ECCENTRIC: a fast and unrestrained approach for high-resolution in vivo metabolic imaging at ultra-high field MR

A novel method for fast and high-resolution metabolic imaging, called ECcentric Circle ENcoding TRajectorIes for Compressed sensing (ECCENTRIC), has been developed and implemented on 7 Tesla human MRI. ECCENTRIC is a non-Cartesian spatial-spectral encoding method optimized for random undersampling of magnetic resonance spectroscopic imaging (MRSI) at ultra-high field. The approach provides flexible and random (k,t) sampling without temporal interleaving to improve spatial response function and spectral quality. ECCENTRIC needs low gradient amplitudes and slew-rates that reduces electrical, mechanical and thermal stress of the scanner hardware, and is robust to timing imperfection and eddy-current delays. Combined with a model-based low-rank reconstruction, this approach enables simultaneous imaging of up to 14 metabolites over the whole-brain at 2-3mm isotropic resolution in 4-10 minutes with high signal-to-noise ratio. In 20 healthy volunteers and 20 glioma patients ECCENTRIC demonstrated unprecedented mapping of fine structural details of metabolism in healthy brains and an extended metabolic fingerprinting of glioma tumors.Comment: 20 pages, 7 figures,2 tables, 10 pages supplementary materia

Modeling Alzheimer’s disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior

IntroductionPeople with DS are highly predisposed to Alzheimer’s disease (AD) and demonstrate very similar clinical and pathological features. Ts65Dn mice are widely used and serve as the best-characterized animal model of DS.MethodsWe undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior.ResultsWe found age related changes in both Ts65Dn and 2N mice. Relative to 2N mice, Ts65Dn mice showed consistent increases in Aβ40, insoluble phospho-Tau, and neurofilament light protein. These changes were correlated with deficits in learning and memory.DiscussionThese data have implications for planning future experiments aimed at preventing disease-related phenotypes and biomarkers. Interventions should be planned to address specific manifestations using treatments and treatment durations adequate to engage targets to prevent the emergence of phenotypes

Characterizing the Syphilis-Causing Treponema pallidum ssp. pallidum Proteome Using Complementary Mass Spectrometry

YesBackground. The spirochete bacterium Treponema pallidum ssp. pallidum is the etiological agent of syphilis, a chronic multistage disease. Little is known about the global T. pallidum proteome, therefore mass spectrometry studies are needed to bring insights into pathogenicity and protein expression profiles during infection. Methodology/Principal Findings. To better understand the T. pallidum proteome profile during infection, we studied T. pallidum ssp. pallidum DAL-1 strain bacteria isolated from rabbits using complementary mass spectrometry techniques, including multidimensional peptide separation and protein identification via matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) and electrospray ionization (ESI-LTQ-Orbitrap) tandem mass spectrometry. A total of 6033 peptides were detected, corresponding to 557 unique T. pallidum proteins at a high level of confidence, representing 54% of the predicted proteome. A previous gel-based T. pallidum MS proteome study detected 58 of these proteins. One hundred fourteen of the detected proteins were previously annotated as hypothetical or uncharacterized proteins; this is the first account of 106 of these proteins at the protein level. Detected proteins were characterized according to their predicted biological function and localization; half were allocated into a wide range of functional categories. Proteins annotated as potential membrane proteins and proteins with unclear functional annotations were subjected to an additional bioinformatics pipeline analysis to facilitate further characterization. A total of 116 potential membrane proteins were identified, of which 16 have evidence supporting outer membrane localization. We found 8/12 proteins related to the paralogous tpr gene family: TprB, TprC/D, TprE, TprG, TprH, TprI and TprJ. Protein abundance was semi-quantified using label-free spectral counting methods. A low correlation (r = 0.26) was found between previous microarray signal data and protein abundance. Conclusions. This is the most comprehensive description of the global T. pallidum proteome to date. These data provide valuable insights into in vivo T. pallidum protein expression, paving the way for improved understanding of the pathogenicity of this enigmatic organism.This work was supported by the grants from the Flanders Research Foundation, SOFI-B Grant to CRK, http://www.fwo.be/, a Public Health Service Grant from the National Institutes of Health to CEC, (grant # AI-051334), https://www.nih.gov/ and a grant from the Grant Agency of the Czech Republic to DS and MS (P302/12/0574, GP14-29596P), https:// gacr.cz/

Development of a RBI Tool for Inspection Management in Chemical Plants

The increasing complexity of chemical and petrochemical installations and in of oil and gas operations, jointed with the growing sensibility to ensure higher levels of safety, have increased the sensibility of the designers and operators to find innovative solutions to ensure safe as well as economically viable operation. It has become crucial to manage operational risk through the use of effective technology and best practices for inspection and maintenance planning. Literature shows several models and methods for taking into account managerial and organizational factor in risk analysis, as Integrates Safety Method (Modarres et al, 1992), WPAM – Work Process Analysis Model (Davoudian et al, 1994), Integrated Risk (Papazoglou et al, 2003), ARAMIS (Salvi and Debray, 2005) etc. A new approach, described by Milazzo et al. ( 2010), is based on the influence of risk prevention measures on the frequency of failure. An innovative methodology recently proposed by Milazzo and Aven (2012), focuses the need for extending the risk's approach to the concept of uncertainty. The development of these innovating methodologies need of further studies and developments, but are very promising for future approach of this problems. Actually, for risk assessment practice in the chemical plant, one of the highest benefit maintenance methodologies is Risk Based Inspection (RBI). The use of a RBI analysis is very important phase to plan the inspection activity. The problem of collecting data that characterizes this analysis is overcome with the help of software inspection manager that encloses all functionalities for an easier management of technical data in the Plant's Inspection. The main target of this paper is to add a new software tool that allows expert technical users to proceed a RBI study compliant to the API standards. The results of the new tool of Inspection Manager for RBI permits to carry out easier the inspection plan. The software permits a guided procedure for the insertion of the data necessary for the analysis, and then the analysis is easier and faster. The identification of risk derives from range proposed by API 581. In the case of not standard operations, the operator can be update the data and, thanks to the saving of the previous analysis to minimize the inserting of repetitive data, the RBI session turns out to be simpler and faster

Helicobacter pylori derived Neutrophil Activating Protein (HP-NAP) increases the life span of monocytes and neutrophils and activates B cells.

An invariable feature of Helicobacter pylori-infected gastric mucosa is the persistent infiltration of inflammatory cells. The neutrophil activating protein (HP-NAP) has a pivotal role in triggering and orchestrating the phlogistic process associated with H. pylori infection. Aim of this study was to address whether HP-NAP might further contribute to the inflammation by increasing the lifespan of inflammatory cells. We report that HP-NAP is able to prolong the lifespan of monocytes, in parallel with the induction of the anti-apoptotic proteins A1, Mcl-1, Bcl-2 and Bcl-XL. This effect does not result from a direct action on the apoptotic machinery, but rather it requires the release of endogenous pro-survival factors, such as IL-1\u3b2, which probably acts in synergy with other unidentified mediators. We also report that HP-NAP promotes the survival of Ficoll-purified neutrophils in a monocyte-dependent fashion: indeed, mononuclear cell depletion of Ficoll-purified neutrophils completely abolished the pro-survival effect by HP-NAP. In conclusion, our data reinforce the notion that HP-NAP has a pivotal role in sustaining a prolonged activation of myeloid cells

Diagnosing the Devil. A Case Study on a Protocol Between an Exorcist and a Psychiatrist in Italy

none1nononeGiuseppe GiordanGiordan, Giusepp