Implementation of the dissection theorem in cadence virtuoso

This paper describes a tool for the Cadence Virtuoso software that implements the Dissection Theorem (DT) or General Network Theorem (GNT) and its applications: the Extra Element Theorem (EET), Chain Theorem (CT) and General Feedback Theorem (GFT). The tool allows a circuit designer to gain additional circuit insight by providing all second- and third-level transfer functions of the DT. In particular, feedback networks are factored into their exact components, enabling a deeper insight into the structure of the loop gain, direct forward transmission and hence closed-loop behaviour

A 16 channel high-voltage driver with 14 bit resolution for driving piezoelectric actuators

A high-voltage, 16 channel driver with a maximum voltage of 72 volt and 14 bit resolution in a high-voltage CMOS (HV-CMOS) process is presented. This design incorporates a 14 bit monotonic by design DAC together with a high-voltage complementary class AB output stage for each channel. All 16 channels are used for driving a piezoelectric actuator within the control loop of a micropositioning system. Since the output voltages are static most of the time, a class AB amplifier is used, implementing voltage feedback to achieve 14 bit accuracy. The output driver consists of a push-pull stage with a built-in output current limitation and high-impedance mode. Also a protection circuit is added which limits the internal current when the output voltage saturates against the high-voltage rail. The 14 bit resolution of each channel is generated with a segmented resistor string DAC which assures monotonic by design behavior by using leapfrogging of the buffers used between segments. A diagonal shuffle layout is used for the resistor strings leading to cancellation of first order process gradients. The dense integration of 16 channels with high peak currents results in crosstalk, countered in this design by using staggered switching and resampling of the output voltages

Design of an integrated analog controller for a Class-D Audio Amplifier

An integrated analog controller for a self-oscillating class-D audio power amplifier is designed in a 0.35 μm CMOS technology for a 3.3 Volt power supply. It is intended to be used with an external output stage and passive filter, for medium power applications of upto a few 100 Watts. The controller was optimized with regard to its loop gain to suppress the distortion of the output stage. In typical commercially available output stages, the distortion is dominated by dead time effects and the THD can be as low as 20 dB. The controller uses self-oscillation to generate the carrier. To control the self-oscillation a second order phase shift network is embedded in the loop. To increase the loop gain a fifth-order loop filter is added. For a switching frequency of 400kHz the controller achieves a loop gain of 51 dB, nearly flat over the audio band. For reasons of flexibility, the order of the controller is made programmable, as well as the dead time and the delay in the loop. Full spice simulations of the controller combined with an external 120 Watt output stage indicate that a THD of upto 80 dB (better than 0.01%) can be obtained even under the worst case condition of a dead time of 50 ns

Tissue-specific Salmonella Typhimurium gene expression during persistence in pigs

Salmonellosis caused by Salmonella Typhimurium is one of the most important bacterial zoonotic diseases. The bacterium persists in pigs resulting in asymptomatic 'carrier pigs', generating a major source for Salmonella contamination of pork. Until now, very little is known concerning the mechanisms used by Salmonella Typhimurium during persistence in pigs. Using in vivo expression technology (IVET), a promoter-trap method based on Delta purA attenuation of the parent strain, we identified 37 Salmonella Typhimurium genes that were expressed 3 weeks post oral inoculation in the tonsils, ileum and ileocaecal lymph nodes of pigs. Several genes were expressed in all three analyzed organs, while other genes were only expressed in one or two organs. Subsequently, the identified IVET transformants were pooled and reintroduced in pigs to detect tissue-specific gene expression patterns. We found that efp and rpoZ were specifically expressed in the ileocaecal lymph nodes during Salmonella peristence in pigs. Furthermore, we compared the persistence ability of substitution mutants for the IVET-identified genes sifB and STM4067 to that of the wild type in a mixed infection model. The Delta STM4067::kanR was significantly attenuated in the ileum contents, caecum and caecum contents and faeces of pigs 3 weeks post inoculation, while deletion of the SPI-2 effector gene sifB did not affect Salmonella Typhimurium persistence. Although our list of identified genes is not exhaustive, we found that efp and rpoZ were specifically expressed in the ileocaecal lymph nodes of pigs and we identified STM4067 as a factor involved in Salmonella persistence in pigs. To our knowledge, our study is the first to identify Salmonella Typhimurium genes expressed during persistence in pigs

