511 research outputs found
Is Section 6861 the Source of Authority for Short-Year Jeopardy Assessments under the Internal Revenue Code?
Seasonality Directs Contrasting Food Collection Behavior and Nutrient Regulation Strategies in Ants
Long-lived animals, including social insects, often display seasonal shifts in foraging behavior. Foraging is ultimately a nutrient consumption exercise, but the effect of seasonality per se on changes in foraging behavior, particularly as it relates to nutrient regulation, is poorly understood. Here, we show that field-collected fire ant colonies, returned to the laboratory and maintained under identical photoperiod, temperature, and humidity regimes, and presented with experimental foods that had different protein (p) to carbohydrate (c) ratios, practice summer- and fall-specific foraging behaviors with respect to protein-carbohydrate regulation. Summer colonies increased the amount of food collected as the p:c ratio of their food became increasingly imbalanced, but fall colonies collected similar amounts of food regardless of the p:c ratio of their food. Choice experiments revealed that feeding was non-random, and that both fall and summer ants preferred carbohydrate-biased food. However, ants rarely ate all the food they collected, and their cached or discarded food always contained little carbohydrate relative to protein. From a nutrient regulation strategy, ants consumed most of the carbohydrate they collected, but regulated protein consumption to a similar level, regardless of season. We suggest that varied seasonal food collection behaviors and nutrient regulation strategies may be an adaptation that allows long-lived animals to meet current and future nutrient demands when nutrient-rich foods are abundant (e.g. spring and summer), and to conserve energy and be metabolically more efficient when nutritionally balanced foods are less abundant
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Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort
Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied. Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data. Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m3 for PM2.5 and from 0.1 to 1.7 μg/m3 for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM. Conclusions: Greater exposure to PM2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy. Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose tolerance during pregnancy: the Project Viva Cohort. Environ Health Perspect 122:378–383; http://dx.doi.org/10.1289/ehp.130706
27874 Correlation of itch response to roflumilast cream with disease severity and patient-reported outcomes in patients with chronic plaque psoriasis
Roflumilast cream is a nonsteroidal, selective phosphodiesterase-4 inhibitor in development for plaque psoriasis (PsO). A Phase 2b, double-blinded trial randomized adults with PsO (2-20% body surface area) to once daily roflumilast 0.3%, roflumilast 0.15%, or vehicle for 12 weeks (NCT03638258). Throughout the trial, itch and its impact were evaluated via patient reported outcomes (PROs): Worst Itch Numeric Rating Scale (WI–NRS), Itch related Sleep Loss (IRSL), and Dermatology Life Quality Index (DLQI). This posthoc analysis reports correlation of WI–NRS with other PROs and with disease severity. Overall, 331 patients were randomized (109 to roflumilast 0.3%, 113 to 0.15%, and 109 to vehicle). At baseline, the mean WI–NRS score was 5.87. Throughout the trial, both roflumilast doses showed similar improvements in WI–NRS starting at Week 2 and were significantly superior to vehicle (P ≤.002). At baseline, Pearson correlation coefficients (PCCs) for WI–NRS and Psoriasis Area and Severity Index (PASI) were 0.189, 0.282, 0.205 for roflumilast 0.3%, roflumilast 0.15%, and vehicle, respectively (P ≤.033 for all correlations); for WI–NRS and IRSL: 0.548, 0.646, 0.652 (P ˂.001); for WI–NRS and DLQI: 0.445, 0.617, 0.422 (P ˂.001). At Week 8, PCCs for WI–NRS and PASI were 0.420, 0.409, 0.365 (P ˂.001); for WI–NRS and IRSL: 0.673, 0.725, 0.696 (P ˂.001); for WI–NRS and DLQI: 0.607, 0.823, 0.529. Treatment with roflumilast resulted in rapid and robust improvement in the severity of itch associated with PsO. Itch response to roflumilast was independent of disease severity and positively correlated with patient-reported sleep loss and quality of life improvement
Effects of dissipation on quantum phase transitions
We discuss the effect of dissipation on quantum phase transitions. In
particular we concentrate on the Superconductor to Insulator and Quantum-Hall
to Insulator transitions. By invoking a phenomenological parameter to
describe the coupling of the system to a continuum of degrees of freedom
representing the dissipative bath, we obtain new phase diagrams for the quantum
Hall and superconductor-insulator problems. Our main result is that, in
two-dimensions, the metallic phases observed in finite magnetic fields
(possibly also strictly zero field) are adiabatically deformable from one to
the other. This is plausible, as there is no broken symmetry which
differentiates them.Comment: 13 pages, 4 figure
Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle
gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle
Aptamer-based multiplexed proteomic technology for biomarker discovery
Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
Picturing the nation : The Celtic periphery as discursive other in the archaeological displays of the museum of Scotland
Using the archaeological displays at the Museum of Scotland in Edinburgh, this paper examines the exhibition as a site of identity creation through the negotiations between categories of same and Other. Through an analysis of the poetics of display, the paper argues that the exhibition constructs a particular relationship between the Celtic Fringe and Scottish National identity that draws upon the historical discourses of the Highlands and Islands of Scotland as a place and a time \u27apart\u27. This will be shown to have implications for the display of archaeological material in museums but also for contemporary understandings of Scottish National identity. <br /
Comparative Effectiveness of Guidelines for the Management of Hyperlipidemia and Hypertension for Type 2 Diabetes Patients
Background: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. Methods and Findings: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT) to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females); a larger range of differences were observed for expected cost per event avoided (ranges, 157,186 for males and 163,775 for females). Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. Conclusions: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs. © 2011 Shah et al
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