4,625 research outputs found

    BKM Lie superalgebra for the Z_5 orbifolded CHL string

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    We study the Z_5-orbifolding of the CHL string theory by explicitly constructing the modular form tilde{Phi}_2 generating the degeneracies of the 1/4-BPS states in the theory. Since the additive seed for the sum form is a weak Jacobi form in this case, a mismatch is found between the modular forms generated from the additive lift and the product form derived from threshold corrections. We also construct the BKM Lie superalgebra, tilde{G}_5, corresponding to the modular form tilde{Delta}_1 (Z) = tilde{Phi}_2 (Z)^{1/2} which happens to be a hyperbolic algebra. This is the first occurrence of a hyperbolic BKM Lie superalgebra. We also study the walls of marginal stability of this theory in detail, and extend the arithmetic structure found by Cheng and Dabholkar for the N=1,2,3 orbifoldings to the N=4,5 and 6 models, all of which have an infinite number of walls in the fundamental domain. We find that analogous to the Stern-Brocot tree, which generated the intercepts of the walls on the real line, the intercepts for the N >3 cases are generated by linear recurrence relations. Using the correspondence between the walls of marginal stability and the walls of the Weyl chamber of the corresponding BKM Lie superalgebra, we propose the Cartan matrices for the BKM Lie superalgebras corresponding to the N=5 and 6 models.Comment: 30 pages, 2 figure

    Missense Mutation R338W in ARHGEF9 in a Family with X-linked Intellectual Disability with Variable Macrocephaly and Macro-Orchidism

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    Non-syndromal X-linked intellectual disability (NS-XLID) represents a broad group of clinical disorders in which ID is the only clinically consistent manifestation. Although in many cases either chromosomal linkage data or knowledge of the >100 existing XLID genes has assisted mutation discovery, the underlying cause of disease remains unresolved in many families. We report the resolution of a large family (K8010) with NS-XLID, with variable macrocephaly and macro-orchidism. Although a previous linkage study had mapped the locus to Xq12-q21, this region contained too many candidate genes to be analyzed using conventional approaches. However, X-chromosome exome sequencing, bioinformatics analysis and segregation analysis revealed a novel missense mutation (c.1012C>T; p.R338W) in ARHGEF9. This gene encodes collybistin (CB), a neuronal GDP-GTP exchange factor previously implicated in several cases of XLID, as well as clustering of gephyrin and GABAA receptors at inhibitory synapses. Molecular modeling of the CB R338W substitution revealed that this change results in the substitution of a long electropositive side-chain with a large non-charged hydrophobic side-chain. The R338W change is predicted to result in clashes with adjacent amino acids (K363 and N335) and disruption of electrostatic potential and local folding of the PH domain, which is known to bind phosphatidylinositol-3-phosphate (PI3P/PtdIns-3-P). Consistent with this finding, functional assays revealed that recombinant CB CB2SH3- (R338W) was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Taken together, these results suggest that the R338W mutation in ARHGEF9 is the underlying cause of NS-XLID in this family

    Understanding the threats posed by non-native species: public vs. conservation managers.

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    Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone

    A rapid co-culture stamping device for studying intercellular communication.

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    Regulation of tissue development and repair depends on communication between neighbouring cells. Recent advances in cell micro-contact printing and microfluidics have facilitated the in-vitro study of homotypic and heterotypic cell-cell interaction. Nonetheless, these techniques are still complicated to perform and as a result, are seldom used by biologists. We report here development of a temporarily sealed microfluidic stamping device which utilizes a novel valve design for patterning two adherent cell lines with well-defined interlacing configurations to study cell-cell interactions. We demonstrate post-stamping cell viability of >95%, the stamping of multiple adherent cell types, and the ability to control the seeded cell density. We also show viability, proliferation and migration of cultured cells, enabling analysis of co-culture boundary conditions on cell fate. We also developed an in-vitro model of endothelial and cardiac stem cell interactions, which are thought to regulate coronary repair after myocardial injury. The stamp is fabricated using microfabrication techniques, is operated with a lab pipettor and uses very low reagent volumes of 20 μl with cell injection efficiency of >70%. This easy-to-use device provides a general strategy for micro-patterning of multiple cell types and will be important for studying cell-cell interactions in a multitude of applications

