Genomic variations associated with attenuation in Mycobacterium avium subsp paratuberculosis vaccine strains

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) whole cell vaccines have been widely used tools in the control of Johne's disease in animals despite being unable to provide complete protection. Current vaccine strains derive from stocks created many decades ago; however their genotypes, underlying mechanisms and relative degree of their attenuation are largely unknown. RESULTS: Using mouse virulence studies we confirm that MAP vaccine strains 316 F, II and 2e have diverse but clearly attenuated survival and persistence characteristics compared with wild type strains. Using a pan genomic microarray we characterise the genomic variations in a panel of vaccine strains sourced from stocks spanning over 40 years of maintenance. We describe multiple genomic variations specific for individual vaccine stocks in both deletion (26-32 Kbp) and tandem duplicated (11-40 Kbp) large variable genomic islands and insertion sequence copy numbers. We show individual differences suitable for diagnostic differentiation between vaccine and wild type genotypes and provide evidence for functionality of some of the deleted MAP-specific genes and their possible relation to attenuation. CONCLUSIONS: This study shows how culture environments have influenced MAP genome diversity resulting in large tandem genomic duplications, deletions and transposable element activity. In combination with classical selective systematic subculture this has led to fixation of specific MAP genomic alterations in some vaccine strain lineages which link the resulting attenuated phenotypes with deficiencies in high reactive oxygen species handling

Non-destructive low-temperature contacts to MoS2\textrm{MoS}_2 nanoribbon and nanotube quantum dots

Molybdenum disulfide nanoribbons and nanotubes are near-one dimensional semiconductors with strong spin-orbit interaction, a nanomaterial highly promising for quantum electronic applications. Here, we demonstrate that a bismuth semimetal layer between the contact metal and this nanomaterial strongly improves the properties of the contacts. Two-point resistances on the order of $100\textrm{k}\Omega$ are observed at room temperature. At cryogenic temperature, Coulomb blockade is visible. The resulting stability diagrams indicate a marked absence of trap states at the contacts and the corresponding disorder, compared to previous devices using low-work function metals as contacts. Single level quantum transport is observed at temperatures below 100mK.Comment: 7 pages, 5 figure

Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer.

BACKGROUND: Sex steroid hormones have been proposed to play a role in the development of non-epithelial ovarian cancers (NEOC) but so far no direct epidemiological data are available.METHODS: A case-control study was nested within the Finnish Maternity Cohort, the world's largest bio-repository of serum specimens from pregnant women. Study subjects were selected among women who donated a blood sample during a singleton pregnancy that led to the birth of their last child preceding diagnosis of NEOC. Case subjects were 41 women with sex-cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three controls, matching the index case for age, parity at the index pregnancy, and date at blood donation were selected (n=171). Odds ratios (OR) and 95% confidence intervals (CI) associated with concentrations of testosterone, androstenedione, 17-OH-progesterone, progesterone, estradiol and sex hormone binding globulin (SHBG) were estimated through conditional logistic regression.RESULTS: For SCST, doubling of testosterone, androstenedione and 17-OH-progesterone concentrations were associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25-3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations remained largely unchanged after excluding women within 2, 4 or 6 years lag-time between blood donation and cancer diagnosis. Sex steroid hormones concentrations were not related to maternal risk of GCT.CONCLUSIONS: This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. Impact: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC

Evaluation of the Ability of LL-37 to Neutralise LPS In Vitro and Ex Vivo

BACKGROUND: Human cathelicidin LL-37 is a cationic antimicrobial peptide (AMP) which possesses a variety of activities including the ability to neutralise endotoxin. In this study, we investigated the role of LPS neutralisation in mediating LL-37's ability to inhibit Pseudomonas aeruginosa LPS signalling in human monocytic cells. METHODOLOGY/PRINCIPAL FINDINGS: Pre-treatment of monocytes with LL-37 significantly inhibited LPS-induced IL-8 production and the signalling pathway of associated transcription factors such as NF-κB. However, upon removal of LL-37 from the media prior to LPS stimulation, these inhibitory effects were abolished. These findings suggest that the ability of LL-37 to inhibit LPS signalling is largely dependent on extracellular LPS neutralisation. In addition, LL-37 potently inhibited cytokine production induced by LPS extracted from P. aeruginosa isolated from the lungs of cystic fibrosis (CF) patients. In the CF lung, polyanionic molecules such as glycosaminoglycans (GAGs) and DNA bind LL-37 and impact negatively on its antibacterial activity. In order to determine whether such interactions interfere with the LPS neutralising ability of LL-37, the status of LL-37 and its ability to bind LPS in CF sputum were investigated. Overall our findings suggest that in the CF lung, the ability of LL-37 to bind LPS and inhibit LPS-induced IL-8 production is attenuated as a result of binding to DNA and GAGs. However, LL-37 levels and its concomitant LPS-binding activity can be increased with a combination of DNase and GAG lyase (heparinase II) treatment. CONCLUSIONS/SIGNIFICANCE: Overall, these findings suggest that a deficiency in available LL-37 in the CF lung may contribute to greater LPS-induced inflammation during CF lung disease

Deep learning-based post-processing of real-time MRI to assess and quantify dynamic wrist movement in health and disease

While morphologic magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of ligamentous wrist injuries, it is merely static and incapable of diagnosing dynamic wrist instability. Based on real-time MRI and algorithm-based image post-processing in terms of convolutional neural networks (CNNs), this study aims to develop and validate an automatic technique to quantify wrist movement. A total of 56 bilateral wrists (28 healthy volunteers) were imaged during continuous and alternating maximum ulnar and radial abduction. Following CNN-based automatic segmentations of carpal bone contours, scapholunate and lunotriquetral gap widths were quantified based on dedicated algorithms and as a function of wrist position. Automatic segmentations were in excellent agreement with manual reference segmentations performed by two radiologists as indicated by Dice similarity coefficients of 0.96 ± 0.02 and consistent and unskewed Bland–Altman plots. Clinical applicability of the framework was assessed in a patient with diagnosed scapholunate ligament injury. Considerable increases in scapholunate gap widths across the range-of-motion were found. In conclusion, the combination of real-time wrist MRI and the present framework provides a powerful diagnostic tool for dynamic assessment of wrist function and, if confirmed in clinical trials, dynamic carpal instability that may elude static assessment using clinical-standard imaging modalities

LLNL input to FY94 hydrogen annual report

This report summarizes the FY 1994 progress made in hydrogen research at the Lawrence Livermore National Laboratory. Research programs covered include: Technical and Economic Assessment of the Transport and Storage of Hydrogen; Research and Development of an Optimized Hydrogen-Fueled Internal Combustion Engine; Hydrogen Storage in Engineered Microspheres; Synthesis, Characterization and Modeling of Carbon Aerogels for Hydrogen Storage; Chemical Kinetic Modeling of H2 Applications; and, Municipal Solid Waste to Hydrogen

Formation of a ZnS Zn S,O bilayer buffer on CuInS2 thin film solar cell absorbers by chemical bath deposition

The application of Zn compounds as buffer layers was recently extended to wide gap CuInS2 CIS based thin film solar cells. Using a new chemical deposition route for the buffer preparation aiming at the deposition of a single layer, nominal ZnS buffer without the need for any toxic reactants such as, e.g. hydrazine, has helped to achieve a similar efficiency as respective CdS buffered reference devices. In order to shed light on the differences of other Zn compound buffers deposited in conventional chemical baths CBD compared to the buffer layers deposited by this alternative CBD process, the composition of the deposited buffers was investigated by x ray excited Auger electron and x ray photoelectron spectroscopy to potentially clarify their superiority in terms of device performance. We have found that in the early stages of this alternative CBD process a thin ZnS layer is formed on the CIS, whereas in the second half of the CBD the growth rate is greatly increased and Zn S,O with a ZnS ZnS ZnO ratio of approx. 80 is deposited. Thus, a ZnS Zn S,O bi layer buffer is deposited on the CIS thin film solar cell absorbers by the alternative chemical deposition route used in this investigation. No major changes of these findings after a postannealing of the buffer CIS sample series and re characterization could be identified