The role of T cell specific factors and RNA Polymerase II pausing in HIV-1 replication in CD4+ T cells

In order to eradicate HIV-1 infection the virus needs to be specifically eliminated from latently infected memory CD4+ T cells. There does not seem to be a single mechanism that promotes HIV-1 latency. RNA Polymerase II (RNAP II) pausing, chromatin structure, tissue specific transcriptional repressors and transcriptional interference have been implicated in regulating HIV-1 transcription. The transcription factor B Lymphocyte-Induced Maturation Protein 1 (Blimp-1) is expressed in B and T cells and upregulated in patients chronically infected with HIV-1. I hypothesized that Blimp-1 is a T cell intrinsic factor that binds to HIV-1 LTR, inhibits HIV-1 transcription and contributes to HIV-1 latency. Blimp-1 is expressed in primary peripheral blood CD4+ T cells and is further induced by T cell activation. Importantly, Blimp-1 is highly expressed in memory CD4+ T cells compared to naïve CD4+ T cells. Ectopic expression of Blimp-1 in CD4+ T cells represses HIV-1 transcription, whereas decreasing Blimp-1 in memory CD4+ populations activates HIV-1 transcription. Reduction of Blimp-1 in infected primary T cells increases RNAP II processivity and histone H3 acetylation. Blimp-1 binds downstream of the HIV-1 5'-LTR to the interferon-stimulated response element (ISRE) in resting primary CD4+ T cells and strongly represses Tat-dependent HIV-1 transcription. Upon T cell activation, Blimp-1 is released from the HIV-1 ISRE and this correlates with significant increase in HIV-1 transcription. These results demonstrate that Blimp-1 acts to limit HIV-1 transcription in memory CD4+ T cells and promotes the establishment and maintenance of latency. I also examined whether neighboring host promoters could impact HIV-1 transcription. Using a set of inducible cell lines I observed that neighboring promoters have minimal impact on HIV-1 transcription and that enabling release of paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus. The implications of my results in the different mechanisms regulating HIV-1 latency are discussed

Building portfolios based on machine learning predictions

This paper demonstrates that portfolio optimization techniques represented by Markowitz mean-variance and Hierarchical Risk Parity (HRP) optimizers increase the risk-adjusted return of portfolios built with stocks preselected with a machine learning tool. We apply the random forest method to predict the cross-section of expected excess returns and choose n stocks with the highest monthly predictions. We compare three different techniques— mean-variance, HRP, and 1/N— for portfolio weight creation using returns of stocks from the S&P500 and STOXX600 for robustness. The out-of-sample results show that both mean-variance and HRP optimizers outperform the 1/N rule. This conclusion is in the opposition to a common criticism of optimizers’ efficiency and presents a new light on their potential practical usage

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Źródła i funkcje turpistycznego obrazowania w wierszu Do... (Przekleństwo podłym – przekleństwo tej babie) Zygmunta Krasińskiego

The article is an attempt to analyse the poem with reference to its connection with tradition and implications of this relation. The author reconstructs the map of biographical impulses which contributed to the creation of the poem and portrays its female protagonist, Zofia z Potockich Kisielewowa, seeking in the literary tradition sources of anti-aesthetic practices intentionally and consistently used by Krasiński. Moreover, the article presents previous applications of the literary topos of vetula – an archetypal character of an unlovable yet licentious old woman (the greatest popularity of the motif is connected with the literature of the Baroque period). The little-known poem can be analysed as a testimony of private sympathy or antipathy, inspiration and reading, but also as a proof of ethical and social views. The ideological layer of the work is based on the affirmation of the Platonic triad. However, the author adapts it with some modifications – in the place of good associated with beauty and truth he situates nobility opposed to meanness. In the first half of the nineteenth century both antonymic terms connoted two meanings: they referred to human morality and the man’s place in the social hierarchy.Tekst jest próbą analizy liryku pod kątem jego łączności z tradycją i implikacji tej relacji. Autorka odtwarza mapę impulsów biograficznych, które przyczyniły się do stworzenia utworu, i kreśli portret jego bohaterki, Zofii z Potockich Kisielewowej, jednocześnie poszukując w tradycji literackiej źródeł zastosowanych przez Krasińskiego zabiegów składających się na zamierzone i konsekwentne operowanie antyestetyką. Przywołuje także wybrane dawniejsze realizacje toposu vetuli – archetypicznej postaci odstręczającej, lecz lubieżnej starki (na gruncie polskim o apogeum popularności motywu można mówić w odniesieniu do literatury baroku). Mało znany wiersz Krasińskiego możemy dziś rozpatrywać jako świadectwo nie tylko prywatnych sympatii i antypatii, inspiracji i lektur, lecz także poglądów na kwestie etyczne i społeczne. Warstwa ideowa utworu zasadza się na afirmacji platońskiej triady, autor adaptuje ją jednak z pewnymi modyfikacjami – w miejscu dobra, związanego najściślej z pięknem i prawdą, sytuując szlachetność, której przeciwieństwem byłaby podłość. Oba antonimiczne względem siebie terminy konotowały w pierwszej połowie XIX wieku po dwa znaczenia: orzekały o moralności człowieka, ale także o jego miejscu w społecznej hierarchii

Magnetite nanoparticles coated with chitosan and poly (acrylic acid) blends for biomedical applications

In recent years, the synthesis and characterization of nanoparticles has been used in many are-as of science. Magnetite nanoparticles have been highly employed in many biomedical applications, such as drugs delivery system, catalysis, and magnetic resonance imaging. The properties of the magnetic materials depends on the stabilizer type, covering their surface. In this study was obtained magnetite nanoparticles with chitosan and poly (acrylic acid). Pure monomer of acrylic acid were subjected to photopolymerization, while a photopolymerization kinetics was followed by FTIR spectroscopy. The band corresponding to the C=C vibrations has been selected for calculation of conversion degree of monomer. The structure and mor-phology of the obtained nanoparticles characterized by ATR-FTIR spectroscopy, X-ray analy-sis, and transmission electron microscopy. Acknowledgements The project was supported by research grant: National Science Centre 2014/15/B/NZ7/00972

Assessment of performance traits in breeding horses in the context of the operation of Training Stations in Poland

Breeders and horse trainers have long been concerned with the problem of assessing the utility value of young horses, in particular their suitability for breeding, sport and recreational uses. The purpose of use is determined by physiological, genetic and morphological factors, as well as the resulting performance traits. The actual value of the horse is reflected in many characteristics such as health status, conformation, constitution, origin, performance, and value of offspring. Therefore, extensive performance tests play a crucial role in horse breeding and methods of performance evaluation are still a subject of considerable research. Training Stations give horses a good start in their sport career. Horse training arouses the characteristics and instincts that are beneficial for the rider while suppressing others that are often unfavourable. The purpose of breaking is to make the horse acquire new behaviours and to produce the required mental state. Research to date has clearly shown that the mental characteristics of horses used for recreation and sport (and evaluated in performance tests) are highly correlated to their performance results because they are highly heritable