Clustering and mobility of hard rods in a quasicrystalline substrate potential

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in J. Chem. Phys. 137, 224705 (2012) and may be found at https://doi.org/10.1063/1.4769839.Recently, we have studied the self-assembly of hard needles in a quasicrystalline substrate potential with decagonal symmetry [P. Kählitz and H. Stark, J. Chem. Phys. 136, 174705 (2012) https://doi.org/10.1063/1.4711086.]. We have identified new structure formation using Monte Carlo simulations. However, hard needles have a zero width. To investigate how the excluded volume of rod-shaped particles influences their phase ordering, we extend here our studies to spherocylinders. We determine phase diagrams and plot them in the relevant variables, strength of substrate potential versus area fraction. At increasing area fraction η short rods form clusters that ultimately destroy directional ordering along the decagonal symmetry directions while surface-induced positional order exists for all η. In contrast, long rods show directional order in the whole density range. However, at high area fractions they assemble into compact clusters which destroy positional ordering. Finally, we also study the rod mobility using the kinetic Monte Carlo method and discuss an unexpected mobility enhancement with increasing density. All these features crucially depend on the non-zero excluded volume of the spherocylinders.DFG, 65143814 , GRK 1524: Self-Assembled Soft-Matter Nanostructures at Interface

Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer

Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to onecancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the twocancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy c-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Constitutive expression differences of DNA repair-associated proteins in fibroblasts of 2C vs. 1C patients, measured by antibody microarrays.

<p>Constitutive expression differences of DNA repair-associated proteins in fibroblasts of 2C vs. 1C patients, measured by antibody microarrays.</p

Western blot showing reduced RAD9A protein levels in a two-cancer patient.

<p>The gel on the left side shows Coomassie blue staining of nuclear and cytoplasmic protein extracts (30 µg each) from untreated fibroblasts of two-cancer patient 2C-7 and the matched one-cancer patient 1C-7. The corresponding gel on the right side is stained with anti-RAD9A antibody, which recognizes a 45 kDA nuclear protein. The calculated 2C/1C RAD9A protein ratio is 0.6.</p

Reduced expression of DNA repair-associated proteins in two-cancer patients.

<p>The relative expression levels in fibroblasts of 2C versus 1C patients are −1.36x (p = 0.017) for BRCA1, −1.27x (p = 0.011) for DDIT3, −1.16x (p = 0.021) for MSH6, −1.18x (p = 0.003) for TP53, −1.38x (p = 0.040) for RAD9A, and −1.37 (p = 0.009) for RAD51. Protein expression was measured by antibody microarrays (normalized by log10 transformation and z scores). Box plots show the distribution of z ratios in matched 2C vs. 1C patients. The median is represented by horizontal lines. The bottom of the box indicates the 25^th percentile, the top the 75^th percentile. The T bars extend from the boxes to at most 1.5 times the height of the box. Outliers are shown as open circles.</p