1,741 research outputs found

    Update: New Cancer Therapies

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    Nation Dreaming: A Consideration of the American Dream in Poland, the U.S., and among Polish Americans

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    This paper examines the cooperation and influences between Poland and the U.S on their respective dreams, including the influence of the American Dream on Polish Americans and their potential distinctness from those who remain in Poland. Attitudes involving the American Dream that are examined include beliefs about freedom, liberty, democracy, getting ahead, status/mobility, and inequality. Although scholars have compared these belief systems across countries, there has been no distinct focus on Poland and the U.S., and those who immigrate between these countries. A conceptual framework that combines the American Dream, American exceptionalism, and beliefs about inequality guides the research. Data from the General Social Survey and the World Values Survey are used to answer the research questions. Findings show that Polish Americans agree with other Americans on a majority of items measuring elements of the American Dream. However, Americans and Poles have significantly different opinions on each of the American Dream items. Usually, (but not always) it is Americans who are more supportive of the American Dream. When considering the three groups, Polish Americans, Americans, and Poles, our conclusions suggest a trend where Polish Americans are a hybrid of other Americans and Poles when it comes to their views on the Dream. However, the differences often run in the direction that Polish Americans’ views are more like other Americans and distinct from Poles. Conclusions and implications are provided within the historical context of the long history of cooperation between the U.S. and Poland in fights for freedom and democracy

    Studies on the cellular site of action of macrophage RNA-antigen complexes

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    Nonadherent spleen cell populations exposed in vitro to ribonucleic acid-rich preparations from mouse macrophages that had been incubated with human [gamma]-globulin (RNA : HGG) were able to produce specific antibody, as measured by rosette-forming cells, in lethally irradiated (800 R), reconstituted, syngeneic mice. Exposure of the RNA to anti-HGG serum abrogated its ability to initiate antibody synthesis, as did monospecific anti-human [gamma] chain and anti-human [kappa] chain serum. Normal rabbit serum, anti-bovine albumin serum, anti-human [mu] chain or anti-human [lambda] chain serum, when substituted for anti-HGG serum had no effect. Thus, the presence of both [gamma] heavy chains and [kappa] light chains of the antigen in the RNA moiety was indicated. Although both an adherent and a nonadherent cell were required by HGG to stimulate rosetteforming cells in irradiated mice, the need for the adherent cell was eliminated when RNA : HGG was substituted for HGG. In addition, anti-[theta]-treated bone marrow cells exposed to the RNA : HGG were capable of rosette-cell formation, suggesting that RNA attachment converted a T cell-dependent antigen to a T cell-independent antigen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21865/1/0000269.pd

    Course-based Science Research Promotes Learning in Diverse Students at Diverse Institutions

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    Course-based research experiences (CREs) are powerful strategies for spreading learning and improving persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation

    Methodology of a reevaluation of cardiovascular outcomes in the RECORD trial: study design and conduct

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    Background In 2010, after regulatory review of rosiglitazone licensing, the US Food and Drug Administration (FDA) requested a reevaluation of cardiovascular end points in the RECORD trial.<p></p> Methods Automated screening of the original clinical trial database and manual case report form review were performed to identify all potential cardiovascular and noncardiovascular deaths, and nonfatal myocardial infarction (MI) and stroke events. Search techniques were used to find participants lost to follow-up, and sites were queried for additional source documents. Suspected events underwent blinded adjudication using both original RECORD end point definitions and new FDA end point definitions, before analysis by the Duke Clinical Research Institute.<p></p> Results The reevaluation effort included an additional 328 person-years of follow-up. Automated screening identified 396 suspected deaths, 2,052 suspected MIs, and 468 suspected strokes. Manual review of documents by Duke Clinical Research Institute clinical events classification (CEC) coordinators identified an additional 31 suspected deaths, 49 suspected MIs, and 28 suspected strokes. There were 127 CEC queries issued requesting additional information on suspected deaths; 43 were closed with no site response, 61 were closed with a response that no additional data were available, and additional data were received for 23. Seventy CEC queries were issued requesting additional information for suspected MI and stroke events; 31 were closed with no site response, 20 were closed with a response that no additional data were available, and 19 resulted in additional data.<p></p> Conclusions Comprehensive procedures were used for rigorous event reascertainment and readjudication in a previously completed open-label, global clinical trial. These procedures used in this unique situation were consistent with other common approaches in the field, were enhanced to address the FDA concerns about the original RECORD trial results, and could be considered by clinical trialists designing event readjudication protocols for drug development programs that have been completed.<p></p&gt

    Results of a reevaluation of cardiovascular outcomes in the RECORD trial

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    Background The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development.<p></p> Methods Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes.<p></p> Results Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results.<p></p> Conclusions Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results.<p></p&gt

    Critical role of mTOR, PPARγ and PPARδ signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth

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    STUDY QUESTION: What are the consequences of inhibiting mTOR, the mechanistic target of rapamycin (mTOR), and the peroxisome proliferator activated receptor gamma (PPARγ) and PPARδ pathways in the early post-implantation period on decidual function, embryo viability and feto-placental growth in the ratγ SUMMARY ANSWER: mTOR inhibition from Days 7 to 9 of pregnancy in rats caused decidual PPARγ and PPARδ upregulation on Day 9 of pregnancy and resulted in embryo resorption by Day 14 of pregnancy. PPARγ and PPARδ inhibition differentially affected decidual mTOR signaling and levels of target proteins relevant to lipid histotrophic nutrition and led to reduced feto-placental weights on Day 14 of pregnancy. WHAT IS KNOWN ALREADY: Although mTOR, PPARγ and PPARδ are nutrient sensors important during implantation, the role of these signaling pathways in decidual function and how they interact in the early post-implantation period are unknown. Perilipin 2 (PLIN2) and fatty acid binding protein 4 (FABP4), two adipogenic proteins involved in lipid histotrophic nutrition, are targets of mTOR and PPAR signaling pathways in a variety of tissues. STUDY DESIGN, SIZE, DURATION: Rapamycin (mTOR inhibitor, 0.75 mg/kg, sc), T0070907 (PPARγ inhibitor, 0.001 mg/kg, sc), GSK0660 (PPARδ inhibitor, 0.1 mg/kg, sc) or vehicle was injected daily to pregnant rats from Days 7 to 9 of pregnancy and the studies were performed on Day 9 of pregnancy (n = 7 per group) or Day 14 of pregnancy (n = 7 per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: On Day 9 of pregnancy, rat decidua were collected and prepared for western blot and immunohistochemical studies. On Day 14 of pregnancy, the resorption rate, number of viable fetuses, crown-rump length and placental and decidual weights were determined. MAIN RESULTS AND THE ROLE OF CHANCE: Inhibition of mTOR in the early post-implantation period led to a reduction in FABP4 protein levels, an increase in PLIN2 levels and an upregulation of PPARγ and PPARδ in 9-day-pregnant rat decidua. Most embryos were viable on Day 9 of pregnancy but had resorbed by Day 14 of pregnancy. This denotes a key function of mTOR in the post-implantation period and suggests that activation of PPAR signaling was insufficient to compensate for impaired nutritional/survival signaling induced by mTOR inhibition. Inhibition of PPARγ signaling resulted in decreased decidual PLIN2 and FABP4 protein expression as well as in inhibition of decidual mTOR signaling in Day 9 of pregnancy. This treatment also reduced feto-placental growth on Day 14 of pregnancy, revealing the relevance of PPARγ signaling in sustaining post-implantation growth. Moreover, following inhibition of PPARδ, PLIN2 levels were decreased and mTOR complex 1 and 2 signaling was altered in decidua on Day 9 of pregnancy. On Day 14 of pregnancy, PPARδ inhibition caused reduced fetoplacental weight, increased decidual weight and increased resorption rate, suggesting a key role of PPARδ in sustaining post-implantation development. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This is an in vivo animal study and the relevance of the results for humans remains to be established. WIDER IMPLICATIONS OF THE FINDINGS: The early post-implantation period is a critical window of development and changes in the intrauterine environment may cause embryo resorption and lead to placental and fetal growth restriction. mTOR, PPARγ and PPARδ signaling are decidual nutrient sensors with extensive cross-talk that regulates adipogenic proteins involved in histotrophic nutrition and important for embryo viability and early placental and fetal development and growth. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Agencia Nacional de Promoción Científica y Tecnológica de Argentina (PICT 2014-411 and PICT 2015-0130), and by the International Cooperation (Grants CONICET-NIH-2014 and CONICETNIH- 2017) to A.J. and T.J. The authors have no conflicts of interest.Fil: Roberti, Sabrina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Higa, Romina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Powell, Theresa L.. State University of Colorado at Boulder; Estados UnidosFil: Jansson, Thomas. State University of Colorado at Boulder; Estados UnidosFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

    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
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