A restoration framework for ultrasonic tissue characterization

Ultrasonic tissue characterization has become an area of intensive research. This procedure generally relies on the analysis of the unprocessed echo signal. Because the ultrasound echo is degraded by the non-ideal system point spread function, a deconvolution step could be employed to provide an estimate of the tissue response that could then be exploited for a more accurate characterization. In medical ultrasound, deconvolution is commonly used to increase diagnostic reliability of ultrasound images by improving their contrast and resolution. Most successful algorithms address deconvolution in a maximum a posteriori estimation framework; this typically leads to the solution of l(2)-norm or (1)-norm constrained optimization problems, depending on the choice of the prior distribution. Although these techniques are sufficient to obtain relevant image visual quality improvements, the obtained reflectivity estimates are, however, not appropriate for classification purposes. In this context, we introduce in this paper a maximum a posteriori deconvolution framework expressly derived to improve tissue characterization. The algorithm overcomes limitations associated with standard techniques by using a nonstandard prior model for the tissue response. We present an evaluation of the algorithm performance using both computer simulations and tissue-mimicking phantoms. These studies reveal increased accuracy in the characterization of media with different properties. A comparison with state-of-the-art Wiener and l(1)-norm deconvolution techniques attests to the superiority of the proposed algorithm.     

Establishment of a real-time PCR method for quantification of geosmin-producing Streptomyces spp. in recirculating aquaculture systems

Geosmin and 2-methylisoborneol (MIB) have been associated with off-flavour problems in fish and seafood products, generating a strong negative impact for aquaculture industries. Although most of the producers of geosmin and MIB have been identified as Streptomyces species or cyanobacteria, Streptomyces spp. are thought to be responsible for the synthesis of these compounds in indoor recirculating aquaculture systems (RAS). The detection of genes involved in the synthesis of geosmin and MIB can be a relevant indicator of the beginning of off-flavour events in RAS. Here, we report a real-time polymerase chain reaction (qPCR) protocol targeting geoA sequences that encode a germacradienol synthase involved in geosmin synthesis. New geoA-related sequences were retrieved from eleven geosmin-producing Actinomycete strains, among them two Streptomyces strains isolated from two RAS. Combined with geoA-related sequences available in gene databases, we designed primers and standards suitable for qPCR assays targeting mainly Streptomyces geoA. Using our qPCR protocol, we succeeded in measuring the level of geoA copies in sand filter and biofilters in two RAS. This study is the first to apply qPCR assays to detect and quantify the geosmin synthesis gene (geoA) in RAS. Quantification of geoA in RAS could permit the monitoring of the level of geosmin producers prior to the occurrence of geosmin production. This information will be most valuable for fish producers to manage further development of off-flavour events.     

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine—Are We There Yet?

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients’ bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.     

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrP^Sc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrP^Sc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrP^Sc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.     

Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.     

A Comprehensive Performance Analysis of Random Early Detection Mechanism

One of the most promising active queue management schemes being proposed for deployment in the Internet is the Random Early Detection (RED) scheme. However, research results on RED performance are highly mixed, especially in the field of tuning its parameters. In this paper, a comprehensive performance analysis of RED is presented. We revisit some features in RED and study them in greater detail. We point out that RED, in general, does not possess proportional loss between flows as claimed and widely adopted in previous research. We suggest the generalization of the PASTA property and give a proof for TCP flows. We also evaluate the performance of the Exponential Weighted Moving Average (EWMA) algorithm in RED. We find that EWMA in RED is an unbiased estimator of the average queue-length, regardless of the weighting value w _q . We also point out the theoretical and practical limits of EWMA in RED. Finally, we propose the use of fuzzy EWMA to RED (fuzzy RED) to alleviate the inflexibility of RED tuning. We use simulations to evaluate the performance of fuzzy RED and compare it with other versions of RED. Our simulations show that, in the case of a high workload and a high level of variation, fuzzy RED, by tracking system variation in an on-line manner, improves RED performance in a number of important router-based metrics like packet loss rate, average queueing delay, link utilization, and global power.     

Reproducible Enhancement of Fluorescence by Bimetal Mediated Surface Plasmon Coupled Emission for Highly Sensitive Quantitative Diagnosis of Double‐Stranded DNA

Plasmonic enhancement of fluorescence from SYBR Green I conjugated with a double‐stranded DNA (dsDNA) amplicon is demonstrated on polymerase chain reaction (PCR) products. Theoretical computation leads to use of the bimetallic (Au 2 nm–Ag 50 nm) surface plasmons due to larger local fields (higher quality factors) than monometallic (Ag or Au) ones at both dye excitation and emission wavelengths simultaneously, optimizing fluorescence enhancement with surface plasmon coupled emission (SPCE). Two kinds of reverse Kretschmann configurations are used, which favor, in signal‐to‐noise ratio, a fluorescence assay that uses optically dense buffer such as blood plasma. The fluorescence enhancement (12.9 fold at maximum) with remarkably high reproducibility (coefficient of variation (CV) < 1%) is experimentally demonstrated. This facilitates credible quantitation of enhanced fluorescence, however unlikely to obtain by localized surface plasmons. The plasmon‐induced optical gain of 46 dB due to SPCE‐active dye molecules is also estimated. The fluorescence enhancement technologies with PCR enables LOD of the dsDNA template concentration of ≈400 fg µL^?1 (CV < 1%), the lowest ever reported in DNA fluorescence assay to date. SPCE also reduces photobleaching significantly. These technologies can be extended for a highly reproducible and sufficiently sensitive fluorescence assay with small volumes of analytes in multiplexed diagnostics.     

Influence of temperature on the compaction of an organic powder and the mechanical strength of tablets

The purpose of this work consists in following the dependence of physical properties on the temperature during the compaction of an organic component. A special thermo-regulated die has been developed to realize uniaxial compression at different constant temperatures. This study has shown that a temperature change modifies the microstructures and the mechanical behaviour of the tablets. The measurement of the tablet porosity during the compression cycle allows us to conclude that temperature influences mainly the phenomena occurring during the isobaric stage of the compression cycle and not the ones during the pressure increase. On the other hand, during the pressure increase, the acoustical activity of the powder is reduced when temperature increases. The tensile strength of tablets realized at different temperatures was also studied and shows a maximum around 60 °C that can be explained by the SEM analysis of the microstructure of the tablets.