, IJAL 24.279-92. Mazateco Whistle Speech by Nancy Freiberger, abstracted from Cowan, George M. 1948. Mazateco Whistle Speech, Language 24.280-86. Voiceless Vowels in Comanche by Bob Beadle, abstracted from Canonge, Elliot D. 1957. Voiceless Vowels in Comanche, IJAL, 23.63-67. Noun Possession in Villa Alta Zapotec by Gwen Young, abstracted from Mary Leal and Otis Leal, 1954. Noun Possession in Villa Alta Zapotec, IJAL 20.215-216. Sound Patterns by Richard Bergman, abstracted from Sapir, Edward. 1925. Sound Patterns in Language. Language, 1.37-51

Chasing up and locking down the virus: Optimal pandemic interventions within a network

During the COVID-19 pandemic countries invested significant amounts of resources into its containment. In early stages of the pandemic most of the (nonpharmaceutical) interventions can be classified into two groups: (i) testing and identification of infected individuals, (ii) social distancing measures to reduce the transmission probabilities. Furthermore, both groups of measures may, in principle, be targeted at certain subgroups of a networked population. To study such a problem, we propose an extension of the SIR model with additional compartments for quarantine and different courses of the disease across several network nodes. We develop the structure of the optimal allocation and study a numerical example of three symmetric regions that are subject to an asymmetric progression of the disease (starting from an initial hotspot). Key findings include that (i) for our calibrations policies are chosen in a “flattening-the-curve,” avoiding hospital congestion; (ii) policies shift from containing spillovers from the hotspot initially to establishing a symmetric pattern of the disease; and (iii) testing that can be effectively targeted allows to reduce substantially the duration of the disease, hospital congestion and the total cost, both in terms of lives lost and economic costs

Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment

Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells

Photonic reservoir computing using a small network of micro-ring resonators

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