Controlling Hierarchy in Solution‐processed Polymer Solar Cells Based on Crosslinked P3HT

Understanding and controlling the morphology of donor/acceptor blends is critical for the development of solution processable organic solar cells. By crosslinking a poly(3‐n‐hexylthiophene‐2,5‐diyl) (P3HT) film we have been able to spin‐coat [6,6]‐phenyl‐C₆₁‐butyric acid methyl ester (PCBM) onto the film to form a structure that is close to a bilayer, thus creating an ideal platform for investigating interdiffusion in this model system. Neutron reflectometry (NR) demonstrates that without any thermal treatment a smaller amount of PCBM percolates throughout the crosslinked P3HT when compared to a non‐crosslinked P3HT film. Using time‐resolved NR we also show thermal annealing increases the rate of diffusion, resulting in a near‐uniform distribution of PCBM throughout the polymer film. XPS measurements confirm the presence of both P3HT and PCBM at the annealed film's surface indicating that the two components are intermixed. Photovoltaic devices fabricated using this bilayer approach and suitable annealing conditions yielded comparable power conversion efficiencies to bulk heterojunction devices made from the same materials. The crosslinking procedure has also enabled the formation of patterned P3HT films by photolithography. Pillars with feature sizes down to 2 μm were produced and after subsequent deposition of PCBM and thermal annealing devices with efficiencies of up to 1.4% were produced.     

Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice

Mice that could be highly repopulated with human hepatocytes would have many potential uses in drug development and research applications. The best available model of liver humanization, the uroplasminogen-activator transgenic model, has major practical limitations. To provide a broadly useful hepatic xenorepopulation system, we generated severely immunodeficient, fumarylacetoacetate hydrolase (Fah)-deficient mice. After pretreatment with a urokinase-expressing adenovirus, these animals could be highly engrafted (up to 90%) with human hepatocytes from multiple sources, including liver biopsies. Furthermore, human cells could be serially transplanted from primary donors and repopulate the liver for at least four sequential rounds. The expanded cells displayed typical human drug metabolism. This system provides a robust platform to produce high-quality human hepatocytes for tissue culture. It may also be useful for testing the toxicity of drug metabolites and for evaluating pathogens dependent on human liver cells for replication.     

Age-Dependent Association among Helicobacter pylori Infection,Serum Pepsinogen Levels and Immune Response of Children to Live Oral Cholera Vaccine CVD 103-HgR

Background

Through its effects on gastric secretion, we hypothesized that Helicobacter pylori infection may influence oral immunization. Accordingly, we examined the association between H. pylori infection, serum pepsinogen (PG) (measures for H. pylori gastritis) and vibriocidal antibody (a correlate of protection) seroconversion following oral immunization with CVD 103-HgR live cholera vaccine among children of different ages.

Methods

Sera from 422 Chilean children who were vaccinated with a single dose of CVD 103-HgR were tested by ELISA for serum IgG antibodies to H. pylori, PG I and PG II levels and antibodies to Shigella flexneri 2a lipopolysaccharide and hepatitis A virus (as markers of low socioeconomic status and exposure to enteric pathogens).

Results

The likelihood of vibriocidal antibody seroconversion following vaccination with CVD 103-HgR was significantly decreased in H. pylori-seropositive children age 6 months to 4 years with PG II>8 µg/L (adjusted OR 0.14 (95% CI 0.03–0.61; P = 0.009), and also in H. pylori seropositives with lower PG II level (adjusted OR 0.34, 95% CI 0.14–0.83; P = 0.017), compared to H. pylori-seronegatives. H. pylori-seropositive children aged 5–9 years with serum PG I>30 µg/L (indicating more severe gastritis) had higher odds of vibriocidal seroconversion than those with lower PG I levels (adjusted OR 4.41, 95%CI 1.26–15.38; P = 0.02). There was no significant association between exposures to S. flexneri 2a or hepatitis A virus and vibriocidal seroconversion.

Conclusions

As H. pylori gastritis progresses with increasing pediatric age in developing country venues, changes in gastric secretion ensue that we believe explain the observed differences in age-related immune responses to immunization with live oral cholera vaccine. The effect of H. pylori and changes of gastric acid secretion on the immunogenicity of various oral vaccines should be studied in different developing, transitional and industrialized country settings.     

Helicobacter pylori Infection and Iron Stores: A Systematic Review and Meta-analysis

Background and Aims:  We carried out a systematic literature review and meta-analysis to evaluate the existing evidence on the association between Helicobacter pylori infection and iron stores.
Methods:  Twelve case reports and case series, 19 observational epidemiologic studies and six intervention trials were included in the review.
Results:  Although only few studies controlled for multiple potential confounders, most studies reported a positive association, linking between H. pylori and decreased body iron stores in symptomatic and asymptomatic H. pylori -infected subjects. H. pylori infection may be regarded as a risk factor for reduction in body iron stores and also for iron deficiency or iron deficiency anemia, especially in high-risk groups. The results of the meta-analysis of thoroughly designed and analyzed studies revealed an increased risk for iron deficiency anemia; pooled odds ratio (OR) 2.8 (95% confidence interval (CI) 1.9, 4.2) and also for iron deficiency; pooled OR 1.38 (95%CI 1.16–1.65) among H. pylori -infected subjects. The biologic mechanism by which H. pylori induces the alteration in the iron stores is not fully understood, but it seems to involve several pathways, including gastrointestinal blood loss, decrease in the absorption of dietary iron, and enhanced uptake of the iron by the bacterium.
Conclusions:  H. pylori is associated with reduced iron stores. Future research is needed to determine whether this relationship is a causal association and to better understand its biologic mechanism. The impact of anti- H. pylori therapy on improvement of iron stores needs to be further evaluated in large and well-controlled trials.     

Tip60 is required for DNA interstrand cross-link repair in the Fanconi anemia pathway

The disease Fanconi anemia is a genome instability syndrome characterized by cellular sensitivity to DNA interstrand cross-linking agents, manifest by decreased cellular survival and chromosomal aberrations after such treatment. There are at least 13 proteins acting in the pathway, with the FANCD2 protein apparently functioning as a late term effecter in the maintenance of genome stability. We find that the chromatin remodeling protein, Tip60, interacts directly with the FANCD2 protein in a yeast two-hybrid system. This interaction has been confirmed by co-immunoprecipitation and co-localization using both endogenous and epitope-tagged FANCD2 and Tip60 from human cells. The observation of decreased cellular survival after exposure to mitomycin C in normal fibroblasts depleted for Tip60 indicates a direct function in interstrand cross-link repair. The coincident function of Tip60 and FANCD2 in one pathway is supported by the finding that depletion of Tip60 in Fanconi anemia cells does not increase sensitivity to DNA cross-links. However, depletion of Tip60 did not reduce monoubiquitination of FANCD2 or its localization to nuclear foci following DNA damage. The observations indicate that Fanconi anemia proteins act in concert with chromatin remodeling functions to maintain genome stability after DNA cross-link damage.     

Detection of Helicobacter pylori in stool samples of young children using real‐time polymerase chain reaction

Background

The aims of this study were to develop and validate a multiplex real‐time polymerase chain reaction (q‐PCR) assay of Helicobacter pylori in stool samples of healthy children. Additionally, we determined the prevalence of clarithromycin resistance and cagA gene in H. pylori‐positive samples.

Materials and methods

Archived stool samples from 188 children aged 6‐9 years and 272 samples of 92 infants aged 2‐18 months were tested for H. pylori antigens using enzyme immunoassay (EIA). A multiplex q‐PCR assay was designed to detect H. pylori 16S rRNA and urease and the human RNase P gene as an internal control. Kappa coefficient was calculated to assess the agreement between q‐PCR and EIA.

Results

Laboratory validation of the q‐PCR assay using quantitated H. pylori ATCC 43504 extracted DNA showed S‐shaped amplification curves for all genes; the limit of detection was 1 CFU/reaction. No cross‐reactivity with other bacterial pathogens was noted. Applying the multiplex q‐PCR to DNA extracted from fecal samples showed clear amplification curves for urease gene, but not for 16S rRNA. The prevalence of H. pylori infection was 50% (95% CI 43%‐57%) by q‐PCR (urease cycle threshold <44) vs 59% (95% CI 52%‐66%) by EIA. Kappa coefficient was .80 (P < .001) and .44 (P < .001) for children aged 6‐9 years and 2‐18 months, respectively. Sixteen samples were positive for cagA and three were positive for clarithromycin resistance mutation (A2143G) as confirmed by sequencing.

Conclusions

The developed q‐PCR can be used as a cotechnique to enhance the accuracy of H. pylori detection in epidemiological studies and in clinical settings.