Domino alkylation-cyclization reaction of propargyl bromides with thioureas/thiopyrimidinones: A new facile synthesis of 2-aminothiazoles and 5H-thiazolo[3,2-a]pyrimidin-5-ones

A new synthesis of 2-aminothiazoles and 5H-thiazolo[3,2-a]pyrimidin-5-ones was developed as a domino alkylation-cyclization reaction of propargyl bromides with thioureas and thio¬pyrimidinones, respectively. Domino reactions were performed under microwave irradiation leading to desired compounds in a few minutes and high yield

Breaking Be: a sterile neutrino solution to the cosmological lithium problem

The possibility that the so-called "lithium problem", i.e. the disagreement between the theoretical abundance predicted for primordial $^7$Li assuming standard nucleosynthesis and the value inferred from astrophysical measurements, can be solved through a non-thermal BBN mechanism has been investigated by several authors. In particular, it has been shown that the decay of a MeV-mass particle, like, e.g., a sterile neutrino, decaying after BBN not only solves the lithium problem, but also satisfies cosmological and laboratory bounds, making such a scenario worth to be investigated in further detail. In this paper, we constrain the parameters of the model with the combination of current data, including Planck 2015 measurements of temperature and polarization anisotropies of the CMB, FIRAS limits on spectral distortions, astrophysical measurements of primordial abundances and laboratory constraints. We find that a sterile neutrino with mass $M_S=4.35_{-0.17}^{+0.13}\,MeV$ (at $95\%$ c.l.), a decay time $\tau_S=1.8_{-1.3}^{+2.5}\cdot 10^5\,s$ (at $95\%$ c.l.) and an initial density $\bar{n}_S/\bar{n}_{cmb}=1.7_{-0.6}^{+3.5}\cdot 10^{-4}$ (at $95\%$ c.l.) in units of the number density of CMB photons, perfectly accounts for the difference between predicted and observed $^7$Li primordial abundance. This model also predicts an increase of the effective number of relativistic degrees of freedom at the time of CMB decoupling $\Delta N_{eff}^{cmb}\equiv N_{eff}^{cmb}-3.046=0.34_{-0.14}^{+0.16}$ at $95\%$ c.l.. The required abundance of sterile neutrinos is incompatible with the standard thermal history of the Universe, but could be realized in a low reheating temperature scenario. We provide forecasts for future experiments finding that the combination of measurements from the COrE+ and PIXIE missions will allow to significantly reduce the permitted region for the sterile lifetime and density.Comment: 28 pages, 13 figures, 4 tables, matching the published versio

Blue Gravity Waves from BICEP2 ?

We present new constraints on the spectral index n_T of tensor fluctuations from the recent data obtained by the BICEP2 experiment. We found that the BICEP2 data alone slightly prefers a positive, "blue", spectral index with n_T=1.36\pm0.83 at 68 % c.l.. However, when a TT prior on the tensor amplitude coming from temperature anisotropy measurements is assumed we get n_T=1.67\pm0.53 at 68 % c.l., ruling out a scale invariant $n_T=0$ spectrum at more than three standard deviations. These results are at odds with current bounds on the tensor spectral index coming from pulsar timing, Big Bang Nucleosynthesis, and direct measurements from the LIGO experiment. Considering only the possibility of a "red", n_T<0 spectral index we obtain the lower limit n_T > -0.76 at 68 % c.l. (n_T>-0.09 when a TT prior is included).Comment: 3 Pages, 4 Figure

POLOCALC: a Novel Method to Measure the Absolute Polarization Orientation of the Cosmic Microwave Background

We describe a novel method to measure the absolute orientation of the polarization plane of the CMB with arcsecond accuracy, enabling unprecedented measurements for cosmology and fundamental physics. Existing and planned CMB polarization instruments looking for primordial B-mode signals need an independent, experimental method for systematics control on the absolute polarization orientation. The lack of such a method limits the accuracy of the detection of inflationary gravitational waves, the constraining power on the neutrino sector through measurements of gravitational lensing of the CMB, the possibility of detecting Cosmic Birefringence, and the ability to measure primordial magnetic fields. Sky signals used for calibration and direct measurements of the detector orientation cannot provide an accuracy better than 1 deg. Self-calibration methods provide better accuracy, but may be affected by foreground signals and rely heavily on model assumptions. The POLarization Orientation CALibrator for Cosmology, POLOCALC, will dramatically improve instrumental accuracy by means of an artificial calibration source flying on balloons and aerial drones. A balloon-borne calibrator will provide far-field source for larger telescopes, while a drone will be used for tests and smaller polarimeters. POLOCALC will also allow a unique method to measure the telescopes' polarized beam. It will use microwave emitters between 40 and 150 GHz coupled to precise polarizing filters. The orientation of the source polarization plane will be registered to sky coordinates by star cameras and gyroscopes with arcsecond accuracy. This project can become a rung in the calibration ladder for the field: any existing or future CMB polarization experiment observing our polarization calibrator will enable measurements of the polarization angle for each detector with respect to absolute sky coordinates.Comment: 15 pages, 5 figures, Accepted by Journal of Astronomical Instrumentatio

Role of autophagy in cancer cell response to nucleolar and endoplasmic reticulum stress

Eukaryotic cells are exposed to many internal and external stimuli that affect their fate. In particular, the exposure to some of these stimuli induces stress triggering a variety of stress responses aimed to re-establish cellular homeostasis. It is now established that the deregulation of stress response pathways plays a central role in cancer initiation and progression, allowing the adaptation of cells to an altered state in the new environment. Autophagy is a tightly regulated pathway which exerts “housekeeping” role in physiological processes. Recently, a growing amount of evidence highlighted the crucial role of autophagy in the regulation of integrated stress responses, including nucleolar and endoplasmic reticulum. In this review, we attempt to afford an overview of the complex role of nucleolar and endoplasmic reticulum stress-response mechanisms in the regulation of autophagy in cancer and cancer treatment

Probing Lorentz-violating electrodynamics with CMB polarization

We perform a comprehensive study of the signatures of Lorentz violation in electrodynamics on the Cosmic Microwave Background (CMB) anisotropies. In the framework of the minimal Standard Model Extension (SME), we consider effects generated by renormalizable operators, both CPT-odd and CPT-even. These operators are responsible for sourcing, respectively, cosmic birefringence and circular polarization. We propagate jointly the effects of all the relevant Lorentz-violating parameters to CMB observables and provide constraints with the most recent CMB datasets. We bound the CPT-even coefficient to $k_{F,E+B} < 2.31 \times 10^{-31}$ at 95\% CL. This improves previous CMB bounds by one order of magnitude. The limits we obtain on the CPT-odd coefficients, i.e. $|k_{(V)00}^{(3)}| < 1.54 \times 10^{-44} \; {\rm GeV}$ and $|\mathbf{k_{AF}}| < 0.74 \times 10^{-44} \; {\rm GeV}$ at 95\% CL, are respectively one and two orders of magnitude stronger than previous CMB-based limits, superseding also bounds from non-CMB searches. This analysis provides the strongest constraints to date on CPT-violating coefficients in the minimal SME from CMB searches

Evolution shapes the responsiveness of the D-box enhancer element to light and reactive oxygen species in vertebrates

The circadian clock is a highly conserved cell-autonomous mechanism that directs daily rhythms in most aspects of biology. Daily entrainment by environmental signals, notably light, is essential for its function. However, our understanding of the mechanisms and the evolution of photic entrainment remains incomplete. Fish represent attractive models for exploring how light regulates the circadian clock due to the direct light sensitivity of their peripheral clocks. Central to this property is the light induced expression of clock genes that is mediated by D-box enhancer elements. Here, using zebrafish cells, we reveal that the light responsive D-box enhancer serves as a nuclear target for reactive oxygen species (ROS). We demonstrate that exposure to short wavelengths of visible light triggers increases in ROS levels via NADPH oxidase activity. Elevated ROS activates the JNK and p38 MAP kinases and in turn, induces clock gene expression via the D-box. In blind cavefish and mammals, where peripheral clocks are no longer entrained by direct illumination, ROS levels are still increased upon light exposure. However, in these species ROS no longer induces D-box driven clock gene transcription. Thus, during evolution, alterations in ROS-responsive signal transduction pathways underlie fundamental changes in peripheral clock photoentrainment.Universidad de Ferrara | Ref. FAR2014–201

Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus

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