Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.

Sub-kiloparsec alma imaging of compact star-forming galaxies at z ~ 2.5: revealing the formation of dense galactic cores in the progenitors of compact quiescent galaxies

We present spatially resolved Atacama Large Millimeter/submillimeter Array (ALMA) 870 μm dust continuum maps of six massive, compact, dusty star-forming galaxies at z ~ 2.5. These galaxies are selected for their small rest-frame optical sizes (r_e,F160W ~ 1.6 kpc) and high stellar mass densities that suggest that they are direct progenitors of compact quiescent galaxies at z ~ 2. The deep observations yield high far-infrared (FIR) luminosities of L_IR = 10^12.3-12.8 L_⨀ and star formation rates (SFRs) of SFR = 200–700 M_⊙ yr^−1, consistent with those of typical star-forming "main sequence" galaxies. The high spatial resolution (FWHM ~ 0 12–0 18) ALMA and Hubble Space Telescope photometry are combined to construct deconvolved, mean radial profiles of their stellar mass and (UV+IR) SFR. We find that the dusty, nuclear IR–SFR overwhelmingly dominates the bolometric SFR up to r ~ 5 kpc, by a factor of over 100× from the unobscured UV–SFR. Furthermore, the effective radius of the mean SFR profile (r_e,SFR ~ 1 kpc) is ~30% smaller than that of the stellar mass profile. The implied structural evolution, if such nuclear starburst last for the estimated gas depletion time of Δt = ±100 Myr, is a 4×increase of the stellar mass density within the central 1 kpc and a 1.6× decrease of the half-mass–radius. This structural evolution fully supports dissipation-driven, formation scenarios in which strong nuclear starbursts transform larger, star-forming progenitors into compact quiescent galaxies.

Modeling chemistry in massive star forming regions with internal PDRs

Over the past decades star formation has been a very attractive field because knowledge of star formation leads to a better understanding of the formation of planets and thus of our solar system but also of the evolution of galaxies. Conditions leading to the formation of high-mass stars are still under investigation but an evolutionary scenario has been proposed: As a cold pre-stellar core collapses under gravitational force, the medium warms up until it reaches a temperature of 100 K and enters the hot molecular core (HMC) phase. The forming central proto-star accretes materials, increasing its mass and luminosity and eventually it becomes sufficiently evolved to emit UV photons which irradiate the surrounding environment forming a hyper compact (HC) and then a ultracompact (UC) HII region. At this stage, a very dense and very thin internal photon-dominated region (PDR) forms between the HII region and the molecular core. Information on the chemistry allows to trace the physical processes occurring in these different phases of star formation. Formation and destruction routes of molecules are influenced by the environment as reaction rates depend on the temperature and radiation field. Therefore, chemistry also allows the determination of the evolutionary stage of astrophysical objects through the use of chemical models including the time evolution of the temperature and radiation field. Because HMCs host a very rich chemistry with high abundances of complex organic molecules (COMs), several astrochemical models have been developed to study the gas phase chemistry as well as grain chemistry in these regions. In addition to HMCs models, models of PDRs have also been developed to study in particular photo-chemistry. So far, few studies have investigated internal PDRs and only in the presence of outflows cavities. Thus, these unique regions around HC/UCHII regions remain to be examined thoroughly. My PhD thesis focuses on the spatio-temporal chemical evolution in HC/UC HII regions with internal PDRs as well as in HMCs. The purpose of this study is first to understand the impact and effects of the radiation field, usually very strong in these regions, on the chemistry. Secondly, the goal is to study the emission of various tracers of HC/UCHII regions and compare it with HMCs models, where the UV radiation field does not impact the region as it is immediately attenuated by the medium. Ultimately we want to determine the age of a given region using chemistry in combination with radiative transfer.

