Improving the Acoustic Performance of Linear Multi-Element Transducers

The electro-acoustic performance of transducers has a direct impact on the performance of ultrasound inspections. The signal/noise ratio and the resolution (both axial and lateral) are key factors for detecting and/or proportioning the indications being sought. The signal/noise ratio partly depends on the sensitivity and the signal/noise ratio of the transducer itself. The axial resolution depends on the length of the signal and therefore, for a given maximum frequency, on the damping of the transducer. Sensitivity and damping are often considered antagonistic, as damping traditionally reduces resonance and therefore sensitivity. Earlier studies have demonstrated the advantages gained through using piezocomposite technology to improve this compromise. These two parameters also depend on the acoustic adaptation to the coupling medium (water, plexiglass, rexolite, steel, etc.), and according to the design used, performance deteriorates more or less as one moves further from the nominal use. In addition to sensitivity and the signal/noise ratio, other parameters such as the angular acceptance and resistance to abrasion are sometimes to be integrated in the expected performances. This article presents the recent developments undertaken and tested in the context of improving the acoustic performance of multi-element probes: - Identification of the components that influence performance; - Simulations; - Selection of the configurations that meet the needs of various applications; - The experimental results obtained; - Comparison with the simulations. These studies have led to the development of a design expertise for responding to requests for custom-made, industrial, multi-element probes with improved performance, for production runs from a single item to dozens, even hundreds. The detailed results will be presented, as well as the possibilities for future development

Ex vivo live cell tracking in kidney organoids using light sheet fluorescence microscopy

Screening cells for their differentiation potential requires a combination of tissue culture models and imaging methods that allow for long-term tracking of the location and function of cells. Embryonic kidney re-aggregation in vitro assays have been established which allow for the monitoring of organotypic cell behaviour in re-aggregated and chimeric renal organoids. However, evaluation of cell integration is hampered by the high photonic load of standard fluorescence microscopy which poses challenges for imaging three-dimensional systems in real-time over a time course. Therefore, we employed light sheet microscopy, a technique that vastly reduces photobleaching and phototoxic effects. We have also developed a new method for culturing the re-aggregates which involves immersed culture, generating organoids which more closely reflect development in vivo. To facilitate imaging from various angles, we embedded the organoids in a freely rotatable hydrogel cylinder. Endpoint fixing and staining were performed to provide additional biomolecular information. We succeeded in imaging labelled cells within re-aggregated kidney organoids over 15 hours and tracking their fate while simultaneously monitoring the development of organotypic morphological structures. Our results show that Wt1-expressing embryonic kidney cells obtained from transgenic mice could integrate into re-aggregated chimeric kidney organoids and contribute to developing nephrons. Furthermore, the nascent proximal tubules that formed in the re-aggregated tissues using the new culture method displayed secretory function, as evidenced by their ability to secrete an organic anion mimic into the tubular lumen

Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome

Major structural changes occur in the spliceosome during its activation just before catalyzing the splicing of pre-messenger RNAs (pre-mRNAs). Whereas changes in small nuclear RNA ( snRNA) conformation are well documented, little is known about remodeling of small nuclear ribonucleoprotein ( snRNP) structures during spliceosome activation. Here, human 45S activated spliceosomes and a previously unknown 35S U5 snRNP were isolated by immunoaffinity selection and were characterized by mass spectrometry. Comparison of their protein components with those of other snRNP and spliceosomal complexes revealed a major change in protein composition during spliceosome activation. Our data also suggest that the U5 snRNP is dramatically remodeled at this stage, with the Prp19 complex and other factors tightly associating, possibly in exchange for other U5 proteins, and suggest that after catalysis the remodeled U5 is eventually released from the postsplicing complex as a 35S snRNP particle

Liquid Chromatography Electron Capture Dissociation Tandem Mass Spectrometry (LC-ECD-MS/MS) versus Liquid Chromatography Collision-induced Dissociation Tandem Mass Spectrometry (LC-CID-MS/MS) for the Identification of Proteins

