Analysis of Sonic Hedgehog signalling pathway gene expression in Basal Cell Carcinoma and in GLII induced systems

PhDEmbryonic development is regulated by a number of signalling pathways, Which are critical for normal growth. Many of these genes then continue to play an important role in the regulation of cell growth and differentiation in adult. One such pathway is the sonic hedgehog (SHH) pathway; SHH protein is secreted which binds to its receptor patched (PTCH), leading to the activation and repression of target genes via zinc-finger GLI family transcription factors. Deregulation of this pathway, leads to a number of human birth defects and diseases such as Basal Cell Carcinoma (BCC) of the skin. In transgenic mouse model systems activation of GLI1 by SHH-signalling is a key step in initiating BCC formation. However, there is limited understanding of the molecular mechanisms involved in response to hedgehog signalling and GLI activity in human BCC formation and how this pathway interacts with other pathways. The aim of this thesis was to establish in vitro and in vivo model systems to investigate the molecular events leading to BCC formation. I have shown that Gl.Il , Gi12, Gi13, PTCH, SMO and KlF4 were induced and a-TUB was repressed in BCC relative to normal skin. Using an in vitro model I further showed that Gl.ll , Gi12, Gi13, PTCH, SMO and a-TUB were induced and KlF4 was repressed in GLII expressing keratinocytes. Collaborative work with Dr Fritz Aberger's laboratory in Salzburg showed that Gl.Il and FOXEI are direct targets of GLI2 and I showed that Gl.I? and FOXEI were expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumour islands suggesting a possible link between hair follicle and BCe. I further showed that epidermal growth factor (EGF) signalling reduces transcription activity of GLI1 by shuttling GLII out of nucleus and altering the expression of PTCH, SMO, Gil2 and Gl.B SHH genes. In addition, I demonstrated that whilst EGF induced Vimentin and Snail2 expression and GLII repressed their expression suggesting that GLI is able to counter epithelial-mesenchymal transition associated with EGF and this may in part explain why Bee very rarely metastasise. Furthermore, GLI1 appears to upregulate stem cell like signature and EGF downregulates this signature. Finally, we were able to generate a KRTI4- Floxed-GFP-Gill transgenic mouse but were unable to activate the target gene (KRTI4-GFP-GiIl). In conclusion, I have identified possible targets of GLI activity and shown interactions between EGF signalling and GLI that will help us to understand the potential molecular actions of SHH signalling with the goal of developing better therapeutic strategies

Wireless Communication in Process Control Loop: Requirements Analysis, Industry Practices and Experimental Evaluation

Wireless communication is already used in process automation for process monitoring. The next stage of implementation of wireless technology in industrial applications is for process control. The need for wireless networked control systems has evolved because of the necessity for extensibility, mobility, modularity, fast deployment, and reduced installation and maintenance cost. These benefits are only applicable given that the wireless network of choice can meet the strict requirements of process control applications, such as latency. In this regard, this paper is an effort towards identifying current industry practices related to implementing process control over a wireless link and evaluates the suitability of ISA100.11a network for use in process control through experiments

Theoretical studies on structural and decay properties of Z=119Z=119 superheavy nuclei

In this manuscript, we analyze the structural properties of $Z=119$ superheavy nuclei in the mass range of 284 $\le$ A $\le$ 375 within the framework of deformed relativistic mean field theory (RMF) and calculate the binding energy, radii, quadrupole deformation parameter, separation energies and density profile. Further, a competition between possible decay modes such as $\alpha-$decay, $\beta-$decay and spontaneous fission (SF) of the isotopic chain of $Z=119$ superheavy nuclei under study is systematically analyzed within self-consistent relativistic mean field model. Moreover, our analysis confirmed that $\alpha-$decay is restricted within the mass range 284 $\leq$ A $\leq$ 296 and thus being the dominant decay channel in this mass range. However, for the mass range 297 $\leq$ A $\leq$ 375 the nuclei are unable to survive fission and hence SF is the principal mode of decay for these isotopes. There is no possibility of $\beta-$decay for the considered isotopic chain. In addition, we forecasted the mode of decay $^{284-296}$119 as one $\alpha$ chain from $^{284}$119 and $^{296}$119, two consistent $\alpha$ chains from $^{285}$119 and $^{295}$119, three consistent $\alpha$ chains from $^{286}$119 and $^{294}$119, four consistent alpha chains from $^{287}$119, six consistent alpha chains from $^{288-293}$119. Also from our analysis we inferred that for the isotopes $^{264-266,269}$Bh both $\alpha$ decay and SF are equally competent and can decay via either of these two modes. Thus, such studies can be of great significance to the experimentalists in very near future for synthesizing $Z=119$ superheavy nuclei.Comment: 14 pages, 6 figures. arXiv admin note: text overlap with arXiv:1611.00232, arXiv:1704.0315

Structural and decay properties of Z=132,138Z=132,138 superheavy nuclei

In this paper, we analyze the structural properties of $Z=132$ and $Z=138$ superheavy nuclei within the ambit of axially deformed relativistic mean-field framework with NL$3^{*}$ parametrization and calculate the total binding energies, radii, quadrupole deformation parameter, separation energies, density distributions. We also investigate the phenomenon of shape coexistence by performing the calculations for prolate, oblate and spherical configurations. For clear presentation of nucleon distributions, the two-dimensional contour representation of individual nucleon density and total matter density has been made. Further, a competition between possible decay modes such as $\alpha$-decay, $\beta$-decay and spontaneous fission of the isotopic chain of superheavy nuclei with $Z=132$ within the range 312 $\le$ A $\le$ 392 and 318 $\le$ A $\le$ 398 for $Z=138$ is systematically analyzed within self-consistent relativistic mean field model. From our analysis, we inferred that the $\alpha$-decay and spontaneous fission are the principal modes of decay in majority of the isotopes of superheavy nuclei under investigation apart from $\beta$ decay as dominant mode of decay in $^{318-322}138$ isotopes.Comment: 16 pages, 10 figures , 8 table

The Influence of Profitability and Leverage on Corporate Social Responsibility Disclosure

This study aims to examine the influence of profitability and leverage on corporate social responsibility disclosure. The study was conducted in companies listed in Indonesia Stock Exchange. Profitability and leverage were treated as independent variables, while disclosure of corporate social responsibility is the dependent variable. The research method was used in this research is a verificative approach. The population in this study is the companies listed in Indonesia Stock Exchange. Sample of the study is the companies included as a member of LQ 45 index for period 2013-2015. Total listed companies were involved in this study is 67 companies. The sampling technique used in this study is nonprobability sampling with the purposive sampling method. The data analysis used in this study is multiple linear regression analysis at a significance level of 5%. The statistical program was used in analyzing data is Eviews version 8. The results showed that profitability influences corporate social responsibility disclosure. However, leverage does not influence corporate social responsibility disclosure. Simultaneously, profitability and leverage influence corporate social responsibility disclosur

Histopathological changes observed in the heart and gizzard of quail chicks Coturnix coturnix japonica administrated by the different levels of chrome shaving

The present study showed the effects of different levels of tannery wastes or chrome shaving on quail hicks up to 9 months. The chrome shaving was given at 2.5 and 5% levels in replacement of animal proteins in chicks feed commercially available. Heart and gizzard were selected for thehistopathological studies and effects of different levels were studied in these tissues. Histopathological changes like splitting of muscle, vacuolation, necrosis, pyknosis, and loss of striation and degenerationin heart and gizzard of quail chicks were observed and more pronounced at 5% chrome shaving levels compared to 2.5% level in last 3 weeks. These changes were time and dose dependent

Seasonality of cognitive function in the general population:the Rotterdam Study

Seasonal variation in cognitive function and underlying cerebral hemodynamics in humans has been suggested, but not consistently shown in previous studies. We assessed cognitive function in 10,276 participants from the population-based Rotterdam Study, aged 45 years and older without dementia, at baseline and at subsequent visits between 1999 and 2016. Seasonality of five cognitive test scores and of a summary measure of global cognition were determined, as well as of brain perfusion. Using linkage with medical records, we also examined whether a seasonal variation was present in clinical diagnoses of dementia. We found a seasonal variation of global cognition (0.05 standard deviations [95% confidence interval: 0.02–0.08]), the Stroop reading task, the Purdue Pegboard test, and of the delayed world learning test, with the best performance in summer months. In line with these findings, there were fewer dementia diagnoses of dementia in spring and summer than in winter and fall. We found no seasonal variation in brain perfusion. These findings support seasonality of cognition, albeit not explained by brain perfusion. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00485-0

Formation of Medium-Heavy Elements in Rapid Neutron Capture Process

We predict the neutron drip-line and simulate the r—process path for Cu — Sn, based on the calculation of binding energy in the frame-work of relativistic and non-relativistic mean field formalisms. We also compare the quadrupole deformation parameterβ2, and one neutron separation energy Sn of these isotopic series with the results of finite range droplet model (FRDM) prediction. the results produced by RMF and ShF are comparable to each other and also agreeable with the FRDM model