Embedded 5V-to-3.3V Voltage Regulator for Supplying Digital ICs in 3.3V CMOS Technology

A fully integrated 5 V-to-3.3 V supply voltage regulator for application in digital IC's has been designed in a 3.3 V 0.5 μm CMOS process. The regulator is able to deliver peak current transients of 300 mA, while the output voltage remains within a margin of 10% around the nominal value. The circuit draw's a static quiescent current of 750 μA during normal operation, and includes a power-down mode with only 10 μA current consumption. The die area is 1 mm2, and can be scaled proportional to the maximum peak current. Special precautions have been taken to allow 5 V in the 3.3 V process

The Multiple Insertion Pyramid: A Fast Parameter-Less Population Scheme

textabstractThe Parameter-less Population Pyramid (P3) uses a novel population scheme, called the population pyramid. This population scheme does not require a fixed population size, instead it keeps adding new solutions to an ever growing set of layered populations. P3 is very efficient in terms of number of fitness function evaluations but its runtime is significantly higher than that of the Gene-pool Optimal Mixing Evolutionary Algorithm (GOMEA) which uses the same method of exploration. This higher run-time is caused by the need to rebuild the linkage tree every time a single new solution is added to the population pyramid.We propose a new population scheme, called the multiple insertion pyramid that results in a faster variant of P3 by inserting multiple solutions at the same time and operating on populations instead of on single solutions

Modeling Population Growth in R with the biogrowth Package

The growth of populations is of interest in a broad variety of fields, such as epidemiology, economics or biology. Although a large variety of growth models are available in the scientific literature, their application usually requires advanced knowledge of mathematical programming and statistical inference, especially when modelling growth under dynamic environmental conditions. This article presents the biogrowth package for R, which implements functions for modelling the growth of populations. It can predict growth under static or dynamic environments, considering the effect of an arbitrary number of environmental factors. Moreover, it can be used to fit growth models to data gathered under static or dynamic environmental conditions. The package allows the user to fix any model parameter prior to the fit, an approach that can mitigate identifiability issues associated to growth models. The package includes common S3 methods for visualization and statistical analysis (summary of the fit, predictions, . . . ), easing result interpretation. It also includes functions for model comparison/selection. We illustrate the functions in biogrowth using examples from food science and economy

Short- and Long-Term Biomarkers for Bacterial Robustness: A Framework for Quantifying Correlations between Cellular Indicators and Adaptive Behavior

The ability of microorganisms to adapt to changing environments challenges the prediction of their history-dependent behavior. Cellular biomarkers that are quantitatively correlated to stress adaptive behavior will facilitate our ability to predict the impact of these adaptive traits. Here, we present a framework for identifying cellular biomarkers for mild stress induced enhanced microbial robustness towards lethal stresses. Several candidate-biomarkers were selected by comparing the genome-wide transcriptome profiles of our model-organism Bacillus cereus upon exposure to four mild stress conditions (mild heat, acid, salt and oxidative stress). These candidate-biomarkers—a transcriptional regulator (activating general stress responses), enzymes (removing reactive oxygen species), and chaperones and proteases (maintaining protein quality)—were quantitatively determined at transcript, protein and/or activity level upon exposure to mild heat, acid, salt and oxidative stress for various time intervals. Both unstressed and mild stress treated cells were also exposed to lethal stress conditions (severe heat, acid and oxidative stress) to quantify the robustness advantage provided by mild stress pretreatment. To evaluate whether the candidate-biomarkers could predict the robustness enhancement towards lethal stress elicited by mild stress pretreatment, the biomarker responses upon mild stress treatment were correlated to mild stress induced robustness towards lethal stress. Both short- and long-term biomarkers could be identified of which their induction levels were correlated to mild stress induced enhanced robustness towards lethal heat, acid and/or oxidative stress, respectively, and are therefore predictive cellular indicators for mild stress induced enhanced robustness. The identified biomarkers are among the most consistently induced cellular components in stress responses and ubiquitous in biology, supporting extrapolation to other microorganisms than B. cereus. Our quantitative, systematic approach provides a framework to search for these biomarkers and to evaluate their predictive quality in order to select promising biomarkers that can serve to early detect and predict adaptive traits

Different carbon sources result in differential activation of sigma B and stress resistance in Listeria monocytogenes

Listeria monocytogenes is an important food-borne pathogen that is ubiquitous in the environment. It is able to utilize a variety of carbon sources, to produce biofilms on food-processing surfaces and to survive food preservation–associated stresses. In this study, we investigated the effect of three common carbon sources, namely glucose, glycerol and lactose, on growth and activation of the general stress response Sigma factor, SigB, and corresponding phenotypes including stress resistance. A fluorescent reporter coupled to the promoter of lmo2230, a highly SigB-dependent gene, was used to determine SigB activation via quantitative fluorescence spectroscopy. This approach, combined with Western blotting and fluorescence microscopy, showed the highest SigB activation in lactose grown cells and lowest in glucose grown cells. In line with this observation, lactose grown cells showed the highest resistance to lethal heat and acid stress, the highest biofilm formation, and had the highest adhesion/invasion capacity in Caco-2-derived C2Bbe1 cell lines. Our data suggest that lactose utilisation triggers a strong SigB dependent stress response and this may have implications for the resistance of L. monocytogenes along the food chain

A single point mutation in the Listeria monocytogenes ribosomal gene rpsU enables SigB activation independently of the stressosome and the anti-sigma factor antagonist RsbV

Microbial population heterogeneity leads to different stress responses and growth behavior of individual cells in a population. Previously, a point mutation in the rpsU gene (rpsUG50C) encoding ribosomal protein S21 was identified in a Listeria monocytogenes LO28 variant, which leads to increased multi-stress resistance and a reduced maximum specific growth rate. However, the underlying mechanisms of these phenotypic changes remain unknown. In L. monocytogenes, the alternative sigma factor SigB regulates the general stress response, with its activation controlled by a series of Rsb proteins, including RsbR1 and anti-sigma factor RsbW and its antagonist RsbV. We combined a phenotype and proteomics approach to investigate the acid and heat stress resistance, growth rate, and SigB activation of L. monocytogenes EGDe wild type and the ΔsigB, ΔrsbV, and ΔrsbR1 mutant strains. While the introduction of rpsUG50C in the ΔsigB mutant did not induce a SigB-mediated increase in robustness, the presence of rpsUG50C in the ΔrsbV and the ΔrsbR1 mutants led to SigB activation and concomitant increased robustness, indicating an alternative signaling pathway for the SigB activation in rpsUG50C mutants. Interestingly, all these rpsUG50C mutants exhibited reduced maximum specific growth rates, independent of SigB activation, possibly attributed to compromised ribosomal functioning. In summary, the increased stress resistance in the L. monocytogenes EGDe rpsUG50C mutant results from SigB activation through an unknown mechanism distinct from the classical stressosome and RsbV/RsbW partner switching model. Moreover, the reduced maximum specific growth rate of the EGDe rpsUG50C mutant is likely unrelated to SigB activation and potentially linked to impaired ribosomal function

Effects of High-Pressure Processing, UV-C Irradiation and Thermoultrasonication on Donor Human Milk Safety and Quality

Holder pasteurization (HoP) is the current recommended treatment for donor human milk. Although this method inactivates microbial contaminants, it also negatively affects various milk components. High-pressure processing (HPP, 400, 500, and 600 MPa), ultraviolet-C irradiation (UV-C, 2,430, 3,645, and 4,863 J/L) and thermoultrasonication (TUS, 1,080 and 1,620 kJ/L) were investigated as alternatives to thermal pasteurization (HoP). We assessed the effects of these methods on microbiological safety, and on concentration and functionality of immunoglobulin A, lactoferrin, lysozyme and bile salt-stimulated lipase, with LC-MS/MS-based proteomics and activity assays. HoP, HPP, TUS, and UV-C at 4863 J/L, achieved >5-log 10 microbial reduction. Native protein levels and functionality showed the highest reduction following HoP, while no significant reduction was found after less intense HPP and all UV-C treatments. Immunoglobulin A, lactoferrin, and lysozyme contents were also preserved after low intensity TUS, but bile salt-stimulated lipase activity was significantly reduced. This study demonstrated that HPP and UV-C may be considered as suitable alternatives to HoP, since they were able to ensure sufficient microbial inactivation while at the same time better preserving the bioactive components of donor human milk. In summary, our results provide valuable insights regarding the evaluation and selection of suitable processing methods for donor human milk treatment, which may replace HoP in the future

ARF-BP1 as a potential therapeutic target

In this review, we discuss the recent identification of ARF-BP1 (also known as Mule, UREB1, E3histone, LASU1, and HectH9). ARF-BP1, a HECT domain-containing E3 ubiquitin ligase, interacts with ARF and p53. Its ubiquitin ligase activity is inhibited by ARF. Inactivation of ARF-BP1 stabilised p53 and induced apoptosis. Notably, inactivation of ARF-BP1 also caused cell growth repression in p53-null cells and breast cancer cells with mutant p53. Thus, ARF-BP1 emerges as a novel therapeutic target against cancer regardless of p53 status

Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn’s disease: an observational study

Background/Objectives: Enteral feeding will induce remission in as many as 80–90% of compliant patients with active Crohn’s disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. Methods/Subjects: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. Results: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. Conclusions: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD