An essential GT motif in the lamin A promoter mediates activation by CREB-binding protein

Lamin A is an important component of nuclear architecture in mammalian cells. Mutations in the human lamin A gene lead to highly degenerative disorders that affect specific tissues. In studies directed towards understanding the mode of regulation of the lamin A promoter, we have identified an essential GT motif at -55 position by reporter gene assays and mutational analysis. Binding of this sequence to Sp transcription factors has been observed in electrophoretic mobility shift assays and by chromatin immunoprecipitation studies. Further functional analysis by co-expression of recombinant proteins and ChIP assays has shown an important regulatory role for CREB-binding protein in promoter activation, which is mediated by the GT motif

Variable Rate LPPT Based Droop Controlled Operation of Photovoltaic System for Microgrid Frequency Regulation

The objective of this thesis is to improve the frequency regulation of an islanded microgrid system consisting of photovoltaic (PV) system. Operating the PV system in Limited power point tracking (LPPT) mode gives provision for the application of droop control on the PV system active power, which in turn enhances the frequency regulation of the microgrid. LPPT is a control technique used for extracting the desired amount of power that may be less than the maximum available power from the PV system. Variable rate LPPT is the superior control technique among the available LPPT control techniques, which is employed in the work. The droop controller implemented in this thesis provides the required power reference command for the limited power operation of a PV system based on the deviation of bus frequency from its nominal value (50 Hz/60 Hz). A case study is presented to validate the effectiveness of the above-mentioned concept

Assessment of Skempton's pore water pressure parameters B and A using a high-capacity tensiometer

Saturation of soils is a prerequisite in many laboratory tests involving consolidation, permeability and stress-strain behaviour. The saturation process is usually time consuming, particularly in clay-rich soils, and this can incur substantial cost and potential delays in reporting findings. The saturation of samples is assessed using the well-established Skempton's pore water pressure parameter B. In a situation where the soil is fully saturated the B-value is approximately one. It is often the case that fine soil samples extracted from the ground, particularly those from below the water table, remain saturated. However, current testing protocols require evidence to verify a complete saturation prior to subsequent laboratory investigations. This paper reports experimental results exploring the hypothesis that, if the sample is ‘perceived’ to be saturated, then further saturation procedures may not be necessary to obtain reliable geotechnical parameters. Laboratory investigations were conducted on three different clays (Kaolin Clay, Belfast Clay and Oxford Clay) in a testing chamber instrumented with a high capacity tensiometer. The confining pressures were applied in a ramped fashion under undrained conditions. The response of the tensiometer confirmed that the samples were saturated from the very beginning of the loading process, as implied by the B-value being close to one. Further supplementary investigations were carried out to assess the Skempton's pore water pressure parameter A and the stress-strain behaviour of the soils. The combined finding provides further evidence to suggest that the saturation process as suggested in standards may not be necessary for fine grained soils to establish reliable geotechnical design parameters

Effect of Benzothiazole based conjugates in causing apoptosis by Regulating p53, PTEN and MAP Kinase proteins affecting miR-195a and miR-101-1

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) accounts for majority of liver cancers and is the leading cause of cancer related death in Asia. Like any other cancer, HCC develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and results in the loss of apoptosis. Therefore, a delicate balance between the expression of various genes involved in proliferation and apoptosis decide the ultimate fate of the cell to undergo rapid proliferation (cancer) or cell death.</p> <p>Results</p> <p>The benzothiazole based compounds exhibited effective cytotoxicity at 4 μM concentration and have shown G1 cell cycle arrest with decrease in levels of G1 cell cycle proteins such as cyclin D1 and Skp2. Involvement of tumour suppressor proteins such as PTEN and p53 was studied. Interestingly these compounds displayed decrease in the phosphorylated forms of AKT, p38 MAPK and ERK1/2 which play a vital role in cell proliferation. Compounds have exhibited strong and significant effect on the expression of micro RNAs such as miR-195a & miR-101-1 which regulate hepatic cell proliferation.</p> <p>Conclusions</p> <p>The cell cycle arrest and apoptotic inducing nature of these compounds was revealed by FACS, BrdU cell proliferation and tunel assays. Compounds affected both tumour suppressor proteins as well as proteins that are involved in active cell proliferation. Micro RNAs whose target is Cyclin D1 such as miR-195a and miR-101-1 that is required for growth of hepatoma cells was drastically affected. These compounds caused apoptosis by activating caspase-3 and PARP.</p

Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one of the most prevalent cancers in the world and more than one million women are diagnosed leading to 410,000 deaths every year. In our previous studies new chalcone-imidazolone conjugates were prepared and evaluated for their anticancer activity in a panel of 53 human tumor cell lines and the lead compounds identified were 6 and 8. This prompted us to investigate the mechanism of apoptotic event.</p> <p>Results</p> <p>Involvement of pro-apoptotic protein (Bax), active caspase-9 and cleavage of retinoblastoma protein was studied. Interestingly, the compounds caused upregulation of p21, check point proteins (Chk1, Chk2) and as well as their phosphorylated forms which are known to regulate the DNA damage pathway. Increased p53BP1 foci by immunolocalisation studies and TRF1 suggested the possible involvement of telomere and associated proteins in the apoptotic event. The telomeric protein such as TRF2 which is an important target for anticancer therapy against human breast cancer was extensively studied along with proteins involved in proper functioning of telomeres.</p> <p>Conclusions</p> <p>The apoptotic proteins such as Bax, active caspase-9 and cleaved RB are up-regulated in the compound treated cells revealing the apoptotic nature of the compounds. Down regulation of TRF2 and upregulation of the TRF1 as well as telomerase assay indicated the decrease in telomeric length revealing telomeric dysfunction and thereby controlling the rapid rate of cell proliferation. In summary, chalcone-imidazolone conjugates displayed significant DNA damage activity particularly at telomeres and caused both apoptosis and senescence-like growth arrest which suggested that these compounds have potential activity against breast carcinoma.</p

The RNA Helicase Rm62 Cooperates with SU(VAR)3-9 to Re-Silence Active Transcription in Drosophila melanogaster

Gene expression is highly dynamic and many genes show a wide range in expression over several orders of magnitude. This regulation is often mediated by sequence specific transcription factors. In addition, the tight packaging of DNA into chromatin can provide an additional layer of control resulting in a dynamic range of gene expression covering several orders of magnitude. During transcriptional activation, chromatin barriers have to be eliminated to allow an efficient progression of the RNA polymerase. This repressive chromatin structure has to be re-established quickly after it has been activated in order to tightly regulate gene activity. We show that the DExD/H box containing RNA helicase Rm62 is targeted to a site of rapid induction of transcription where it is responsible for an increased degree of methylation at H3K9 at the heat shock locus after removal of the heat shock stimulus. The RNA helicase interacts with the well-characterized histone methyltransferase SU(VAR)3-9 via its N-terminus, which provides a potential mechanism for the targeting of H3K9 methylation to highly regulated genes. The recruitment of SU(VAR)3-9 through interaction with a RNA helicase to a site of active transcription might be a general mechanism that allows an efficient silencing of highly regulated genes thereby enabling a cell to fine tune its gene activity over a wide range

Performance Improvement of a Nine-Phase Induction Machine using Octadecagonal SVPWM Control Technique

It is well known that multi-phase induction machine drives (IMD) are best suitable for high power application compared to the conventional 3-phase IMDs. However, with the implementation of multi-phase space vector pulse width modulation (SVPWM) presented in the literature, improvement in the linear modulation region is less significant as the number of phase increases. To overcome the abovementioned limitation, this paper proposes an octadecagonal SVPWM control technique for a nine-phase induction machine. With the implementation of octadecagonal SVPWM control technique, the linear modulation region is improved by 26.03% compared to nine-phase sinusoidal pulse width modulation and 24.2S% compared to nine-phase SVPWM. In addition, the lower order dominant time harmonics in the air-gap flux are eliminated even though the phase currents of nine-phase induction machine consist of lower-order harmonics. The absence of lower-order dominant harmonics in the air-gap flux results in reduced torque pulsations of the IMD. ANSYS Maxwell simulation and experimentation results are presented to validate the proposed control technique

18-Sided polygon voltage space vector fed nine-phase induction machine drive for high power applications

The advantages such as better fault-tolerant capability, less space harmonic content, and requirement of power semiconductor devices with reduced voltage ratings etc., made the multi-phase induction machines drives (IMD) best desirable for the high power applications. However, as the number of phase increases, the improvement in the LMR of the multi-phase IMDs is not significant using the conventional SVPWM techniques provided in the literature. To address the above-mentioned limitation, 18-sided polygon (octadecagon) based voltage space vector generation for a nine-phase IMD is proposed in this article without compromising in the torque harmonic profile. Using the proposed octadecagonal voltage space vector generation technique, the LMR of nine-phase IMD is significantly improved by 26.03%, 24.28%, and 9.15% in comparison to the nine-phase sinusoidal pulse width modulation, nine-phase SVPWM and individual hexagonal SVPWM techniques, respectively. Efficacy of the proposed control technique is substantiated using the results obtained from ANSYS Maxwell simulation and experimentation on 5-hp nine-phase IMD prototype in the laboratory

An Improved SVPWM Control Technique to Reduce Winding Losses of 9-Phase Induction Motor

The improvement in the linear modulation reduces with increase in the number of phases of the induction machine (IM) by using the multiphase space vector pulse width modulation (SVPWM) control technique. For example, for a nine-phase IM, the linear modulation region is improved by only 1.54% by using nine-phase SVPWM control technique compared to nine-phase sinusoidal pulse width modulation. On the other hand, the octadecagonal SVPWM control technique helps in attaining improved linear modulation region and better harmonic profile compared to nine phase SVPWM control technique. However, the phase voltages and currents consists of lower order dominant harmonics of the order 5 th , 7 th , 11 th , and 13 th … In this paper, an improved control technique using vector space decomposition is presented to limit the lower order dominant harmonics in the phase voltages and currents. With the presented control technique, one can choose between the improvement in the linear modulation region and the minimization of lower order dominant harmonic components. To validate the presented concept, experimentation is performed on laboratory prototype of a 9-phase IM