212 research outputs found

    There\u27s a Problem With Buybacks, But It\u27s Not What Senators Think

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    In a deeply divided Washington, one of the few issues on which leading lawmakers on both sides of the aisle appear to agree is that corporations should be discouraged from buying back their stock from shareholders. This short article argues that, while this anti-buyback sentiment is misguided, there nevertheless are good tax policy arguments for reforming the tax treatment of buybacks. The article recommends adoption of a 1969 proposal made by Professor Marvin Chirelstein that would recharacterize (for tax purposes) buybacks as a pro rata cash dividend, followed by sales of shares from the shareholders who participate in the buyback to the shareholders who do not

    Biochemical characterisation and structure-function relationship of the four recombinant Old Yellow Enzyme homologues from Shewanella oneidensis

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    Debbie van den Hemel PhD Thesis Biochemistry 12-21-2005 University of Ghent Biochemical characterisation and structure-function relationship of the four recombinant Old Yellow Enzyme homologues from Shewanella oneidensis Old Yellow Enzyme (OYE) of Saccharomyces cerevisiae is the oldest flavoprotein known. Homologous proteins are present in yeasts, plants, protozoa and bacteria. The enzymes’ fold is an eight-stranded α,β-barrel with one molecule of FMN bound on top. The enzymes use NADH or NADPH as a reductant and catalyse the reduction of diverse substrates as nitro-esters, α,β-unsaturated aldehydes and carbonyls, morphinone,… The catalytical mechanism has been characterised in detail and the structures of six homologues have been published. Despite this, the physiological function and substrate are not known for most of the homologues. Recent studies indicate functions for OYEs in yeast and bacteria in an oxidative stress response. Shewanella oneidensis is a Gram-negative, highly versatile bacterium. It possesses 4 OYE homologues. In this thesis we proceeded to characterise these enzymes by different means (biochemically, structurally and functionally) in order to determine the functionality of these enzymes. We named the four homologues SYE1-SYE4 (Shewanella Yellow Enzyme). SYE2 could not be expressed in soluble form and was excluded from the characterisation. In general, the conclusions of this work are the following : (1) We were able to divide the SYE enzymes in two subgroups, comprising SYE1 and SYE3 on the one hand, and SYE4 on the other, based on their biochemical characteristics (2) Structural analysis of SYE1 and protein modelling of the different SYEs learned us that (i) SYE1 has some specific characteristics different from other OYE family members, and that (ii) the biochemical differences of SYE4 are manifested in structural differences of the capping subdomain (3) By expression analysis we were only able to show the expression of SYE4 in vivo under conditions of oxidative and other stresses

    Effectiveness of attentional bias modification training as add-on to regular treatment in alcohol and cannabis use disorder:A multicenter randomized control trial

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    BACKGROUND: Attentional bias for substance-relevant cues has been found to contribute to the persistence of addiction. Attentional bias modification (ABM) interventions might, therefore, increase positive treatment outcome and reduce relapse rates. The current study investigated the effectiveness of a newly developed home-delivered, multi-session, internet-based ABM intervention, the Bouncing Image Training Task (BITT), as an add-on to treatment as usual (TAU). METHODS: Participants (N = 169), diagnosed with alcohol or cannabis use disorder, were randomly assigned to one of two conditions: the experimental ABM group (50%; TAU+ABM); or the control group (50%; split in two subgroups the TAU+placebo group and TAU-only group, 25% each). Participants completed baseline, post-test, and 6 and 12 months follow-up measures of substance use and craving allowing to assess long-term treatment success and relapse rates. In addition, attentional bias (both engagement and disengagement), as well as secondary physical and psychological complaints (depression, anxiety, and stress) were assessed. RESULTS: No significant differences were found between conditions with regard to substance use, craving, relapse rates, attentional bias, or physical and psychological complaints. CONCLUSIONS: The findings may reflect unsuccessful modification of attentional bias, the BITT not targeting the relevant process (engagement vs. disengagement bias), or may relate to the diverse treatment goals of the current sample (i.e., moderation or abstinence). The current findings provide no support for the efficacy of this ABM approach as an add-on to TAU in alcohol or cannabis use disorder. Future studies need to delineate the role of engagement and disengagement bias in the persistence of addiction, and the role of treatment goal in the effectiveness of ABM interventions

    Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme

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    Background: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.Methods: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (&lt; CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.Results: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between &lt; CIN2 and CIN3+ for all markers (p &lt; 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p &lt; 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation&gt; 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.Conclusion: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.</p

    Towards the systematic construction of domain-specific transformation languages

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    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-09195-2-13Proceedings of 10th European Conference, ECMFA 2014, Held as Part of STAF 2014, York, UK, July 21-25, 2014General-purpose transformation languages, like ATL or QVT, are the basis for model manipulation in Model-Driven Engineering (MDE). However, as MDE moves to more complex scenarios, there is the need for specialized transformation languages for activities like model merging, migration or aspect weaving, or for specific domains of wide use like UML. Such domain-specific transformation languages (DSTLs) encapsulate transformation knowledge within a language, enabling the reuse of recurrent solutions to transformation problems. Nowadays, many DSTLs are built in an ad-hoc manner, which requires a high development cost to achieve a full-featured implementation. Alternatively, they are realised by an embedding into general-purpose transformation or programming languages like ATL or Java. In this paper, we propose a framework for the systematic creation of DSTLs. First, we look into the characteristics of domain-specific transformation tools, deriving a categorization which is the basis of our framework. Then, we propose a domain-specific language to describe DSTLs, from which we derive a ready-to-run workbench which includes the abstract syntax, concrete syntax and translational semantics of the DSTL.This work has been funded by the Spanish Ministry of Economy and Competitivity with project “Go Lite” (TIN2011-24139

    The IGF2 methylation score for adrenocortical cancer:an ENSAT validation study

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    Adrenocortical carcinoma (ACC) is diagnosed using the histopathological Weiss score (WS), but remains clinically elusive unless it has metastasized or grows locally invasive. Previously, we proposed the objective IGF2 methylation score as diagnostic tool for ACC. This multicenter European cohort study validates these findings. Patient and tumor characteristics were obtained from adrenocortical tumor patients. DNA was isolated from frozen specimens, where after DMR2, CTCF3, and H19 were py rosequenced. The predictive value of the methylation score for malignancy, defined by the WS or metastasis development, was assessed using receiver operating characteristic curves and logistic and Cox regression analyses. Seventy-six ACC patients and 118 patients with adrenocortical adenomas were included from seven centers. The methylation score and tumor size were independently associated with the pathological ACC diagnosis (OR 3.756 95% CI 2.224-6.343; OR 1.467 95% CI 1.202-1.792, respectively; Hosmer-Lemeshow test P = 0.903), with an area under the curve (AUC) of 0.957 (95% CI 0. 930-0.984). The methylation score alone resulted in an AUC of 0.910 (95% CI 0.8 66-0.952). Cox regression analysis revealed that the methylation score, WS and tumor size predicted development of metastases in univariate analysis. In multivariate analysis, only the WS predicted development of metastasis (OR 1.682 95% CI 1.285-2.202; P <0.001). In conclusion, we validated the high diagnostic accuracy of the IGF2 methylation score for diagnosing ACC in a multicenter European cohort study. Considering the known limitations of the WS, the objective IGF2 methylation score could potentially provide extra guidance on decisions on postoperative strategies in adrenocortical tumor patients

    Brief of Tax Law Professors as \u3ci\u3eAmici Curiae\u3c/i\u3e in Support of Petitioner in \u3ci\u3eLoudoun County, Virginia v. Dulles Duty Free, LLC\u3c/i\u3e

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    Amici are professors of tax law at universities across the United States. As scholars and teachers, they have considered the doctrinal roots and practical consequences of judicial limits on state and local taxation. Amici join this brief solely on their own behalf and not as representatives of their universities. A full list of amici appears in the Appendix to this brief
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