Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy.

The article The hidden therapist: evidence for a central role of music in psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris, was originally published electronically on the publisher's internet portal

M-CSF instructs myeloid lineage fate in single haematopoietic stem cells

Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors, but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors, leaving cytokines to ensure survival and proliferation of the progeny cells. Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified HSCs with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1(+) cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs and induced a PU.1-dependent myeloid differentiation preference. Our data demonstrate that lineage-specific cytokines can act directly on HSCs in vitro and in vivo to instruct a change of cell identity. This fundamentally changes the current view of how HSCs respond to environmental challenge and implicates stress-induced cytokines as direct instructors of HSC fate

High-quality permanent draft genome sequence of Rhizobium sullae strain WSM1592; a Hedysarum coronarium microsymbiont from Sassari, Italy

Rhizobium sullae strain WSM1592 is an aerobic, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen (N2) fixing root nodule formed on the short-lived perennial legume Hedysarum coronarium (also known as Sulla coronaria or Sulla). WSM1592 was isolated from a nodule recovered from H. coronarium roots located in Ottava, bordering Sassari, Sardinia in 1995. WSM1592 is highly effective at fixing nitrogen with H. coronarium, and is currently the commercial Sulla inoculant strain in Australia. Here we describe the features of R. sullae strain WSM1592, together with genome sequence information and its annotation. The 7,530,820 bp high-quality permanent draft genome is arranged into 118 scaffolds of 118 contigs containing 7.453 protein-coding genes and 73 RNA-only encoding genes. This rhizobial genome is sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

hEGR1 is induced by EGF, inhibited by gefitinib in bladder cell lines and related to EGF receptor levels in bladder tumours

The effect of EGF and gefitinib on two EGFR-positive human bladder cancer cell lines has been investigated using array-based gene expression profiling. The most prominent transcript, increased up to 6.7-fold by EGF compared with controls in RT112 cells, was human early growth response protein 1 (hEGR1). This induction was prevented by gefitinib. The hEGR1 mRNA in EGF-treated samples was reduced in the presence of gefitinib, as was hEGR1 protein in cell lysates. In the RT4 cells, hEGR1 expression was halved in the presence of EGF and gefitinib in combination. In bladder tumour samples, there was a significant correlation between hEGR1 mRNA detected by RT-PCR and EGFR detected by ligand binding, (P=0.042). The induction by EGF of the hEGR1 gene, mRNA and protein in RT112 cells, and its inhibition by gefitinib, together with the detection of hEGR1 mRNA in bladder tumours, suggests that hEGR1 may be important in the EGFR growth-signalling pathway in bladder cancer and should be further investigated for its prognostic significance and as a potential therapeutic target

Quasi-Elastic Scattering in the Inclusive (3^3He, t) Reaction

The triton energy spectra of the charge-exchange $^{12}$C($^3$He,t) reaction at 2 GeV beam energy are analyzed in the quasi-elastic nucleon knock-out region. Considering that this region is mainly populated by the charge-exchange of a proton in $^3$He with a neutron in the target nucleus and the final proton going in the continuum, the cross-sections are written in the distorted-wave impulse approximation. The t-matrix for the elementary exchange process is constructed in the DWBA, using one pion- plus rho-exchange potential for the spin-isospin nucleon- nucleon potential. This t-matrix reproduces the experimental data on the elementary pn $\rightarrow$np process. The calculated cross-sections for the $^{12}$C($^3$He,t) reaction at $2^o$ to $7^o$ triton emission angle are compared with the corresponding experimental data, and are found in reasonable overall accord.Comment: 19 pages, latex, 11 postscript figures available at [email protected], submitted to Phy.Rev.

