Depth Profile of Optically Recorded Patterns in Light-Sensitive Liquid Crystal Elastomers

We investigated nonlinear absorption and photobleaching processes in a liquid crystal elastomer (LCE) doped with light-sensitive azobenzene moiety. A conventional one-dimensional holographic grating was recorded in the material with the use of two crossed UV laser beams and the angular dependence of the diffraction efficiency in the vicinity of the Bragg peak was analyzed. These measurements gave information on the depth to which trans to cis isomerisation had progressed into the sample as a function of the UV irradiation time. Using a numerical model that takes into account the propagation of writing beams and rate equations for the local concentration of the absorbing trans conformer, we computed the expected spatial distribution of the trans and cis conformers and the shape of the corresponding Bragg diffraction peak for different irradiation doses. Due to residual absorption of the cis conformers the depth of the recording progresses logarithmically with time and is limited by the thermal relaxation from the cis to trans conformation.Comment: 19 pages (incl. figs), 6 figure

Role of the aryl hydrocarbon receptor in Sugen 5416-induced experimental pulmonary hypertension

Rationale: Rats dosed with the vascular endothelial growth factor (VEGF) inhibitor Sugen 5416 (Su), placed in hypoxia then restored to normoxia has become a widely used model of pulmonary arterial hypertension (PAH). The mechanism by which Su exaccerbates pulmonary hypertension is, however, unclear. Objectives: We investigated Su-activation of the aryl hydrocarbon receptor (AhR) in patient human pulmonary arterial smooth muscle cells (hPASMCs) and patient blood outgrowth endothelial cells (BOECs). We also examined the effect of AhR on aromatase and estrogen levels in the lung. Methods, Measurements and Main Results: Protein and mRNA analysis demonstrated that CYP1A1 was very highly induced in the lungs of Su/hypoxic (Su/Hx) rats. The AhR antagonist CH223191 (8mg/kg/day) reversed the development of PAH in this model in vivo and normalized lung CYP1A1 expression. Increased lung aromatase and estrogen levels in Su/Hx rats were also normalized by CH223191 as was AhR nuclear translocator (ARNT [HIF-1β]) which is shared by HIF-1α and AhR. Su reduced HIF1α expression in hPASMCs. Su induced proliferation in BOECs and increased apoptosis in human pulmonary microvascular endothelial cells (hPMECs) and also induced translocation of AhR to the nucleus in hPASMCs. Under normoxic conditions, hPASMCs do not proliferate to Su. However when grown in hypoxia (1%) Su induced hPASMC proliferation. Conclusion: In combination with hypoxia, Su is proliferative in patient hPASMCs and patient BOECs and Su/Hx-induced PAH in rats may be facilitated by AhR-induced CYP1A1, ARNT and aromatase. Inhibition of the AhR receptor may be a novel approach to the treatment of pulmonary hypertension

O pojmu časa, prostora in vzročnosti pri Aravkancih. Ali: Po čem si je treba zapomniti Juana Benigarja?

Juan (Ivan, Janez) Benigar, antropolog/etnolog, filolog, teozof, filozof in »politični aktivist«, je med letoma 1922 in 1925 napisal tri razprave, ki veljajo za jedro Benigarjevega etnološkega dela: o času, prostoru in vzročnosti med Aravkanci. Z njimi se je zelo približal Lévi-Straussovemu konceptu »divje misli«, a mu dispozitiv vednosti (epistemološki okvir) časa ni omogočal izostrene teoretske formulacije. Članek med drugim skuša predstaviti prevečkrat zanemarjen politični angažma Juana Benigarja in postaviti raziskave o njem onstran nacionalnega diskurza. Sklepna teza članka je, da si je treba Benigarja zapomniti predvsem kot človeka (ontološko) in kot kritičnega (angažiranega) intelektualca (teoretsko oziroma profesionalno). *** Juan Benigar, an anthropologist/ethnologist, philologist, theosophist, philosopher and “political activist” wrote three essays: on time, space and causality among the Araucanians between the years 1922 and 1925. In his essays Benigar approached Levi-Strauss’s concept of the “savage mind”. It was the dispositif (apparatus) of knowledge of his time (the epistemological framework) that prevented him to conceptualise it. The article tries also to stress the somehow forgotten “political engagement” of Juan Benigar and to conceptualise this scientist beyond national discourse. The final horizon of this article is that we should remember Benigar as a human being (ontologically speaking) and as a critical (socially engaged) intellectual (theoretically and professionally speaking)

Human Papillomavirus (HPV) and Cervical Cancer

Human papillomavirus (HPV) is one of the most common sexually transmitted diseases with more than 100 types. The American Cancer Society (2019) reports, “Most men and women who have ever had sexual contact will get HPV at some time in their lives.” Certain strands are more detrimental than others, however it is important to understand how it spreads and ways to minimize its occurrence. Preventative actions are available to women, such as pap smear screenings, which can allow for early identification and treatment of abnormalities. As an advanced practicing nurse, it is essential to provide education to women surrounding HPV, the HPV vaccine, and the importance of routine screenings to avoid potential progression to cervical cancer. The pathophysiology, signs and symptoms, treatment, among other imperative information related to HPV and cervical cancer will be discussed within the poster