Electron capture dissociation (ECD) offers many advantages over the more traditional fragmentation techniques for the analysis of peptides and proteins, although the question remains: How suitable is ECD for incorporation within proteomic strategies for the identification of proteins? Here, we compare LC-ECD-MS/MS and LC-CID-MS/MS as techniques for the identification of proteins.Experiments were performed on a hybrid linear ion trap–Fourier transform ion cyclotron resonance mass spectrometer. Replicate analyses of a six-protein (bovine serum albumin, apo-transferrin,lysozyme, cytochrome c, alcohol dehydrogenase, and β-galactosidase) tryptic digest were performed and the results analyzed on the basis of overall protein sequence coverage and sequence tag lengths within individual peptides. The results show that although protein coverage was lower for LC-ECDMS/MS than for LC-CID-MS/MS, LC-ECD-MS/MS resulted in longer peptide sequence tags,providing greater confidence in protein assignment

Silver segregation to \theta' (Al2Cu)-Al interfaces in Al-Cu-Ag alloys

\theta' (Al2Cu) precipitates in Al-Cu-Ag alloys were examined using high angle annular dark field scanning transmission electron microscopy (HAADF-STEM). The precipitates nucleated on dislocation loops on which assemblies of {\gamma}' (AlAg2) precipitates were present. These dislocation loops were enriched in silver prior to \theta' precipitation. Coherent, planar interfaces between the aluminium matrix and \theta' precipitates were decorated by a layer of silver of two atomic layers in thickness. It is proposed that this layer lowers the chemical component of the Al-\theta' interfacial energy. The lateral growth of the \theta' precipitates was accompanied by the extension of this silver bi-layer, resulting in the loss of silver from neighbouring \gamma' precipitates and contributing to the deterioration of the \gamma' precipitate assemblies.Comment: Pre-print. 12 pages, 7 figure

assessment of pd 1 pd l1 colocalization in hepatocellular carcinoma hcc using bright field double labeling and quantitative digital image analysis

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Developing a novel tool to assess the ability to self-administer medication - A systematic evaluation of patients' video recordings in the ABLYMED study

Background: Older people often experience medication management problems due to multimorbidity, polypharmacy and medication complexity. There is often a large gap between patients' self-reported and actual abilities to handle the self -administration of their medication. Here we report on the development and evaluation of a new tool to assess the ability of non-demented hospitalized patients to self-administer medication in different dosage forms. To this end, we video-recorded the patients' medication management performance and implemented a novel assessment scheme, which was applied by several independent raters.Methods: Sixty-seven in-patients > 70 years of age and regularly taking > 5 different drugs autonomously of the ABLYMED study agreed to the video recording of their medication management performance with five different dosage forms. All raters underwent a training and applied a standardized assessment form and written guide with rating rules for evaluation. In a pilot phase, video recordings of three patients were rated by 19 raters (15 medical students, two expert raters to determine a reference standard, and two main raters who later rated the total sample). In the rating phase, based on the ratings obtained from the two main raters, we determined interrater (assessed every section of 20 patients as agreement between the raters at one point of time) and intrarater (assessed as consistency within each rater across three points of time) agreement by intraclass correlation analysis.Results: In the pilot phase we obtained an overall sufficient agreement pattern, with an adjustment of the rating rules for patches. In the rating phase we achieved satisfactory agreement between the two raters (interrater reliability) and across different points of time (intrarater reliability). For two dosage forms (eye-drops and pen), rater training needed to be repeated to reach satisfactory levels.Discussion: Our novel rating procedure was found to be objective, valid and reproducible, given appropriate training of the raters. Our findings are an important part of a larger research project to implement a novel assessment for the ability to self-administer medication in different dosage forms. Further, they can support the development of patient trainings to improve medication management and secure independent living.Paul-Kuth Foundatio

A common core RNP structure shared between the small nuclear box C/D RNPs and the spliceosomal U 4 snRNP.

AbstractThe box C/D snoRNAs function in directing 2′-O-methylation and/or as chaperones in the processing of ribosomal RNA. We show here that Snu13p (15.5kD in human), a component of the U4/U6.U5 tri-snRNP, is also associated with the box C/D snoRNAs. Indeed, genetic depletion of Snu13p in yeast leads to a major defect in RNA metabolism. The box C/D motif can be folded into a stem-internal loop-stem structure, almost identical to the 15.5kD binding site in the U4 snRNA. Consistent with this, the box C/D motif binds Snu13p/15.5kD in vitro. The similarities in structure and function observed between the U4 snRNP (chaperone for U6) and the box C/D snoRNPs raises the interesting possibility that these particles may have evolved from a common ancestral RNP