Cholesterol and Alzheimer's Disease Risk: A Meta-Meta-Analysis

Background: Alzheimer''s disease (AD) is the most common subtype of dementia. In the last ten years, the relationship between cholesterol and AD has been investigated. Evidence suggests that cholesterol is associated with AD and represents promising targets for intervention. However, the causality of these associations is unclear. Therefore, we sought to conduct a meta-meta-analysis to determine the effect of cholesterol on the development AD. Then, we assessed the effect of serum levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG), on AD risk. Methods: A systematic search of meta-analyses was conducted. Scopus, Web of Science, Science direct, PubMed and Google academic system databases were reviewed. Results: We found 100 primary studies and five meta-analyses to analyze the relationships between cholesterol and AD. The total effect of cholesterol on risk of AD was significant and heterogeneous. Subgroup analysis shows that LDL-C levels influence the development of AD. However, non-significant effects of HDL-C, TC and TG levels on AD were found. Conclusions: These results strengthen the evidence that LDL-C cholesterol levels increase risk for AD. More initiatives to investigate the relationship between cholesterol and AD are needed

Measurement of the Stray Light in the Advanced Virgo Input Mode Cleaner Cavity using an instrumented baffle

A new instrumented baffle was installed in Spring 2021 at Virgo surrounding the suspended mirror in the input mode cleaner triangular cavity. It serves as a demonstrator of the technology designed to instrument the baffles in the main arms in the near future. We present, for the first time, results on the measured scattered light distribution inside the cavity as determined by the new device using data collected between May and July 2021, with Virgo in commissioning phase and operating with an input laser power in the cavity of 28.5~W. The sensitivity of the baffle is discussed and the data is compared to scattered light simulations.Comment: 4 pages, 5 figures, 1 tabl

Strength and ductility demands on wind turbine towers due to earthquake and wind load

In earthquake prone areas, wind and earthquake loads are assumed to be statistically uncorrelated, therefore their interaction is ignored by existing design guidelines. However, the fact that strong earthquake events are commonly followed by aftershocks and that wind is constantly flowing at high speeds around wind farms increase the probability of their joint occurrence, thus making current design assumptions questionable. This investigation shows that multi-hazard scenarios magnify strength demands of wind turbine towers designed against isolated load conditions, hence modifying their performance level. It is also shown that, under certain conditions, the probabilities associated to the joint occurrence of earthquake and low to strong wind events match or exceed those related to the original design, thus rendering wind energy infrastructure susceptible to unforeseen damage

An instrumented baffle for the Advanced Virgo Input Mode Cleaner End Mirror

A novel instrumented baffle surrounding the suspended end mirror in the input mode cleaner cavity of the Virgo interferometer was installed in spring 2021. Since then, the device has been regularly operated in the experiment and the obtained results indicate a good agreement with simulations of the stray light inside the optical cavity. The baffle will operate in the upcoming O4 observation run, serving as a demonstrator of the technology designed to instrument the baffles in front of the main mirrors in time for O5. In this paper we present a detailed description of the baffle design, including mechanics, front-end electronics, data acquisition, as well as optical and vacuum tests, calibration and installation procedures, and performance results.Comment: 12 pages, 21 figures, 3 tables, to be submitted to PR

Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells

Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome

Mutational Analysis of the Cyanobacterial Nitrogen Regulator PipX

PipX provides a functional link between the cyanobacterial global transcriptional regulator NtcA and the signal transduction protein PII, a protein found in all three domains of life as integrators of signals of the nitrogen and carbon balance. PipX, which is toxic in the absence of PII, can form alternative complexes with NtcA and PII and these interactions are respectively stimulated and inhibited by 2-oxoglutarate, providing a mechanism by which PII can modulate expression at the NtcA regulon. Structural information on PipX-NtcA complexes suggests that PipX coactivates NtcA controlled genes by stabilizing the active conformation of NtcA bound to 2-oxoglutarate and by possibly helping recruit RNA polymerase. To get insights into PipX functions, we perform here a mutational analysis of pipX informed by the structures of PipX-PII and PipX-NtcA complexes and evaluate the impact of point mutations on toxicity and gene expression. Two amino acid substitutions (Y32A and E4A) were of particular interest, since they increased PipX toxicity and activated NtcA dependent genes in vivo at lower 2-oxoglutarate levels than wild type PipX. While both mutations impaired complex formation with PII, only Y32A had a negative impact on PipX-NtcA interactions

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Observation of the Bs0→J/ψϕϕB_s^0 \rightarrow J/\psi \phi \phi decay

The $B_s^0 \rightarrow J/\psi \phi \phi$ decay is observed in $pp$ collision data corresponding to an integrated luminosity of 3 fb$^{-1}$ recorded by the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first observation of this decay channel, with a statistical significance of 15 standard deviations. The mass of the $B_s^0$ meson is measured to be $5367.08\,\pm \,0.38\,\pm\, 0.15$ MeV/c$^2$. The branching fraction ratio $\mathcal{B}(B_s^0 \rightarrow J/\psi \phi \phi)/\mathcal{B}(B_s^0 \rightarrow J/\psi \phi)$ is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}. In both cases, the first uncertainty is statistical and the second is systematic. No evidence for non-resonant $B_s^0 \rightarrow J/\psi \phi K^+ K^-$ or $B_s^0 \rightarrow J/\psi K^+ K^- K^+ K^-$ decays is found.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-033.htm