A modular multilevel voltage-boosting Marx pulse-waveform generator for electroporation applications

In order to overcome the limitations of the existing classical and solid-state Marx pulse generators, this paper proposes a new modular multilevel voltage-boosting Marx pulse generator (BMPG). The proposed BMPG has hardware features that allow modularity, redundancy, and scalability as well as operational features that alleviate the need of series-connected switches and allows generation of a wide range of pulse waveforms. In the BMPG, a controllable, low-voltage input boost converter supplies, via directing/blocking (D/B) diodes, two arms of a series modular multilevel converter half-bridge sub-modules (HB-SMs). At start up, all the arm's SM capacitors are resonantly charged in parallel from 0 V, simultaneously via directing diodes, to a voltage in excess of the source voltage. After the first pulse delivery, the energy of the SM capacitors decreases due to the generated pulse. Then, for continuous operation without fully discharging the SM capacitors or having a large voltage droop as in the available Marx generators, the SM capacitors are continuously recharged in parallel, to the desired boosted voltage level. Because all SMs are parallelly connected, the boost converter duty ratio is controlled by a single voltage measurement at the output terminals of the boost converter. Due to the proposed SMs structure and the utilization of D/B diodes, each SM capacitor is effectively controlled individually without requiring a voltage sensor across each SM capacitor. Generation of the commonly used pulse waveforms in electroporation applications is possible, while assuring balanced capacitors, hence SM voltages. The proposed BMPG has several topological variations such as utilizing a buck-boost converter at the input stage and replacing the HB-SM with full-bridge SMs. The proposed BMPG topology is assessed by simulation and scaled-down proof-of-concept experimentation to explore its viability for electroporation applications

Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity

The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion

Case study: Unattended ground sensor phenomenology and signal processing

In the fall of 1995, a unique unattended ground sensor experiment was conducted at the Nevada Test Site. In the experiment, a variety of electro-mechanical equipment was operated, while data was gathered using a number of different types of unattended sensors at different locations. The sensors in this study included seismometers, accelerometers, electric dipole sensors, magnetometers and microphones. In this paper, the authors present some key results form the signal processing of the data from this experiment. The goal of the signal processing was to quantify some of the effects of range on signal propagation, and to determine the ability to detect signals from the equipment, to identify the equipment and to locate the equipment. Some of the physical phenomenon which can affect unattended ground sensor performance will be discussed. The paper will also include a discussion of how the geophysical site characteristics can affect the performance of unattended ground-deployed sensors. While data from a number of different types of sensors were gathered in this experiment, in this paper the authors concentrate on physical phenomenon which can affect seismic sensors and the processing of seismic data

Hypervirulent Clostridium difficile Strains in Hospitalized Patients, Canada1

To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004–2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008

High-voltage pulse generator based on sequentially charged MMC-SMs operating in a voltage-boost mode

Pulse forming networks and Marx generators are the classical rectangular waveform pulse generators (PGs). They are inflexible and their capacitors must be fully charged to the required voltage from 0V before delivering each high-voltage (HV) pulse. They are only able to generate unipolar pulses; if bipolar pulses are sought another generator fed from a negative supply voltage is added. Recently, several power electronics based PGs have been proposed. This paper presents an HV power electronics based PG, which is based on Half-Bridge Modular Multilevel Converter (HB-MMC) sub-modules (SMs) charged sequentially in a voltage boost mode. Each SM capacitor and main switch form a boost converter with the charging input supply and inductor. As a result, all SM capacitors are charged to a voltage greater than the input. During the discharging process the SM capacitors are connected in series, producing a rectangular HV pulse across the load. The proposed charging method allows a reduction in the converter footprint in comparison with recently proposed MMC sequentially charged PG topologies. Although only rectangular pulse waveforms are sought in this paper, a SM capacitor voltage balance method allows multilevel pulse generation. The viability of the proposed converter is confirmed by MATLAB/Simulink simulation and scaled-down experimentation

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure