Designing probiotic therapies with broad-spectrum activity against a wildlife pathogen

Host-associated microbes form an important component of immunity that protect against infection by pathogens. Treating wild individuals with these protective microbes, known as probiotics, can reduce rates of infection and disease in both wild and captive settings. However, the utility of probiotics for tackling wildlife disease requires that they offer consistent protection across the broad genomic variation of the pathogen that hosts can encounter in natural settings. Here we develop multi-isolate probiotic consortia with the aim of effecting broad-spectrum inhibition of growth of the lethal amphibian pathogen Batrachochytrium dendrobatidis (Bd) when tested against nine Bd isolates from two distinct lineages. Though we achieved strong growth inhibition between 70 and 100% for seven Bd isolates, two isolates appeared consistently resistant to inhibition, irrespective of probiotic strategy employed. We found no evidence that genomic relatedness of the chytrid predicted similarity of inhibition scores, nor that increasing the genetic diversity of the bacterial consortia could offer stronger inhibition of pathogen growth, even for the two resistant isolates. Our findings have important consequences for the application of probiotics to mitigate wildlife diseases in the face of extensive pathogen genomic variation

Static internal performance of ventral and rear nozzle concepts for short-takeoff and vertical-landing aircraft

The internal performance of two exhaust system concepts applicable to single-engine short-take-off and vertical-landing tactical fighter configurations was investigated. These concepts involved blocking (or partially blocking) tailpipe flow to the rear (cruise) nozzle and diverting it through an opening to a ventral nozzle exit for vertical thrust. A set of variable angle vanes at the ventral nozzle exit were used to vary ventral nozzle thrust angle between 45 and 110 deg relative to the positive axial force direction. In the vertical flight mode the rear nozzle (or tailpipe flow to it) was completely blocked. In the transition flight mode flow in the tailpipe was split between the rear and ventral nozzles and the flow was vectored at both exits for aircraft control purposes through this flight regime. In the cruise flight mode the ventral nozzle was sealed and all flow exited through the rear nozzle

Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects

The profoundly elevated concentrations of low-density lipoproteins (LDL) present in homozygous familial hypercholesterolemia lead to symptomatic cardiovascular disease and death by early adulthood. Studies conducted in nonhepatic tissues demonstrated defective cellular recognition and metabolism of LDL in these patients. Since mammalian liver removes at least half of the LDL in the circulation, the metabolism of LDL by cultured hepatocytes isolated from familial hypercholesterolemic homozygotes was compared to hepatcytes from normal individuals. Fibroblast studies demonstrated that the familial hypercholesterolemic subjects studied were LDL receptor-negative (less than 1% normal receptor activity) and LDL receptor-de fective (18% normal receptor activity). Cholesterol-depleted hepatocytes from normal subjects bound and internalized 125I-labeled LDL (Bmax = 2.2 μg LDL/mg cell protein). Preincubation of normal hepatocytes with 200 μg/ml LDL reduced binding and internalization by approx. 40%. In contrast, 125I-labeled LDL binding and internalization by receptor-negative familial hypercholesterolemic hepatocytes was unaffected by cholesterol loading and considerably lower than normal. This residual LDL uptake could not be ascribed to fluid phase endocytosis as determined by [14C]sucrose uptake. The residual LDL binding by familial hypercholesterolemia hepatocytes led to a small increase in hepatocyte cholesterol content which was relatively ineffective in reducing hepatocyte 3-hydroxy-3-methylglutaryl-CoA reductase activity. Receptordefective familial hypercholesterolemia hepatocytes retained some degree of regulatable 125I-labeled LDL uptake, but LDL uptake did not lead to normal hepatocyte cholesterol content or 3-hydroxy-3-methylglutaryl-CoA reductase activity. These combined results indicate that the LDL receptor abnormality present in familial hypercholesterolemia fibroblasts reflects deranged hepatocyte LDL recognition and metabolism. In addition, a low-affinity, nonsaturable uptake process for LDL is present in human liver which does not efficiently modulate hepatocyte cholesterol content or synthesis. © 1986

The a-number of hyperelliptic curves

It is known that for a smooth hyperelliptic curve to have a large $a$-number, the genus must be small relative to the characteristic of the field, $p>0$, over which the curve is defined. It was proven by Elkin that for a genus $g$ hyperelliptic curve $C$ to have $a_C=g-1$, the genus is bounded by $g<\frac{3p}{2}$. In this paper, we show that this bound can be lowered to $g <p$. The method of proof is to force the Cartier-Manin matrix to have rank one and examine what restrictions that places on the affine equation defining the hyperelliptic curve. We then use this bound to summarize what is known about the existence of such curves when $p=3,5$ and $7$.Comment: 7 pages. v2: revised and improved the proof of the main theorem based on suggestions from the referee. To appear in the proceedings volume of Women in Numbers Europe-

Radio Spectra and NVSS Maps of Decametric Sources

We constructed radio spectra for ~1400 UTR-2 sources and find that 46% of them have concave curvature. Inspection of NVSS maps of 700 UTR sources suggests that half of all UTR sources are either blends of two or more sources or have an ultra-steep spectrum (USS). The fraction of compact USS sources in UTR may be near 10%. Using NVSS and the Digitized Sky Survey(s) we expect to double the UTR optical identification rate from currently ~19%.Comment: 2 pages, no figures; to appear in Proc. "Observational Cosmology with the New Radio Surveys", eds. M. Bremer, N. Jackson & I. Perez-Fournon, Kluwer Acad. Pres

A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS):study protocol for a randomised controlled trial

BACKGROUND Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010-2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women. METHODS/DESIGN We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter. DISCUSSION If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women. TRIAL REGISTRATION Current Controlled trials: ISRCTN06039270. Registered 16th January 2014

BKM Lie superalgebra for the Z_5 orbifolded CHL string

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

Co-constructing a new framework for evaluating social innovation in marginalized rural areas

The EU funded H2020 project \u2018Social Innovation in Marginalised Rural Areas\u2019 (SIMRA; www.simra-h2020.eu) has the overall objective of advancing the state-of-the-art in social innovation. This paper outlines the process for co- developing an evaluation framework with stakeholders, drawn from across Europe and the Mediterranean area, in the fields of agriculture, forestry and rural development. Preliminary results show the importance of integrating process and outcome-oriented evaluations, and implementing participatory approaches in evaluation practice. They also raise critical issues related to the comparability of primary data in diverse regional contexts and highlight the need for mixed methods approaches in evaluation

Space-efficient Feature Maps for String Alignment Kernels

String kernels are attractive data analysis tools for analyzing string data. Among them, alignment kernels are known for their high prediction accuracies in string classifications when tested in combination with SVM in various applications. However, alignment kernels have a crucial drawback in that they scale poorly due to their quadratic computation complexity in the number of input strings, which limits large-scale applications in practice. We address this need by presenting the first approximation for string alignment kernels, which we call space-efficient feature maps for edit distance with moves (SFMEDM), by leveraging a metric embedding named edit sensitive parsing (ESP) and feature maps (FMs) of random Fourier features (RFFs) for large-scale string analyses. The original FMs for RFFs consume a huge amount of memory proportional to the dimension d of input vectors and the dimension D of output vectors, which prohibits its large-scale applications. We present novel space-efficient feature maps (SFMs) of RFFs for a space reduction from O(dD) of the original FMs to O(d) of SFMs with a theoretical guarantee with respect to concentration bounds. We experimentally test SFMEDM on its ability to learn SVM for large-scale string classifications with various massive string data, and we demonstrate the superior performance of SFMEDM with respect to prediction accuracy, scalability and computation efficiency.Comment: Full version for ICDM'19 pape