304 research outputs found
Effects of natural light on nitrogen cycling rates in the Mississippi River plume
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110596/1/lno19974220273.pd
Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity.
The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the growth of multiple types of subcutaneously transplanted tumors in wild-type, but not FAP-null immune-competent syngeneic mice. The antitumor effects could be augmented by multiple injections of the CAR T cells, by using CAR T cells with a deficiency in diacylglycerol kinase, or by combination with a vaccine. A major mechanism of action of the muFAP-CAR T cells was the augmentation of the endogenous CD8(+) T-cell antitumor responses. Off-tumor toxicity in our models was minimal following muFAP-CAR T-cell therapy. In summary, inhibiting tumor growth by targeting tumor stroma with adoptively transferred CAR T cells directed to FAP can be safe and effective, suggesting that further clinical development of anti-human FAP-CAR is warranted
Tertiary-Treated Municipal Wastewater is a Significant Point Source of Antibiotic Resistance Genes Into Duluth-Superior Harbor
In this study, the impact of tertiary-treated municipal wastewater on the quantity of several antibiotic resistance determinants in Duluth-Superior Harbor was investigated by collecting surface water and sediment samples from 13 locations in Duluth-Superior Harbor, the St. Louis River, and Lake Superior. Quantitative PCR (qPCR) was used to target three different genes encoding resistance to tetracycline (tet(A), tet(X), and tet(W)), the gene encoding the integrase of class 1 integrons (intI1), and total bacterial abundance (16S rRNA genes) as well as total and human fecal contamination levels (16S rRNA genes specific to the genus Bacteroides). The quantities of tet(A), tet(X), tet(W), intI1, total Bacteroides, and human-specific Bacteroides were typically 20-fold higher in the tertiary-treated wastewater than in nearby surface water samples. In contrast, the quantities of these genes in the St. Louis River and Lake Superior were typically below detection. Analysis of sequences of tet(W) gene fragments from four different samples collected throughout the study site supported the conclusion that tertiary-treated municipal wastewater is a point source of resistance genes into Duluth-Superior Harbor. This study demonstrates that the discharge of exceptionally treated municipal wastewater can have a statistically significant effect on the quantities of antibiotic resistance genes in otherwise pristine surface waters
E.M.B.A. International Field Studies: A Comparative Perspective
Almost 80% of EMBA programs include a significant international study experience. The content and process, though, vary considerably in length, location, and method. To provide insight to the scope, format, of different approaches, the researchers conducted extensive interviews with 40 EMBA program directors. Results of the investigation are presented providing information that EMBA directors, faculty and administrators may find useful in improving the quality and effectiveness of their international field studies
The influence of mixing on seasonal carbon dioxide and methane fluxes in ponds
Inland waters are important sources of the greenhouse gases carbon dioxide (CO2) and methane (CH4). Ponds have amongst the highest CO2 and CH4 fluxes of all aquatic ecosystems, yet seasonal variation in fluxes remain poorly characterized, creating challenges for accurately estimating annual emissions. Further, ponds can exhibit a range of mixing regimes, yet the impact of mixing regimes on gas emissions remains unclear. Here, we assessed annual dynamics of CO2 and CH4 in four temperate ponds (Minnesota, USA) that varied in mixing regimes. The ponds ranged from annual sinks to sources of CO2 (−1 to 15 mol m−2 yr−1) and were all significant sources of CH4 (4.3–8.2 mol m−2 yr−1), with annual fluxes in CO2 equivalents of 1.8–4.1 kg CO2-eq. m−2 yr−1. Mixing regimes impacted CO2 and CH4 dynamics, as stratified periods were associated with more anoxia, greater accumulation of gases in the bottom waters, higher emissions of CH4, and lower fluxes of CO2. Ponds with stronger summer stratification also had increased CO2 and CH4 fluxes associated with fall turnover. Overall, the two ponds with the strongest stratification had higher annual fluxes (2.6, 4.1 kg CO2-eq. m−2 yr−1) compared to the two ponds that more frequently mixed (1.8, 2.2 kg CO2-eq. m−2 yr−1).publishedVersio
Organic phosphorus in the terrestrial environment: a perspective on the state of the art and future priorities
Background
The dynamics of phosphorus (P) in the environment is important for regulating nutrient cycles in natural and managed ecosystems and an integral part in assessing biological resilience against environmental change. Organic P (Po) compounds play key roles in biological and ecosystems function in the terrestrial environment being critical to cell function, growth and reproduction.
Scope
We asked a group of experts to consider the global issues associated with Po in the terrestrial environment, methodological strengths and weaknesses, benefits to be gained from understanding the Po cycle, and to set priorities for Po research.
Conclusions
We identified seven key opportunities for Po research including: the need for integrated, quality controlled and functionally based methodologies; assessment of stoichiometry with other elements in organic matter; understanding the dynamics of Po in natural and managed systems; the role of microorganisms in controlling Po cycles; the implications of nanoparticles in the environment and the need for better modelling and communication of the research. Each priority is discussed and a statement of intent for the Po research community is made that highlights there are key contributions to be made toward understanding biogeochemical cycles, dynamics and function of natural ecosystems and the management of agricultural systems
Dynamical Boson Stars
The idea of stable, localized bundles of energy has strong appeal as a model
for particles. In the 1950s John Wheeler envisioned such bundles as smooth
configurations of electromagnetic energy that he called {\em geons}, but none
were found. Instead, particle-like solutions were found in the late 1960s with
the addition of a scalar field, and these were given the name {\em boson
stars}. Since then, boson stars find use in a wide variety of models as sources
of dark matter, as black hole mimickers, in simple models of binary systems,
and as a tool in finding black holes in higher dimensions with only a single
killing vector. We discuss important varieties of boson stars, their dynamic
properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in
Relativity; major revision in 201
Absence of arsenate in DNA from arsenate-grown GFAJ-1 cells
A strain of Halomonas bacteria, GFAJ-1, has been reported to be able to use
arsenate as a nutrient when phosphate is limiting, and to specifically
incorporate arsenic into its DNA in place of phosphorus. However, we have found
that arsenate does not contribute to growth of GFAJ-1 when phosphate is
limiting and that DNA purified from cells grown with limiting phosphate and
abundant arsenate does not exhibit the spontaneous hydrolysis expected of
arsenate ester bonds. Furthermore, mass spectrometry showed that this DNA
contains only trace amounts of free arsenate and no detectable covalently bound
arsenate.Comment: Originally submitted to Science January 30 2012. This is the revised
version, resubmitted on April 13 2012. It has not been officially accepte
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