Mit, stereotyp i fantazmat – między szablonem a inną wizją przeszłości w szkolnym kursie historii (przypadek ikonografii)

The article is an attempt to guide a reader from the guidelines included in the standards/requirements of the examination for the upper secondary school, relating to work with different types of information sources, through the three interpretative spaces of a pictures, with which a pupil is being acquainted during the three educational stages, to – finally – specific iconographical sources, representing the mythical, stereotyped and phantasmatic evocation of the past. The title versions of the past reality: template (myth and stereotype) and other (phantasm), found in the selected works of Witold Pruszkowski, are not alternative to each other. They are rather the pictorial narratives running parallel, although requiring a slightly different approach and equipment from the interpreter

Musicafatta spirituale. Aquilino Coppini’s contrafacta of Monteverdi’s Fifth Book of Madrigals

This article focuses on Aquilino Coppini’s contrafacta of Monteverdi madrigals from the Fifth Book, Musica tolta da i Madrigali di Claudio Monteverde, e d’altri autori [...] e fatta spirituale, published in Milan in 1607. Coppini (d. 1629), a Milanese priest, professor of rhetoric at the University of Pavia and man of letters, was Monteverdi’s personal friend and admirer. He was associated with the circle of Cardinal Federico Borromeo (1564-1631), Archbishop of Milan and a great connoisseur of the arts, and his cousin, Cardinal Carlo [Charles] Borromeo (1538-1584), principally responsible for the Tridentine reform of church music, to whom Coppini dedicated the first of his three collections of contrafacta discussed here. Coppini’s efforts in re-texting Monteverdi’s compositions and transforming them into madrigali spirituali were very much welcomed by the mighty Borromeo family, as they allowed the newest stylistic achievements of the seconda prattica to be transferred to church music. Coppini’s contrafacta are of interest for their concentration on madrigals by Monteverdi, as Coppini chose to work on eleven madrigals from Monteverdi’s controversial Fifth Book. His treatment of the poetic text is quite elaborate. First, his Latin contrafacta are creative re-textings in which he reproduces the metric structure and the sound quality of Guarini’s original Italian texts through the careful placement of phonemes, vowels and consonants. Second, he transforms them into madrigali spirituali, always following their original affetti, creating strong associations and often profound intertextual relationships among the original and the new texts, in which he elevates the profane situations from Guarini’s texts to the spiritual level of the Gospel teachings. In this respect, Coppini’s work remains a fascinating contribution to the enduring discussion on the thin line between the sacred and the profane

Musica fatta spirituale. Aquilino Coppini’s contrafacta of Monteverdi’s Fifth Book of Madrigals

This article focuses on Aquilino Coppini’s contrafacta of Monteverdi madrigals from the Fifth Book, Musica tolta da i Madrigali di Claudio Monteverde, e d’altri autori […] e fatta spirituale, published in Milan in 1607. Coppini (d. 1629), a Milanese priest, professor of rhetoric at the University of Pavia and man of letters, was Monteverdi’s personal friend and admirer. He was associated with the circle of Cardinal Federico Borromeo (1564–1631), Archbishop of Milan and a great connoisseur of the arts, and his cousin, Cardinal Carlo [Charles] Borromeo (1538–1584), principally responsible for the Tridentine reform of church music, to whom Coppini dedicated the fi rst of his three collections of contrafacta discussed here. Coppini’s efforts in re-texting Monteverdi’s compositions and transforming them into madrigali spirituali were very much welcomed by the mighty Borromeo family, as they allowed the newest stylistic achievements of the seconda prattica to be transferred to church music. Coppini’s contrafacta are of interest for their concentration on madrigals by Monteverdi, as Coppini chose to work on eleven madrigals from Monteverdi’s controversial Fifth Book. His treatment of the poetic text is quite elaborate. First, his Latin contrafacta are creative re-textings in which he reproduces the metric structure and the sound quality of Guarini’s original Italian texts through the careful placement of phonemes, vowels and consonants. Second, he transforms them into madrigali spirituali, always following their original affetti, creating strong associations and often profound intertextual relationships among the original and the new texts, in which he elevates the profane situations from Guarini’s texts to the spiritual level of the Gospel teachings. In this respect, Coppini’s work remains a fascinating contribution to the enduring discussion on the thin line between the sacred and the profane

