21 research outputs found

    Planck early results XXIV : Dust in the diffuse interstellar medium and the Galactic halo

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    Peer reviewe

    Planck early results XVIII : The power spectrum of cosmic infrared background anisotropies

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    Peer reviewe

    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

    Synthesis and Visible-Light-Driven Photocatalytic Activity of Ta<sup>4+</sup> Self-Doped Gray Ta<sub>2</sub>O<sub>5</sub> Nanoparticles

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    C-impregnated/Ta<sup>4+</sup> self-doped ultrafine Ta<sub>2</sub>O<sub>5</sub> nanoparticles (NPs) were prepared by a one-step solvothermal method through reaction of Ta­(V) chloride with benzyl alcohol. These NPs showed a large specific surface area of 253.4 m<sup>2</sup> g<sup>–1</sup>, mean diameter of 2–3 nm, and superior photocatalytic activity in the photodegradation of Rhodamine B dye (RhB), compared to TiO<sub>2</sub> (P25) and Ta<sub>2</sub>O<sub>5</sub> commercial NPs. The obtained materials were annealed at different temperatures and their structure, morphology and optical and photocatalytic properties were investigated in detail. The C-impregnated Ta<sup>4+</sup> self-doped Ta<sub>2</sub>O<sub>5</sub> NPs presented enhanced and extended absorption in the visible range of the solar spectrum, increasing significantly their photocatalytic activity. The best photocatalyst could completely remove RhB after only 12 min of UV irradiation and yielded 68% and 43% of RhB photodegradation after 120 min of simulated sunlight and visible irradiation, respectively, with an apparent quantum efficiency of 3.6% at 447 nm. This enhanced photocatalytic performance is ascribed to the combined effects of better light harvesting properties, high surface area and longer electron lifetimes in the excited sub-band, due to the presence both of oxygen vacancies neighboring Ta<sup>4+</sup> and Ta–O–C on the Ta<sub>2</sub>O<sub>5</sub> surface. The photocatalyst systems presented good stability, confirming their promise as candidates for photocatalytic applications

    Addressing the Magnitude of the Nonlinear Refraction Response in Perovskite Nanocrystals

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    Colloidal perovskite nanocrystals (PNCs) are among the most studied optical materials in the last decade. Because of their remarkable optical properties, such as high photoluminescence quantum yield, narrow emission spectra, and high tunability in the visible range, they have become important candidates for several applications in optoelectronics technologies. Most recently, several reports have claimed that this class of nanomaterials also possesses outstanding third-order nonlinear optical properties, such as a high two-photon absorption cross section and a high nonlinear refractive index. In this paper, we investigate the nonlinear optical response for a series of CsPbBr3 PNCs and show that their nonlinear optical response is not particularly high. Different from what has been claimed in the literature, we show that no evidence is found to support that the nonlinear refractive index for these PNCs is larger than those observed for other semiconductors, as the measured magnitude varies between 10–14 and 10–13 cm2/W, the same order of magnitude as bulk semiconductors with a similar band gap energy
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