A Finite Representation of the Narrowing Space

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-14125-1_4Narrowing basically extends rewriting by allowing free variables in terms and by replacing matching with unification. As a consequence, the search space of narrowing becomes usually infinite, as in logic programming. In this paper, we introduce the use of some operators that allow one to always produce a finite data structure that still represents all the narrowing derivations. Furthermore, we extract from this data structure a novel, compact equational representation of the (possibly infinite) answers computed by narrowing for a given initial term. Both the finite data structure and the equational representation of the computed answers might be useful in a number of areas, like program comprehension, static analysis, program transformation, etc.Nishida, N.; Vidal, G. (2013). A Finite Representation of the Narrowing Space. En Logic-Based Program Synthesis and Transformation. Springer. 54-71. doi:10.1007/978-3-319-14125-1_4S5471Albert, E., Vidal, G.: The Narrowing-Driven Approach to Functional Logic Program Specialization. New Generation Computing 20(1), 3–26 (2002)Alpuente, M., Falaschi, M., Vidal, G.: Partial Evaluation of Functional Logic Programs. ACM Transactions on Programming Languages and Systems 20(4), 768–844 (1998)Alpuente, M., Falaschi, M., Vidal, G.: Compositional Analysis for Equational Horn Programs. In: Rodríguez-Artalejo, M., Levi, G. (eds.) ALP 1994. LNCS, vol. 850, pp. 77–94. Springer, Heidelberg (1994)Antoy, S., Ariola, Z.: Narrowing the Narrowing Space. In: Hartel, P.H., Kuchen, H. (eds.) PLILP 1997. LNCS, vol. 1292, pp. 1–15. Springer, Heidelberg (1997)Arts, T., Giesl, J.: Termination of term rewriting using dependency pairs. Theoretical Computer Science 236(1–2), 133–178 (2000)Arts, T., Zantema, H.: Termination of Logic Programs Using Semantic Unification. In: Proietti, M. (ed.) LOPSTR 1995. LNCS, vol. 1048, pp. 219–233. Springer, Heidelberg (1996)Baader, F., Nipkow, T.: Term Rewriting and All That. Cambridge University Press (1998)Bae, K., Escobar, S., Meseguer, J.: Abstract Logical Model Checking of Infinite-State Systems Using Narrowing. In: Proceedings of the 24th International Conference on Rewriting Techniques and Applications. LIPIcs, vol. 21, pp. 81–96. Schloss Dagstuhl - Leibniz-Zentrum für Informatik (2013)De Schreye, D., Glück, R., Jørgensen, J., Leuschel, M., Martens, B., Sørensen, M.: Conjunctive partial deduction: foundations, control, algorihtms, and experiments. Journal of Logic Programming 41(2&3), 231–277 (1999)Escobar, S., Meadows, C., Meseguer, J.: A rewriting-based inference system for the NRL Protocol Analyzer and its meta-logical properties. Theoretical Computer Science 367(1–2), 162–202 (2006)Escobar, S., Meseguer, J.: Symbolic Model Checking of Infinite-State Systems Using Narrowing. In: Baader, F. (ed.) RTA 2007. LNCS, vol. 4533, pp. 153–168. Springer, Heidelberg (2007)Fribourg, L.: SLOG: A Logic Programming Language Interpreter Based on Clausal Superposition and Rewriting. In: Proceedings of the Symposium on Logic Programming, pp. 172–185. IEEE Press (1985)Gnaedig, I., Kirchner, H.: Proving weak properties of rewriting. Theoretical Computer Science 412(34), 4405–4438 (2011)Hanus, M.: The integration of functions into logic programming: From theory to practice. Journal of Logic Programming 19&20, 583–628 (1994)Hanus, M. (ed.): Curry: An integrated functional logic language (vers. 0.8.3) (2012). http://www.curry-language.orgHermenegildo, M., Rossi, F.: On the Correctness and Efficiency of Independent And-Parallelism in Logic Programs. In: Lusk, E., Overbeck, R. (eds.) Proceedings of the 1989 North American Conf. on Logic Programming, pp. 369–389. The MIT Press, Cambridge (1989)Hölldobler, S. (ed.): Foundations of Equational Logic Programming. LNCS, vol. 353. Springer, Heidelberg (1989)Meseguer, J., Thati, P.: Symbolic Reachability Analysis Using Narrowing and its Application to Verification of Cryptographic Protocols. Electronic Notes in Theoretical Computer Science 117, 153–182 (2005)Middeldorp, A., Okui, S.: A Deterministic Lazy Narrowing Calculus. Journal of Symbolic Computation 25(6), 733–757 (1998)Nishida, N., Sakai, M., Sakabe, T.: Generation of Inverse Computation Programs of Constructor Term Rewriting Systems. IEICE Transactions on Information and Systems J88–D–I(8), 1171–1183 (2005) (in Japanese)Nishida, N., Sakai, M., Sakabe, T.: Partial Inversion of Constructor Term Rewriting Systems. In: Giesl, J. (ed.) RTA 2005. LNCS, vol. 3467, pp. 264–278. Springer, Heidelberg (2005)Nishida, N., Vidal, G.: Program inversion for tail recursive functions. In: Schmidt-Schauß, M. (ed.) Proceedings of the 22nd International Conference on Rewriting Techniques and Applications. LIPIcs, vol. 10, pp. 283–298. Schloss Dagstuhl - Leibniz-Zentrum für Informatik (2011)Nishida, N., Vidal, G.: Computing More Specific Versions of Conditional Rewriting Systems. In: Albert, E. (ed.) LOPSTR 2012. LNCS, vol. 7844, pp. 137–154. Springer, Heidelberg (2013)Nutt, W., Réty, P., Smolka, G.: Basic Narrowing Revisited. Journal of Symbolic Computation 7(3/4), 295–317 (1989)Ohlebusch, E.: Advanced Topics in Term Rewriting. Springer, London, UK (2002)Palamidessi, C.: Algebraic Properties of Idempotent Substitutions. In: Paterson, M. (ed.) ICALP 1990. LNCS, vol. 443, pp. 386–399. Springer, Heidelberg (1990)Ramos, J.G., Silva, J., Vidal, G.: Fast Narrowing-Driven Partial Evaluation for Inductively Sequential Systems. In: Danvy, O., Pierce, B.C. (eds.) Proceedings of the 10th ACM SIGPLAN International Conference on Functional Programming, pp. 228–239. ACM Press (2005)Slagle, J.R.: Automated theorem-proving for theories with simplifiers, commutativity and associativity. Journal of the ACM 21(4), 622–642 (1974