Przedszkolaki filozofują

Przedszkolaki filozofuj

The development of a mathematical modelling framework to translate TB vaccine responses between species and predict the most immunogenic dose in humans using animal data

Background: Preclinical animal experiments measuring vaccine immunogenicity and safety are essential, not only to establish if the vaccine should progress further, but to generate information on how the vaccine should be administered in humans. Animal models that represent human vaccine responses well are vital to translate information about vaccine dose to clinical phases. Vaccine dose is a key aspect in creating an effective vaccine. However, if the wrong dose is chosen, vaccine candidates may be mistakenly discarded and considerable resources wasted. Current methods of finding optimal vaccine dose are mostly empirically based, which may be leading to sub-optimal doses progressing into later clinical trials. A current example of this is in the tuberculosis (TB) vaccine developmental pipeline, where a series of adjuvanted subunit vaccines, the H-series, have progressed through to later stages of clinical development with a high dose that has been shown to less immunogenic than lower doses. In drug development, mathematical model-based methods are routinely used alongside empirical evaluations, to inform dose-finding. I hypothesised that vaccine development may benefit from the application of similar quantitative methods. As such, I launched the new field of vaccine immunostimulation/immunodynamic (IS/ID) mathematical modelling. My aims for this thesis were 1) to establish differences in Bacillus Calmette–Guérin (BCG) Interferon-Gamma (IFN-γ) response by human subpopulation, then develop a IS/ID model to represent these response dynamics and identify the most representative macaque subpopulation for human BCG responses. Aim 2) was to predict human H-series vaccine IFN-γ response using IS/ID model calibrated to mouse multi-dose IFN-γ data and allometric scaling. Methods: For aim 1, longitudinal data on IFN-γ emitting CD4+ T cells following vaccination BCG were available in humans and macaques. Human (sub)population covariates were: baseline BCG vaccination status, time since BCG vaccination, gender and monocyte/lymphocyte cell count ratio. The macaque (sub)population covariate was colony of origin. I developed a two-compartmental mathematical model describing the post-BCG IFN-γ immune response dynamics. The model was calibrated to the human and macaque data using 4 Nonlinear Mixed Effects Modelling (NLMEM) to establish if there were differences in IFN-γ dynamics for both species subpopulations. I then established which macaque subpopulation best described human data. For aim 2, longitudinal data on IFN-γ emitting CD4+ T cells following two vaccinations with five doses of novel TB vaccine H56+IC31 in mice were generated. I then assessed the shape of the dose response curve at early and late time points. I calibrated the T cell model to the mouse data and established the change in key model parameters across dose. Using the change in model parameters across dose found in the mice, I predicted the immune response dynamics in humans for different doses and which dose was most immunogenic. Results: In aim 1, I found that BCG status in humans (baseline BCG-naïve or baseline BCG-vaccinated) was associated with differences in the peak and end IFN-γ response after vaccination with BCG. When the mathematical model was calibrated to the BCG data for both macaques and humans, significant differences (p<0.05) in key model parameters were found after stratification by macaque colony and human baseline-BCG status. Indonesian cynomolgus macaques had the closest immune response dynamics to the baseline BCG-naïve humans. In aim 2, a peaked curve was the best description of the mouse H56+IC31 dose response curve for early and late time points. Calibrating a revaccination model to the data and mapping changes in the estimated mouse model parameters across dose group to the estimated human model parameters, I found at day 224 (a latest time point), the model-predicted median number of human IFN-γ secreting CD4+ T cells were the highest for the dose group in the range 1-10μg H56/H1+500 nmol IC31. This suggests a dose of 1-10μg may be the most immunogenic in humans. Discussion: Finding the most predictive animal model and optimal vaccine dose is essential for efficiently accelerating the development of new, effective, TB vaccines. I demonstrated that mathematical modelling was a useful tool to quantify BCG immune response dynamics in macaques and humans. I established which macaque subpopulation should be used to represent a human BCG (or potentially new TB vaccine) induced IFN-γ response in future clinical trials. Using IFN-γ as marker of vaccine immunogenicity, mathematical modelling predictions using preclinical data suggested that doses in current novel TB vaccines clinical 5 trials on healthy BCG-vaccinated participants should be between 1-10μg H56/H1+500 nmol IC31, a result which has been recently corroborated in an empirical H56+IC31 dose-ranging trial. This project has demonstrated the potential utility of mathematical modelling in vaccine development. I believe future work on IS/ID modelling should include data on more complex immune response networks and different animal and human subpopulations. This future work is entirely feasible and would establish IS/ID modelling as a legitimate tool to accelerate vaccine development