Application of the DIVA principle to Salmonella Typhimurium vaccines in pigs avoids interference with serosurveillance programmes

Salmonellosis is one of the most important bacterial zoonotic diseases in humans and Salmonella infections are often linked with the consumption of contaminated pork. In order to reduce Salmonella Typhimurium infections in humans, minimization of the Salmonella intake into the food chain is important. Vaccination has been proposed to control Salmonella infections in pigs. However, pigs vaccinated with the current vaccines cannot be discriminated from infected pigs with the lipopolysaccharide (LPS) -based serological tests used in European serosurveillance programmes. We therefore examined which LPS encoding genes of Salmonella Typhimurium can be deleted to allow differentiation of infected and vaccinated pigs, without affecting the vaccine strain’s protective capacity. For this purpose, deletion mutants in Salmonella strain 112910a, used as vaccine strain, were constructed in the LPS encoding genes: ∆rfbA, ∆rfaL, ∆rfaJ, ∆rfaI, ∆rfaG and ∆rfaF. Inoculation of BALB/c mice with the parent strain, ∆rfaL, ∆rfbA or ∆rfaJ strains but not the ∆rfaG, ∆rfaF or ∆rfaI strains protected significantly against subsequent infection with the virulent Salmonella Typhimurium strain NCTC12023. Immunization of piglets with the ∆rfaJ or ∆rfaL mutants resulted in the induction of a serological response lacking detectable antibodies against LPS. This allowed a differentiation between sera from pigs immunized with the ∆rfaJ or ∆rfaL strains and sera from pigs infected with their isogenic wild type strain

Cigarette smoke induces apoptosis in the follicle-associated epithelium of murine Peyer's patches

Background: Recently, cigarette smoking has been associated with the development of several auto-immune diseases, including rheumatoid arthritis and inflammatory bowel disease (IBD). The cellular and molecular mechanisms through which cigarette smoking predisposes to IBD are unknown. Cigarette smoke-induced apoptosis is described in several in vivo and in vitro experiments, and might play a role in the pathogenesis of several smoke-associated diseases. The aim of this study was to quantify apoptosis in normal murine Follicle-Associated Epithelium (FAE) and compare this to apoptosis in FAE of smoking mice. Methods: 8 C57BL/6 male mice were exposed to cigarette smoke for 24 weeks (chronic exposure); a control group of 8 mice was exposed to air during the same period. After 24 weeks the mice were sacrificed and Peyer’s patches of each mouse were dissected for histology. Immunohistochemistry for caspase-3 was performed on paraffin-embedded tissue sections of 11 Peyer’s patches of smoking animals and 11 Peyer’s patches of controls. To compare apoptotic activities between smokers and controls, the apoptotic index (percentage of apoptotic cells per 100 cells) in the FAE was calculated. An unpaired student T-test was applied. Results: A statistically significant increase in apoptosis of FAE cells was observed in smoking mice compared to air-exposed mice (P=0.002). In the FAE of smoking animals, the mean apoptotic index was 1.82 with a range of 1.11 to 3.00, whereas the mean apoptotic index in non-smoking animals was 0.92 (range 0.24 -2.06). Most apoptotic cells in both groups were seen at the apex of the FAE. Conclusion: We quantified rates of apoptosis in the FAE of murine Peyer’s patches. Furthermore we compared apoptosis in the FAE of smoking mice versus non-smoking siblings and observed an increased apoptotic index in the FAE of smoking animals. Our results demonstrate that cigarette smoke induces a significant increase of apoptosis in the FAE of murine Peyer’s patches and may point to a role for smoking in the pathogenesis of intestinal inflammation. Further investigation needs to clarify whether this increase in apoptosis influences normal function of the FAE