Toward the perfect membrane material for environmental x ray photoelectron spectroscopy

We outline our achievements in developing electron transparent, leak tight membranes required for environmental photoelectron spectroscopy PES . We discuss the mechanical constraints limiting the achievable membrane size and review the development of growth protocols for the chemical vapor deposition CVD of single crystalline graphene on highly 111 textured Cu foils serving as membrane material. During CVD growth, Cu tends to develop a mesoscopic staircase morphology consisting of alternating inclined surface planes, irrespective of whether the covering graphene film or the substrate are single crystalline. This morphology remains imprinted even when converting the film into freestanding graphene, which affects its mechanical properties. Determining the number of carbon layers in freestanding graphene, we show that membranes reported to suspend over distances larger than 20 m most likely consist of few layer graphene. The Raman band signature often used to confirm monolayer graphene rather relates to graphene with turbostratic stacking. The vertical corrugation of freestanding graphene was shown to be almost absent for tri and four layer thick graphene but substantial for bilayer and especially for monolayer graphene. The corrugation is reduced when mechanically straining the freestanding graphene through thermal expansion of the supporting frame, especially flattening membrane areas with imprinted staircase morphology. The electron signal attenuation through supported and freestanding graphene was determined as a function of the electron kinetic energy, verifying that large area graphene based electron windows have sufficient electron transparency required for environmental PES. Meanwhile, we managed to cover 100 m sized single holes by few layer graphene up to a coverage fraction of over 99.9998 , as deduced when applying 10 mbar air on one side of the sealing membrane without detecting any measurable pressure increase on its ultrahigh vacuum side. The reported achievements will pave the way toward the development of laboratory based environmental PE

A blood based 12-miRNA signature of Alzheimer disease patients

Background: Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. Results: We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. Conclusions: The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases

Identification of lung cancer with high sensitivity and specificity by blood testing

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a very frequent and lethal tumor with an identifiable risk population. Cytological analysis and chest X-ray failed to reduce mortality, and CT screenings are still controversially discussed. Recent studies provided first evidence for the potential usefulness of autoantigens as markers for lung cancer.</p> <p>Methods</p> <p>We used extended panels of arrayed antigens and determined autoantibody signatures of sera from patients with different kinds of lung cancer, different common non-tumor lung pathologies, and controls without any lung disease by a newly developed computer aided image analysis procedure. The resulting signatures were classified using linear kernel Support Vector Machines and 10-fold cross-validation.</p> <p>Results</p> <p>The novel approach allowed for discriminating lung cancer patients from controls without any lung disease with a specificity of 97.0%, a sensitivity of 97.9%, and an accuracy of 97.6%. The classification of stage IA/IB tumors and controls yielded a specificity of 97.6%, a sensitivity of 75.9%, and an accuracy of 92.9%. The discrimination of lung cancer patients from patients with non-tumor lung pathologies reached an accuracy of 88.5%.</p> <p>Conclusion</p> <p>We were able to separate lung cancer patients from subjects without any lung disease with high accuracy. Furthermore, lung cancer patients could be seprated from patients with other non-tumor lung diseases. These results provide clear evidence that blood-based tests open new avenues for the early diagnosis of lung cancer.</p

New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing

The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Otztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to similar to 60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis

miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

<p>Abstract</p> <p>Background</p> <p>Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. Due to their inherent stability miRNAs may offer themselves for blood based tumor diagnosis. Here we addressed the question whether there is a sufficient number of miRNAs deregulated in blood cells of cancer patients to be able to distinguish between cancer patients and controls.</p> <p>Methods</p> <p>We synthesized 866 human miRNAs and miRNA star sequences as annotated in the Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression in 17 blood cell samples of patients with non-small cell lung carcinomas (NSCLC) and in 19 blood samples of healthy controls.</p> <p>Results</p> <p>Using t-test, we detected 27 miRNAs significantly deregulated in blood cells of lung cancer patients as compared to the controls. Some of these miRNAs were validated using qRT-PCR. To estimate the value of each deregulated miRNA, we grouped all miRNAs according to their diagnostic information that was measured by Mutual Information. Using a subset of 24 miRNAs, a radial basis function Support Vector Machine allowed for discriminating between blood cellsamples of tumor patients and controls with an accuracy of 95.4% [94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of 92.5% [91.8%-92.5%].</p> <p>Conclusion</p> <p>Our findings support the idea that neoplasia may lead to a deregulation of miRNA expression in blood cells of cancer patients compared to blood cells of healthy individuals. Furthermore, we provide evidence that miRNA patterns can be used to detect human cancers from blood cells.</p