    BPS black holes, the Hesse potential, and the topological string

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    The Hesse potential is constructed for a class of four-dimensional N=2 supersymmetric effective actions with S- and T-duality by performing the relevant Legendre transform by iteration. It is a function of fields that transform under duality according to an arithmetic subgroup of the classical dualities reflecting the monodromies of the underlying string compactification. These transformations are not subject to corrections, unlike the transformations of the fields that appear in the effective action which are affected by the presence of higher-derivative couplings. The class of actions that are considered includes those of the FHSV and the STU model. We also consider heterotic N=4 supersymmetric compactifications. The Hesse potential, which is equal to the free energy function for BPS black holes, is manifestly duality invariant. Generically it can be expanded in terms of powers of the modulus that represents the inverse topological string coupling constant, gsg_s, and its complex conjugate. The terms depending holomorphically on gsg_s are expected to correspond to the topological string partition function and this expectation is explicitly verified in two cases. Terms proportional to mixed powers of gsg_s and gˉs\bar g_s are in principle present.Comment: 28 pages, LaTeX, added comment

    A systematic review of models to predict recruitment to multicentre clinical trials

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    <p>Abstract</p> <p>Background</p> <p>Less than one third of publicly funded trials managed to recruit according to their original plan often resulting in request for additional funding and/or time extensions. The aim was to identify models which might be useful to a major public funder of randomised controlled trials when estimating likely time requirements for recruiting trial participants. The requirements of a useful model were identified as usability, based on experience, able to reflect time trends, accounting for centre recruitment and contribution to a commissioning decision.</p> <p>Methods</p> <p>A systematic review of English language articles using MEDLINE and EMBASE. Search terms included: randomised controlled trial, patient, accrual, predict, enrol, models, statistical; Bayes Theorem; Decision Theory; Monte Carlo Method and Poisson. Only studies discussing prediction of recruitment to trials using a modelling approach were included. Information was extracted from articles by one author, and checked by a second, using a pre-defined form.</p> <p>Results</p> <p>Out of 326 identified abstracts, only 8 met all the inclusion criteria. Of these 8 studies examined, there are five major classes of model discussed: the unconditional model, the conditional model, the Poisson model, Bayesian models and Monte Carlo simulation of Markov models. None of these meet all the pre-identified needs of the funder.</p> <p>Conclusions</p> <p>To meet the needs of a number of research programmes, a new model is required as a matter of importance. Any model chosen should be validated against both retrospective and prospective data, to ensure the predictions it gives are superior to those currently used.</p

    Crossings, Motzkin paths and Moments

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    Kasraoui, Stanton and Zeng, and Kim, Stanton and Zeng introduced certain qq-analogues of Laguerre and Charlier polynomials. The moments of these orthogonal polynomials have combinatorial models in terms of crossings in permutations and set partitions. The aim of this article is to prove simple formulas for the moments of the qq-Laguerre and the qq-Charlier polynomials, in the style of the Touchard-Riordan formula (which gives the moments of some qq-Hermite polynomials, and also the distribution of crossings in matchings). Our method mainly consists in the enumeration of weighted Motzkin paths, which are naturally associated with the moments. Some steps are bijective, in particular we describe a decomposition of paths which generalises a previous construction of Penaud for the case of the Touchard-Riordan formula. There are also some non-bijective steps using basic hypergeometric series, and continued fractions or, alternatively, functional equations.Comment: 21 page

    Clinical Performance of an Automated Reader in Interpreting Malaria Rapid Diagnostic Tests in Tanzania.

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    Parasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization (WHO) to reduce inappropriate use of anti-malarial drugs. Widespread implementation of rapid diagnostic tests (RDTs) is regarded as an effective strategy to achieve this goal. However, the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal. Feasible RDT quality control programmes in these settings are challenging. Collection of information regarding diagnostic events is also very deficient in low-resource countries. A prospective cohort of consecutive patients aged more than one year from both genders, seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania, were enrolled into the study after signing an informed consent form. Blood samples were taken for thick blood smear (TBS) microscopic examination and malaria RDT (SD Bioline Malaria Antigen Pf/PanTM (SD RDT)). RDT results were interpreted by both visual interpretation and DekiReaderTM device. Results of visual interpretation were used for case management purposes. Microscopy was considered the "gold standard test" to assess the sensitivity and specificity of the DekiReader interpretation and to compare it to visual interpretation. In total, 1,346 febrile subjects were included in the final analysis. The SD RDT, when used in conjunction with the DekiReader and upon visual interpretation, had sensitivities of 95.3% (95% CI, 90.6-97.7) and 94.7% (95% CI, 89.8--97.3) respectively, and specificities of 94.6% (95% CI, 93.5--96.1) and 95.6% (95% CI, 94.2--96.6), respectively to gold standard. There was a high percentage of overall agreement between the two methods of interpretation. The sensitivity and specificity of the DekiReader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation (>98%). The results of the study reflect the situation in real practice and show good performance characteristics of DekiReader on interpreting malaria RDTs in the hands of local laboratory technicians. They also suggest that a system like this could provide great benefits to the health care system. Further studies to look at ease of use by community health workers, and cost benefit of the system are warranted

    Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

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    Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification
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