Metatranscriptomic Sequencing of a Cyanobacterial Soil-Surface Consortium with and without a Diverse Underlying Soil Microbiome.

Soil surface consortia are easily observed and sampled, allowing examination of their interactions with soil microbiomes. Here, we present metatranscriptomic sequences from Dark Green 1 (DG1), a cyanobacterium-based soil surface consortium, in the presence and absence of an underlying soil microbiome and/or urea

Forecasting the cytokine storm following systemic interleukin (IL)-2 administration

Extensive clinical experience has shown that systemic interleukin (IL)-2 administration can induce complete or partial regression of renal cell cancer (RCC) metastases in 15 to 20 % of patients. Since IL-2 has no direct anti-cancer effects, it is believed that cancer regression is mediated either by a direct modulation of immune cell effector functions or through the mediation of soluble factors released as a result of IL-2 administration. We previously observed that transcriptional and protein changes induced by systemic IL-2 administration affect predominantly mononuclear phagocytes with little effect, particularly within the tumor microenvironment, on T cell activation, localization and proliferation. It further appeared that mononuclear phagocyte activation could be best explained by the indirect mediation of a secondary release of cytokines by IL-2 responsive cells either in the circulation or in peripheral tissues. To better characterize the cytokine outburst that follows systemic IL-2 administration we followed the serum levels of 68 soluble factors in ten patients with RCC undergoing high dose (720,000 IU/kg intravenously every 8 hours) IL-2 therapy. Serum was collected before therapy, 3 hours after the 1(st )and 4(th )dose and assayed on a multiplexed protein array platform. This study demonstrated that 1) the serum concentration of more than half the soluble factors studied changed significantly during therapy; 2) changes became more dramatic with increasing doses; 3) subclasses of soluble factors displayed different kinetics and 4) cytokine patterns varied quantitatively among patients. This study shows that the cytokine storm that follows systemic IL-2 administration is complex and far-reaching inclusive of soluble factors with disparate, partly redundant and partly contrasting effects on immune function. Therefore comparing in parallel large number of soluble factors, it sets a comprehensive foundation for further elucidation of "cytokine storm" in larger patient pools. Based on this analysis, we propose a prospective collection of serum samples in a larger cohort of patients undergoing IL-2 administration with the purpose of discerning patterns predictive of clinical outcome and toxicity

Comparing the MRI Appearance of the Lymph Nodes and Spleen in Wild-Type and Immuno-Deficient Mouse Strains

The goal of this study was to investigate the normal MRI appearance of lymphoid organs in immuno-competent and immuno-deficient mice commonly used in research. Four mice from each of four different mouse strains (nude, NOG, C57BL/6, CB-17 SCID (SCID)) were imaged weekly for one month. Images were acquired with a 3D balanced steady state free precession (bSSFP) sequence. The volume of the lymph nodes and spleens were measured from MR images. In images of nude and SCID mice, lymph nodes sometimes contained a hyperintense region visible on MRI images. Volumes of the nodes were highly variable in nude mice. Nodes in SCID mice were smaller than in nude or C57Bl/6 mice (p<0.0001). Lymph node volumes changed slightly over time in all strains. The spleens of C57Bl/6 and nude mice were similar in size and appearance. Spleens of SCID and NOG mice were significantly smaller (p<0.0001) and abnormal in appearance. The MRI appearance of the normal lymph nodes and spleen varies considerably in the various mouse strains examined in this study. This is important to recognize in order to avoid the misinterpretation of MRI findings as abnormal when these strains are used in MRI imaging studies

Asymptomatic Carotid Stenosis Is Associated With Circadian and Other Variability in Embolus Detection

Background and Purpose: Variability in transcranial Doppler (TCD) detection of embolic signals (ES) is important for risk stratification. We tested the effect of time of day on ES associated with 60–99% asymptomatic carotid stenosis.Materials and Methods: Subjects were from the Asymptomatic Carotid Stenosis Embolus Detection (ASED) Study such that half were previously ES-positive and half ES-negative with 6-monthly 60-min TCD monitoring. All underwent bilateral TCD monitoring for two 12-h sessions separated by 24 h. ES detection rates were calculated using 6 and 4-h intervals from midnight and effective TCD monitoring time.Results: Ten subjects (8 male, mean age 79.5 years) were monitored. Over 24 h, 5/10 study arteries with 60–99% asymptomatic carotid stenosis were ES-positive (range 1–28 ES/artery, 56 total ES from 177.9 total effective monitoring hours). The remaining five study arteries and all eight successfully monitored contralateral arteries were ES-negative. Using 6-h intervals the mean ES detection rate peaked at 0600-midday (0.64/h) and was lowest 1800-midnight (0.09/h) with an incidence rate ratio of 7.26 (95% CI 2.52–28.64, P ≤ 0.001). Using 4-h intervals the mean ES detection rate peaked at 0800-midday (0.64/h) and was lowest midnight-0400 (0.12/h) with an incidence rate ratio of 5.51 (95% CI 1.78–22.67, P = 0.001).Conclusions: Embolism associated with asymptomatic carotid stenosis shows circadian variation with highest rates 4–6 h before midday. This corresponds with peak circadian incidence of stroke and other vascular complications. These and ASED Study results show that monitoring frequency, duration, and time of day are important in ES detection

Mechanized Metatheory for the Masses: The \u3cb\u3ePOPLMARK\u3c/b\u3e Challenge

How close are we to a world where every paper on programming languages is accompanied by an electronic appendix with machinechecked proofs? We propose an initial set of benchmarks for measuring progress in this area. Based on the metatheory of System F, a typed lambda-calculus with second-order polymorphism, subtyping, and records, these benchmarks embody many aspects of programming languages that are challenging to formalize: variable binding at both the term and type levels, syntactic forms with variable numbers of components (including binders), and proofs demanding complex induction principles. We hope that these benchmarks will help clarify the current state of the art, provide a basis for comparing competing technologies, and motivate further research

Reviews

Charles Williams: The Third Inkling. Grevel Lindop. Reviewed by Scott McLaren. The Chapel of the Thorn: A Dramatic Poem. Charles Williams. Edited and Introduced by Sørina Higgins. Reviewed by Scott McLaren. Women and C.S. Lewis: What His Life and Literature Reveal For Today’s Culture. Carolyn Curtis and Mary Pomroy Key, eds. Reviewed by Rebekah Choat. Tolkien Among the Moderns. Edited by Ralph C. Wood. Reviewed by Andrew C. Stout. Tolkien. Raymond Edwards. Reviewed by Cait Coker. Children into Swans: Fairy Tales and the Pagan Imagination. Jan Beveridge. Reviewed by Brian Roberts. Trilby/The Crumb Fairy. Charles Nodier. Translated and adapted by Ruth Berman. Reviewed by Kelly Orazi. The Prince of the Aquamarines. Louise Cavalier Levesque. Trans. and with an afterword by Ruth Berman. Reviewed by Kelly Orazi. The Lessons of Nature in Mythology. Rachel S. McCoppin. Reviewed by Kristine Larsen. Hither Shore: Jahrbuch der Deutschen Tolkien Gesellschaft. Special issue: Nature and Landscape in Tolkien. Ed. Thomas Fornet-Ponse et al. Reviewed by Janet Brennan Croft. Seven: An Anglo-American Literary Review. Ed. Marjorie Lamp Mead. Reviewed by Janet Brennan Croft. Tolkien Studies: An Annual Scholarly Review. Ed. Michael D.C. Drout, Verlyn Flieger, and David Bratman. Reviewed by Janet Brennan Croft. The Skill of a Seeker: Rowling, Religion and Gen 9/11. Marilyn R. Pukkila. Reviewed by Emily Moniz Mirova. Light: C.S. Lewis\u27s First and Final Short Story. Charlie W. Starr. Reviewed by Melody Green. The Story of Kullervo. J.R.R. Tolkien. Edited and introduced by Verlyn Flieger. Reviewed by Mike Foster. The Victorian Approach to Modernism in the Fiction of Dorothy L. Sayers. Aoife Leahy. Reviewed by Joe R. Christopher. Reading Joss Whedon. Rhonda V. Wilcox, Tanya R. Cochran, Cynthea Masson, and David Lavery, eds. Reviewed by by Janet Brennan Croft

IXPE Mission System Concept and Development Status

The Goal of the Imaging X-Ray Polarimetry Explorer (IXPE) Mi SMEX), is to expand understanding of high-energy astrophysical processes and sources, in support of NASAs first science objective in Astrophysics: Discover how the universe works. IXPE, an international collaboration, will conduct X-ray imaging polarimetry for multiple categories of cosmic X-ray sources such as neutron stars, stellar-mass black holes, supernova remnants and active galactic nuclei. The Observatory uses a single science operational mode capturing the X-ray data from the targets. The IXPE Observatory consists of spacecraft and payload modules built up in parallel to form the Observatory during system integration and test. The payload includes three X-ray telescopes each consisting of a polarization-sensitive, gas pixel X-ray detector, paired with its corresponding grazing incidence mirror module assembly (MMA). A deployable boom provides the correct separation (focal length) between the detector units (DU) and MMAs. These payload elements are supported by the IXPE spacecraft which is derived from the BCP-small spacecraft architecture. This paper summarizes the IXPE mission science objectives, updates the Observatory implementation concept including the payload and spacecraft ts and summarizes the mission status since last years conference

Barriers and incentives to orphan care in a time of AIDS and economic crisis: a cross-sectional survey of caregivers in rural Zimbabwe

BACKGROUND: Africa is in an orphan-care crisis. In Zimbabwe, where one-fourth of adults are HIV-positive and one-fifth of children are orphans, AIDS and economic decline are straining society's ability to care for orphans within their extended families. Lack of stable care is putting thousands of children at heightened risk of malnourishment, emotional underdevelopment, illiteracy, poverty, sexual exploitation, and HIV infection, endangering the future health of the society they are expected to sustain. METHODS: To explore barriers and possible incentives to orphan care, a quantitative cross-sectional survey in rural eastern Zimbabwe asked 371 adults caring for children, including 212 caring for double orphans, about their well-being, needs, resources, and perceptions and experiences of orphan care. RESULTS: Survey responses indicate that: 1) foster caregivers are disproportionately female, older, poor, and without a spouse; 2) 98% of non-foster caregivers are willing to foster orphans, many from outside their kinship network; 3) poverty is the primary barrier to fostering; 4) financial, physical, and emotional stress levels are high among current and potential fosterers; 5) financial need may be greatest in single-orphan AIDS-impoverished households; and 6) struggling families lack external support. CONCLUSION: Incentives for sustainable orphan care should focus on financial assistance, starting with free schooling, and development of community mechanisms to identify and support children in need, to evaluate and strengthen families' capacity to provide orphan care, and to initiate and support placement outside the family when necessary