Effect of the Synthetic Bile Salt Analog CamSA on the Hamster Model of Clostridium difficile Infection

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the mean time to death, compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days postchallenge and showed no signs of colonic tissue damage. In a delayed-treatment model of hamster CDI, CamSA was unable to prevent infection signs and death. These data support a putative model in which CamSA reduces the number of germinating C. difficile spores but does not keep all of the spores from germinating. Vancomycin halts division of any vegetative cells that are able to grow from spores that escape CamSA

Iodide and chloride ions diffusivity, pore characterization and microstructures of concrete incorporating ground granulated blast furnace slag

Innovative approaches are under research to study the resistance of chloride ion penetration in concrete containing chloride ions, to minimize the impact of chloride ion penetration test errors in coastal reinforced concrete (RC), which is helpful to the design of coastal RC structures. In this study, the diffusion depth, free ion concentration and diffusion coefficient of chloride, iodide ions with different curing ages and GGBFS content were measured by the Rapid Chloride Migration Test (RCM) and Rapid Iodide Migration tests (RIM). The SEM-EDS and MIP were used to analyze the microstructures, pore size distribution and the hydrated products. The results show that the performance of GGBFS concrete against the diffusion of corrosive ions is affected by the curing age and the content of GGBFS. With the increase of GGBFS content, especially concrete with 60% GGBFS, the influence of chloride, iodide ion penetrating into concrete gradually becomes smaller. The long-age curing system is more conducive to the concrete resistance to the migration and diffusion of chloride, iodine ions. Compared with the ordinary concrete, the total porosity of concrete mixed with GGBFS is lower, the internal microstructures have fewer cracks and defects, the density is better, and the diffusion coefficient of chloride and iodide ions is also lower. In addition, using the concept of corrosive ion adjustment coefficient (conversion coefficient of diffusion between chloride ion and iodide ion) and applying the data regression analysis (DRA), it is found that there is a good quadratic parabolic function relationship between the GGBFS content and the ions adjustment coefficient

Spatial normalization of reverse phase protein array data.

Reverse phase protein arrays (RPPA) are an efficient, high-throughput, cost-effective method for the quantification of specific proteins in complex biological samples. The quality of RPPA data may be affected by various sources of error. One of these, spatial variation, is caused by uneven exposure of different parts of an RPPA slide to the reagents used in protein detection. We present a method for the determination and correction of systematic spatial variation in RPPA slides using positive control spots printed on each slide. The method uses a simple bi-linear interpolation technique to obtain a surface representing the spatial variation occurring across the dimensions of a slide. This surface is used to calculate correction factors that can normalize the relative protein concentrations of the samples on each slide. The adoption of the method results in increased agreement between technical and biological replicates of various tumor and cell-line derived samples. Further, in data from a study of the melanoma cell-line SKMEL-133, several slides that had previously been rejected because they had a coefficient of variation (CV) greater than 15%, are rescued by reduction of CV below this threshold in each case. The method is implemented in the R statistical programing language. It is compatible with MicroVigene and SuperCurve, packages commonly used in RPPA data analysis. The method is made available, along with suggestions for implementation, at http://bitbucket.org/rppa_preprocess/rppa_preprocess/src

Analysis of Yarrowia lipolytica Growth, Catabolism, and Terpenoid Biosynthesis during Utilization of Lipid-derived Feedstock

This study employs biomass growth analyses and 13C-isotope tracing to investigate lipid feedstock utilization by Yarrowia lipolytica. Compared to glucose, oil-feedstock in the minimal medium increases the yeast\u27s biomass yields and cell sizes, but decreases its protein content (\u3c20% of total biomass) and enzyme abundances for product synthesis. Labeling results indicate a segregated metabolic network (the glycolysis vs. the TCA cycle) during co-catabolism of sugars (glucose or glycerol) with fatty acid substrates, which facilitates resource allocations for biosynthesis without catabolite repressions. This study has also examined the performance of a β-carotene producing strain in different growth mediums. Canola oil-containing yeast-peptone (YP) has resulted in the best β-carotene titer (121 ± 13 mg/L), two-fold higher than the glucose based YP medium. These results highlight the potential of Y. lipolytica for the valorization of waste-derived lipid feedstock

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype

The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior

First Observation of the Doubly Charmed Baryon Xi_cc^+

We observe a signal for the doubly charmed baryon Xi_cc^+ in the charged decay mode Xi_cc^+ --> Lambda_c^+ K- pi+ in data from SELEX, the charm hadro-production experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1 +/- 0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is (3519 +/- 1) MeV/c^2. The Gaussian mass width of this state is 3MeV/c^2, consistent with resolution; its lifetime is less than 33fsec at 90% confidence.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter

First observation of a narrow charm-strange meson DsJ(2632) -> Ds eta and D0 K+

We report the first observation of a charm-strange meson DsJ(2632) at a mass of 2632.6+/-1.6 MeV/c^2 in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, Ds eta and D0 K+. In the Ds eta decay mode we observe an excess of 49.3 events with a significance of 7.2sigma at a mass of 2635.9+/-2.9 MeV/c^2. There is a corresponding peak of 14 events with a significance of 5.3sigma at 2631.5+/-1.9 MeV/c^2 in the decay mode D0 K+. The decay width of this state is <17 MeV/c^2 at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(Dseta) is 0.16+/-0.06. The mechanism which keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the Ds eta decay mode.Comment: 5 pages, 3 included eps figures. v2 as accepted for publication by PR

Confirmation of the Double Charm Baryon Xi_cc+ via its Decay to p D+ K-

We observes a signal for the double charm baryon Xi_cc+ in the charged decay mode Xi_cc+ -> p D+ K- to complement the previously reported decay Xi_cc+ -> Lambda_c K- pi+ in data from SELEX, the charm hadro-production experiment (E781) at Fermilab. In this new decay mode we observe an excess of 5.62 events over an expected background estimated by event mixing to be 1.38+/-0.13 events. The Poisson probability that a background fluctuation can produce the apparent signal is less than 6.4E-4. The observed mass of this state is (3518+/-3)MeV/c^2, consistent with the published result. Averaging the two results gives a mass of (3518.7+/-1.7)MeV/c^2. The observation of this new weak decay mode confirms the previous SELEX suggestion that this state is a double charm baryon. The relative branching ratio Gamma(Xi_cc+ -> pD+K-)/Gamma(Xi_cc+ -> Lambda_c K- pi+) = 0.36+/-0.21.Comment: 11 pages, 6 included eps figures. v2 includes improved statistical method to determine significance of observation. Submitted to PL