Reflective Journaling: A Theoretical Model and Digital Prototype for Developing Resilience and Creativity

Reflection is commonly discussed as a tool for personal and professional development that is becoming increasingly important in today’s global and digital world. In this paper, we propose a model that suggests ways in which reflection, in the form of Reflective Journaling, can support the development of creativity and resilience, which are needed to enable individuals to function effectively in a fast-changing environment. In addition, the model proposes ways in which external support and progress monitoring can be used in conjunction with skills in adaptive resilience and structured creativity, to support the maintenance of reflective journaling as a habit, in the longer term, thus creating virtuous cycles of skills and behaviours that can reinforce each other. Based on our model, and additional user research, we describe the design of a first digital prototype that aims to support the use of Reflective Journaling and to develop creativity and resilience through suggested mechanisms. Initial evaluations of our prototype are positive. It has been well-received by early test users, and has the potential to address all the connections defined. We therefore suggest that the theoretical model can be used to develop digital tools, such as the one included, to help those who wish to develop the habit of reflective journaling, and through that a range of other skills associated with resilience and creative thinking. We see this as a starting point for investigating this potential in more depth

Evaluation of Cage Designs and Feeding Regimes for Honey Bee (Hymenoptera: Apidae) Laboratory Experiments

The aim of this study was to improve cage systems for maintaining adult honey bee (Apis mellifera L.) workers under in vitro laboratory conditions. To achieve this goal, we experimentally evaluated the impact of different cages, developed by scientists of the international research network COLOSS (Prevention of honey bee COlony LOSSes), on the physiology and survival of honey bees. We identified three cages that promoted good survival of honey bees. The bees from cages that exhibited greater survival had relatively lower titers of deformed wing virus, suggesting that deformed wing virus is a significant marker reflecting stress level and health status of the host. We also determined that a leak- and drip-proof feeder was an integral part of a cage system and a feeder modified from a 20-ml plastic syringe displayed the best result in providing steady food supply to bees. Finally, we also demonstrated that the addition of protein to the bees' diet could significantly increase the level of vitellogenin gene expression and improve bees' survival. This international collaborative study represents a critical step toward improvement of cage designs and feeding regimes for honey bee laboratory experiment

In situ and in vitro models to investigate the role of oestrogen and oestrogen metabolism in pulmonary vascular disease

Pulmonary arterial hypertension is an incurable vasculopathy, which affects significantly more women than men. Hence, female sex hormones may be intimately involved in the initiation and progression of disease pathogenesis. Indeed, current evidence suggests dysregulated oestrogen biosynthesis and metabolism, result in microenvironment favouring excessive proliferation of pulmonary artery smooth muscle cells, leading to significant vascular remodelling. Impairment of signalling via the bone morphogenetic protein receptor II (BMPRII) signalling pathway might also be partially accountable for increased cellular proliferation, and the sex dimorphism associated with the disease. Much of the currently available evidence regarding the pathophysiological mechanism of this vasculopathy was gained using experimental animal models of pulmonary hypertension, we aimed to develop and employ in situ and in vitro models to investigate the role of oestrogen and its metabolism in pulmonary arterial hypertension. Signalling through aryl hydrocarbon receptor results in altered expression of Phase I and II metabolising enzymes, including oestrogen metabolising enzymes. Using an in-silico approach, we demonstrated that the importance of aryl hydrocarbon receptor in experimental animal model of pulmonary hypertension induced by exposure to Sugen 5416 and chronic hypoxia. Initial quantitative real-time polymerase chain reaction analysis revealed that expression of CYP1A1 gene might be decreased in cultured pulmonary arterial smooth muscle cells from female patients, rats exposed to chronic hypoxia and Smad1 heterozygous mice. CYP1A1 gene expression was, however, greatly increased in the Sugen 5416/hypoxic experimental animal model. We further demonstrated that in this specific model several genes under the transcriptional activation of the aryl hydrocarbon receptor, such as NAD(P)H quinone dehydrogenase 1 and aryl hydrocarbon receptor repressor, are increased. In vitro stimulation of human pulmonary arterial smooth muscle cells with Sugen 5416, which is a potent agonist of the aryl hydrocarbon receptor, resulted in increased expression of CYP1A1 and 1B1. We further demonstrated by employing R.E.A.P. fractionation protocol, that stimulation of smooth muscle cells with Sugen 5416 resulted in the translocation of the aryl hydrocarbon receptor from the cytoplasm to the nucleus, where it was able to exert its transcriptional activity. The blockade of the aryl hydrocarbon receptor pathway by CH223191, resulted in attenuated expression of these oestrogen metabolising enzymes only in smooth muscle cells derived from pulmonary arteries of control subjects. In human pulmonary microvascular endothelial cells, simulation with Sugen 5416 and aryl hydrocarbon receptor inhibitor, FICZ, increased apoptosis of these cells as assessed via reduced cell number and increased cleavage of Caspase 3. Hence, Sugen 5416 may induce vascular injury, leading to initiation of pathophysiological mechanisms of experimental PH. Even though the aryl hydrocarbon receptor pathway interacts with hypoxia-inducible factor signalling, we showed that stimulation of pulmonary artery smooth muscle cells does not alter mediators involved in the latter pathway. Furthermore, we showed that sex dimorphism might exist in the basal expression of mediators involved in the hypoxia-inducible factors signalling pathway (HIFs). In smooth muscle cells derived from pulmonary arteries of female PAH patients, the expression of HIF1α was significantly increased, while the regulators of HIF1α proteasomal degradation were significantly decreased. Equally, in smooth muscle cells derived from pulmonary arteries of male PAH patients, protein expression regulators of HIF1α proteasomal degradation were significantly decreased. In vitro, we demonstrated that there a possible synergy exists between the aryl hydrocarbon receptor and hypoxia-inducible factor signalling pathways, where co-stimulation with Sugen 5416 and hypoxia resulted in increased proliferation of smooth muscle cells derived from pulmonary arteries of female PAH. We also aimed to develop and employ an in vitro model to investigate the role of oestrogen and its metabolism in the pathophysiological mechanism of pulmonary arterial hypertension, and to quantitatively assess oestrogen metabolism in this model. We showed that stimulation with 2-methoxyoestrogens increased expression of prostacyclin synthase in pulmonary microvascular endothelial cells from female control subject. Using immunoblotting technique, we further demonstrated that in smooth muscle cells derived from pulmonary arteries of male control subjects 2-methoxyoestradiol increased protein expression of Id3 and had no significant effect in smooth muscle cells derived from pulmonary arteries of female control subjects. It appears that in female pulmonary artery smooth muscle cells 2-methoxyoestradiol increased the expression of p27/Kip1 in a concentration-dependent manner. In fact, in vitro stimulation with 2-methoxyoestradiol attenuated serum-induced proliferation in smooth muscle cells derived from pulmonary arteries of control subjects of both sexes. In smooth muscle cells derived from pulmonary arteries of PAH patients, 2-methoxyoestradiol only reduced cellular proliferation in female cells, while having no effect in male cells. We have also examined the effects of 2- and 4-hydroxyoestradiol on serum-induced proliferation in pulmonary artery smooth muscle cells from male control subjects. Here we found both metabolites mediated attenuation of cellular proliferation, with 2-hydroxyoestradiol mediating its effects through its biotransformation into 2-methoxyoestradiol, as catechol-O-methyl transferase inhibition restored cellular proliferation. Inhibition of catechol-O-methyl transferase did not have an effect on 4-hydroxyoestradiol-mediated reduction of serum-induced proliferation. Using the in vitro model of pulmonary arterial hypertension employing pulmonary artery smooth muscle cells, we have assessed the effects of treprostinil on oestrogen metabolism in these cells using high performance liquid chromatography/flux analysis. We demonstrated that pulmonary artery smooth muscle cells derived from female and male PAH patients might metabolise 17β-oestradiol differently than those derived from control subjects. Moreover, treprostinil might affect the metabolism of 17β-oestradiol to oestrone, probably by affecting the activity of 17β-hydroxysteroid dehydrogenase type 2. Basal protein expression level as assessed by immunoblotting technique indicated that the latter enzyme might be increased in pulmonary artery smooth muscle cells derived from male PAH patients. To overcome certain shortcomings of high performance liquid chromatography/flux analysis for investigation of oestrogen metabolism, we aimed to develop and optimise a liquid chromatography tandem mass spectrometry approach. We have established the technique, and optimised separation of methoxyoestrogens and wash steps. The novel approach was used to assess oestrogen metabolism in in vitro model of pulmonary arterial hypertension, showing that smooth muscle cells derived from female PAH patients produce significantly more oestrone and 17α-isomer of oestradiol. Moreover, smooth muscle cells derived from male PAH patients metabolised the least 17β-oestradiol in comparison with female patient cells. Although the technique is now established, further optimisation is required to achieve reliable quantification of oestrogen metabolites in reasonable concentration ranges, as currently the method appears unreliable at concentration ranges for some oestrogen metabolites. Using a hypothesis-free metabolomic screen we also demonstrated that certain metabolic pathways associated with energy reactive oxygen species and L-tryptophan metabolism might be affected in pulmonary artery smooth muscle cells. Using in situ model we showed that induction of the aryl hydrocarbon receptor by Sugen 5416 leads to alterations in the expression of oestrogen metabolising enzymes, such as CYP1B1 and CYP1A1. Thereby possibly affecting the pathogenic mechanisms by introducing an imbalance of oestrogen metabolism. By using in vitro model of pulmonary arterial hypertension, we also showed methoxyoestrogen the role of methoxyoestrogens, 2-and 4-hydroxyoestrogens in the attenuation of cellular proliferation in pulmonary artery smooth muscle cells. Furthermore, we established oestrogen metabolic profile in pulmonary artery smooth muscle cells derived from controls and patients of both sexes and quantified these metabolites. We have therefore successfully applied in situ and in vitro approaches to investigate the role of oestrogen and oestrogen metabolism in the pathogenesis of pulmonary arterial hypertension