An extensive photometric study of the Blazhko RR Lyrae star MW Lyr: II. Changes in the physical parameters

The analysis of the multicolour photometric observations of MW Lyr, a large modulation amplitude Blazhko variable, shows for the first time how the mean global physical parameters vary during the Blazhko cycle. About 1-2 percent changes in the mean radius, luminosity and surface effective temperature are detected. The mean radius and temperature changes are in good accordance with pulsation model results, which show that these parameters do indeed vary within this order of magnitude if the amplitude of the pulsation changes significantly. We interpret the phase modulation of the pulsation to be a consequence of period changes. Its magnitude corresponds exactly what one expects from the detected changes of the mean radius assuming that the pulsation constant remains the same during the modulation. Our results indicate that during the modulation the pulsation remains purely radial, and the underlying mechanism is most probably a periodic perturbation of the stellar luminosity with the modulation period.Comment: 10 figures, 2 tables. Accepted for publication in MNRA

The paradoxical role of insight in mental illness: the experience of stigma and shame in schizophrenia, mood disorders, and anxiety disorders

This study examined the factor structure of the Hungarian version of the Birchwood Insight Scale (BIS) and analyzed its association with socio-demographics, diagnosis, internalized stigma, and shame using confirmatory factor analysis (CFA) with covariates. Mentally ill patients (N = 200) completed self-report questionnaires. CFA supported a two-factor structure. While previous hospitalizations and diagnosis were associated with insight, insight predicted higher internalized stigma and shame. Efforts to increase insight should be matter of importance in the wider spectrum of mental diagnoses. However, such efforts should be conducted with special care as further research is needed to understand the impact of insight on wellbeing

An extensive photometric study of the Blazhko RR Lyrae star MW Lyr - II. Changes in the physical parameters

The analysis of the multicolour photometric observations of MW Lyr, a large modulation amplitude Blazhko variable, shows for the first time how the mean global physical parameters vary during the Blazhko cycle. About 1-2 per cent changes in the mean radius, luminosity and surface effective temperature are detected. The mean radius and temperature changes are in good accordance with pulsation model results, which show that these parameters do indeed vary within this order of magnitude if the amplitude of the pulsation changes significantly. We interpret the phase modulation of the pulsation to be a consequence of period changes. Its magnitude corresponds exactly what one expects from the detected changes of the mean radius assuming that the pulsation constant remains the same during the modulation. Our results indicate that during the modulation the pulsation remains purely radial, and the underlying mechanism is most probably a periodic perturbation of the stellar luminosity with the modulation perio

Measuring and managing liquidity risk in the Hungarian practice

The crisis that unfolded in 2007/2008 turned the attention of the financial world toward liquidity, the lack of which caused substantial losses. As a result, the need arose for the traditional financial models to be extended with liquidity. Our goal is to discover how Hungarian market players relate to liquidity. Our results are obtained through a series of semistructured interviews, and are hoped to be a starting point for extending the existing models in an appropriate way. Our main results show that different investor groups can be identified along their approaches to liquidity, and they rarely use sophisticated models to measure and manage liquidity. We conclude that although market players would have access to complex liquidity measurement and management tools, there is a limited need for these, because the currently available models are unable to use complex liquidity information effectively

Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting.

We previously found higher level of endothelial cell (EC) activation in patients who suffered from in-stent restenosis after bare-metal stenting compared to subjects who underwent drug-eluting stenting (DES) showing no complications. Here we investigated the potential transcriptional and post-transcriptional regulatory mechanisms by which everolimus attenuated EC activation after DES. We studied the effect of everolimus on E-selectin (SELE) and VCAM1 mRNA levels when human coronary artery (HCAECs) and human umbilical vein ECs were challenged with recombinant TNF-alpha (100 ng/mL) for 1-24 hours in the presence or absence of everolimus using 0.5 muM concentration locally maintained by DES. EC activation was evaluated via the levels of IL-1beta and IL-6 mRNAs with miR-155 expression by RT-qPCR as well as the nuclear translocation of nuclear factor kappa beta (NF-kappaB) detected by fluorescence microscopy. To investigate the transcriptional regulation of E-selectin and VCAM-1, TNF-alpha-induced enhancer RNA (eRNA) expression at p65-bound enhancers in the neighboring genomic regions of SELE and VCAM1 genes, including SELE_-11Kb and VCAM1_-10Kb, were measured in HCAECs. Mature and precursor levels of E-selectin and VCAM-1 repressor miR-181b were quantified to analyze the post-transcriptional regulation of these genes in HCAECs. Circulating miR-181b was analyzed in plasma samples of stented subjects by stem-loop RT-qPCR. TNF-alpha highly elevated E-selectin and VCAM-1 expression at transcriptional level in ECs. Levels of mature, pre- and pri-miR-181b were repressed in ECs by TNF-alpha, while everolimus acted as a negative regulator of EC activation via inhibited translocation of NF-kappaB p65 subunit into cell nuclei, lowered eRNA expression at SELE and VCAM1 genes-associated enhancers and modulated expression of their post-transcriptional repressor miR-181b. Significant negative correlation was observed between plasma miR-181b and soluble E-selectin and VCAM-1 in patients. In conclusion, everolimus attenuates EC activation via reduced NF-kappaB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES

Expression and In Vivo Rescue of Human ABCC6 Disease-Causing Mutants in Mouse Liver

Loss-of-function mutations in ABCC6 can cause chronic or acute forms of dystrophic mineralization described in disease models such as pseudoxanthoma elasticum (OMIM 26480) in human and dystrophic cardiac calcification in mice. The ABCC6 protein is a large membrane-embedded organic anion transporter primarily found in the plasma membrane of hepatocytes. We have established a complex experimental strategy to determine the structural and functional consequences of disease-causing mutations in the human ABCC6. The major aim of our study was to identify mutants with preserved transport activity but failure in intracellular targeting. Five missense mutations were investigated: R1138Q, V1298F, R1314W, G1321S and R1339C. Using in vitro assays, we have identified two variants; R1138Q and R1314W that retained significant transport activity. All mutants were transiently expressed in vivo, in mouse liver via hydrodynamic tail vein injections. The inactive V1298F was the only mutant that showed normal cellular localization in liver hepatocytes while the other mutants showed mostly intracellular accumulation indicating abnormal trafficking. As both R1138Q and R1314W displayed endoplasmic reticulum localization, we tested whether 4-phenylbutyrate (4-PBA), a drug approved for clinical use, could restore their intracellular trafficking to the plasma membrane in MDCKII and mouse liver. The cellular localization of R1314W was significantly improved by 4-PBA treatment, thus potentially rescuing its physiological function. Our work demonstrates the feasibility of the in vivo rescue of cellular maturation of some ABCC6 mutants in physiological conditions very similar to the biology of the fully differentiated human liver and could have future human therapeutic application

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids