247 research outputs found

    E.M.B.A. International Field Studies: A Comparative Perspective

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    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

    Effects of natural light on nitrogen cycling rates in the Mississippi River plume

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    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.

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    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

    Absence of arsenate in DNA from arsenate-grown GFAJ-1 cells

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    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

    Effects of High-Molecular-Weight Dissolved Organic Matter on Nitrogen Dynamics in the Mississippi River Plume

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    The dynamics of N and its interactions with labile dissolved organic C (DOC), bacteria, and phytoplankton were studied to determine potential effects of dissolved organic matter (DOM) and light on N dynamics in surface waters of the Mississippi River (USA) plume in the Gulf of Mexico. Bacterial uptake of added labeled N compounds ( 15NH4+ or 15N-labeled dissolved free amino acids. DFAA) was stimulated more by high-molecular-weight (HMW, \u3el kDa) DOM than by low-molecular-weight (LMW, \u3c l kDa) DOM. An index that inversely indicated the presence of labile DOC was defined as the fraction of assimilated Amino acid-15N that was Recovered as 15N -Ammonium (ANRA), following the additions of high-levels (4 µM) of 15N -DFAA. ANRA ratios were high in the absence of other available carbon sources because heterotrophic bacteria were forced to use the added amino acids as a carbon source for respiration rather than as a nutrient source for biomass formation. In dynamic light/dark experiments, conducted with in situ populations of organisms, uptake rates of added 15NH4+ were significantly enhanced both by the presence of light and by the addition of HMW DOM. Uptake rates of added 15N -labeled DFAA were increased by the addition of HMW DOM but not by light. ANRA ratios were consistently lower in the presence of added HMW DOM than in controls. Added HMW DOM thus appeared to stimulate the incorporation of assimilated DFAA into bacterial biomass. Bacterial growth rates were relatively high in both light and dark bottles with DFAA additions and in light bottles with HMW DOM plus NH4+ additions, but they remained comparatively low in dark bottles with added NH4+ These results are consistent with the idea that bacterial N dynamics in these euphotic waters may be tightly coupled to photosynthetic activities over short time scales

    Influence of \u3cem\u3eβ\u3c/em\u3e-Lactam Infusion Strategy on Acute Kidney Injury

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    Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: β-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged β-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI

    Tertiary-Treated Municipal Wastewater is a Significant Point Source of Antibiotic Resistance Genes Into Duluth-Superior Harbor

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    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
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