pinecone/core-2020-05-10-deduplication huggingface dataset:
C13orf31 (FAMIN) is a central regulator of immunometabolic function

Single-nucleotide variations in $\small \textit{C13orf31 (LACC1)}$ that encode p.C284R and p.I254V in a protein of unknown function (called ‘FAMIN’ here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn’s disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.Supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement 260961, the Wellcome Trust (investigator award 106260/Z/14/Z; a PhD fellowship for clinicians; and a Career Re-Entry Fellowship), the Wellcome Trust Sanger Institute, the US National Institutes of Health (5U420D011174 and 5U54HG006348), the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre, the European Crohn’s and Colitis Organisation and the Swedish Medical Research Council and the Olle Engkvist foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ni.353
Comparative genomics of Neisseria meningitidis strains: new targets for molecular diagnostics.

In 2010, Jaton et al. (False-negative PCR result due to gene polymorphism: the example of Neisseria meningitidis. J Clin Microbiol 2010;48:4590-2) reported an isolate of Neisseria meningitidis serogroup B that was not detected by the ctrA quantitative real-time PCR (qRT-PCR) used in our diagnostic laboratory. Sequence analysis of ctrA revealed several single nucleotide polymorphisms responsible for the negative qRT-PCR. Therefore, we sequenced the genome of this isolate and performed comparative genomics to propose new gene targets for the specific detection of N. meningitidis from clinical specimens. We identified 11 genes as specific to N. meningitidis genomes and common to at least 177 (97%) of the 183 genomes available. Among them, three genes (metA, tauE and shlA) were selected to develop new qRT-PCRs for the detection of N. meningitidis DNA. The three qRT-PCRs were highly sensitive and specific, and they exhibited a good reproducibility when tested on plasmidic positive controls and genomic DNA extracted from strains of N. meningitidis and other relevant bacterial species. The clinical sensitivity and specificity of metA and tauE qRT-PCRs were both 100% based on a testing of cerebrospinal fluid samples positive for N. meningitidis or other clinically relevant bacteria. Despite a 100% specificity, the sensitivity of the shlA qRT-PCR was only 70%. We thus recommend using the metA and/or tauE qRT-PCRs developed here. To prevent PCR failure in the presence of new polymorphic strains, the detection of dual targets by duplex qRT-PCR would be more accurate and suitable for the diagnosis of N. meningitidis from clinical specimens
Postmating-prezygotic isolation between two allopatric populations of Drosophila montana: fertilisation success differs under sperm competition

Postmating but prezygotic (PMPZ) interactions are increasingly recognized as a potentially important early-stage barrier in the evolution of reproductive isolation. A recent study described a potential example between populations of the same species: single matings between Drosophila montana populations resulted in differential fertilisation success because of the inability of sperm from one population (Vancouver) to penetrate the eggs of the other population (Colorado). As the natural mating system of D. montana is polyandrous (females remate rapidly), we set up double matings of all possible crosses between the same populations to test whether competitive effects between ejaculates influence this PMPZ isolation. We measured premating isolation in no-choice tests, female fecundity, fertility and egg-to-adult viability after single and double matings as well as second-male paternity success (P-2). Surprisingly, we found no PMPZ reproductive isolation between the two populations under a competitive setting, indicating no difficulty of sperm from Vancouver males to fertilize Colorado eggs after double matings. While there were subtle differences in how P-2 changed over time, suggesting that Vancouver males' sperm are somewhat less competitive in a first-male role within Colorado females, these effects did not translate into differences in overall P-2. Fertilisation success can thus differ dramatically between competitive and noncompetitive conditions, perhaps because the males that mate second produce higher quality ejaculates in response to sperm competition. We suggest that unlike in more divergent species comparisons, where sperm competition typically increases reproductive isolation, ejaculate tailoring can reduce the potential for PMPZ isolation when recently diverged populations interbreed
Resurgence in η-deformed Principal Chiral Models.

We study the SU(2) Principal Chiral Model (PCM) in the presence of an integrable η-deformation. We put the theory on  R×S1R×S1  with twisted boundary conditions and then reduce the circle to obtain an effective quantum mechanics associated with the Whittaker-Hill equation. Using resurgent analysis we study the large order behaviour of perturbation theory and recover the fracton events responsible for IR renormalons. The fractons are modified from the standard PCM due to the presence of this η-deformation but they are still the constituents of uniton-like solutions in the deformed quantum field theory. We also find novel  SL(2,C)SL(2,C) saddles, thus strengthening the conjecture that the semi-classical expansion of the path integral gives rise to a resurgent transseries once written as a sum over Lefschetz thimbles living in a complexification of the field space. We conclude by connecting our quantum mechanics to a massive deformation of the  NN  = 2 4-d gauge theory with gauge group SU(2) and Nf = 2
Modifying the osteoblastic niche with zoledronic acid in vivo - potential implications for breast cancer bone metastasis

INTRODUCTION: Bone metastasis is the most common complication of advanced breast cancer. The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid. Clinical trials have shown that zoledronic acid also reduces breast cancer recurrence in bone; potentially by modifying the bone microenvironment surrounding disseminated tumour cells. We have characterised the early effects of zoledronic acid on key cell types of the metastatic niche in vivo, and investigated how these modify the location of breast tumour cells homing to bone. METHODS: Female mice were treated with a single, clinically achievable dose of zoledronic acid (100μg/kg) or PBS. Bone integrity, osteoclast and osteoblast activity and number/mm trabecular bone on 1, 3, 5 and 10days after treatment were assessed using μCT, ELISA (TRAP, PINP) and bone histomorphometry, respectively. The effect of zoledronic acid on osteoblasts was validated in genetically engineered mice with GFP-positive osteoblastic cells. The effects on growth plate cartilage were visualised by toluidine blue staining. For tumour studies, mice were injected i.c. with DID-labelled MDA-MB-231-NW1-luc2 breast cancer cells 5days after zoledronic acid treatment, followed by assessment of tumour cell homing to bone and soft tissues by multiphoton microscopy, flow cytometry and ex vivo cultures. RESULTS: As early as 3days after treatment, animals receiving zoledronic acid had significantly increased trabecular bone volume vs. control. This rapid bone effect was reflected in a significant reduction in osteoclast and osteoblast number/mm trabecular bone and reduced bone marker serum levels (day 3-5). These results were confirmed in mice expressing GFP in osteoblastic linage cells. Pre-treatment with zoledronic acid caused accumulation of an extra-cellular matrix in the growth plate associated with a trend towards preferential [1] homing of tumour cells to osteoblast-rich areas of bone, but without affecting the total number of tumour cells. The number of circulating tumour cells was reduced in ZOL treated animals. CONCLUSION: A single dose of zoledronic acid caused significant changes in the bone area suggested to contain the metastatic niche. Tumour cells arriving in this modified bone microenvironment appeared to preferentially locate to osteoblast-rich areas, supporting that osteoblasts may be key components of the bone metastasis niche and therefore a potential therapeutic target in breast cancer.Marie-Therese Haider, Ingunn Holen, T. Neil Dear, Keith Hunter, Hannah K. Brow
Learning International Literary Connections as a Means of Promoting Tolerance: Specificity of the Early Stage of F. M. Dostoevsky's Work Reception in Great Britain

The paper describes a new approach to learning and teaching foreign language communication stressing the significance of promoting tolerance in the learners. It suggests including history of the writer's work reception in the course programme of EFL students. To illustrate the approach, the article analyses the key tendencies of Dostoevsky's early reception in the United Kingdom, explains the significance of “The Russian Novel” by French diplomat and critic E. M. de Vogue as one of the important factors determining the Russian writer's work interpretation, considers H. Vizetelly and F. Whishaw's contribution to introduction of the first English translations to the British readers. The paper summarises the reviews of Dostoevsky's works placed in the British literary periodicals. It also describes the impact of Anglo-French rapprochement on the literary and cultural interchanges and Dostoevsky's reception in particular
Herschel PACS far-IR spectral imaging of a jet from an intermediate mass protostar in the OMC-2 region

We present the first detection of a jet in the far-IR [O I] lines from an intermediate mass protostar. This jet was detected in a Herschel/PACS spectral mapping study in the [O I] lines of OMC-2 FIR 3 and FIR 4, two of the most luminous protostars in Orion outside of the Orion Nebula. The spatial morphology of the fine structure line emission reveals the presence of an extended photodissociation region (PDR) and a narrow, but intense jet connecting the two protostars. The jet seen in [O I] emission is spatially aligned with the Spitzer/IRAC 4.5 μm jet and the CO (6-5) molecular outflow centered on FIR 3. The mass-loss rate derived from the total [O I] 63 μm line luminosity of the jet is 7.7 × 10Myr, more than an order of magnitude higher than that measured for typical low-mass class 0 protostars. The implied accretion luminosity is significantly higher than the observed bolometric luminosity of FIR 4, indicating that the [O I] jet is unlikely to be associated with FIR 4. We argue that the peak line emission seen toward FIR 4 originates in the terminal shock produced by the jet driven by FIR 3. The higher mass-loss rate that we find for FIR 3 is consistent with the idea that intermediate-mass protostars drive more powerful jets than their low-mass counterparts. Our results also call into question the nature of FIR 4. © ESO, 2016.M.O. and A.K.D.R. acknowledge support from MINECO (Spain) AYA2011-3O228-CO3-01 and AYA2014-57369-C3-3-P grants (co-funded with FEDER funds).Peer Reviewe
Wishart ratios with dependent structure : new members of the bimatrix beta type IV

In multivariate statistics under normality, the problems of interest are random covariance matrices
(known as Wishart matrices) and "ratios" of Wishart matrices that arise in multivariate analysis of
variance (MANOVA). The bimatrix variate beta type IV distribution (also known in the
literature as bimatrix variate generalised beta; matrix variate generalization of a bivariate beta type I)
arises from "ratios" of Wishart matrices. In this paper, we add a further independent Wishart random
variate to the "denominator" of one of the ratios; this results in deriving the exact expression for the
density function of the bimatrix variate extended beta type IV distribution. The latter leads to the
proposal of the bimatrix variate extended F distribution. Some interesting characteristics of these newly
introduced bimatrix distributions are explored. Lastly, we focus on the bivariate variate extended beta
type IV distribution (that is an extension of bivariate Jones’ beta).Andriëtte Bekker is grateful to the National Research Foundation, South Africa
for support through the grant (Unlocking the future: FA2007043000003).http://www.elsevier.com/locate/la
An adjustment cost model of social mobility

We analyze herein the effects of the human capital adjustment cost on social mobility.
Such an adjustment cost is modeled as a rising marginal cost schedule for augmenting
human capital. We use a general human capital technology, which disentangles the
adjustment cost from the depreciation cost of the human capital. Missing credit markets
prevent individuals from equalizing the initial differences in the human capital. We find
that a higher adjustment cost for human capital acquisition slows down the social mobility
and results in a persistent inequality across generations. On the other hand, a higher rate of
human capital depreciation could increase mobility via a positive effect on new investment.
The quantitative analysis of our model suggests that the human capital adjustment
cost is nontrivial to account for the observed persistence of inequality and social mobility.
In addition, we find that the government redistribution policy could account for the large
observed variation in estimates of social mobility.http://www.elsevier.com/locate/jmacro2016-06-30hb201
Common but different : the expanding realm of Cladosporium

The genus Cladosporium (Cladosporiaceae, Dothideomycetes), which represents one of the largest genera of dematiaceous hyphomycetes, has been
intensively investigated during the past decade. In the process, three major species complexes (C. cladosporioides, C. herbarum and C. sphaerospermum) were resolved
based on morphology and DNA phylogeny, and a monographic revision of the genus (s. lat.) published reflecting the current taxonomic status quo. In the present study a
further 19 new species are described based on phylogenetic characters (nuclear ribosomal RNA gene operon, including the internal transcribed spacer regions ITS1 and
ITS2, as well as partial actin and translation elongation factor 1-α gene sequences) and morphological differences. For a selection of the species with ornamented
conidia, scanning electron microscopic photos were prepared to illustrate the different types of surface ornamentation. Surprisingly, during this study Cladosporium
ramotenellum was found to be a quite common saprobic species, being widely distributed and occurring on various substrates. Therefore, an emended species
description is provided. Furthermore, the host range and distribution data for several previously described species are also expanded.http://www.studiesinmycology.orgam2016Forestry and Agricultural Biotechnology Institute (FABI
On lower bounds for the L2-discrepancy

AbstractThe L2-discrepancy measures the irregularity of the distribution of a finite point set. In this note, we prove lower bounds for the L2-discrepancy of arbitrary N-point sets. Our main focus is on the two-dimensional case. Asymptotic upper and lower estimates of the L2-discrepancy in dimension 2 are well known, and are of the sharp order logN. Nevertheless, the gap in the constants between the best-known lower and upper bounds is unsatisfactorily large for a two-dimensional problem. Our lower bound improves upon this situation considerably. The main method is an adaption of Roth’s method, using the Fourier coefficients of the discrepancy function with respect to the Haar basis. We obtain the same improvement in the quotient of lower and upper bounds in the general d-dimensional case. Our lower bounds are also valid for the weighted discrepancy
On the algebraic approximation of Lusternik–Schnirelmann category

AbstractAlgebraic approximations have proved to be very useful in the investigation of Lusternik–Schnirelmann category. In this paper the L.-S. category and its approximations are studied from the point of view of abstract homotopy theory. We introduce three notions of L.-S. category for monoidal cofibration categories, i.e., cofibration categories with a suitably incorporated tensor product. We study the fundamental properties of the abstract invariants and discuss, in particular, their behaviour with respect to cone attachments and products. Besides the topological L.-S. category the abstract concepts cover classical algebraic approximations of the L.-S. category such as the Toomer invariant, rational category, and the A- and M-categories of Halperin and Lemaire. We also use the abstract theory to introduce a new algebraic approximation of L.-S. category. This invariant which we denote by ℓ is the first algebraic approximation of the L.-S. category which is not necessarily ⩽1 for spaces having the same Adams–Hilton model as a wedge of spheres. For a space X the number ℓ(X) can be determined from an Anick model of X. Thanks to the general theory one knows a priori that ℓ is a lower bound of the L.-S. category which satisfies the usual product inequality and increases by at most 1 when a cone is attached to a space
Non-linear tearing of 3D null point current sheets.

The manner in which the rate of magnetic reconnection scales with the Lundquist number in realistic three-dimensional (3D) geometries is still an unsolved problem. It has been demonstrated that in 2D rapid non-linear tearing allows the reconnection rate to become almost independent of the Lundquist number (the “plasmoid instability”). Here, we present the first study of an analogous instability in a fully 3D geometry, defined by a magnetic null point. The 3D null current layer is found to be susceptible to an analogous instability but is marginally more stable than an equivalent 2D Sweet-Parker-like layer. Tearing of the sheet creates a thin boundary layer around the separatrix surface, contained within a flux envelope with a hyperbolic structure that mimics a spine-fan topology. Efficient mixing of flux between the two topological domains occurs as the flux rope structures created during the tearing process evolve within this envelope. This leads to a substantial increase in the rate of reconnection between the two domains
On the Fučik spectrum of the wave operator and an asymptotically linear problem

AbstractWe study generalized solutions of the nonlinear wave equationutt−uss=au+−bu−+p(s,t,u), with periodic conditions in t and homogeneous Dirichlet conditions in s, under the assumption that the ratio of the period to the length of the interval is two. When p≡0 and λ is a nonzero eigenvalue of the wave operator, we give a proof of the existence of two families of curves (which may coincide) in the Fučik spectrum intersecting at (λ,λ). This result is known for some classes of self-adjoint operators (which does not cover the situation we consider here), but in a smaller region than ours. Our approach is based on a dual variational formulation and is also applicable to other operators, such as the Laplacian. In addition, we prove an existence result for the non-homogeneous situation, when the pair (a,b) is not ‘between’ the Fučik curves passing through (λ,λ)≠(0,0) and p is a continuous function, sublinear at infinity
Open–closed strings: Two-dimensional extended TQFTs and Frobenius algebras

AbstractWe study a special sort of 2-dimensional extended Topological Quantum Field Theories (TQFTs). These are defined on open–closed cobordisms by which we mean smooth compact oriented 2-manifolds with corners that have a particular global structure in order to model the smooth topology of open and closed string worldsheets. We show that the category of open–closed TQFTs is equivalent to the category of knowledgeable Frobenius algebras. A knowledgeable Frobenius algebra (A,C,ı,ı*) consists of a symmetric Frobenius algebra A, a commutative Frobenius algebra C, and an algebra homomorphism ı:C→A with dual ı*:A→C, subject to some conditions. This result is achieved by providing a description of the category of open–closed cobordisms in terms of generators and the well-known Moore–Segal relations. In order to prove the sufficiency of our relations, we provide a normal form for such cobordisms which is characterized by topological invariants. Starting from an arbitrary such cobordism, we construct a sequence of moves (generalized handle slides and handle cancellations) which transforms the given cobordism into the normal form. Using the generators and relations description of the category of open–closed cobordisms, we show that it is equivalent to the symmetric monoidal category freely generated by a knowledgeable Frobenius algebra. Our formalism is then generalized to the context of open–closed cobordisms with labeled free boundary components, i.e. to open–closed string worldsheets with D-brane labels at their free boundaries
Ultradispersed Electro-explosive Iron Powders as Catalysts for Synthesis of Liquid Hydrocarbons of CO and H2

AbstractCatalytic activity of ultradispersed iron powders (UDIP) obtained by electric explosion of the conductor in media of nitrogen, carbon monoxide, and carbon dioxide in synthesis of liquid hydrocarbons by Fischer-Tropsch method was studied. It was shown that iron powder obtained in media of CO2 has the highest specific surface area. A sample of powder was pelletized at pressure of 21MPa during 30seconds with use of 10 mass% polyvinyl alcohol as adhesive for experimentation in catalytic system. Catalyst fraction of 1-2mm was selected for study. The experiments were carried out under conditions of 1MPa, 300 mln/min of total reactants consumption, and varied values of temperature and reactants ratio. The maximal conversion level of CO was reached at 290°С and reactants ratio of H2:CO = 2 in the initial mixture. It was shown that UDIP has high activity at lowered concentration of hydrogen in the initial mixture. The obtained mixture of liquid hydrocarbons is applicable for further refining for upgrading and improving of operating features