2,118 research outputs found
Ezetimibe therapy: mechanism of action and clinical update.
The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Although statin therapy is the mainstay for LDL-C lowering, a significant percentage of patients prescribed these agents either do not achieve targets with statin therapy alone or have partial or complete intolerance to them. For such patients, the use of adjuvant therapy capable of providing incremental LDL-C reduction is advised. One such agent is ezetimibe, a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border. Its primary target of action is the cholesterol transport protein Nieman Pick C1 like 1 protein. Ezetimibe is an effective LDL-C lowering agent and is safe and well tolerated. In response to significant controversy surrounding the use and therapeutic effectiveness of this drug, we provide an update on the biochemical mechanism of action for ezetimibe, its safety and efficacy, as well as the results of recent randomized studies that support its use in a variety of clinical scenarios
Better reporting of interventions : template for intervention description and replication (TIDieR) checklist and guide
Peer reviewedPublisher PD
Evaluation of a Bayesian inference network for ligand-based virtual screening
Background
Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity.
Results
Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought.
Conclusion
A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening
Composition and distribution of the peracarid crustacean fauna along a latitudinal transect off Victoria Land (Ross Sea, Antarctica) with special emphasis on the Cumacea
The following study was the first to describe composition and structure of the peracarid fauna systematically along a latitudinal transect off Victoria Land (Ross Sea, Antarctica). During the 19th Antarctic expedition of the Italian research vessel “Italica” in February 2004, macrobenthic samples were collected by means of a Rauschert dredge with a mesh size of 500 m at depths between 85 and 515 m. The composition of peracarid crustaceans, especially Cumacea was investigated. Peracarida contributed 63% to the total abundance of the fauna. The peracarid samples were dominated by amphipods (66%), whereas cumaceans were represented with 7%. Previously, only 13 cumacean species were known, now the number of species recorded from the Ross Sea increased to 34. Thus, the cumacean fauna of the Ross Sea, which was regarded as the poorest in terms of species richness, has to be considered as equivalent to that of other high Antarctic areas. Most important cumacean families concerning abundance and species richness were Leuconidae, Nannastacidae, and Diastylidae. Cumacean diversity was lowest at the northernmost area (Cape Adare). At the area off Coulman Island, which is characterized by muddy sediment, diversity was highest. Diversity and species number were higher at the deeper stations and abundance increased with latitude. A review of the bathymetric distribution of the Cumacea from the Ross Sea reveals that most species distribute across the Antarctic continental shelf and slope. So far, only few deep-sea records justify the assumption of a shallow-water–deep-sea relationship in some species of Ross Sea Cumacea, which is discussed from an evolutionary point of view
Improving the performance of bright quantum dot single photon sources using amplitude modulation
Single epitaxially-grown semiconductor quantum dots have great potential as
single photon sources for photonic quantum technologies, though in practice
devices often exhibit non-ideal behavior. Here, we demonstrate that amplitude
modulation can improve the performance of quantum-dot-based sources. Starting
with a bright source consisting of a single quantum dot in a fiber-coupled
microdisk cavity, we use synchronized amplitude modulation to temporally filter
the emitted light. We observe that the single photon purity, temporal overlap
between successive emission events, and indistinguishability can be greatly
improved with this technique. As this method can be applied to any triggered
single photon source, independent of geometry and after device fabrication, it
is a flexible approach to improve the performance of solid-state systems, which
often suffer from excess dephasing and multi-photon background emission
Risk, Unexpected Uncertainty, and Estimation Uncertainty: Bayesian Learning in Unstable Settings
Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free) reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter) estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free) reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating
Transformation of spin information into large electrical signals via carbon nanotubes
Spin electronics (spintronics) exploits the magnetic nature of the electron,
and is commercially exploited in the spin valves of disc-drive read heads.
There is currently widespread interest in using industrially relevant
semiconductors in new types of spintronic devices based on the manipulation of
spins injected into a semiconducting channel between a spin-polarized source
and drain. However, the transformation of spin information into large
electrical signals is limited by spin relaxation such that the magnetoresistive
signals are below 1%. We overcome this long standing problem in spintronics by
demonstrating large magnetoresistance effects of 61% at 5 K in devices where
the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron
gap between epitaxial electrodes of the highly spin polarized manganite
La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes
is long due the small spin-orbit coupling of carbon, because the high nanotube
Fermi velocity permits the carrier dwell time to not significantly exceed this
spin lifetime, because the manganite remains highly spin polarized up to the
manganite-nanotube interface, and because the interfacial barrier is of an
appropriate height. We support these latter statements regarding the interface
using density functional theory calculations. The success of our experiments
with such chemically and geometrically different materials should inspire
adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and
references. New author include
Extreme-ultraviolet brightenings in the quiet Sun: Signatures in spectral and imaging data from the Interface Region Imaging Spectrograph
CONTEXT: Localised transient EUV brightenings, sometimes named ‘campfires’, occur throughout the quiet Sun. However, there are still many open questions about these events, in particular regarding their temperature range and dynamics. AIM: We aim to determine whether any transition region response can be detected for small-scale extreme-ultraviolet (EUV) brightenings and, if so, to identify whether the measured spectra correspond to any previously reported bursts in the transition region, such as explosive events (EEs). METHODS: EUV brightenings were detected in a ∼29.4 min dataset sampled by the Solar Orbiter Extreme Ultraviolet Imager (EUI) on 8 March 2022 using an automated detection algorithm. Any potential transition region response was inferred through analysis of imaging and spectral data sampled through coordinated observations conducted by the Interface Region Imaging Spectrograph (IRIS). RESULTS: EUV brightenings display a range of responses in IRIS slit-jaw imager (SJI) data. Some events have clear signatures in the Mg II and Si IV SJI filters, whilst others have no discernible counterpart. Both extended and more complex EUV brightenings are sometimes found to have responses in IRIS SJI data. Examples of EUI intensities peaking before, during, and after their IRIS counterparts were found in light curves constructed co-spatial to EUV brightenings. Importantly, therefore, it is likely that not all EUV brightenings are driven in the same way, with some events seemingly being magnetic reconnection driven and others not. A single EUV brightening occurred co-spatial to the IRIS slit, with the returned spectra matching the properties of EEs. CONCLUSIONS: EUV brightening is a term used to describe a range of small-scale events in the solar corona. The physics behind all EUV brightenings is likely not the same. More research is therefore required to assess their importance for global questions in the field, such as coronal heating
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