STAR Modeling of Pulmonary Tuberculosis Delay-Time in Diagnosis

Understanding what characterizes patients who suffer great delays in diagnosis of pulmonary tuberculosis is of great importance when establishing screening strategies to better control TB. Greater delays in diagnosis imply a higher chance for susceptible individuals to become infected by a bacilliferous patient. A Structured Additive Regression model is attempted in this study in order to potentially contribute to a better characterization of bacilliferous prevalence in Portugal. The main findings suggest the existence of significant regional differences in Portugal, with the fact of being female and/or alcohol dependent contributing to an increased delay-time in diagnosis, while being dependent on intravenous drugs and/or being diagnosed with HIV are factors that increase the chance of an earlier diagnosis of pulmonary TB. A decrease in 2010 to 77% on treatment success in Portugal underlines the importance of conducting more research aimed at better TB control strategies.

A double chance to investigate populist influence: The Five Star Movement.

In the last decade, new kinds of European populist parties and movements characterized by a left wing, right wing or “eclectic” attitude have succeeded in entering in governments where they could exert a direct populist influence on their coalition partners or, conversely, become victims themselves of the influence of the institutional background. Such a scenario brought this research to formulate two questions: (i) “To what extent did populist parties succeed in influencing their government coalition partners, leading them to adopt populist rhetoric and change their policy positions?” and (ii) “Have populist parties been able to retain their populist “outside mainstream politics” identity, or have they been assimilated to mainstream parties?”. As a case study this project chose the Italian Five Star Movement. Since 2018 this eclectic populist actor has experienced three different governments first with the radical right wing populist League (2018-2019) and then with the mainstream center left Democratic Party (2019-2021). In addition to this, currently the Five Star Movement is a coalition partner of the ongoing Draghi’s government. Theoretically based on the ideological definition of populism (Mudde, 2004), on a new “revised” model of the inclusionary - exclusionary framework to classify populist parties and on a novel definition of “populist influence”,this research made use of both quantitative (bidimensional and text analysis) and qualitative methods (semi-structured interviews) and mainly focuses on the years 2017- 2020.The importance of this study is threefold. First it contributes to the study of populist influence in government in relation to the ideological attachment of the political actors involved. Second, it contributes to understand if populists in power necessarily need to tone down their anti-system character in order to survive. Third, this study introduces conceptual and methodological novelties within the study of populism and populist influence in government.

New indicators of star cluster dynamical evolution

This thesis presents a study of globular clusters (GCs), based on analysis of Monte Carlo simulations of globular clusters (GCs) with the aim to define new empirical parameters measurable from observations and able to trace the different phases of their dynamical evolution history. During their long term dynamical evolution, due to mass segregation and and dynamical friction, massive stars transfer kinetic energy to lower-mass objects, causing them to sink toward the cluster center. This continuous transfer of kinetic energy from the core to the outskirts triggers the runaway contraction of the core, known as "core collapse" (CC), followed by episodes of expansion and contraction called gravothermal oscillations. Clearly, such an internal dynamical evolution corresponds to significant variations also of the structure of the system. Determining the dynamical age of a cluster can be challenging as it depends on various internal and external properties. The traditional classification of GCs as CC or post-CC systems relies on detecting a steep power-law cusp in the central density profile, which may not always be reliable due to post-CC oscillations or other processes. In this thesis, based on the normalized cumulative radial distribution (nCRD) within a fraction of the half-mass radius is analyzed, and three diagnostics (A5, P5, and S2.5) are defined. These diagnostics show sensitivity to dynamical evolution and can distinguish pre-CC clusters from post-CC clusters.The analysis performed using multiple simulations with different initial conditions, including varying binary fractions and the presence of dark remnants showed the time variations of the diagnostics follow distinct patterns depending on the binary fraction and the retention or ejection of black holes. This analysis is extended to a larger set of simulations matching the observed properties of Galactic GCs, and the parameters show a potential to distinguish the dynamical stages of the observed clusters as well.

Obscured AGN in deep fields: tracing accretion and star-formation up to z ∼ 5

The discovery of scaling relations between the mass of the SMBH and some key physical properties of the host galaxy suggests that the growth of the SMBH and that of the galaxy are coupled, with the AGN activity and the star-formation (SF) processes influencing each other. Although the mechanism of this co-evolution are still a matter of debate, all scenarios agree that a key phase of the co-evolution is represented by the obscured accretion phase. This phase is of the co-evolution is the least studied, mostly due to the challenge in detecting and recognizing such obscured AGN. My thesis aims at investigating the AGN-galaxy co-evolution paradigm by identifying and studying AGN in the obscured accretion phase. The study of obscured AGN is key for our understanding of the feedback processes and of the mutual influence of the SF and the AGN activity. Moreover, these obscured and elusive AGN are needed to explain the X-ray background spectrum and to reconcile the measurements and the theoretical prediction of the BH accretion rate density. In this thesis, we firstly investigate the synergies between IR and X-ray missions in detecting and characterizing AGN, with a particular focus on the most obscured ones. We exploited UV/optical emission lines to select high-redshift obscured AGN at the cosmic noon, where the highest SFR density and BH accretion rate density are expected. We provide X-ray spectral analysis and UV-to-far-IR SED-fitting. We show that our samples host a significant fraction of very obscured sources; many of these are highly accreting. Finally, we performe a thoughtful investigation of a galaxy at z~5 with unusual and peculiar features, that lead us to identify a second extremely young population of stars and hidden AGN activity.

The molecular gas content of star-forming galaxies in the ALPINE fields.

In this thesis, I aim to study the evolution with redshift of the gas mass fraction of a sample of 53 sources (from z ∼ 0.5 to z > 5) serendipitously detected in ALMA band 7 as part of the ALMA Large Program to INvestigate C II at Early Times (ALPINE). First, I used SED-fitting software CIGALE, which is able to implement energy balancing between the optical and the far infrared part, to produce a best-fit template of my sources and to have an estimate of some physical properties, such as the star formation rate (SFR), the total infrared luminosity and the total stellar mass. Then, using the tight correlation found by Scoville et al. (2014) between the ISM molecular gas mass and the rest-frame 850 μm luminosity, I used the latter, extrapolating it from the best-fit template using a code that I wrote in Python, as a tracer for the molecular gas. For my sample, I then derived the most important physical properties, such as molecular gas mass, gas mass fractions, specific star formation rate and depletion timescales, which allowed me to better categorize them and find them a place within the evolutionary history of the Universe. I also fitted our sources, via another code I wrote again in Python, with a general modified blackbody (MBB) model taken from the literature (Gilli et al. (2014), D’Amato et al. (2020)) to have a direct method of comparison with similar galaxies. What is evident at the end of the paper is that the methods used to derive the physical quantities of the sources are consistent with each other, and these in turn are in good agreement with what is found in the literature.

Beam-energy Dependence Of The Directed Flow Of Protons, Antiprotons, And Pions In Au+au Collisions.

Rapidity-odd directed flow (v1) measurements for charged pions, protons, and antiprotons near midrapidity (y=0) are reported in sNN=7.7, 11.5, 19.6, 27, 39, 62.4, and 200 GeV Au+Au collisions as recorded by the STAR detector at the Relativistic Heavy Ion Collider. At intermediate impact parameters, the proton and net-proton slope parameter dv1/dy|y=0 shows a minimum between 11.5 and 19.6 GeV. In addition, the net-proton dv1/dy|y=0 changes sign twice between 7.7 and 39 GeV. The proton and net-proton results qualitatively resemble predictions of a hydrodynamic model with a first-order phase transition from hadronic matter to deconfined matter, and differ from hadronic transport calculations.

Vascular Pattern In Enchondroma And Chondrosarcoma: Clinical And Immunohistologic Study.

Although cartilaginous tumors have low microvascular density, vessels are important for the provision of nutrition so that the tumor can grow and generate metastasis. The aim of this study was to assess the value of the vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and its relation with vascular endothelial growth factor (VEGF) expression. This was a retrospective study of 21 enchondromas and 57 conventional CSs. Clinical data and outcome were retrieved from medical files. CSs histologic grades (on a scale of 1 to 3) were determined according to the World Health Organization classification. The vascular pattern (on a scale of A to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also evaluated. Poor outcome was significantly associated with vascular pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a clear correlation was found between VEGF overexpression and B/C vascular patterns. Only 18 (benign and malignant) tumors stained for CD105. The results point to the use of the vascular pattern classification as a prognostic tool in CSs and to differentiate low-grade from moderate-grade/high-grade CSs. Vascular pattern might be also used to complement histologic grade, VEGF immunostaining, and microvascular density, for indicating a patient's prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the slow growth rate of these tumors.

