Detection and measurement of paracaspase MALT1 activity.

The paracaspase MALT1 is a Cys-dependent, Arg-specific protease that plays an essential role in the activation and proliferation of lymphocytes during the immune response. Oncogenic activation of MALT1 is associated with the development of specific forms of B-cell lymphomas. Through specific cleavage of its substrates, MALT1 controls various aspects of lymphocyte activation, including the activation of transcriptional pathways, the stabilization of mRNAs, and an increase in cellular adhesion. In lymphocytes, the activity of MALT1 is tightly controlled by its inducible monoubiquitination, which promotes the dimerization of MALT1. Here, we describe both in vitro and in vivo assays that have been developed to assess MALT1 activity.

Unedited in vivo detection and quantification of γ-aminobutyric acid in the occipital cortex using short-TE MRS at 3 T.

Short-TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ-aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short-TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal-to-noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal-to-noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short-TE MRS in the occipital cortex of 14 healthy volunteers. Short-TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short-TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within-session reproducibility was assessed in the same 14 subjects using four consecutive short-TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short-TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright © 2013 John Wiley & Sons, Ltd.

Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms.

PURPOSE: To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS: The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS: Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION: Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.

Application de nanoparticules luminescentes pour la detection de traces papillaires

Après avoir situé le contexte de la recherche et défini les enjeux principaux du travail, différents types de nanoparticules, ainsi que leurs principales caractéristiques, sont parcourues. L'élaboration de critères de sélection ayant permis de déterminer les types de nanoparticules potentiellement adaptés à !a détection de traces papillaires, l'étude s'est alors focalisée sur deux familles de composés: les quantum dots et les nanoparticules d'oxyde de silicium. Deux types de quantum dots ont été synthétisés : le tellurure de cadmium et le sulfure de zinc). Ils n'ont toutefois pas permis la détection de traces papillaires réalistes. En effet, seules des traces fraîches et enrichies en sécrétions ont pu être mises en évidence. Toutefois, des résultats ont été obtenus avec les deux types de quantum dots pour la détection de traces papillaires sanglantes. Après optimisation, les techniques rivalisent avec les méthodes couramment appliquées en routine. Cependant, l'interaction se produisant entre les traces et les nanoparticules n'a pas pu être déterminé. Les nanoparticules d'oxyde de silicium ont dès lors été appliquées dans le but de comprendre plus en détails les interactions avec les traces papillaires. Ces nanoparticules ont l'avantage d'offrir un très bon contrôle de surface, permettant ainsi une étude détaillée des phénomènes en jeu. Des propriétés de surface variables ont dès lors été obtenues en greffant diverses molécules à la surface des nanoparticules d'oxyde de silicium. Après avoir exploré différentes hypothèses d'interaction, il a pu être déterminé qu'une réaction chimique se produit lors qu'un groupement de type carboxyle est présent à la surface des particules. Ce groupement réagit avec les fonctions amines primaires des sécrétions. L'interaction chimique a ensuite pu être renforcée par l'utilisation d'un catalyseur, permettant d'accélérer la réaction. Dans la dernière partie du travail, les nanoparticules d'oxyde de silicium ont été comparées à une technique utilisée en routine, la fumigation de cyanoacrylate. Bien que des études plus approfondies soient nécessaires, il s'avère que l'application de nanoparticules d'oxyde de silicium permet une détection de très bonne qualité, moins dépendante du donneur que les techniques courantes. Ces résultats sont prometteurs en vue du développement d'une technique possédant une sensibilité et une sélectivité accrue. - Having situated the background of research and identified key issues of work, different types of nanoparticles and their main features are reviewed. The development of selection criteria lead to the identification of nanoparticles types potentially suitable for fingermarks detection. The study focused then On two families of compounds: quantum dots and silicon oxide nanoparticles. Two types of quantum dots were synthesized and characterised: cadmium telluride and zinc sulphide. Unfortunally, they did not allow the detection realistic fingermarks. Indeed, only fresh and groomed fingermarks have been detected. However, results have been obtained with both types of quantum dots for the detection of fingermarks in blood. After optimization procedures, the quantum dots based teshniques compete with the methods currently used in routine. However, the interaction occurring between fingermarks and nanoparticles could not be determined. Silicon oxide nanoparticles have therefore been applied in order to understand in detail the interactions With fingermarks. These nanoparticles have the advantage of providing a very good surface control, allowing am in-depth study of the phenomena involved. Versatile surface properties were therefore obtained by grafting various molecules on the surface of silicon oxide nanoparticles. Different hypotheses were investigated and it was determined that a chemical reaction occurred between the surface functionalised nanoparticles and the fingermark residues. The carboxyl groups on the surface of the particles react with primary amines of the secretions. Therefore, this interaction was improved by the use of a catalyst. In the last part of the work, silicon oxide nanoparticles were compared to a routinely used technique: cyanocrylate fuming. Although further studies are still needed, it appears that the application of silicon oxide nanoparticles allows fingermark detection of very good quality, with a lowered donor dependency. These results are promising for the development of techniques with greater sensitivity and selectivity.

Non-invasive detection of coronary endothelial response to sequential handgrip exercise in coronary artery disease patients and healthy adults.

OBJECTIVES: Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects. BACKGROUND: Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD). METHODS: Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period. RESULTS: In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: -6.4%±2.0% vs. -5.0%±2.4%, p = 0.22; PDFV: -4.0%±4.6% vs. -4.2%±5.3%, p = 0.83; blood-flow: -9.7%±5.1% vs. -8.7%±6.3%, p = 0.38). CONCLUSION: MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.

Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.

This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab')2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with 123I-labeled F(ab')2 (n = 14) or Fab (n = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintigraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.

Performance of microcalorimetry for early detection of methicillin resistance in clinical isolates of Staphylococcus aureus.

We describe a calorimetric assay for the detection of methicillin-resistant Staphylococcus aureus (MRSA) within 5 h. Microbial heat was calculated in culture with and without cefoxitin. Among 30 genetically distinct clinical isolates, 19/20 MRSA (95%) and 10/10 methicillin-susceptible Staphylococcus aureus (100%) were correctly identified. Microcalorimetry may be useful for rapid MRSA screening.

An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients.

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL(-1) and a linear detection range (LDR) of 0-0.1 U mL(-1). Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.

Performance of the 47-Kilodalton Membrane Protein versus DNA Polymerase I Genes for Detection of Treponema pallidum by PCR in Ulcers.

Treponema pallidum PCR (Tp-PCR) is a direct diagnostic method for primary and secondary syphilis, but there is no recommendation regarding the best choice of target gene. In this study, we sequentially tested 272 specimens from patients with sexually transmitted ulcers using Tp-PCR targeting the tpp47 and then polA genes. The two methods showed similar accuracies and an almost-perfect agreement.

Risk evaluation for spoofing against a sensor supplied with liveness detection

The aim of this paper is to evaluate the risks associated with the use of fake fingerprints on a livescan supplied with a method of liveness detection. The method is based on optical properties of the skin. The sensor uses several polarizations and illuminations to capture the information of the different layers of the human skin. These experiments also allow for the determination under which conditions the system is deceived and if there is an influence respectively of the nature of the fake, the mould used for the production or the individuals involved in the attack. These experiments showed that current multispectral sensors can be deceived by the use of fake fingerprints created with or without the cooperation of the subject. Fakes created from direct casts perform better than those produced by fakes created from indirect casts. The results showed that the success of the attack is influenced by two main factors. The first is the quality of the fakes, and by extension the quality of the original fingerprint. The second is the combination of the general patterns involved in the attacks since an appropriate combination can strongly increase the rates of successful attacks.

