1,457 research outputs found

    Calibration of the NASA-GSFC high energy cosmic ray experiment

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    Calibration of high energy cosmic ray experimen

    Sex-specific fundamental and formant frequency patterns in a cross-sectional study

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    An extensive developmental acoustic study of the speech patterns of children and adults was reported by Lee and colleagues [Lee et al., J. Acoust. Soc. Am. 105, 1455-1468 (1999)]. This paper presents a reexamination of selected fundamental frequency and formant frequency data presented in their report for 10 monophthongs by investigating sex-specific and developmental patterns using two different approaches. The first of these includes the investigation of age- and sex-specific formant frequency patterns in the monophthongs. The second, the investigation of fundamental frequency and formant frequency data using the critical band rate (bark) scale and a number of acoustic-phonetic dimensions of the monophthongs from an age- and sex-specific perspective. These acoustic-phonetic dimensions include: vowel spaces and distances from speaker centroids; frequency differences between the formant frequencies of males and females; vowel openness/closeness and frontness/backness; the degree of vocal effort; and formant frequency ranges. Both approaches reveal both age- and sex-specific development patterns which also appear to be dependent on whether vowels are peripheral or non-peripheral. The developmental emergence of these sex-specific differences are discussed with reference to anatomical, physiological, sociophonetic and culturally determined factors. Some directions for further investigation into the age-linked sex differences in speech across the lifespan are also proposed

    IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

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    Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

    Episodic photic zone euxinia in the northeastern Panthalassic Ocean during the end-Triassic extinction

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    Severe changes in ocean redox, nutrient cycling, and marine productivity accompanied most Phanerozoic mass extinctions. However, evidence for marine photic zone euxinia (PZE) as a globally important extinction mechanism for the end-Triassic extinction (ETE) is currently lacking. Fossil molecular (biomarker) and nitrogen isotopic records from a sedimentary sequence in western Canada provide the first conclusive evidence of PZE and disrupted biogeochemistry in neritic waters of the Panthalassic Ocean during the end Triassic. Increasing water-column stratification and deoxygenation across the ETE led to PZE in the Early Jurassic, paralleled by a perturbed nitrogen cycle and ecological turnovers among noncalcifying groups, including eukaryotic algae and prokaryotic plankton. If such conditions developed widely in the Panthalassic Ocean, PZE might have been a potent mechanism for the ETE.National Science Foundation (U.S.) (Grant EAR-1147402)Exobiology Program (U.S.) (Grants NNX09AM88G and NNA08CN84A)American Association of Petroleum Geologists (Grant-In-Aid)Mary-Hill and Bevan M. French Fund for Impact Geolog

    Late Maastrichtian carbon isotope stratigraphy and cyclostratigraphy of the Newfoundland Margin (Site U1403, IODP Expedition 342)

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    Earth’s climate during the Maastrichtian (latest Cretaceous) was punctuated by brief warming and cooling episodes, accompanied by perturbations of the global carbon cycle. Superimposed on a long-term cooling trend, the middle Maastrichtian is characterized by deep-sea warming and relatively high values of stable carbon-isotope ratios, followed by strong climatic variability towards the end of the Cretaceous. A lack of knowledge on the timing of climatic change inhibits our understanding of underlying causal mechanisms. We present an integrated stratigraphy from Integrated Ocean Drilling Program (IODP) Site U1403, providing an expanded deep ocean record from the North Atlantic (Expedition 342, Newfoundland Margin). Distinct sedimentary cyclicity suggests that orbital forcing played a major role in depositional processes, which is confirmed by statistical analyses of high resolution elemental data obtained by X-ray fluorescence (XRF) core scanning. Astronomical calibration reveals that the investigated interval encompasses seven 405-kyr cycles (Ma4051 to Ma4057) and spans the 2.8 Myr directly preceding the Cretaceous/Paleocene (K/Pg) boundary. A high-resolution carbon-isotope record from bulk carbonates allows us to identify global trends in the late Maastrichtian carbon cycle. Low-amplitude variations (up to 0.4‰) in carbon isotopes at Site U1403 match similar scale variability in records from Tethyan and Pacific open-ocean sites. Comparison between Site U1403 and the hemipelagic restricted basin of the Zumaia section (northern Spain), with its own well-established independent cyclostratigraphic framework, is more complex. Whereas the pre-K/Pg oscillations and the negative values of the Mid-Maastrichtian Event (MME) can be readily discerned in both the Zumaia and U1403 records, patterns diverge during a ~ 1 Myr period in the late Maastrichtian (67.8–66.8 Ma), with Site U1403 more reliably reflecting global carbon cycling. Our new carbon isotope record and cyclostratigraphy offer promise for Site U1403 to serve as a future reference section for high-resolution studies of late Maastrichtian paleoclimatic change

    Drawbacks of a Dual Systems Approach to Family Firms: Can We Expand Our Thinking?

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    Conceptualizing the family firm as a dual system with properties of both the family and the business has prevented the field from fully examining the nature of these firms and has biased our observations and interventions. Too narrow a focus on the contribution of subsystems leads to a stereotyping of subsystem functioning, inconsistent and inadequate analysis of interpersonal dynamics, exaggerated notions of subsystem boundaries, and an underanalysis of whole system characteristics. Each of these drawbacks is discussed, and a beginning view of the family firm as a single entity is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67216/2/10_1111_j_1741-6248_1991_00383_x.pd

    Beveridge on idleness

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    Beveridge's wartime proposals to eliminate idleness relied on the precepts of Keynesian economics and substantial extensions in the powers of central government to regulate industry and labour. Using convention theory, this paper demonstrates how these stipulations proved politically untenable. With the disappearance of full employment in the 1980s, the labour market problems Beveridge encountered in his youth have re-emerged accompanied by old problems of working poverty. Established forms of labour market analysis are obsolescent and employment rights disappear. The paper suggests a more decentralized and variable analysis of relations between work and idleness may offer a way forward

    Tumor-Derived Microvesicles Induce, Expand and Up-Regulate Biological Activities of Human Regulatory T Cells (Treg)

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    Background: Tumor-derived microvesicles (TMV) or exosomes are present in body fluids of patients with cancer and might be involved in tumor progression. The frequency and suppressor functions of peripheral blood CD4 + CD25 high FOXP3 + Treg are higher in patients with cancer than normal controls. The hypothesis is tested that TMV contribute to induction/ expansion/and activation of human Treg. Methodology/Principal Findings: TMV isolated from supernatants of tumor cells but not normal cells induced the generation and enhanced expansion of human Treg. TMV also mediated conversion of CD4 + CD25 neg T cells into CD4 + CD25 high FOXP3 + Treg. Upon co-incubation with TMV, Treg showed an increased FasL, IL-10, TGF-b1, CTLA-4, granzyme B and perforin expression (p,0.05) and mediated stronger suppression of responder cell (RC) proliferation (p,0.01). Purified Treg were resistant to TMV-mediated apoptosis relative to other T cells. TMV also increased phospho-SMAD2/3 and phospho-STAT3 expression in Treg. Neutralizing Abs specific for TGF-b1 and/or IL-10 significantly inhibited TMV ability to expand Treg. Conclusions/Significance: This study suggests that TMV have immunoregulatory properties. They induce Treg, promote Treg expansion, up-regulate Treg suppressor function and enhance Treg resistance to apoptosis. Interactions of TMV wit
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