A Tesla-Blumlein PFL-Bipolar pulsed power generator

A Tesla-Blumlein PFL-Bipolar pulsed power generator, has been successfully designed, manufactured and demonstrated. The compact Tesla transformer that it employs has successfully charged capacitive loads to peak voltages up to 0.6 MV with an overall energy efficiency in excess of 90%. The Tesla driven Blumlein PFL generator is capable of producing a voltage impulse approaching 0.6 MV with a rise time close to 2 ns, generating a peak electrical power of up to 10 GW for 5 ns when connected to a 30 Ω resistive load. Potentially for medical application, a bipolar former has been designed and successfully implemented as an extension to the system and to enable the generation of a sinusoid-like voltage impulse with a peak-to-peak value reaching 650 kV and having a frequency bandwidth beyond 1 GHz. This thesis describes the application of various numerical techniques used to design a successful generator, such as filamentary modelling, electrostatic and transient (PSpice) circuit analysis, and Computer Simulation Technology (CST) simulation. All the major parameters of both the Tesla transformer, the Blumlein pulse forming line and the bipolar former were determined, enabling accurate modelling of the overall unit to be performed. The wide bandwidth and ultrafast embedded sensors used to monitor the dynamic characteristics of the overall system are also presented. Experimental results obtained during this major experimental programme are compared with theoretical predictions and the way ahead towards connecting to an antenna for medical application is considered

A 10 GW Tesla-driven Blumlei pulsed power generator

A repetitive 0.6 MV, 10 GW Tesla-driven Blumlein pulsed power generator, with an overall energy efficiency in excess of 90%, has been designed, manufactured and demonstrated by the Pulsed Power Group at Loughborough University. The paper describes the application of various numerical techniques used to design a successful generator, such as filamentary modelling and electrostatic and transient circuit analysis. All the major parameters of both the Tesla transformer and the Blumlein pulse forming line were determined, enabling accurate modelling of the overall unit to be performed. The wide bandwidth embedded sensors used to monitor the dynamic characteristics of the overall system are also presented. Experimental results obtained during this major experimental program are compared with theoretical predict ions and the way ahead towards generating faster output voltage impulses is considered

Bipolar modulation of the output of a 10-GW pulsed power generator

A bipolar Blumlein former has been designed and successfully implemented as an extension to an existing 10-GW-Tesla-driven Blumlein pulsed power generator. The new system is capable of generating a voltage impulse with a peak-to-peak value reaching 650 kV and having a high-frequency limit of the bandwidth well in excess of 1 GHz. Constructional details are provided, together with experimental results and analysis using the 3-D software modeling of the bipolar former that provides the results in good agreement with experimental data

Temperature dependence of Kerr constant for water at 658 nm and for pulsed intense electric fields

The temperature dependence of the Kerr constant for water has been determined over the range 19 °C-45 °C at a wavelength of 658 nm. This paper presents the experimental arrangement used for this purpose and the data obtained, for which a polynomial fit is provided. A formula is also suggested to help estimate the variation of the Kerr constant for water with both temperature and wavelength

Ribosomal DNA copy number amplification and loss in human cancers is linked to tumor genetic context, nucleolus activity, and proliferation

<div><p>Ribosomal RNAs (rRNAs) are transcribed from two multicopy DNA arrays: the 5S ribosomal DNA (rDNA) array residing in a single human autosome and the 45S rDNA array residing in five human autosomes. The arrays are among the most variable segments of the genome, exhibit concerted copy number variation (cCNV), encode essential components of the ribosome, and modulate global gene expression. Here we combined whole genome data from >700 tumors and paired normal tissues to provide a portrait of rDNA variation in human tissues and cancers of diverse mutational signatures, including stomach and lung adenocarcinomas, ovarian cancers, and others of the TCGA panel. We show that cancers undergo coupled 5S rDNA array expansion and 45S rDNA loss that is accompanied by increased estimates of proliferation rate and nucleolar activity. These somatic changes in rDNA CN occur in a background of over 10-fold naturally occurring rDNA CN variation across individuals and cCNV of 5S-45S arrays in some but not all tissues. Analysis of genetic context revealed associations between cancer rDNA CN amplification or loss and the presence of specific somatic alterations, including somatic SNPs and copy number gain/losses in protein coding genes across the cancer genome. For instance, somatic inactivation of the tumor suppressor gene <i>TP53</i> emerged with a strong association with coupled 5S expansion / 45S loss in several cancers. Our results uncover frequent and contrasting changes in the 5S and 45S rDNA along rapidly proliferating cell lineages with high nucleolar activity. We suggest that 5S rDNA amplification facilitates increased proliferation, nucleolar activity, and ribosomal synthesis in cancer, whereas 45S rDNA loss emerges as a byproduct of transcription-replication conflict in rapidly replicating tumor cells. The observations raise the prospects of using the rDNA arrays as re-emerging targets for the design of novel strategies in cancer therapy.</p></div

The 5S rDNA is increased through 1q42 segmental duplications and 5S array expansion.

<p>(A) Most cancers displayed significantly increased 1q42.13 ploidy. (B) Significant 5S CN amplification was still observed in STAD when only considering patients that are closest to diploidy at 1q42.13 (P-value from one-tailed Wilcoxon rank sum test). Only patients with 5S rDNA CN estimated for both tumor and adjacent tissues are shown in B.</p

Cancer types with rDNA CN estimated in this study.

<p>Cancer types with rDNA CN estimated in this study.</p

Associations between tumor proliferation and rDNA copy number.

<p>(A-B) Spearman rank correlations between PRI (YW gene set) and 45S CN, 5S CN and 5S/45S ratio in LUAD tumor samples. (C) Changes in tumor PRI relative to normal adjacent tissue are positively correlated with changes in the 5S/45S ratio between tumor and normal adjacent tissue. The 31 LUAD patients with paired adjacent-tumor data (DNAseq and RNAseq) were used in C.</p

Pan-cancer linear associations between somatic <i>TP53</i> mutations and the 5S / 45S ratio^*.

<p>Pan-cancer linear associations between somatic <i>TP53</i> mutations and the 5S / 45S ratio^{<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006994#t002fn001" target="_blank">*</a>}.</p

Variable manifestation of concerted copy number variation (cCNV) across tissues.

<p>Pearson correlation between the 5S and 45S rDNA arrays is variable among tissues. The correlation is significant and similarly manifested in normal and cancer lineages of LUAD and BLCA.</p