Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

Mammals express the sialic acids ​N-acetylneuraminic acid (​Neu5Ac) and ​N-glycolylneuraminic acid (​Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). ​Neu5Gc is synthesized from ​Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only ​Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize ​Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of ​Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains

Commuting self-adjoint extensions of symmetric operators defined from the partial derivatives

We consider the problem of finding commuting self-adjoint extensions of the partial derivatives {(1/i)(\partial/\partial x_j):j=1,...,d} with domain C_c^\infty(\Omega) where the self-adjointness is defined relative to L^2(\Omega), and \Omega is a given open subset of R^d. The measure on \Omega is Lebesgue measure on R^d restricted to \Omega. The problem originates with I.E. Segal and B. Fuglede, and is difficult in general. In this paper, we provide a representation-theoretic answer in the special case when \Omega=I\times\Omega_2 and I is an open interval. We then apply the results to the case when \Omega is a d-cube, I^d, and we describe possible subsets \Lambda of R^d such that {e^(i2\pi\lambda \dot x) restricted to I^d:\lambda\in\Lambda} is an orthonormal basis in L^2(I^d).Comment: LaTeX2e amsart class, 18 pages, 2 figures; PACS numbers 02.20.Km, 02.30.Nw, 02.30.Tb, 02.60.-x, 03.65.-w, 03.65.Bz, 03.65.Db, 61.12.Bt, 61.44.B

Motivations for innovation in the built environment: new directions for research

Innovation in the built environment involves multiple actors with diverse motivations. Policy-makers find it difficult to promote changes that require cooperation from these numerous and dispersed actors and to align their sometimes divergent interests. Established research traditions on the economics and management of innovation pay only limited attention to stakeholder choices, engagement and motivation. This paper reviews the insights that emerge as research in these traditions comes into contact with work on innovation from sociological and political perspectives. It contributes by highlighting growing areas of research on user involvement in complex innovation, collective action, distributed innovation and transition management. To differing extents, these provide approaches to incorporate the motivations of different actors into theoretical understanding. These indicate new directions for research that promise to enrich understanding of innovation

(Never) Mind your p's and q's: Von Neumann versus Jordan on the Foundations of Quantum Theory

In two papers entitled "On a new foundation [Neue Begr\"undung] of quantum mechanics," Pascual Jordan (1927b,g) presented his version of what came to be known as the Dirac-Jordan statistical transformation theory. As an alternative that avoids the mathematical difficulties facing the approach of Jordan and Paul A. M. Dirac (1927), John von Neumann (1927a) developed the modern Hilbert space formalism of quantum mechanics. In this paper, we focus on Jordan and von Neumann. Central to the formalisms of both are expressions for conditional probabilities of finding some value for one quantity given the value of another. Beyond that Jordan and von Neumann had very different views about the appropriate formulation of problems in quantum mechanics. For Jordan, unable to let go of the analogy to classical mechanics, the solution of such problems required the identication of sets of canonically conjugate variables, i.e., p's and q's. For von Neumann, not constrained by the analogy to classical mechanics, it required only the identication of a maximal set of commuting operators with simultaneous eigenstates. He had no need for p's and q's. Jordan and von Neumann also stated the characteristic new rules for probabilities in quantum mechanics somewhat differently. Jordan (1927b) was the first to state those rules in full generality. Von Neumann (1927a) rephrased them and, in a subsequent paper (von Neumann, 1927b), sought to derive them from more basic considerations. In this paper we reconstruct the central arguments of these 1927 papers by Jordan and von Neumann and of a paper on Jordan's approach by Hilbert, von Neumann, and Nordheim (1928). We highlight those elements in these papers that bring out the gradual loosening of the ties between the new quantum formalism and classical mechanics.Comment: New version. The main difference with the old version is that the introduction has been rewritten. Sec. 1 (pp. 2-12) in the old version has been replaced by Secs. 1.1-1.4 (pp. 2-31) in the new version. The paper has been accepted for publication in European Physical Journal

Restrictions and extensions of semibounded operators

We study restriction and extension theory for semibounded Hermitian operators in the Hardy space of analytic functions on the disk D. Starting with the operator zd/dz, we show that, for every choice of a closed subset F in T=bd(D) of measure zero, there is a densely defined Hermitian restriction of zd/dz corresponding to boundary functions vanishing on F. For every such restriction operator, we classify all its selfadjoint extension, and for each we present a complete spectral picture. We prove that different sets F with the same cardinality can lead to quite different boundary-value problems, inequivalent selfadjoint extension operators, and quite different spectral configurations. As a tool in our analysis, we prove that the von Neumann deficiency spaces, for a fixed set F, have a natural presentation as reproducing kernel Hilbert spaces, with a Hurwitz zeta-function, restricted to FxF, as reproducing kernel.Comment: 63 pages, 11 figure

Biological Activity of CXCL8 Forms Generated by Alternative Cleavage of the Signal Peptide or by Aminopeptidase-Mediated Truncation

Posttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH(2)-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others.status: publishe

SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines

BACKGROUND: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. METHODOLOGY/PRINCIPAL FINDINGS: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. CONCLUSIONS/SIGNIFICANCE: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium

Unmanned aircraft systems as a new source of disturbance for wildlife: A systematic review.

The use of small Unmanned Aircraft Systems (UAS; also known as "drones") for professional and personal-leisure use is increasing enormously. UAS operate at low altitudes (<500 m) and in any terrain, thus they are susceptible to interact with local fauna, generating a new type of anthropogenic disturbance that has not been systematically evaluated. To address this gap, we performed a review of the existent literature about animals' responses to UAS flights and conducted a pooled analysis of the data to determine the probability and intensity of the disturbance, and to identify the factors influencing animals' reactions towards the small aircraft. We found that wildlife reactions depended on both the UAS attributes (flight pattern, engine type and size of aircraft) and the characteristics of animals themselves (type of animal, life-history stage and level of aggregation). Target-oriented flight patterns, larger UAS sizes, and fuel-powered (noisier) engines evoked the strongest reactions in wildlife. Animals during the non-breeding period and in large groups were more likely to show behavioral reactions to UAS, and birds are more prone to react than other taxa. We discuss the implications of these results in the context of wildlife disturbance and suggest guidelines for conservationists, users and manufacturers to minimize the impact of UAS. In addition, we propose that the legal framework needs to be adapted so that appropriate actions can be undertaken when wildlife is negatively affected by these emergent practices