A study of super-luminous stars with the Fermi Large Area Telescope

The $\gamma$-ray emission from stars is induced by the interaction of cosmic rays with stellar atmospheres and photon fields. This emission is expected to come in two components: a stellar disk emission, where $\gamma$-rays are mainly produced in atmospheric showers generated by hadronic cosmic rays, and an extended halo emission, where the high density of soft photons in the surroundings of stars create a suitable environment for $\gamma$-ray production via inverse Compton (IC) scattering by cosmic-ray electrons. Besides the Sun, no other disk or halo from single stars has ever been detected in $\gamma$-rays. However, by assuming a cosmic-ray spectrum similar to that observed on Earth, the predicted $\gamma$-ray emission of super-luminous stars, like e.g. Betelgeuse and Rigel, could be high enough to be detected by the Fermi Large Area Telescope (LAT) after its first decade of operations. In this work, we use 12 years of Fermi-LAT observations along with IC models to study 9 super-luminous nearby stars, both individually and via stacking analysis. Our results show no significant $\gamma$-ray emission, but allow us to restrict the stellar $\gamma$-ray fluxes to be on average $<3.3 \times 10^{-11}$ ph cm$^{-2}$ s$^{-1}$ at a 3$\sigma$ confidence level, which translates to an average local density of electrons in the surroundings of our targets to be less than twice of that observed for the Solar System.Comment: 8 pages, 4 figure

Efficient District Heating in a Decarbonisation Perspective: A Case Study in Italy

The European and national regulations in the decarbonisation path towards 2050 promote district heating in achieving the goals of efficiency, energy sustainability, use of renewables, and reduction of fossil fuel use. Improved management and optimisation, use of RES, and waste heat/cold sources decrease the overall demand for primary energy, a condition that is further supported by building renovations and new construction of under (almost) zero energy buildings, with a foreseeable decrease in the temperature of domestic heating systems. Models for the simulation of efficient thermal networks were implemented and described in this paper, together with results from a real case study in Italy, i.e., University Campus of Parma. Activities include the creation and validation of calculation codes and specific models in the Modelica language (Dymola software), aimed at investigating stationary regimes and dynamic behaviour as well. An indirect heat exchange substation was coupled with a resistive-capacitive model, which describes the building behaviour and the thermal exchanges by the use of thermos-physical parameters. To optimise indoor comfort conditions and minimise consumption, dynamic simulations were carried out for different operating sets: modulating the supply temperature in the plant depending on external conditions (Scenario 4) decreases the supplied thermal energy (-2.34%) and heat losses (-8.91%), even if a lower temperature level results in higher electricity consumption for pumping (+12.96%), the total energy consumption is reduced by 1.41%. A simulation of the entire heating season was performed for the optimised scenario, combining benefits from turning off the supply in the case of no thermal demand (Scenario 3) and from the modulation of the supply temperature (Scenario 4), resulting in lower energy consumption (the thermal energy supplied by the power plant -3.54%, pumping +7.76%), operating costs (-2.40), and emissions (-3.02%). The energy balance ex-ante and ex-post deep renovation in a single user was then assessed, showing how lowering the network operating temperature at 55 degrees C decreases the supplied thermal energy (-22.38%) and heat losses (-22.11%) with a slightly higher pumping consumption (+3.28%), while maintaining good comfort conditions. These promising results are useful for evaluating the application of low-temperature operations to the existing district heating networks, especially for large interventions of building renovation, and confirm their potential contribution to the energy efficiency targets

A Smo/Gli multitarget hedgehog pathway inhibitor impairs tumor growth

Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to effectively overcome the drug resistance, particularly at the level of Smo. Here, we combined the pharmacophores targeting Smo and Gli1 into a single and individual isoflavone, compound 22, which inhibits the Hh pathway at both upstream and downstream level. We demonstrate that this multitarget agent suppresses medulloblastoma growth in vitro and in vivo through antagonism of Smo and Gli1, which is a novel mechanism of action in Hh inhibition

Impact of a Shorter Brine Soaking Time on Nutrient Bioaccessibility and Peptide Formation in 30-Months-Ripened Parmigiano Reggiano Cheese

Reducing the salt content in food is an important nutritional strategy for decreasing the risk of diet-related diseases. This strategy is particularly effective when applied to highly appreciated food having good nutritional characteristics, if it does not impact either upon sensory or nutritional properties of the final product. This work aimed at evaluating if the reduction of salt content by decreasing the brine soaking time modifies fatty acid and protein bioaccessibility and bioactive peptide formation in a 30-month-ripened Parmigiano Reggiano cheese (PRC). Hence, conventional and hyposodic PRC underwent in vitro static gastrointestinal digestion, and fatty acid and protein bioaccessibility were assessed. The release of peptide sequences during digestion was followed by LC–HRMS, and bioactive peptides were identified using a bioinformatic approach. At the end of digestion, fatty acid and protein bioaccessibility were similar in conventional and hyposodic PRC, but most of the bioactive peptides, mainly the ACE-inhibitors, were present in higher concentrations in the low-salt cheese. Considering that the sensory profiles were already evaluated as remarkably similar in conventional and hyposodic PRC, our results confirmed that shortening brine soaking time represents a promising strategy to reduce salt content in PRC

