Full Counting Statistics of Superconductor--Normal-Metal Heterostructures

The article develops a powerful theoretical tool to obtain the full counting statistics. By a slight extension of the standard Keldysh method we can access immediately all correlation functions of the current operator. Embedded in a quantum generalization of the circuit theory of electronic transport, we are able to study the full counting statistics of a large class of two-terminal contacts and multi-terminal structures, containing superconductors and normal metals as elements. The practical use of the method is demonstrated in many examples.Comment: 35 pages, contribution to "Quantum Noise", ed. by Yu.V. Nazarov and Ya.M. Blanter, minor changes in text, references adde

The core genome of the anaerobic oral pathogenic bacterium Porphyromonas gingivalis

<p>Abstract</p> <p>Background</p> <p>The Gram negative anaerobic bacterium <it>Porphyromonas gingivalis </it>has long been recognized as a causative agent of periodontitis. Periodontitis is a chronic infectious disease of the tooth supporting tissues eventually leading to tooth-loss. Capsular polysaccharide (CPS) of <it>P. gingivalis </it>has been shown to be an important virulence determinant. Seven capsular serotypes have been described. Here, we used micro-array based comparative genomic hybridization analysis (CGH) to analyze a representative of each of the capsular serotypes and a non-encapsulated strain against the highly virulent and sequenced W83 strain. We defined absent calls using <it>Arabidopsis thaliana </it>negative control probes, with the aim to distinguish between aberrations due to mutations and gene gain/loss.</p> <p>Results</p> <p>Our analyses allowed us to call aberrant genes, absent genes and divergent regions in each of the test strains. A conserved core <it>P. gingivalis </it>genome was described, which consists of 80% of the analyzed genes from the sequenced W83 strain. The percentage of aberrant genes between the test strains and control strain W83 was 8.2% to 13.7%. Among the aberrant genes many CPS biosynthesis genes were found. Most other virulence related genes could be found in the conserved core genome. Comparing highly virulent strains with less virulent strains indicates that <it>hmuS, </it>a putative CobN/Mg chelatase involved in heme uptake, may be a more relevant virulence determinant than previously expected. Furthermore, the description of the 39 W83-specific genes could give more insight in why this strain is more virulent than others.</p> <p>Conclusion</p> <p>Analyses of the genetic content of the <it>P. gingivalis </it>capsular serotypes allowed the description of a <it>P. gingivalis </it>core genome. The high resolution data from three types of analysis of triplicate hybridization experiments may explain the higher divergence between <it>P. gingivalis </it>strains than previously recognized.</p

RNA isolation for transcriptomics of human and mouse small skin biopsies

<p>Abstract</p> <p>Background</p> <p>Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies.</p> <p>Findings</p> <p>We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms.</p> <p>Conclusions</p> <p>Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.</p

Monitoring cardiac fibrosis: a technical challenge

The heart contains a collagen network that contributes to the contractility of the heart and provides cardiac strength. In cardiac diseases, an increase in collagen deposition is often observed. This fibrosis formation causes systolic and diastolic dysfunction, and plays a major role in the arrythmogenic substrate. Therefore, accurate detection of cardiac fibrosis and its progression is of clinical importance with regard to diagnostics and therapy for patients with cardiac disease. To evaluate cardiac collagen deposition, both invasive and non-invasive techniques are used. In this review the different techniques that are currently used in clinical and experimental setting are summarised, and the advantages and disadvantages of these techniques are discussed

The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study

BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement

The complexities of breast cancer desmoplasia

The stromal, or 'desmoplastic', responses seen histologically in primary breast carcinomas can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagen to being a dense acellular tissue. The mechanisms underlying the stromal response are complex; paracrine activation of myofibroblasts by growth factors is important but the contribution of cytokines/chemokines should not be ignored. A recent xenograft study has proposed that platelet-derived growth factor (PDGF) is the initiator of the desmoplastic response, but this has not been confirmed by (limited) analyses in vivo. Further studies are required to elaborate the mechanisms of the desmoplastic response, to determine its role in breast cancer progression and whether it is the same for all carcinomas

Occupational exposures and genetic susceptibility to occupational exposures are related to sickness absence in the Lifelines cohort study

In this cross-sectional study, we investigated the association between occupational exposures and sickness absence (SA), the mediating role of respiratory symptoms, and whether genetic susceptibility to SA upon occupational exposures exists. Logistic regression was used to examine associations and structural equation modelling was used for mediation analyses. Genetic susceptibility was investigated by including interactions between occupational exposures and 11 candidate single nucleotide polymorphisms (SNPs). Biological dust, mineral dust, and pesticides exposure were associated with a lower prevalence of any SA (OR (95% CI) = 0.72 (0.58–0.89), 0.88 (0.78–0.99), and 0.70 (0.55–0.89), respectively) while gases/fumes exposure was associated with a higher prevalence of long-term SA (1.46 (1.11–1.91)). Subjects exposed to solvents and metals had a higher prevalence of any (1.14 (1.03–1.26) and 1.68 (1.26–2.24)) and long-term SA (1.26 (1.08–1.46) and 1.75 (1.15–2.67)). Chronic cough and chronic phlegm mediated the association between high gases/fumes exposure and long-term SA. Two of 11 SNPs investigated had a positive interaction with exposure on SA and one SNP negatively interacted with exposure on SA. Exposure to metals and gases/fumes showed a clear dose–response relationship with a higher prevalence of long-term SA; contrary, exposure to pesticides and biological/mineral dust showed a protective effect on any SA. Respiratory symptoms mediated the association between occupational exposures and SA. Moreover, gene-by-exposure interactions exist

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice

Contains fulltext : 98302.pdf (publisher's version ) (Closed access)PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated. METHODS: Groups of kidney-specific megalin-deficient mice and wild-type mice were injected with (111)In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic (SPECT) images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured. RESULTS: Megalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice