463 research outputs found

    Highway Interchange Constructed With Slurry Walls

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    The use of slurry walls to support 40 feet high embankments and bridge structures at Techwood-Spring Connector, part of Williams Street Interchange in Atlanta, is described. Advantages of using slurry walls in lieu of conventional walls are discussed

    Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes

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    BACKGROUND: The autism spectrum encompasses a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. RESULTS: Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map closely in silico to chromosomal regions containing previously reported autism candidate genes or quantitative trait loci. CONCLUSION: Our results provide evidence that novel candidate genes for autism may be differentially expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism based on expressed biomarkers in peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism

    Quantum-limited measurements of optical signals from a geostationary satellite

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    The measurement of quantum signals that traveled through long distances is of fundamental and technological interest. We present quantum-limited coherent measurements of optical signals, sent from a satellite in geostationary Earth orbit to an optical ground station. We bound the excess noise that the quantum states could have acquired after having propagated 38600 km through Earth's gravitational potential as well as its turbulent atmosphere. Our results indicate that quantum communication is feasible in principle in such a scenario, highlighting the possibility of a global quantum key distribution network for secure communication.Comment: 8 pages (4 pages main article, 4 pages supplementary material), 9 figures (4 figures main article, 5 figures supplementary material), Kevin G\"unthner and Imran Khan contributed equally to this wor

    Herausforderungen bei der Schätzung von Trends in Schulleistungsstudien. Eine Skalierung der deutschen PISA-Daten

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    Internationale Schulleistungsstudien wie das Programme for International Student Assessment (PISA) dienen den teilnehmenden Ländern zur Feststellung der Leistungsfähigkeit ihrer Schulsysteme. In PISA wird die Zielpopulation (15-jährige Schülerinnen und Schüler) alle 3 Jahre getestet. Von besonderer Bedeutung sind dabei die Trendinformationen, die für die Zielpopulation ausweisen, ob sich ihre Leistungen gegenüber denen aus früheren Erhebungen verändert haben. Um solche Trends valide interpretieren zu können, sollten die PISA-Erhebungen unter möglichst vergleichbaren Bedingungen durchgeführt und die verwendeten statistischen Verfahren vergleichbar bleiben. In PISA 2015 wurde erstmalig computerbasiert getestet; zuvor mittels Papier-und-Bleistift-Tests. Es wurde das Skalierungsmodell verändert und in den Naturwissenschaften wurden neue Aufgabenformate eingesetzt. Im vorliegenden Beitrag gehen wir anhand der nationalen PISA-Stichproben von 2000 bis 2015 der Frage nach, inwiefern der Wechsel des Testmodus und der Wechsel des Skalierungsmodells die Interpretation der Trendschätzungen beeinflussen. Die Analysen belegen, dass die Veränderung von Papier-und-Bleistift-Tests auf Computertestung die Trendschätzung für Deutschland verzerrt haben könnte. (DIPF/Orig.)International large-scale assessments, for instance, the Programme for International Student Assessment (PISA), are conducted to provide information on the effectiveness of educational systems. In PISA, the target population of 15-year-old students is assessed every 3 years. Trends show whether competencies have changed for the target population between PISA cycles. To ensure valid trend information, it is necessary to keep the test conditions and statistical methods in all PISA cycles as constant as possible. In PISA 2015, however, several changes were established; the test model changed from paper pencil to computer tests, scaling methods were changed, and new types of tasks were used in science. In this article, we investigate the effects of these changes on trend estimation in PISA using German data from all PISA cycles (2000 - 2015). Findings suggest that the change from paper pencil to computer tests could have biased the trend estimation. (DIPF/Orig.

    A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

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    Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

    Diversity oriented biosynthesis via accelerated evolution of modular gene clusters.

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    Erythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular polyketide synthase multienzymes by an assembly-line process in which each module of enzymes in turn specifies attachment of a particular chemical unit. Although polyketide synthase encoding genes have been successfully engineered to produce novel analogues, the process can be relatively slow, inefficient, and frequently low-yielding. We now describe a method for rapidly recombining polyketide synthase gene clusters to replace, add or remove modules that, with high frequency, generates diverse and highly productive assembly lines. The method is exemplified in the rapamycin biosynthetic gene cluster where, in a single experiment, multiple strains were isolated producing new members of a rapamycin-related family of polyketides. The process mimics, but significantly accelerates, a plausible mechanism of natural evolution for modular polyketide synthases. Detailed sequence analysis of the recombinant genes provides unique insight into the design principles for constructing useful synthetic assembly-line multienzymes

    The PHENIX Experiment at RHIC

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    The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

    Current concepts of the management of dental extractions for patients taking warfarin

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    The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Controversy has surrounded the correct management of patients therapeutically anticoagulated with warfarin who require dental extractions. The risk of bleeding must be weighed up against the risk of thromboembolism when deciding whether to interfere with a patient's warfarin regimen. An improved understanding of the importance of fibrinolytic mechanisms in the oral cavity has resulted in the development of various local measures to enable these patients to be treated on an outpatient basis. Methods: A review of the literature was undertaken. This was supplemented by the authors' clinical trials and extensive clinical experience with anticoagulated patients. Results: Various protocols for treating patients taking warfarin have been reviewed and summarized and an overview of the haemostatic and fibrinolytic systems is presented. A protocol for management of warfarinized patients requiring dental extractions in the outpatient setting is proposed. Conclusions: Patients therapeutically anticoagulated with warfarin can be treated on an ambulatory basis, without interruption of their warfarin regimen provided appropriate local measures are used.G Carter, AN Goss, JV Lloyd, R Tocchett

    Optimism/pessimism and health-related quality of life during pregnancy across three continents: a matched cohort study in China, Ghana, and the United States

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    <p>Abstract</p> <p>Background</p> <p>Little is known about how optimism/pessimism and health-related quality of life compare across cultures.</p> <p>Methods</p> <p>Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.). Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors. A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies. Anovas with post-hoc pairwise comparisons were used to compare results across the cohorts. Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism.</p> <p>Results</p> <p>LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis. Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001). Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure. U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample.</p> <p>Conclusion</p> <p>This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women. Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.</p
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