Ultrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke

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Multiwavelength Variability Power Spectrum Analysis of the Blazars 3C 279 and PKS 1510-089 on Multiple Timescales

We present the results of variability power spectral density (PSD) analysis using multiwavelength radio to GeV gamma-ray light curves covering timescales of decades/years to days/minutes for the blazars 3C 279 and PKS 1510-089. The PSDs are modeled as single power laws, and the best-fit spectral shape is derived using the "power spectral response" method. With more than 10 yr of data obtained with weekly/daily sampling intervals, most of the PSDs cover similar to 2-4 decades in temporal frequency; moreover, in the optical band, the PSDs cover similar to 6 decades for 3C 279 due to the availability of intranight light curves. Our main results are the following: (1) on timescales ranging from decades to days, the synchrotron and the inverse-Compton spectral components, in general, exhibit red-noise (slope similar to 2) and flicker-noise (slope similar to 1) type variability, respectively; (2) the slopes of gamma-ray variability PSDs obtained using a 3 hr integration bin and 3 weeks total duration exhibit a range between similar to 1.4 and similar to 2.0 (mean slope = 1.60 +/- 0.70), consistent within errors with the slope on longer timescales; (3) comparisons of fractional variability indicate more power on timescales <= 100 days at gamma-ray frequencies compared to longer wavelengths, in general (except between the gamma-ray and optical wavelengths for PKS 1510-089); (4) the normalization of intranight optical PSDs for 3C 279 appears to be a simple extrapolation from longer timescales, indicating a continuous (single) process driving the variability at optical wavelengths; and (5) the emission at optical/infrared wavelengths may involve a combination of disk and jet processes for PKS 1510-089

Stochastic Modeling of Multiwavelength Variability of the Classical BL Lac Object OJ287 on Timescales Ranging from Decades to Hours

We present the results of our power spectral density analysis for the BL Lac object OJ 287, utilizing the Fermi-LAT survey at high-energy.-rays, Swift-XRT in X-rays, several ground-based telescopes and the Kepler satellite in the optical, and radio telescopes at GHz frequencies. The light curves are modeled in terms of continuous-time autoregressive moving average (CARMA) processes. Owing to the inclusion of the Kepler data, we were able to construct for the first time the optical variability power spectrum of a blazar without any gaps across similar to 6 dex in temporal frequencies. Our analysis reveals that the radio power spectra are of a colored-noise type on timescales ranging from tens of years down to months, with no evidence for breaks or other spectral features. The overall optical power spectrum is also consistent with a colored noise on the variability timescales ranging from 117 years down to hours, with no hints of any quasi-periodic oscillations. The X-ray power spectrum resembles the radio and optical power spectra on the analogous timescales ranging from tens of years down to months. Finally, the.-ray power spectrum is noticeably different from the radio, optical, and X-ray power spectra of the source: we have detected a characteristic relaxation timescale in the Fermi-LAT data, corresponding to similar to 150 days, such that on timescales longer than this, the power spectrum is consistent with uncorrelated (white) noise, while on shorter variability timescales there is correlated (colored) noise

On the origin of the Fanaroff-Riley dichotomy

A small fraction of double radio sources show a peculiar and striking hybrid morphology; they have a distinctly FRI structure on one side of the nucleus, and a FRII structure on the other. We argue that the mere existence of these HYMORS is quite incompatible with the theoretical explanations for the Fanaxoff-Riley dichotomy that are based upon the nature of the jet plasma, or those invoking an intrinsic property of the central engine. Rather, these HYMORS strongly support models that explain the difference between FRI and FRII sources in terms of asymmetry of interaction of the jets with the external environments. We further show that a model for radio source dynamics we had earlier proposed can neatly reproduce the observed dependence of the radio power dividing the two FR classes on the optical luminosity of the host galaxy, as found by Owen and White and Ledlow Owen

Global cellular response to chemotherapy-induced apoptosis

How cancer cells globally struggle with a chemotherapeutic insult before succumbing to apoptosis is largely unknown. Here we use an integrated systems-level examination of transcription, translation, and proteolysis to understand these events central to cancer treatment. As a model we study myeloma cells exposed to the proteasome inhibitor bortezomib, a first-line therapy. Despite robust transcriptional changes, unbiased quantitative proteomics detects production of only a few critical anti-apoptotic proteins against a background of general translation inhibition. Simultaneous ribosome profiling further reveals potential translational regulation of stress response genes. Once the apoptotic machinery is engaged, degradation by caspases is largely independent of upstream bortezomib effects. Moreover, previously uncharacterized non-caspase proteolytic events also participate in cellular deconstruction. Our systems-level data also support co-targeting the anti-apoptotic regulator HSF1 to promote cell death by bortezomib. This integrated approach offers unique, in-depth insight into apoptotic dynamics that may prove important to preclinical evaluation of any anti-cancer compound. © Wiita et al

Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.

Funder: Gates Cambridge TrustFunder: Biotechnology and Biological Sciences Research CouncilFunder: Centre for Misfolding Diseases, University of CambridgeFunder: Frances and Augustus Newman FoundationThe rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials

Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.

Funder: FP7 Ideas: European Research Council; doi: 10.13039/100011199; Grant(s): 337969The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials

Can the twin-exhaust model explain radio jets?

The distinctions between compact cores in various powerful extragalactic sources have proved difficult to interpret. In a few source categories (for example radio galaxies and quasistellar radio sources) extended structure on much larger scales exist; their energy is undoubtedly supplied through the narrow channels that are being increasingly observed and seem to be directed from the compact cores. Continuous production of high-energy plasma in a high-pressure region at the core centre is necessary to account for the energetics and channel structures1. The twin-exhaust mechanism 2 is one means of forming double jets in active galactic nuclei. As originally envisaged , the 'central engine' continuously releases hot gas in the centre of a flat-bottomed potential well formed by the stellar cluster in a galactic centre. This potential well holds a cloud of cooler gas which confines the hot gas in a central cavity. If the cooler gas cloud is flattened (for example, by rotation), buoyancy forces can accelerate the hot gas into two collimated jets via de Laval nozzles. These jets may correspond to the observed radio jets in quasars and radio galaxies, and result in the formation of extended double sources. Here, we combine new results from numerical calculations5 of the Blandford-Rees model, with severe observational and theoretical constraints, to reach conclusions concerning the nature of the allowed flows. In particular, we conclude that high-velocity, high-powered jets cannot be produced in gravitational potentials produced by stellar clusters. However, the more general notion of the twin-exhaust mechanism1, in which the central potential can be cusp-like near a massive black hole, is not ruled out for the high-powered radio sources. Note also that more compex twin-exhaust models (for example, magnetohydrodynamic flows) may lead to less severe constraints