Inhibition of p38 MAP kinase pathway induces apoptosis and prevents Epstein Barr virus reactivation in Raji cells exposed to lytic cycle inducing compounds

BACKGROUND: EBV lytic cycle activators, such as phorbol esters, anti-immunoglobulin, transforming growth factor β (TGFβ), sodium butyrate, induce apoptosis in EBV-negative but not in EBV-positive Burkitt's lymphoma (BL) cells. To investigate the molecular mechanisms allowing EBV-infected cells to be protected, we examined the expression of viral and cellular antiapoptotic proteins as well as the activation of signal transduction pathways in BL-derived Raji cells exposed to lytic cycle inducing agents. RESULTS: Our data show that, following EBV activation, the latent membrane protein 1 (LMP1) and the cellular anti-apoptotic proteins MCL-1 and BCL-2 were quickly up-regulated and that Raji cells remained viable even when exposed simultaneously to P(BU)(2), sodium butyrate and TGFβ. We report here that inhibition of p38 pathway, during EBV activation, led to a three fold increment of apoptosis and largely prevented lytic gene expression. CONCLUSION: These findings indicate that, during the switch from the latent to the lytic phase of EBV infection, p38 MAPK phosphorylation plays a key role both for protecting the host cells from apoptosis as well as for inducing viral reactivation. Because Raji cells are defective for late antigens expression, we hypothesize that the increment of LMP1 gene expression in the early phases of EBV lytic cycle might contribute to the survival of the EBV-positive cells

Effect of Sprouting on Biomolecular and Antioxidant Features of Common Buckwheat (Fagopyrum esculentum)

Buckwheat is a pseudo-cereal widely grown and consumed throughout the world. Buckwheat is recognized as a good source of nutrients and, in combination with other health-promoting components, is receiving increasing attention as a potential functional food. Despite the high nutritional value of buckwheat, a variety of anti-nutritional features makes it difficult to exploit its full potential. In this framework, sprouting (or germination) may represent a process capable of improving the macromolecular profile, including reducing anti-nutritional factors and/or synthesizing or releasing bioactives. This study addressed changes in the biomolecular profile and composition of buckwheat that was sprouted for 48 and 72 h. Sprouting increased the content of peptides and free-phenolic compounds and the antioxidant activity, caused a marked decline in the concentration of several anti-nutritional components, and affected the metabolomic profile with an overall improvement in the nutritional characteristics. These results further confirm sprouting as a process suitable for improving the compositional traits of cereals and pseudo-cereals, and are further steps towards the exploitation of sprouted buckwheat as a high-quality ingredient in innovative products of industrial interest

Determinants of SARS-CoV-2 Contagiousness in Household Contacts of Symptomatic Adult Index Cases

BACKGROUND: Identifying determinants of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in settings of contagion is fundamental to inform containment strategies. We assessed SARS-CoV-2 cycle threshold value (Ct) from the first diagnostic nasal–pharyngeal swab of symptomatic index cases and which demographic or clinical characteristics among cases and contacts are associated with transmission risk within households. METHODS: This is a retrospective prevalence study on secondary SARS-CoV-2 cases (SC) among the household contacts of symptomatic adult index cases randomly sampled from all the SARS-CoV-2-positive diagnostic nasopharyngeal swabs analyzed at our regional referral hospital (Amedeo di Savoia Hospital, Turin, Italy) in March, 2020. Index cases underwent a telephone survey to collect their demographic and clinical data and all their household contacts. The Ct value of RdRp gene from the first diagnostic swab of index cases was recorded and index cases were grouped according to Ct tertiles (A < first tertile, first ≤ B ≤ second tertile, C ≥ second tertile). Post hoc analysis was performed in SC as well as contacts that did not undergo SARS-CoV-2 testing but developed compatible signs and symptoms. Non-parametric tests and generalized linear models were run. RESULTS: Index (n = 72) and contact (n = 164) median age was 54 (48–63) and 32 (20–56) years, respectively. A total of 60, 50, and 54 subjects were contacts of group A, B, and C index cases, respectively; 35.9% of contacts were SC. Twenty-four further subjects (14.6%) met the criteria for symptom-based likely positive SC. The secondary attack rate was 36.0% (28.6–43.4), assuming a mean incubation period of 5 days and a maximum infectious period of 20 days. SC prevalence differed between Ct groups (53.3% A, 32.0% B, 20.4% C; p < 0.001). No difference in SC was found according to sex, presence of signs/symptoms, and COVID-19 severity of index cases, or according to contacts’ sex and number per household. The age of both index cases [aOR 4.52 (1.2–17.0) for 60 vs. ≤45 years old] and contacts [aOR 3.66 (1.3–10.6) for 60 vs. ≤45years old] and the Ct of the index [aOR 0.17 (0.07–0.4) for Ct ≥ 31.8 vs. Ct < 24.4] independently associated with SC risk. Sensitivity analysis including symptoms-based likely positive SC supported all the previous results. CONCLUSION: In confined transmission settings such as households, PCR Ct values may inform on the contagiousness of infected subjects and age may modulate transmission/contagion risk

Poor efficacy of palbociclib in second-line treatment of metastatic lobular breast cancer in a case series: Use before or never more?

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