Trends Biochem Sci

The metabolic network has a modular architecture, is robust to perturbations, and responds to biological stimuli and environmental conditions. Through monitoring by metabolite responsive macromolecules, metabolic pathways interact with the transcriptome and proteome. Whereas pathway interconnecting cofactors and substrates report on the overall state of the network, specialised intermediates measure the activity of individual functional units. Transitions in the network affect many of these regulatory metabolites, facilitating the parallel regulation of the timing and control of diverse biological processes. The metabolic network controls its own balance, chromatin structure and the biosynthesis of molecular cofactors; moreover, metabolic shifts are crucial in the response to oxidative stress and play a regulatory role in cancer

Resonance fluorescence in a band gap material: Direct numerical simulation of non-Markovian evolution

A numerical method of calculating the non-Markovian evolution of a driven atom radiating into a structured continuum is developed. The formal solution for the atomic reduced density matrix is written as a Markovian algorithm by introducing a set of additional, virtual density matrices which follow, to the level of approximation of the algorithm, all the possible trajectories of the photons in the electromagnetic field. The technique is perturbative in the sense that more virtual density matrices are required as the product of the effective memory time and the effective coupling strength become larger. The number of density matrices required is given by $3^{M}$ where $M$ is the number of timesteps per memory time. The technique is applied to the problem of a driven two-level atom radiating close to a photonic band gap and the steady-state correlation function of the atom is calculated.Comment: 14 pages, 9 figure

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Representation and misrepresentation of scientific evidence in contemporary tobacco regulation:a review of tobacco industry submissions to the UK Government consultation on standardised packaging

BACKGROUND: Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. METHODS AND FINDINGS: We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. CONCLUSIONS: The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation, particularly stakeholder consultation, provide an opportunity for highly resourced corporations to slow, weaken, or prevent public health policies

Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene

BACKGROUND: Recovery of iodide uptake in thyroid cancer cells by means of obtaining the functional expression of the sodium/iodide symporter (NIS) represents an innovative strategy for the treatment of poorly differentiated thyroid cancer. However, the NIS gene expression alone is not always sufficient to restore radioiodine concentration ability in these tumour cells. METHODS: In this study, the anaplastic thyroid carcinoma ARO cells were stably transfected with a Pax8 gene expression vector. A quantitative RT-PCR was performed to assess the thyroid specific gene expression in selected clones. The presence of NIS protein was detected by Western blot and localized by immunofluorescence. A iodide uptake assay was also performed to verify the functional effect of NIS induction and differentiation switch. RESULTS: The clones overexpressing Pax8 showed the re-activation of several thyroid specific genes including NIS, Pendrin, Thyroglobulin, TPO and TTF1. In ARO-Pax8 clones NIS protein was also localized both in cell cytoplasm and membrane. Thus, the ability to uptake the radioiodine was partially restored, associated to a high rate of efflux. In addition, ARO cells expressing Pax8 presented a lower rate of cell growth. CONCLUSION: These finding demonstrate that induction of Pax8 expression may determine a re-differentiation of thyroid cancer cells, including a partial recovery of iodide uptake, fundamental requisite for a radioiodine-based therapeutic approach for thyroid tumours

Silicon and Germanium Nanostructures for Photovoltaic Applications: Ab-Initio Results

Actually, most of the electric energy is being produced by fossil fuels and great is the search for viable alternatives. The most appealing and promising technology is photovoltaics. It will become truly mainstream when its cost will be comparable to other energy sources. One way is to significantly enhance device efficiencies, for example by increasing the number of band gaps in multijunction solar cells or by favoring charge separation in the devices. This can be done by using cells based on nanostructured semiconductors. In this paper, we will present ab-initio results of the structural, electronic and optical properties of (1) silicon and germanium nanoparticles embedded in wide band gap materials and (2) mixed silicon-germanium nanowires. We show that theory can help in understanding the microscopic processes important for devices performances. In particular, we calculated for embedded Si and Ge nanoparticles the dependence of the absorption threshold on size and oxidation, the role of crystallinity and, in some cases, the recombination rates, and we demonstrated that in the case of mixed nanowires, those with a clear interface between Si and Ge show not only a reduced quantum confinement effect but display also a natural geometrical separation between electron and hole

A Standard Siren Measurement of the Hubble Constant from GW170817 without the Electromagnetic Counterpart

We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago

Increasing the Astrophysical Reach of the Advanced Virgo Detector via the Application of Squeezed Vacuum States of Light

Current interferometric gravitational-wave detectors are limited by quantum noise over a wide range of their measurement bandwidth. One method to overcome the quantum limit is the injection of squeezed vacuum states of light into the interferometer’s dark port. Here, we report on the successful application of this quantum technology to improve the shot noise limited sensitivity of the Advanced Virgo gravitational-wave detector. A sensitivity enhancement of up to 3.2±0.1  dB beyond the shot noise limit is achieved. This nonclassical improvement corresponds to a 5%–8% increase of the binary neutron star horizon. The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time. During this period several gravitational-wave candidates have been recorded

Virgo Detector Characterization and Data Quality during the O3 run

The Advanced Virgo detector has contributed with its data to the rapid growth of the number of detected gravitational-wave signals in the past few years, alongside the two LIGO instruments. First, during the last month of the Observation Run 2 (O2) in August 2017 (with, most notably, the compact binary mergers GW170814 and GW170817) and then during the full Observation Run 3 (O3): an 11 months data taking period, between April 2019 and March 2020, that led to the addition of about 80 events to the catalog of transient gravitational-wave sources maintained by LIGO, Virgo and KAGRA. These discoveries and the manifold exploitation of the detected waveforms require an accurate characterization of the quality of the data, such as continuous study and monitoring of the detector noise. These activities, collectively named {\em detector characterization} or {\em DetChar}, span the whole workflow of the Virgo data, from the instrument front-end to the final analysis. They are described in details in the following article, with a focus on the associated tools, the results achieved by the Virgo DetChar group during the O3 run and the main prospects for future data-taking periods with an improved detector.Comment: 86 pages, 33 figures. This paper has been divided into two articles which supercede it and have been posted to arXiv on October 2022. Please use these new preprints as references: arXiv:2210.15634 (tools and methods) and arXiv:2210.15633 (results from the O3 run

Virgo Detector Characterization and Data Quality: results from the O3 run

The Advanced Virgo detector has contributed with its data to the rapid growth of the number of detected gravitational-wave (GW) signals in the past few years, alongside the two Advanced LIGO instruments. First during the last month of the Observation Run 2 (O2) in August 2017 (with, most notably, the compact binary mergers GW170814 and GW170817), and then during the full Observation Run 3 (O3): an 11-months data taking period, between April 2019 and March 2020, that led to the addition of about 80 events to the catalog of transient GW sources maintained by LIGO, Virgo and now KAGRA. These discoveries and the manifold exploitation of the detected waveforms require an accurate characterization of the quality of the data, such as continuous study and monitoring of the detector noise sources. These activities, collectively named {\em detector characterization and data quality} or {\em DetChar}, span the whole workflow of the Virgo data, from the instrument front-end hardware to the final analyses. They are described in details in the following article, with a focus on the results achieved by the Virgo DetChar group during the O3 run. Concurrently, a companion article describes the tools that have been used by the Virgo DetChar group to perform this work.Comment: 57 pages, 18 figures. To be submitted to Class. and Quantum Grav. This is the "Results" part of preprint arXiv:2205.01555 [gr-qc] which has been split into two companion articles: one about the tools and methods, the other about the analyses of the O3 Virgo dat