Probing primordial black holes at high redshift with future gravitational wave detector

We analyze the detection prospects for potential Primordial Black Hole Binary (PBHB) populations buried in the Stellar-Origin Black Hole Binary (SOBHB) population inferred by the LVK collaboration. We consider different PBHB population scenarios and several future Gravitational Wave (GW) detectors. To separate the PBHB component from the SOBHB one, we exploit the prediction that the PBHB merger rate does not decline as fast as the SOBHB one at high redshift. However, only a tiny fraction of PBHB events may be resolved individually, and the sub-threshold events may yield an undetectable Stochastic GW Background (SGWB). For this reason, we determine the statistical significance of the PBHB contributions in the number of resolvable events seen in future Earth-based detectors and the SGWB measured at LISA. We find that the synergy between these probes will consistently help assess whether or not a sizeable PBHB population is present.Comment: 31 pages, 8 figure

Numerical study of a confined slot impinging jet with nanofluids

<p>Abstract</p> <p>Background</p> <p>Heat transfer enhancement technology concerns with the aim of developing more efficient systems to satisfy the increasing demands of many applications in the fields of automotive, aerospace, electronic and process industry. A solution for obtaining efficient cooling systems is represented by the use of confined or unconfined impinging jets. Moreover, the possibility of increasing the thermal performances of the working fluids can be taken into account, and the introduction of nanoparticles in a base fluid can be considered.</p> <p>Results</p> <p>In this article, a numerical investigation on confined impinging slot jet working with a mixture of water and Al₂O₃nanoparticles is described. The flow is turbulent and a constant temperature is applied on the impinging. A single-phase model approach has been adopted. Different geometric ratios, particle volume concentrations and Reynolds number have been considered to study the behavior of the system in terms of average and local Nusselt number, convective heat transfer coefficient and required pumping power profiles, temperature fields and stream function contours.</p> <p>Conclusions</p> <p>The dimensionless stream function contours show that the intensity and size of the vortex structures depend on the confining effects, given by <it>H/</it>W ratio, Reynolds number and particle concentrations. Furthermore, for increasing concentrations, nanofluids realize increasing fluid bulk temperature, as a result of the elevated thermal conductivity of mixtures. The local Nusselt number profiles show the highest values at the stagnation point, and the lowest at the end of the heated plate. The average Nusselt number increases for increasing particle concentrations and Reynolds numbers; moreover, the highest values are observed for <it>H/W </it>= 10, and a maximum increase of 18% is detected at a concentration equal to 6%. The required pumping power as well as Reynolds number increases and particle concentrations grow, which is almost 4.8 times greater than the values calculated in the case of base fluid.</p> <p> <b>List of symbols</b> </p

Relationship between Latitude and Melanoma in Italy

Objective. Evaluate the ecological relationship between skin melanoma epidemiology and latitude in Italy. Methods. We used data from the Italian network of cancer registries (Airtum). In a Poisson model, we evaluated the effect on incidence, mortality, and survival of latitude, adjusting for some demographic, social, phenotypic, and behavioural variables. Results. Incidence increased in Italy by 17% for each degree of increase in latitude. The effect of latitude was statistically significantly present also adjusting for other variables (incidence rate ratio = 1.08). The effect of latitude on increasing mortality (mortality rate ratio = 1.27) and improving survival (relative excess risk of death = 0.93) was no longer present in the multivariate model. Conclusion. Melanoma incidence, mortality, and survival vary in Italy according to latitude. After adjustment for several confounders, incidence still grows with growing latitude. Presumably, latitude expresses other variables that might be related to individual susceptibility and/or local care

How Far from Equilibrium Is Active Matter?

Active matter systems are driven out of thermal equilibrium by a lack of generalized Stokes-Einstein relation between injection and dissipation of energy at the microscopic scale. We consider such a system of interacting particles, propelled by persistent noises, and show that, at small but finite persistence time, their dynamics still satisfy a time-reversal symmetry. To do so, we compute perturbatively their steady-state measure and show that, for short persistent times, the entropy production rate vanishes. This endows such systems with an effective fluctuation-dissipation theorem akin to that of thermal equilibrium systems. Last, we show how interacting particle systems with viscous drags and correlated noises can be seen as in equilibrium with a viscoelastic bath but driven out of equilibrium by nonconservative forces, hence providing energetic insight into the departure of active systems from equilibrium.JT was supported by ANR project Bactterns. CN was supported by EPSRC grant Nr. EP/J007404.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the American Physical Society

A highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection

Highly pathogenic (HP) PRRSV isolates have been discovered within both PRRSV-1 and PRRSV-2 genotypes and investigated in recent years especially for their ability to cause extremely severe disease in conventional pig herds. The exacerbation of general and respiratory clinical signs has been attributed not only to an efficient replication (virulence) but also to the ability to dysregulate viral recognition and induce mechanisms of immune evasion or immune enhancement of humoral and cellular anti-viral responses differently from non-HP PRRSV isolates in terms of intensity and temporal onset. Thus, the understanding of the immunopathogenesis of HP PRRSV is a major concern for the study of virus biology and development of efficacious vaccines. The present study aims at addressing the modulation of relevant immune cell subsets by flow cytometry in the blood of 4- week-old pigs experimentally infected with the recently discovered PR40/2014 HP PRRSV-1.1 strain phenotypically characterized in Canelli et al. (2017) compared to pigs infected with a non-HP PRRSV isolate (PR11/ 2014) and uninfected controls. PR40 infected animals showed an early and marked reduction of pro-inflammatory CD172α+ CD14+CD16+ and CD14+CD163+ monocytes and TCRγδ+CD8α+/CD8α- lymphocytes when pigs were most infected, possibly due to a recruitment sustaining an acute inflammatory response in target tissues. The prolonged increased CD3+CD16+ NKT cell levels may sustain peripheral inflammation and/ or the anti-viral response. The late reduction (potential depletion) of γ/δ T lymphocytes and CD3+CD4+CD8α- naïve Th lymphocytes paralleled with the delayed increase of CD3+CD4+CD8α+ memory and CD3+CD4- CD8α/β+cytotoxic T lymphocytes. In addition, PR40 infection showed an early depletion of activated CD4+CD25+ T lymphocytes and Tregs together with an intense and lasting depletion of CD21+ B lymphocytes. Overall, these features demonstrate that the more severe clinical signs observed upon infection with the HP PR40 strain are sustained by remarkable changes in the peripheral blood distribution of immune cells and provide further insights into the immune regulation/immunopathogenesis induced by PRRSV-1 subtype 1 European isolates

Structural determinants in the group III truncated hemoglobin from Campylobacter jejuni.

Truncated hemoglobins (trHbs) constitute a distinct lineage in the globin superfamily, distantly related in size and fold to myoglobin and monomeric hemoglobins. Their phylogenetic analyses revealed that three groups (I, II, and III) compose the trHb family. Group I and II trHbs adopt a simplified globin fold, essentially composed of a 2-on-2 alpha-helical sandwich, wrapped around the heme group. So far no structural data have been reported for group III trHbs. Here we report the three-dimensional structure of the group III trHbP from the eubacterium Campylobacter jejuni. The 2.15-angstrom resolution crystal structure of C. jejuni trHbP (cyano-met form) shows that the 2-on-2 trHb fold is substantially conserved in the trHb group III, despite the absence of the Gly-based sequence motifs that were considered necessary for the attainment of the trHb specific fold. The heme crevice presents important structural modifications in the C-E region and in the FG helical hinge, with novel surface clefts at the proximal heme site. Contrary to what has been observed for group I and II trHbs, no protein matrix tunnel/cavity system is evident in C. jejuni trHbP. A gating movement of His(E7) side chain (found in two alternate conformations in the crystal structure) may be instrumental for ligand entry to the heme distal site. Sequence conservation allows extrapolating part of the structural results here reported to the whole trHb group III

TMEM219 regulates the transcription factor expression and proliferation of beta cells

Pancreatic beta cells replenishment is considered the next therapeutic option for type 1 diabetes; while stimulating endogenous beta cells proliferation is the “holy grail” for those patients with exhausted beta cell mass. Here we are demonstrating that the pro-apoptotic receptor TMEM219 is expressed in fetal pancreas, in beta cell precursors and in in vitro embryonic-derived endocrine progenitors. TMEM219 signaling negatively regulates beta cells at early stages and induces Caspase 8-mediated cell death. Pharmacological blockade of TMEM219 further rescued beta cell precursor and proliferation markers, and decreased cell death, both in islets and in in vitro-derived endocrine progenitors, allowing for beta cell preservation. While addressing the upstream controlling TMEM219 expression, we determined the TMEM219 miRNet; indeed, one of those miRNAs, miR-129-2, is highly expressed in human islets, particularly in patients at risk or with established type 1 diabetes. miR-129-2 mimic downregulated TMEM219 expression in islets, in in vitro embryonic-derived endocrine progenitors and in highly proliferating insulinoma-derived cells. Moreover, miR-129-2 inhibitor induced a TMEM219 overexpression in insulinoma-derived cells, which restored cell proliferation and functional markers, thus acting as endogenous regulator of TMEM219 expression. The TMEM219 upstream regulator miR129-2 controls the fate of beta cell precursors and may unleash their regenerative potentials to replenish beta cells in type 1 diabetes

Stochastic gravitational wave background from stellar origin binary black holes in LISA

We use the latest constraints on the population of stellar origin binary black holes (SOBBH) from LIGO/Virgo/KAGRA (LVK) observations, to estimate the stochastic gravitational wave background (SGWB) they generate in the frequency band of LISA. We account for the faint and distant binaries, which contribute the most to the SGWB, by extending the merger rate at high redshift assuming it tracks the star formation rate. We adopt different methods to compute the SGWB signal: an analytical evaluation, Monte Carlo sums over SOBBH population realisations, and a method that accounts for the role of the detector by simulating LISA data and iteratively removing resolvable signals until only the confusion noise is left, allowing for the extraction of both the expected SGWB and the number of resolvable SOBBHs. Since the latter are few for SNR thresholds larger than five, we confirm that the spectral shape of the SGWB in the LISA band follows the analytical prediction of a power law. We infer the probability distribution of the SGWB amplitude from the LVK GWTC-3 posterior of the binary population model; its interquartile range of $h^2\Omega_\mathrm{GW}(f=3\times10^{-3}\,\mathrm{Hz}) \in [5.65,\,11.5]\times10^{-13}$ is in agreement with most previous estimates. We perform a MC analysis to assess LISA's capability to detect and characterise this signal. Accounting for both the instrumental noise and the galactic binaries foreground, with four years of data, LISA will be able to detect the SOBBH SGWB with percent accuracy, narrowing down the uncertainty on the amplitude by one order of magnitude with respect to the range of possible amplitudes inferred from the population model. A measurement of this signal by LISA will help to break the degeneracy among some of the population parameters, and provide interesting constraints, in particular on the redshift evolution of the SOBBH merger rate.Comment: 39 pages, 15 figure

Analysis of Non-Structural Carbohydrates and Xylem Anatomy of Leaf Petioles Offers New Insights in the Drought Response of Two Grapevine Cultivars

In grapevine, the anatomy of xylem conduits and the non-structural carbohydrates (NSCs) content of the associated living parenchyma are expected to influence water transport under water limitation. In fact, both NSC and xylem features play a role in plant recovery from drought stress. We evaluated these traits in petioles of Cabernet Sauvignon (CS) and Syrah (SY) cultivars during water stress (WS) and recovery. In CS, the stress response was associated to NSC consumption, supporting the hypothesis that starch mobilization is related to an increased supply of maltose and sucrose, putatively involved in drought stress responses at the xylem level. In contrast, in SY, the WS-induced increase in the latter soluble NSCs was maintained even 2 days after re-watering, suggesting a different pattern of utilization of NSC resources. Interestingly, the anatomical analysis revealed that conduits are constitutively wider in SY in well-watered (WW) plants, and that water stress led to the production of narrower conduits only in this cultivar

Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumourcells

The aim of the present study was to assess the cytotoxicity of manumycin, a specific inhibitor of farnesyl:protein transferase, as well as its effects on protein isoprenylation and kinase-dependent signal transduction in COLO320-DM human colon adenocarcinoma which harbours a wild-type K- ras gene. Immunoblot analysis of isolated cell membranes and total cellular lysates of COLO320-DM cells demonstrated that manumycin dose-dependently reduced p21 ras farnesylation with a 50% inhibitory concentration (IC50) of 2.51 ± 0.11 μM and 2.68 ± 0.20 μM, respectively, while the geranylgeranylation of p21 rhoA and p21 rap1 was not affected. Manumycin dose-dependently inhibited (IC50= 2.40 ± 0.67 μM) the phosphorylation of the mitogen-activated protein kinase/extracellular-regulated kinase 2 (p42MAPK/ERK2), the main cytoplasmic effector of p21 ras, as well as COLO320-DM cell growth (IC50= 3.58 ± 0.27 μM) without affecting the biosynthesis of cholesterol. Mevalonic acid (MVA, 100 μM), a substrate of the isoprenoid synthesis, was unable to protect COLO320-DM cells from manumycin cytotoxicity. Finally, manumycin 1–25 μM for 24–72 h induced oligonucleosomal fragmentation in a dose- and time-dependent manner and MVA did not protect COLO320-DM cells from undergoing DNA cleavage. The present findings indicate that the inhibition of p21 ras processing and signal transduction by manumycin is associated with marked inhibition of cell proliferation and apoptosis in colon cancer cells and the effect on cell growth does not require the presence of a mutated ras gene for maximal expression of chemotherapeutic activity. © 2000 Cancer Research Campaig