Human rights, Public health and Medicinal cannabis use

This paper explores the interplay between the human rights and drug control frameworks and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medici-nal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the State and the individual within the drug policy field. The leading medicinal cannabis case in the UK highlights the judiciary’s failure to engage with an individual’s human right to health as they adopt an arbitrary, externalist view, focussing on the legality of cannabis to the exclusion of other concerns. Drawing on some international comparisons, the paper considers how a human rights perspective can lead to an approach to medicinal cannabis use which facilitates a holistic understanding of public health

Three dimensional (3D) microstructure-based modeling of interfacial decohesion in particle reinforced metal matrix composites

Modeling and prediction of the overall elastic–plastic response and local damage mechanisms in heterogeneous materials, in particular particle reinforced composites, is a very complex problem. Microstructural complexities such as the inhomogeneous spatial distribution of particles, irregular morphology of the particles, and anisotropy in particle orientation after secondary processing, such as extrusion, significantly affect deformation behavior. We have studied the effect of particle/matrix interface debonding in SiC particle reinforced Al alloy matrix composites with (a) actual microstructure consisting of angular SiC particles and (b) idealized ellipsoidal SiC particles. Tensile deformation in SiC particle reinforced Al matrix composites was modeled using actual microstructures reconstructed from serial sectioning approach. Interfacial debonding was modeled using user-defined cohesive zone elements. Modeling with the actual microstructure (versus idealized ellipsoids) has a significant influence on: (a) localized stresses and strains in particle and matrix, and (b) far-field strain at which localized debonding takes place. The angular particles exhibited higher degree of load transfer and are more sensitive to interfacial debonding. Larger decreases in stress are observed in the angular particles, because of the flat surfaces, normal to the loading axis, which bear load. Furthermore, simplification of particle morphology may lead to erroneous results