Radiological detection of dissolved cocaine

Introduction: Smuggling dissolved drugs, especially cocaine, in bottled liquids is a problem at borders nowadays. Common fluoroscopy of packages at the border cannot detect contaminated liquids. To find a dissolved drug, an immunological test using a drug-test panel has to be performed. This means that a control sample of the cargo must be opened to perform the test. As it is not possible to open all boxes, and as smugglers hide the drugcontaining boxes between regularly filled boxes, contaminated cargos can be overlooked. Investigators sometimes cannot perform the drug-test panel because they try not to arouse the smugglers' suspicion in order to follow the cargo and to find the recipient. Aims: The objective of our studies was to define non-invasive examination techniques to investigate cargos that are suspicions to contain dissolved cocaine without leaving traces on the samples. We examined vessels containing cocaine by radiological cross-section techniques such as multidetector computed tomography (MDCT) and magnetic resonance spectroscopy (MRS). Methods: In a previous study, we examined bottles of wine containing dissolved cocaine in different quantities using an MDCT unit. To distinguish between bottles containing red wine and those where cocaine was solved in the wine, cross sectional 2D-images have been reconstructed and the absorption of X-rays was quantified by measuring the mean density of the liquid inside the bottles. In our new study, we investigated phantoms containing cocaine dissolved in water with or without ethanol as well as cocaine dissolved in different sorts of commercially available wine by the use of a clinical magnetic resonance unit (3 tesla). To find out if dissolved cocaine could be detected, magnetic resonance spectroscopy (1H MRS) was performed. Results: By using a MDCT-unit and measuring the mean attenuation of X-rays, it is possible to distinguish weather substances are dissolved in a liquid or not, if a comparative liquid without any solutions is available. The increase of the mean density indicates the presence of dissolved substances without the possibility to identify the substance. By using magnetic resonance spectroscopy, dissolved cocaine can be clearly identified because it produces distinctive resonances in the spectrum. In contrast to MDCT, this technique shows a high sensitivity (detection of 1 mM cocaine in wine). Conclusions: Cross-sectional imaging techniques such as MDCT and MRS appropriated to examine cargos that are suspicious to contain dissolved cocaine. They allow to perform non-invasive investigations without leaving any trace on the cargo. While an MDCT scan can detect dissolved substances in liquids, identification of cocaine can be obtained by MR-spectroscopy. Acknowledgment: This work was supported by the Centre d'Imagerie BioMédicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hôpitaux Universitaire de Genève (HUG) and the Leenaards and the Jeantet Foundations.

Detection of new cross-reacting carcinoembryonic antigen(s) on cultured tumor cells by mixed hemadsorption assay.

Antisera highly specific for carcinoembryonic antigen (CEA) from New Zealand White rabbits and a goat reacted strongly in antibody binding tests with cultured tumor cell lines, irrespective of the ability of the cell lines to produce CEA. The most reactive were colon carcinoma and melanoma cell lines, the former known to produce CEA and the latter not associated with CEA production. The reactivity was not diminished by absorption with perchloric acid extracts of normal lung or spleen, whereas absoprtion with purified CEA preparations abolished the reactivity. Quantitative absorption studies indicated that reactivity against CEA-producing cell lines could be totally removed by absorption with other CEA-producing lines but not with melanoma cell lines. Reactivity against melanoma cell lines could be completely removed by colon carcinoma cells as well as by melanoma cells. Antisera raised against purified CEA, after absorption with extracts of normal lung, still contained two populations of antibodies, one that binds a newly described antigen cross-reacting with CEA which is present on melanoma cells.

Detection and Characterization of Preferential Flow Paths in the Downstream Area of a Hazardous Landfill

We have used surface-based electrical resistivity tomography to detect and characterize preferential hydraulic pathways in the immediate downstream area of an abandoned, hazardous landfill. The landfill occupies the void left by a former gravel pit and its base is close to the groundwater table and lacking an engineered barrier. As such, this site is remarkably typical of many small- to medium-sized waste deposits throughout the densely populated and heavily industrialized foreland on both sides of the Alpine arc. Outflows of pollutants lastingly contaminated local drinking water supplies and necessitated a partial remediation in the form of a synthetic cover barrier, which is meant to prevent meteoric water from percolating through the waste before reaching the groundwater table. Any future additional isolation of the landfill in the form of lateral barriers thus requires adequate knowledge of potential preferential hydraulic pathways for outflowing contaminants. Our results, inferred from a suite of tomographically inverted surfaced-based electrical resistivity profiles oriented roughly perpendicular to the local hydraulic gradient, indicate that potential contaminant outflows would predominantly occur along an unexploited lateral extension of the original gravel deposit. This finds its expression as a distinct and laterally continuous high-resistivity anomaly in the resistivity tomograms. This interpretation is ground-truthed through a litholog from a nearby well. Since the probed glacio-fluvial deposits are largely devoid of mineralogical clay, the geometry of hydraulic and electrical pathways across the pore space of a given lithological unit can be assumed to be identical, which allows for an order-of-magnitude estimation of the overall permeability structure. These estimates indicate that the permeability of the imaged extension of the gravel body is at least two to three orders-of-magnitude higher than that of its finer-grained embedding matrix. This corroborates the preeminent role of the high-resistivity anomaly as a potential preferential flow path.