Temporal and spatial dynamics of CO2 air-sea flux in the Gulf of Maine

Ocean surface layer carbon dioxide (CO2) data collected in the Gulf of Maine from 2004 to 2008 are presented. Monthly shipboard observations are combined with additional higher‐resolution CO2 observations to characterize CO2 fugacity ( fCO2) and CO2 flux over hourly to interannual time scales. Observed fCO2 andCO2 flux dynamics are dominated by a seasonal cycle, with a large spring influx of CO2 and a fall‐to‐winter efflux back to the atmosphere. The temporal results at inner, middle, and outer shelf locations are highly correlated, and observed spatial variability is generally small relative to the monthly to seasonal temporal changes. The averaged annual flux is in near balance and is a net source of carbon to the atmosphere over 5 years, with a value of +0.38 mol m−2 yr−1. However, moderate interannual variation is also observed, where years 2005 and 2007 represent cases of regional source (+0.71) and sink (−0.11) anomalies. We use moored daily CO2 measurements to quantify aliasing due to temporal undersampling, an important error budget term that is typically unresolved. The uncertainty of our derived annual flux measurement is ±0.26 mol m−2 yr−1 and is dominated by this aliasing term. Comparison of results to the neighboring Middle and South Atlantic Bight coastal shelf systems indicates that the Gulf of Maine exhibits a similar annual cycle and range of oceanic fCO2 magnitude but differs in the seasonal phase. It also differs by enhanced fCO2 controls by factors other than temperature‐driven solubility, including biological drawdown, fall‐to‐winter vertical mixing, and river runoff

Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae

Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35. IL-12/23 p40, interferon γ (IFN-γ), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae–pulsed dendritic cell culture supernatants elicit T cell IL-17 production in a IL-23–dependent manner. However, the importance of IL-23 during in vivo pulmonary challenge is unknown. We show that IL-12/23 p40–deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19−/−, IL-17R−/−, and IL-12 p35−/− mice also show increased susceptibility to infection. p40−/− mice fail to generate pulmonary IFN-γ, IL-17, or IL-17F responses to infection, whereas p35−/− mice show normal IL-17 and IL-17F induction but reduced IFN-γ. Lung IL-17 and IL-17F production in p19−/− mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (103 CFU), despite normal IFN-γ induction. Administration of IL-17 restored bacterial control in p19−/− mice and to a lesser degree in p40−/− mice, suggesting an additional host defense requirement for IFN-γ in this strain. Together, these data demonstrate independent requirements for IL-12 and IL-23 in pulmonary host defense against K. pneumoniae, the former of which is required for IFN-γ expression and the latter of which is required for IL-17 production

Students as ecologists: Strategies for successful mentorship of undergraduate researchers

Guiding undergraduates through the ecological research process can be incredibly rewarding and present opportunities to break down barriers to inclusion and diversity in scientific disciplines. At the same time, mentoring undergraduate researchers is a complicated process that requires time and flexibility. While many academics receive extensive guidance on how to be successful in research endeavors, we pay much less attention to training in mentorship and working collaboratively with undergraduate students. This paper seeks to provide a framework for successfully collaborating with undergraduates including initial recruitment, development of a contract, fostering student ownership of research projects, and submission of a polished manuscript.While institutions worldwide encourage undergraduate research and publication, little training and professional development are provided to potential mentors. Our paper fills a critical gap in knowledge and provides a framework for academic mentors of all career stages to successfully guide students from question to publication.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149365/1/ece35090_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149365/2/ece35090.pd

Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1 , CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer

This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m2 day 1, orally divided in two doses of 1250 mg m-2 in the morning and evening for 14 days every 21 days and MMC 7 mg m-2 (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24–85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7–49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand–foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.S Rao, D Cunningham, T Price, M E Hill, P J Ross, N Tebbutt, A R Norman, J Oates and P Shellit

Modeling the climate response to a massive methane release from gas hydrates

[1] The climate response to a massive release of methane from gas hydrates is simulated in two 2500-year-long numerical experiments performed with a three-dimensional, global coupled atmosphere-sea ice-ocean model of intermediate complexity. Two different equilibrium states were used as reference climates; the first state with preindustrial forcing conditions and the second state with a four times higher atmospheric CO2 concentration. These climates were perturbed by prescribing a methane emission scenario equivalent to that computed for the Paleocene/Eocene thermal maximum (PETM; similar to 55.5 Ma), involving a sudden release of 1500 Gt of carbon into the atmosphere in 1000 years. In both cases, this produced rapid atmospheric warming (up to 10°C at high latitudes) and a reorganization of the global overturning ocean circulation. In the ocean, maximum warming (2-4°C) occurred at intermediate depths where methane hydrates are stored in the upper slope sediments, suggesting that further hydrate instability could result from the prescribed scenario

Mu2e Technical Design Report

The Mu2e experiment at Fermilab will search for charged lepton flavor violation via the coherent conversion process mu- N --> e- N with a sensitivity approximately four orders of magnitude better than the current world's best limits for this process. The experiment's sensitivity offers discovery potential over a wide array of new physics models and probes mass scales well beyond the reach of the LHC. We describe herein the preliminary design of the proposed Mu2e experiment. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2 approval.Comment: compressed file, 888 pages, 621 figures, 126 tables; full resolution available at http://mu2e.fnal.gov; corrected typo in background summary, Table 3.

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure

<p>Abstract</p> <p>Background</p> <p><it>Pneumocystis spp</it>. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. <it>Pneumocystis </it>colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to <it>Pneumocystis</it>.</p> <p>Methods</p> <p>To analyze the role of SP-A in protecting the immunocompetent host from <it>Pneumocystis </it>colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to <it>P. murina </it>colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Detection of <it>P. murina </it>specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to <it>P. murina </it>within the animal facility. However, P. <it>murina </it>mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, <it>P. murina </it>cyst forms were also only detected in KO mice. <it>P. murina </it>mRNA was detected in <it>SCID </it>mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.</p> <p>Conclusion</p> <p>These data support an important role for SP-A in protecting the immunocompetent host from <it>P. murina </it>colonization, and provide a model to study <it>Pneumocystis </it>colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to <it>P. murina </it>even when housed under barrier conditions.</p