Dielectron Mass Spectra From Au+au Collisions At √[s(nn)]=200 gev.

We report the STAR measurements of dielectron (e(+)e(-)) production at midrapidity (|y(ee)|<1) in Au+Au collisions at √[s(NN)]=200  GeV. The measurements are evaluated in different invariant mass regions with a focus on 0.30-0.76 (ρ-like), 0.76-0.80 (ω-like), and 0.98-1.05 (ϕ-like)   GeV/c(2). The spectrum in the ω-like and ϕ-like regions can be well described by the hadronic cocktail simulation. In the ρ-like region, however, the vacuum ρ spectral function cannot describe the shape of the dielectron excess. In this range, an enhancement of 1.77±0.11(stat)±0.24(syst)±0.33(cocktail) is determined with respect to the hadronic cocktail simulation that excludes the ρ meson. The excess yield in the ρ-like region increases with the number of collision participants faster than the ω and ϕ yields. Theoretical models with broadened ρ contributions through interactions with constituents in the hot QCD medium provide a consistent description of the dilepton mass spectra for the measurement presented here and the earlier data at the Super Proton Synchrotron energies.

Antimicrobial And Antiproliferative Potential Of Anadenanthera Colubrina (vell.) Brenan.

The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC = 0.031 mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P > 0.05). SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells.

Beam-energy Dependence Of Charge Separation Along The Magnetic Field In Au+au Collisions At Rhic.

Local parity-odd domains are theorized to form inside a quark-gluon plasma which has been produced in high-energy heavy-ion collisions. The local parity-odd domains manifest themselves as charge separation along the magnetic field axis via the chiral magnetic effect. The experimental observation of charge separation has previously been reported for heavy-ion collisions at the top RHIC energies. In this Letter, we present the results of the beam-energy dependence of the charge correlations in Au+Au collisions at midrapidity for center-of-mass energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After background subtraction, the signal gradually reduces with decreased beam energy and tends to vanish by 7.7 GeV. This implies the dominance of hadronic interactions over partonic ones at lower collision energies.

Measurement Of Longitudinal Spin Asymmetries For Weak Boson Production In Polarized Proton-proton Collisions At Rhic.

We report measurements of single- and double-spin asymmetries for W^{±} and Z/γ^{*} boson production in longitudinally polarized p+p collisions at sqrt[s]=510  GeV by the STAR experiment at RHIC. The asymmetries for W^{±} were measured as a function of the decay lepton pseudorapidity, which provides a theoretically clean probe of the proton's polarized quark distributions at the scale of the W mass. The results are compared to theoretical predictions, constrained by polarized deep inelastic scattering measurements, and show a preference for a sizable, positive up antiquark polarization in the range 0.05

Observation Of D0 Meson Nuclear Modifications In Au+au Collisions At Sqrt[s(nn)] = 200 Gev.

We report the first measurement of charmed-hadron (D(0)) production via the hadronic decay channel (D(0) → K(-) + π(+)) in Au+Au collisions at sqrt[s(NN)] = 200 GeV with the STAR experiment. The charm production cross section per nucleon-nucleon collision at midrapidity scales with the number of binary collisions, N(bin), from p+p to central Au+Au collisions. The D(0) meson yields in central Au + Au collisions are strongly suppressed compared to those in p+p scaled by N(bin), for transverse momenta p(T) > 3 GeV/c, demonstrating significant energy loss of charm quarks in the hot and dense medium. An enhancement at intermediate p(T) is also observed. Model calculations including strong charm-medium interactions and coalescence hadronization describe our measurements.