6,002 research outputs found

    Using network reification for adaptive networks:Discussion

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    IMF and [Na/Fe] abundance ratios from optical and NIR Spectral Features in Early-type Galaxies

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    We present a joint analysis of the four most prominent sodium-sensitive features (NaD, NaI8190, NaI1.14, and NaI2.21), in the optical and Near-Infrared spectral range, of two nearby, massive (sigma~300km/s), early-type galaxies (named XSG1 and XSG2). Our analysis relies on deep VLT/X-Shooter long-slit spectra, along with newly developed stellar population models, allowing for [Na/Fe] variations, up to 1.2dex, over a wide range of age, total metallicity, and IMF slope. The new models show that the response of the Na-dependent spectral indices to [Na/Fe] is stronger when the IMF is bottom heavier. For the first time, we are able to match all four Na features in the central regions of massive early-type galaxies, finding an overabundance of [Na/Fe], in the range 0.5-0.7dex, and a bottom-heavy IMF. Therefore, individual abundance variations cannot be fully responsible for the trends of gravity-sensitive indices, strengthening the case towards a non-universal IMF. Given current limitations of theoretical atmosphere models, our [Na/Fe] estimates should be taken as upper limits. For XSG1, where line strengths are measured out to 0.8Re, the radial trend of [Na/Fe] is similar to [Mg/Fe] and [C/Fe], being constant out to 0.5Re, and decreasing by 0.2-0.3dex at 0.8Re, without any clear correlation with local metallicity. Such a result seems to be in contrast with the predicted increase of Na nucleosynthetic yields from AGB stars and TypeII SNe. For XSG1, the Na-inferred IMF radial profile is consistent, within the errors, with that derived from TiO features and the Wing-Ford band, presented in a recent paper

    Improving the quality of cognitive screening assessments: ACEmobile, an iPad-based version of the Addenbrooke's Cognitive Examination-III.

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    INTRODUCTION: Ensuring reliable administration and reporting of cognitive screening tests are fundamental in establishing good clinical practice and research. This study captured the rate and type of errors in clinical practice, using the Addenbrooke's Cognitive Examination-III (ACE-III), and then the reduction in error rate using a computerized alternative, the ACEmobile app. METHODS: In study 1, we evaluated ACE-III assessments completed in National Health Service (NHS) clinics (n = 87) for administrator error. In study 2, ACEmobile and ACE-III were then evaluated for their ability to capture accurate measurement. RESULTS: In study 1, 78% of clinically administered ACE-IIIs were either scored incorrectly or had arithmetical errors. In study 2, error rates seen in the ACE-III were reduced by 85%-93% using ACEmobile. DISCUSSION: Error rates are ubiquitous in routine clinical use of cognitive screening tests and the ACE-III. ACEmobile provides a framework for supporting reduced administration, scoring, and arithmetical error during cognitive screening

    Fluoxetine: a case history of its discovery and preclinical development

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    Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

    The mRNA expression of SETD2 in human breast cancer: Correlation with clinico-athological parameters

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    BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer

    On the complexity of color-avoiding site and bond percolation

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    The mathematical analysis of robustness and error-tolerance of complex networks has been in the center of research interest. On the other hand, little work has been done when the attack-tolerance of the vertices or edges are not independent but certain classes of vertices or edges share a mutual vulnerability. In this study, we consider a graph and we assign colors to the vertices or edges, where the color-classes correspond to the shared vulnerabilities. An important problem is to find robustly connected vertex sets: nodes that remain connected to each other by paths providing any type of error (i.e. erasing any vertices or edges of the given color). This is also known as color-avoiding percolation. In this paper, we study various possible modeling approaches of shared vulnerabilities, we analyze the computational complexity of finding the robustly (color-avoiding) connected components. We find that the presented approaches differ significantly regarding their complexity.Comment: 14 page

    How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

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    Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

    A High Deuterium Abundance at z=0.7

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    Of the light elements, the primordial abundance of deuterium, (D/H)_p, provides the most sensitive diagnostic for the cosmological mass density parameter Omega_B. Recent high redshift (D/H) measurements are highly discrepant, although this may reflect observational uncertainties. The larger (D/H) values, which imply a low Omega_B and require the Universe to be dominated by non-baryonic matter (dynamical studies indicate a higher total density parameter), cause problems for galactic chemical evolution models since they have difficulty in reproducing the large decline down to the lower present-day (D/H). Conversely, low (D/H) values imply an Omega_B greater than derived from ^7Li and ^4He abundance measurements, and may require a deuterium abundance evolution that is too low to easily explain. Here we report the first measurement at intermediate redshift, where the observational difficulties are smaller, of a gas cloud with ideal characteristics for this experiment. Our analysis of the z = 0.7010 absorber toward 1718+4807 indicates (D/H) = 2.0 +/- 0.5 x 10^{-4} which is in the high range. This and other independent observations suggests there may be a cosmological inhomogeneity in (D/H)_p of at least a factor of ten.Comment: 6 pages, 1 figur
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