Editorial comment on: increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells

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Modeling of Small-Scale Wind Power System with Virtual Synchronous Generator

Wind power systems are the most commonly used systems for a renewable energy source over the past few decades. Most of the current wind turbines are large scale wind turbines which produce mega watts power. This thesis is prepared to develop a small scale wind turbine with axial flux permanent magnet synchronous generator for regional areas and small commercial industries. This thesis mainly focuses on the Axial Flux PMSG which is a small scale prototype with the characteristics of the large scale wind turbine generator and having a super capacitor embedded in it. The first objective is to create the dynamic wind gust model. The second objective is to study the background of the large scale wind turbine synchronous generator characteristics and to derive the equations to model the AFPMSG. The next objective is to implement the super capacitor model with a controller. The other main objective of this thesis is to design a Virtual Synchronous Generator to emulate the inertia and damping same as the conventional synchronous generator to maintain output power and the frequency stable when there is a change in the load. The model will be tested using the MATLAB-Simulink environment and the results will be discussed

Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target

K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder

The human fibroblast growth factor receptor 3 (FGFR3) gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 activating mutations as a ‘driver’ of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1) activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer

Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 nuclear bodies

Background: Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids. Results: We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons. Conclusion: Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs

Experimental studies and theoretical models for concrete columns confined with FRP composites: a review

Advanced fibre reinforced polymer (FRP) composites have been increasingly used over the last two decades for strengthening, upgrading, and restoring degraded civil engineering infrastructure. Substantial experimental investigations have been conducted in recent years to understand the compressive behaviour of FRP-confined concrete columns. A considerable number of confinement models to predict the compressive behaviour of FRP strengthened concrete columns have been developed from the results of these experimental investigations. The purpose of this paper is to present a comprehensive review of experimental investigations and theoretical models of circular and non-circular concrete columns confined with FRP reinforcement. The paper reviews previous experimental test results on circular and non-circular concrete columns confined with FRP reinforcement under concentric and eccentric loading conditions and highlights the behaviour and mechanics of FRP confinement in these columns. The paper also reviews existing confinement models for concrete columns confined with FRP composites in both circular and non-circular sections. This paper demonstrates that the performance and effectiveness of FRP confinement in concrete columns have been extensively investigated and proven effective in enhancing the structural performance and ductility of strengthened columns. The strength and ductility enhancement depend on the number of FRP layers, concrete compressive strength, corner radius for non-circular columns, and intensity of load eccentricity for eccentrically loaded columns. The impact of existing theoretical models and directions for future research are also presented. Potential researchers will gain insight into existing experimental and theoretical studies and future research directions

Change in outbreak epicentre and its impact on the importation risks of COVID-19 progression: A modelling study

Background The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first detected in the city of Wuhan, China has now spread to every inhabitable continent, but now the attention has shifted from China to other epicentres. This study explored early assessment of the influence of spatial proximities and travel patterns from Italy on the further spread of SARS-CoV-2 worldwide. Methods Using data on the number of confirmed cases of COVID-19 and air travel data between countries, we applied a stochastic meta-population model to estimate the global spread of COVID-19. Pearson's correlation, semi-variogram, and Moran's Index were used to examine the association and spatial autocorrelation between the number of COVID-19 cases and travel influx (and arrival time) from the source country. Results We found significant negative association between disease arrival time and number of cases imported from Italy (r = −0.43, p = 0.004) and significant positive association between the number of COVID-19 cases and daily travel influx from Italy (r = 0.39, p = 0.011). Using bivariate Moran's Index analysis, we found evidence of spatial interaction between COVID-19 cases and travel influx (Moran's I = 0.340). Asia-Pacific region is at higher/extreme risk of disease importation from the Chinese epicentre, whereas the rest of Europe, South-America and Africa are more at risk from the Italian epicentre. Conclusion We showed that as the epicentre changes, the dynamics of SARS-CoV-2 spread change to reflect spatial proximities

A Plasmodium falciparum Histone Deacetylase Regulates Antigenic Variation and Gametocyte Conversion

SummaryThe asexual forms of the malaria parasite Plasmodium falciparum are adapted for chronic persistence in human red blood cells, continuously evading host immunity using epigenetically regulated antigenic variation of virulence-associated genes. Parasite survival on a population level also requires differentiation into sexual forms, an obligatory step for further human transmission. We reveal that the essential nuclear gene, P. falciparum histone deacetylase 2 (PfHda2), is a global silencer of virulence gene expression and controls the frequency of switching from the asexual cycle to sexual development. PfHda2 depletion leads to dysregulated expression of both virulence-associated var genes and PfAP2-g, a transcription factor controlling sexual conversion, and is accompanied by increases in gametocytogenesis. Mathematical modeling further indicates that PfHda2 has likely evolved to optimize the parasite’s infectious period by achieving low frequencies of virulence gene expression switching and sexual conversion. This common regulation of cellular transcriptional programs mechanistically links parasite transmissibility and virulence