Small-Molecule Hormones: Molecular Mechanisms of Action

Small-molecule hormones play crucial roles in the development and in the maintenance of an adult mammalian organism. On the molecular level, they regulate a plethora of biological pathways. Part of their actions depends on their transcription-regulating properties, exerted by highly specific nuclear receptors which are hormone-dependent transcription factors. Nuclear hormone receptors interact with coactivators, corepressors, basal transcription factors, and other transcription factors in order to modulate the activity of target genes in a manner that is dependent on tissue, age and developmental and pathophysiological states. The biological effect of this mechanism becomes apparent not earlier than 30–60 minutes after hormonal stimulus. In addition, small-molecule hormones modify the function of the cell by a number of nongenomic mechanisms, involving interaction with proteins localized in the plasma membrane, in the cytoplasm, as well as with proteins localized in other cellular membranes and in nonnuclear cellular compartments. The identity of such proteins is still under investigation; however, it seems that extranuclear fractions of nuclear hormone receptors commonly serve this function. A direct interaction of small-molecule hormones with membrane phospholipids and with mRNA is also postulated. In these mechanisms, the reaction to hormonal stimulus appears within seconds or minutes

Phylogenetic Analysis of Mitochondrial Outer Membrane β-Barrel Channels

Transport of molecules across mitochondrial outer membrane is pivotal for a proper function of mitochondria. The transport pathways across the membrane are formed by ion channels that participate in metabolite exchange between mitochondria and cytoplasm (voltage-dependent anion-selective channel, VDAC) as well as in import of proteins encoded by nuclear genes (Tom40 and Sam50/Tob55). VDAC, Tom40, and Sam50/Tob55 are present in all eukaryotic organisms, encoded in the nuclear genome, and have β-barrel topology. We have compiled data sets of these protein sequences and studied their phylogenetic relationships with a special focus on the position of Amoebozoa. Additionally, we identified these protein-coding genes in Acanthamoeba castellanii and Dictyostelium discoideum to complement our data set and verify the phylogenetic position of these model organisms. Our analysis show that mitochondrial β-barrel channels from Archaeplastida (plants) and Opisthokonta (animals and fungi) experienced many duplication events that resulted in multiple paralogous isoforms and form well-defined monophyletic clades that match the current model of eukaryotic evolution. However, in representatives of Amoebozoa, Chromalveolata, and Excavata (former Protista), they do not form clearly distinguishable clades, although they locate basally to the plant and algae branches. In most cases, they do not posses paralogs and their sequences appear to have evolved quickly or degenerated. Consequently, the obtained phylogenies of mitochondrial outer membrane β-channels do not entirely reflect the recent eukaryotic classification system involving the six supergroups: Chromalveolata, Excavata, Archaeplastida, Rhizaria, Amoebozoa, and Opisthokonta