IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

‘Mutirão Agroflorestal’: herramienta de red de agroforestería del Vale do Paraíba, Brasil

Difundir los sistemas agroforestales (SAFs) en la cuenca del río Paraíba do Sul, Estado de São Paulo, Brasil, es el propósito de esfuerzo conjunto en Polo Regional/APTA, en Pindamonhangaba. Los SAFs se basan en consorcios de cultivos agrícolas, arbustos y árboles, aprovechando los mismos recursos (agua, luz y nutrientes). Entre los años 2010-2013, unas 330 personas de diversos orígenes participaron en esfuerzos conjuntos agroforestales. La metodología participativa incluye la planificación para la preparación y manejo de los SAFs, después de conciencia a través de conferencias y excursión. El método "mutirão agroforestal” promueve el intercambio de conocimiento, el rescate de los saberes populares y los recursos genéticos. El enfoque de SAFs en la restauración de las áreas ribereñas con producción diversificada amplificando la biodiversidad de la selva atlántica. La producción se basa en especies comestibles, entre ellos: Maranta arundinaceae, Colocasia esculenta, Pereskia sp., Talinum paniculatum, Xanthosoma sagittifolium, Manihot esculenta, plátano resistente - Musa sp.; de árboles nativo para madera (Calophyllum brasiliense e Centrolobium tomentosum), frutas (Euterpe edulis, Rolinia mucosa) y plantas fertilizantes (Cajanus cajan, Flemingia macrophylla, Tithonia diversifolia, Gliricidia sepium, Sesbania sp., Inga sp.). Se evalúan indicadores de sostenibilidad para balisar la gestión: resistencia a la penetración de una barra de hierro, tasa de cobertura del suelo por la proyección de la plantas de dosel, cantidad y calidad de vegetación espontánea, la presencia de organismos vivos en la capa superior del suelo, contenido de materia orgánica por la reacción del suelo con peróxido de hidrógeno, calidad de especies de anclaje y la cantidad de hojarasca del suelo. Como resultado, un grupo multidisciplinario ha sido articular la formación de Red de Agroforestería del Vale do Paraíba, de difundir los SAFs en la cuenca y los recursos genéticos de estas unidades pasan a los productores

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

Changes in biodiversity and trade-offs among ecosystem services, stakeholders, and components of well-being: the contribution of the International Long-Term Ecological Research network (ILTER) to Programme on Ecosystem Change and Society (PECS)

The International Long-Term Ecological Research (ILTER) network comprises > 600 scientific groups conducting site-based research within 40 countries. Its mission includes improving the understanding of global ecosystems and informs solutions to current and future environmental problems at the global scales. The ILTER network covers a wide range of social-ecological conditions and is aligned with the Programme on Ecosystem Change and Society (PECS) goals and approach. Our aim is to examine and develop the conceptual basis for proposed collaboration between ILTER and PECS. We describe how a coordinated effort of several contrasting LTER site-based research groups contributes to the understanding of how policies and technologies drive either toward or away from the sustainable delivery of ecosystem services. This effort is based on three tenets: transdisciplinary research; cross-scale interactions and subsequent dynamics; and an ecological stewardship orientation. The overarching goal is to design management practices taking into account trade-offs between using and conserving ecosystems toward more sustainable solutions. To that end, we propose a conceptual approach linking ecosystem integrity, ecosystem services, and stakeholder well-being, and as a way to analyze trade-offs among ecosystem services inherent in diverse management options. We also outline our methodological approach that includes: (i) monitoring and synthesis activities following spatial and temporal trends and changes on each site and by documenting cross-scale interactions; (ii) developing analytical tools for integration; (iii) promoting trans-site comparison; and (iv) developing conceptual tools to design adequate policies and management interventions to deal with trade-offs. Finally, we highlight the heterogeneity in the social-ecological setting encountered in a subset of 15 ILTER sites. These study cases are diverse enough to provide a broad cross-section of contrasting ecosystems with different policy and management drivers of ecosystem conversion; distinct trends of biodiversity change; different stakeholders’ preferences for ecosystem services; and diverse components of well-being issues

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis

BACKGROUND: The Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations. RESULTS: We found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays. CONCLUSIONS: The greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1928-z) contains supplementary material, which is available to authorized users

Measurements of the branching fractions of B+→ppK+ decays

The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts