682 research outputs found
Personalisation and recommender systems in digital libraries
Widespread use of the Internet has resulted in digital libraries that are increasingly used by diverse communities of users for diverse purposes and in which sharing and collaboration have become important social elements. As such libraries become commonplace, as their contents and services become more varied, and as their patrons become more experienced with computer technology, users will expect more sophisticated services from these libraries. A simple search function, normally an integral part of any digital library, increasingly leads to user frustration as user needs become more complex and as the volume of managed information increases. Proactive digital libraries, where the library evolves from being passive and untailored, are seen as offering great potential for addressing and overcoming these issues and include techniques such as personalisation and recommender systems. In this paper, following on from the DELOS/NSF Working Group on Personalisation and Recommender Systems for Digital Libraries, which met and reported during 2003, we present some background material on the scope of personalisation and recommender systems in digital libraries. We then outline the working groupâs vision for the evolution of digital libraries and the role that personalisation and recommender systems will play, and we present a series of research challenges and specific recommendations and research priorities for the field
Drug resistance in non-B subtype HIV-1: Impact of HIV-1 reverse transcriptase inhibitors
Human immunodeficiency virus (HIV) causes approximately 2.5 million new infections every year, and nearly 1.6 million patients succumb to HIV each year. Several factors, including cross-species transmission and error-prone replication have resulted in extraordinary genetic diversity of HIV groups. One of these groups, known as group M (main) contains nine subtypes (A-D, F-H and J-K) and causes âŒ95% of all HIV infections. Most reported data on susceptibility and resistance to anti-HIV therapies are from subtype B HIV infections, which are prevalent in developed countries but account for only âŒ12% of all global HIV infections, whereas non-B subtype HIV infections that account for âŒ88% of all HIV infections are prevalent primarily in low and middle-income countries. Although the treatments for subtype B infections are generally effective against non-B subtype infections, there are differences in response to therapies. Here, we review how polymorphisms, transmission efficiency of drug-resistant strains, and differences in genetic barrier for drug resistance can differentially alter the response to reverse transcriptase-targeting therapies in various subtypes
A Randomized Trial Evaluating Prosaptideâą for HIV-Associated Sensory Neuropathies: Use of an Electronic Diary to Record Neuropathic Pain
Objectives: To examine the efficacy and safety of Prosaptideâą (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN). Design: A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain. Setting: Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain. Participants: Eligible participants included adults with neurologist-confirmed painful HIV-SN.Interventions 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.Outcome Measures Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events. Results: 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were â0.12 (0.23), â0.24 (0.35), â0.15 (0.32), â0.18 (0.34), and â0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.Conclusions 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods. Trial Registration: Current Controlled Trials NCT0028637
Antenatal glucocorticoid treatment induces adaptations in adult midbrain dopamine neurons, which underpin sexually dimorphic behavioral resilience
We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16-19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA function in adult rats. We show that in adulthood, enrichment of striatal DA fiber density paralleled AGT-induced increases in the numbers of midbrain DA neurons, which retained normal basal electrophysiological properties. This was co-incident with changes in (i) striatal D2-type receptor levels (increased, both sexes); (ii) D1-type receptor levels (males decreased; females increased); (iii) DA transporter levels (males increased; females decreased) in striatal regions; and (iv) amphetamine-induced mesolimbic DA release (males increased; females decreased). However, despite these profound, sexually dimorphic changes in markers of DA neurotransmission, in-utero glucocorticoid overexposure had a modest or no effect on a range of conditioned and unconditioned appetitive behaviors known to depend on mesolimbic DA activity. These findings provide empirical evidence for enduring AGT-induced adaptive mechanisms within the midbrain DA circuitry, which preserve some, but not all, functions, thereby casting further light on the vulnerability of these systems to environmental perturbations. Furthermore, they demonstrate these effects are achieved by different, often opponent, adaptive mechanisms in males and females, with translational implications for sex biases commonly found in midbrain DA-associated disorders
Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux
<p>Abstract</p> <p>Background</p> <p>Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT).</p> <p>Results</p> <p>In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E<sub>2</sub>), estrone (E<sub>1</sub>), and estriol (E<sub>3</sub>)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, ÎČ, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E<sub>2</sub>-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca<sup>2+</sup>-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E<sub>2</sub>-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERÎČ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10<sup>-9 </sup>M E<sub>2 </sub>treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERÎČ (inhibitory) away from the plasma membrane. In contrast, E<sub>1 </sub>and E<sub>3 </sub>can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane.</p> <p>Conclusion</p> <p>Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.</p
Erosion Surface and Granitic Morphology in the Sierra de Lihuel Calel, Province of La Pampa, Argentina
Fil: Aguilera, Emilia Yolanda. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Sato, Ana MarĂa. Centro de Investigaciones GeolĂłgicas (CIG). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: LlambĂas, Eduardo Jorge. Centro de Investigaciones GeolĂłgicas (CIG). Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Tickyj, Hugo. Departamento de Ciencias Naturales. Facultad de Ciencias Exactas y Naturales. Universidad Nacional de La Pampa; Argentin
Galileons as Wess-Zumino Terms
We show that the galileons can be thought of as Wess-Zumino terms for the
spontaneous breaking of space-time symmetries. Wess-Zumino terms are terms
which are not captured by the coset construction for phenomenological
Lagrangians with broken symmetries. Rather they are, in d space-time
dimensions, d-form potentials for (d+1)-forms which are non-trivial co-cycles
in Lie algebra cohomology of the full symmetry group relative to the unbroken
symmetry group. We introduce the galileon algebras and construct the
non-trivial (d+1)-form co-cycles, showing that the presence of galileons and
multi-galileons in all dimensions is counted by the dimensions of particular
Lie algebra cohomology groups. We also discuss the DBI and conformal galileons
from this point of view, showing that they are not Wess-Zumino terms, with one
exception in each case.Comment: 49 pages. v2 minor changes, version appearing in JHE
Impact of ultraviolet radiation on marine crustacean zooplankton and ichthyoplankton:a synthesis of results from the estuary and Gulf of St. Lawrence, Canada
Transit Photometry as an Exoplanet Discovery Method
Photometry with the transit method has arguably been the most successful
exoplanet discovery method to date. A short overview about the rise of that
method to its present status is given. The method's strength is the rich set of
parameters that can be obtained from transiting planets, in particular in
combination with radial velocity observations; the basic principles of these
parameters are given. The method has however also drawbacks, which are the low
probability that transits appear in randomly oriented planet systems, and the
presence of astrophysical phenomena that may mimic transits and give rise to
false detection positives. In the second part we outline the main factors that
determine the design of transit surveys, such as the size of the survey sample,
the temporal coverage, the detection precision, the sample brightness and the
methods to extract transit events from observed light curves. Lastly, an
overview over past, current and future transit surveys is given. For these
surveys we indicate their basic instrument configuration and their planet
catch, including the ranges of planet sizes and stellar magnitudes that were
encountered. Current and future transit detection experiments concentrate
primarily on bright or special targets, and we expect that the transit method
remains a principal driver of exoplanet science, through new discoveries to be
made and through the development of new generations of instruments.Comment: Review chapte
Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women
Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αÎČ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND
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