Membranes, molecules and biophysics: enhancing monocyte derived dendritic cell (MDDC) immunogenicity for improved anti-cancer therapy

Despite great medical advancement in the treatment of cancer, cancer remains a disease of global significance. Chemotherapeutics can be very expensive and drain medical resources at a national level and in some cases the cost of treatment is so great that it prohibits their use by local health authorities. Drug resistance is also a major limiting factor to the successful treatment of cancer with many patients initially responding well but then becoming refractory to treatment with the same drug and in some case may become multi-drug resistant. The immune system is known to be important in the prevention of tumors by eliminating pre-cancerous or cancerous cells. This concept of immune surveillance has largely been super-ceded by the concept of immunoediting whereby the immune system imposes a selective pressure on tumor cells which may either control tumor growth or inadvertently select for tumor cells which have evolved to escape the immune response and which may induce tumor development. Stimulation of the immune system by vaccination offers many benefits in the treatment of cancer. It is highly cost effective and vaccines can be manipulated to include multi-antigens which in some cases may overcome equilibrium (and selective pressure) while also preventing the establishment of reactivated cancer cells, since cancer antigen-specific memory would be induced following the initial vaccination/booster phase. To date studies using vaccination as a treatment for cancer have been a little disappointing, probably due to insufficient level of immunogenicity. In this review we will discuss methods of manipulation of the immune system to increase the anti-cancer activity of dendritic cells in vivo and how monocyte derived dendritic cells may be manipulated ex vivo to provide more robust, patient-specific treatments

The enigmatic B[e]-star Henize 2-90: The non-spherical mass loss history from an analysis of forbidden lines

(abridged) We study the optical spectrum of the exciting B[e] star Hen 2-90 based on new high-resolution observations that cover the innermost 2". Our investigation is splitted in two parts, a qualitative study of the presence of the numerous emission lines and the classification of their line profiles which indicate a circumstellar environment of high complexity, and a quantitative analysis of numerous forbidden lines, e.g. [OI], [OII], [OIII], [SII], [SIII], [ArIII], [ClII], [ClIII] and [NII]. We find a correlation between the different ionization states of the elements and the velocities derived from the line profiles: the highly ionized atoms have the highest outflow velocity while the neutral lines have the lowest outflow velocity. The recent HST image of Hen 2-90 reveals a bipolar, highly ionized region, a neutral disk-like structure and an intermediate region of moderate ionization. It seems that a non-spherical stellar wind model is a good option to explain the ionization and spatial distribution of the circumstellar material. We modelled the forbidden lines under the assumption of a non-spherically symmetric wind based on the HST image. We find that in order to fit the observed line luminosities, the mass flux, surface temperature, and terminal wind velocities need to be latitude dependent, which might be explained in terms of a rapidly rotating central star. A rotation speed of 75-80 % of the critical velocity has been derived. The total mass loss rate of the star was determined to be of order 3 10^{-5} M_sun/yr. Such a wind scenario and the fact that compared to solar abundances C, O, and N seem to be underabundant while S, Ar and Cl have solar abundances, might be explained in terms of a rapidly rotating post-AGB star.Comment: 16 pages, 13 figures, accepted for publication in A&A. Table 4 is included at the end of the paper. This table will only be available in the online version of the paper and will not appear in the printed versio

Muography for Underground Geological Surveys: Ongoing Application at the Lousal Mine (Iberian Pyrite Belt, Portugal)

The use of muons for geophysical surveys has been proved successful in numerous projects around the planet. The use of muography in an underground environment has an easy side, when compared to the surface, due to the absence of the background radiation. On the other hand, the muon flux is much lower than what is measured on the surface. Geological and underground conditions should be considered when defining the required exposure time and developing suitable muon telescopes for the observation. A collaboration has been established between the Institute of Earth Sciences (ICT), University of Evora, the Laboratory of Instrumentation and Experimental Particle Physics (LIP), and the Lousal Ciencia Viva Center to develop muon detectors and evaluate the muography potential in the Lousal Mine, with the general aim to create the conditions to use muography as a novel method for geophysical surveys in Portugal. The Lousal Mine (Iberian Pyrite Belt) was exploited until 1988 and is presently an excellent European example of environmental rehabilitation and social improvement based on museum, scientific, and educational activities. The observations are done from the Waldemar mine gallery, about 18 m below the surface. The telescopes, developed by LIP, use robust RPC detectors to observe the crossing muons in real time. The aim is to do a first geological survey of the region with muography, mapping already known structures and ore lenses and measuring their densities. The new data will then be used to improve the existing information, but the full process also serves to test the performance of the muon telescope and of the muography analysis tools. A reference 3D model is being created by joining pre-existing geological and geophysical information and new measurements, done, namely, with seismic refraction and Ground Penetrating Radar (GPR). This model provides a reference against which to compare the muography results. Ideally, muography could be used to produce an equivalent 3D map of densities. This reference 3D model constructed with independent methods will be used to cross-check the muography results.This R&D project is financed by National Funds through the FCT - Foundation for Science and Technology, reference EXPL/FIS-OUT/1185/2021. The FCT also finances the Ph.D. scholarship, integrated into the LouMu, reference PD/BD/150490/2019, andwithin the scope of ICT, the project with reference UIDB/04683/2020. A grateful thanks go to the Lousal Ciˆencia Viva team fortheir support of the project

A Memetic Analysis of a Phrase by Beethoven: Calvinian Perspectives on Similarity and Lexicon-Abstraction

This article discusses some general issues arising from the study of similarity in music, both human-conducted and computer-aided, and then progresses to a consideration of similarity relationships between patterns in a phrase by Beethoven, from the first movement of the Piano Sonata in A flat major op. 110 (1821), and various potential memetic precursors. This analysis is followed by a consideration of how the kinds of similarity identified in the Beethoven phrase might be understood in psychological/conceptual and then neurobiological terms, the latter by means of William Calvin’s Hexagonal Cloning Theory. This theory offers a mechanism for the operation of David Cope’s concept of the lexicon, conceived here as a museme allele-class. I conclude by attempting to correlate and map the various spaces within which memetic replication occurs

J/psi azimuthal anisotropy relative to the reaction plane in Pb-Pb collisions at 158 GeV per nucleon

The J/$\psi$ azimuthal distribution relative to the reaction plane has been measured by the NA50 experiment in Pb-Pb collisions at 158 GeV/nucleon. Various physical mechanisms related to charmonium dissociation in the medium created in the heavy ion collision are expected to introduce an anisotropy in the azimuthal distribution of the observed J/$\psi$ mesons at SPS energies. Hence, the measurement of J/$\psi$ elliptic anisotropy, quantified by the Fourier coefficient v$_2$ of the J/$\psi$ azimuthal distribution relative to the reaction plane, is an important tool to constrain theoretical models aimed at explaining the anomalous J/$\psi$ suppression observed in Pb-Pb collisions. We present the measured J/$\psi$ yields in different bins of azimuthal angle relative to the reaction plane, as well as the resulting values of the Fourier coefficient v$_{2}$ as a function of the collision centrality and of the J/$\psi$ transverse momentum. The reaction plane has been estimated from the azimuthal distribution of the neutral transverse energy detected in an electromagnetic calorimeter. The analysis has been performed on a data sample of about 100 000 events, distributed in five centrality or p$_{\rm T}$ sub-samples. The extracted v$_{2}$ values are significantly larger than zero for non-central collisions and are seen to increase with p$_{\rm T}$.Comment: proceedings of HP08 conference corrected a typo in one equatio

He II lambda-4686 in Eta Carinae: Collapse of the Wind-Wind Collision Region During Periastron Passage

The periodic spectroscopic events in Eta Carinae are now well established and occur near the periastron passage of two massive stars in a very eccentric orbit. Several mechanisms have been proposed to explain the variations of different spectral features, such as an eclipse by the wind-wind collision boundary, a shell ejection from the primary star or accretion of its wind onto the secondary. All of them have problems explaining all the observed phenomena. To better understand the nature of the cyclic events we performed a dense monitoring of Eta Carinae with 5 Southern telescopes during the 2009 low excitation event, resulting in a set of data of unprecedented quality and sampling. The intrinsic luminosity of the He II lambda-4686 emission line (L approx 310 solar L) just before periastron reveals the presence of a very luminous transient source of extreme UV radiation emitted in the wind-wind collision (WWC) region. Clumps in the primary's wind probably explain the flare-like behavior of both the X-ray and He II lambda-4686 light-curves. After a short-lived minimum, He II lambda-4686 emission rises again to a new maximum, when X-rays are still absent or very weak. We interpret this as a collapse of the WWC onto the "surface" of the secondary star, switching off the hard X-ray source and diminishing the WWC shock cone. The recovery from this state is controlled by the momentum balance between the secondary's wind and the clumps in the primary's wind

The dependence of the anomalous J/psi suppression on the number of participant nucleons

The observation of an anomalous J/psi suppression in Pb-Pb collisions by the NA50 Collaboration can be considered as the most striking indication for the deconfinement of quarks and gluons at SPS energies. In this Letter, we determine the J/psi suppression pattern as a function of the forward hadronic energy E-ZDC measured in a Zero Degree Calorimeter (ZDC). The direct connection between EZDC and the geometry of the collision allows us to calculate, within a Glauber approach, the precise relation between the number of participant nucleons N-part and E-ZDC. Then, we check if the experimental data can be better explained by a sudden or a smooth onset of the anomalous J/psi suppression as a function of the number of participants. (C) 2001 Elsevier Science B.V. All rights reserved.info:eu-repo/semantics/publishedVersio