244 research outputs found

    Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles

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    Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells

    Balance Assessment Using a Smartwatch Inertial Measurement Unit with Principal Component Analysis for Anatomical Calibration

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    Balance assessment, or posturography, tracks and prevents health complications for a variety of groups with balance impairment, including the elderly population and patients with traumatic brain injury. Wearables can revolutionize state-of-the-art posturography methods, which have recently shifted focus to clinical validation of strictly positioned inertial measurement units (IMUs) as replacements for force-plate systems. Yet, modern anatomical calibration (i.e., sensor-to-segment alignment) methods have not been utilized in inertial-based posturography studies. Functional calibration methods can replace the need for strict placement of inertial measurement units, which may be tedious or confusing for certain users. In this study, balance-related metrics from a smartwatch IMU were tested against a strictly placed IMU after using a functional calibration method. The smartwatch and strictly placed IMUs were strongly correlated in clinically relevant posturography scores (r = 0.861–0.970, p \u3c 0.001). Additionally, the smartwatch was able to detect significant variance (p \u3c 0.001) between pose-type scores from the mediolateral (ML) acceleration data and anterior-posterior (AP) rotation data. With this calibration method, a large problem with inertial-based posturography has been addressed, and wearable, “at-home” balance-assessment technology is within possibility

    Improving Test Score Reporting: Perspectives From the ETS Score Reporting Conference

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    This volume includes 3 papers based on presentations at a workshop on communicating assessment information to particular audiences, held at Educational Testing Service (ETS) on November 4th, 2010, to explore some issues that influence score reports and new advances that contribute to the effectiveness of these reports. Jessica Hullman, Rebecca Rhodes, Fernando Rodriguez, and Priti Shah present the results of recent research on graph comprehension and data interpretation, especially the role of presentation format, the impact of prior quantitative literacy and domain knowledge, the trade‐off between reducing cognitive load and increasing active processing of data, and the affective influence of graphical displays. Rebecca Zwick and Jeffrey Sklar present the results of the Instructional Tools in Educational Measurement and Statistics for School Personnel (ITEMS) project, funded by the National Science Foundation and conducted at the University of California, Santa Barbara to develop and evaluate 3 web‐based instructional modules intended to help educators interpret test scores. Zwick and Sklar discuss the modules and the procedures used to evaluate their effectiveness. Diego Zapata‐Rivera presents a new framework for designing and evaluating score reports, based on work on designing and evaluating score reports for particular audiences in the context of the CBAL (Cognitively Based Assessment of, for, and as Learning) project (Bennett & Gitomer, 2009), which has been applied in the development and evaluation of reports for various audiences including teachers, administrators and students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108325/1/ets202281.pd

    Bayes and health care research.

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    Bayes’ rule shows how one might rationally change one’s beliefs in the light of evidence. It is the foundation of a statistical method called Bayesianism. In health care research, Bayesianism has its advocates but the dominant statistical method is frequentism. There are at least two important philosophical differences between these methods. First, Bayesianism takes a subjectivist view of probability (i.e. that probability scores are statements of subjective belief, not objective fact) whilst frequentism takes an objectivist view. Second, Bayesianism is explicitly inductive (i.e. it shows how we may induce views about the world based on partial data from it) whereas frequentism is at least compatible with non-inductive views of scientific method, particularly the critical realism of Popper. Popper and others detail significant problems with induction. Frequentism’s apparent ability to avoid these, plus its ability to give a seemingly more scientific and objective take on probability, lies behind its philosophical appeal to health care researchers. However, there are also significant problems with frequentism, particularly its inability to assign probability scores to single events. Popper thus proposed an alternative objectivist view of probability, called propensity theory, which he allies to a theory of corroboration; but this too has significant problems, in particular, it may not successfully avoid induction. If this is so then Bayesianism might be philosophically the strongest of the statistical approaches. The article sets out a number of its philosophical and methodological attractions. Finally, it outlines a way in which critical realism and Bayesianism might work together. </p

    An ecological approach to anomaly detection: the EIA Model.

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    The presented work proposes a new approach for anomaly detection. This approach is based on changes in a population of evolving agents under stress. If conditions are appropriate, changes in the population (modeled by the bioindicators) are representative of the alterations to the environment. This approach, based on an ecological view, improves functionally traditional approaches to the detection of anomalies. To verify this assertion, experiments based on Network Intrussion Detection Systems are presented. The results are compared with the behaviour of other bioinspired approaches and machine learning techniques

    Facts, Values and Quanta

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    Quantum mechanics is a fundamentally probabilistic theory (at least so far as the empirical predictions are concerned). It follows that, if one wants to properly understand quantum mechanics, it is essential to clearly understand the meaning of probability statements. The interpretation of probability has excited nearly as much philosophical controversy as the interpretation of quantum mechanics. 20th century physicists have mostly adopted a frequentist conception. In this paper it is argued that we ought, instead, to adopt a logical or Bayesian conception. The paper includes a comparison of the orthodox and Bayesian theories of statistical inference. It concludes with a few remarks concerning the implications for the concept of physical reality.Comment: 30 pages, AMS Late

    A Potent and Selective Inhibitor of Cdc42 GTPase

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    Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family
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