Probing the pressure dependence of sound speed and attenuation in bubbly media: Experimental observations, a theoretical model and numerical calculations.

The problem of attenuation and sound speed of bubbly media has remained partially unsolved. Comprehensive data regarding pressure-dependent changes of the attenuation and sound speed of a bubbly medium are not available. Our theoretical understanding of the problem is limited to linear or semi-linear theoretical models, which are not accurate in the regime of large amplitude bubble oscillations. Here, by controlling the size of the lipid coated bubbles (mean diameter of ≈5.4µm), we report the first time observation and characterization of the simultaneous pressure dependence of sound speed and attenuation in bubbly water below, at and above microbubbles resonance (frequency range between 1-3 MHz). With increasing acoustic pressure (between 12.5-100 kPa), the frequency of the peak attenuation and sound speed decreases while maximum and minimum amplitudes of the sound speed increase. We propose a nonlinear model for the estimation of the pressure dependent sound speed and attenuation with good agreement with the experiments. The model calculations are validated by comparing with the linear and semi-linear models predictions. One of the major challenges of the previously developed models is the significant overestimation of the attenuation at the bubble resonance at higher void fractions (e.g. 0.005). We addressed this problem by incorporating bubble-bubble interactions and comparing the results to experiments. Influence of the bubble-bubble interactions increases with increasing pressure. Within the examined exposure parameters, we numerically show that, even for low void fractions (e.g. 5.1×10-6) with increasing pressure the sound speed may become 4 times higher than the sound speed in the non-bubbly medium.

Profile hidden Markov model sequence analysis can help remove putative pseudogenes from DNA barcoding and metabarcoding datasets.

BACKGROUND: Pseudogenes are non-functional copies of protein coding genes that typically follow a different molecular evolutionary path as compared to functional genes. The inclusion of pseudogene sequences in DNA barcoding and metabarcoding analysis can lead to misleading results. None of the most widely used bioinformatic pipelines used to process marker gene (metabarcode) high throughput sequencing data specifically accounts for the presence of pseudogenes in protein-coding marker genes. The purpose of this study is to develop a method to screen for nuclear mitochondrial DNA segments (nuMTs) in large COI datasets. We do this by: (1) describing gene and nuMT characteristics from an artificial COI barcode dataset, (2) show the impact of two different pseudogene removal methods on perturbed community datasets with simulated nuMTs, and (3) incorporate a pseudogene filtering step in a bioinformatic pipeline that can be used to process Illumina paired-end COI metabarcode sequences. Open reading frame length and sequence bit scores from hidden Markov model (HMM) profile analysis were used to detect pseudogenes. RESULTS: Our simulations showed that it was more difficult to identify nuMTs from shorter amplicon sequences such as those typically used in metabarcoding compared with full length DNA barcodes that are used in the construction of barcode libraries. It was also more difficult to identify nuMTs in datasets where there is a high percentage of nuMTs. Existing bioinformatic pipelines used to process metabarcode sequences already remove some nuMTs, especially in the rare sequence removal step, but the addition of a pseudogene filtering step can remove up to 5% of sequences even when other filtering steps are in place. CONCLUSIONS: Open reading frame length filtering alone or combined with hidden Markov model profile analysis can be used to effectively screen out apparent pseudogenes from large datasets. There is more to learn from COI nuMTs such as their frequency in DNA barcoding and metabarcoding studies, their taxonomic distribution, and evolution. Thus, we encourage the submission of verified COI nuMTs to public databases to facilitate future studies.

Nonlinear power loss in the oscillations of coated and uncoated bubbles: Role of thermal, radiation and encapsulating shell damping at various excitation pressures.

This study presents the fundamental equations governing the pressure dependent disipation mechanisms in the oscillations of coated bubbles. A simple generalized model (GM) for coated bubbles accounting for the effect of compressibility of the liquid is presented. The GM was then coupled with nonlinear ODEs that account for the thermal effects. Starting with mass and momentum conservation equations for a bubbly liquid and using the GM, nonlinear pressure dependent terms were derived for power dissipation due to thermal damping (Td), radiation damping (Rd) and dissipation due to the viscosity of liquid (Ld) and coating (Cd). The pressure dependence of the dissipation mechanisms of the coated bubble have been analyzed. The dissipated energies were solved for uncoated and coated 2-20 µm in bubbles over a frequency range of 0.25fr-2.5fr (fr is the bubble resonance) and for various acoustic pressures (1 kPa-300 kPa). Thermal effects were examined for air and C3F8 gas cores. In the case of air bubbles, as pressure increases, the linear thermal model looses accuracy and accurate modeling requires inclusion of the full thermal model. However, for coated C3F8 bubbles of diameter 1-8 µm, which are typically used in medical ultrasound, thermal effects maybe neglected even at higher pressures. For uncoated bubbles, when pressure increases, the contributions of Rd grow faster and become the dominant damping mechanism for pressure dependent resonance frequencies (e.g. fundamental and super harmonic resonances). For coated bubbles, Cd is the strongest damping mechanism. As pressure increases, Rd contributes more to damping compared to Ld and Td. For coated bubbles, the often neglected compressibility of the liquid has a strong effect on the oscillations and should be incorporated in models. We show that the scattering to damping ratio (STDR), a measure of the effectiveness of the bubble as contrast agent, is pressure dependent and can be maximized for specific frequency ranges and pressures.

MDM2 antagonist-loaded targeted micelles in combination with doxorubicin: effective synergism against human glioblastoma via p53 re-activation.

p53, The tumour suppressor protein encoded by P53 gene, is the most commonly altered protein in the human malignancies. MDM2 controls the p53 activity through an autoregulatory feedback loop. p53 activates the expression of MDM2 and in return, MDM2 blocks the p53 activity through various mechanisms. Nutlins, including nutlin-3, are a new class of small molecules that bind to MDM2 and prevent its interaction with p53. This antagonism results in increased p53 activity and can also re-activates the p53 pathway and resensitize the glioblastoma cells to apoptosis. Here we used nutlin-3 in combination with another potent anticancer drug, doxorubicin, to investigate the synergism between these drugs. We encapsulated both water-insoluble drugs in the PEG-PE-based micellar nanocarriers efficiently and evaluate their efficacy against U87MG cells in 2 D and 3 D models. These nanomedicine formulations successfully re-activated the p53 levels in cells, increased the apoptosis and showed strong synergistic cytotoxic effect.

Widespread occurrence and phylogenetic placement of a soil clone group adds a prominent new branch to the fungal tree of life.

Fungi are one of the most diverse groups of Eukarya and play essential roles in terrestrial ecosystems as decomposers, pathogens and mutualists. This study unifies disparate reports of unclassified fungal sequences from soils of diverse origins and anchors many of them in a well-supported clade of the Ascomycota equivalent to a subphylum. We refer to this clade as Soil Clone Group I (SCGI). We expand the breadth of environments surveyed and develop a taxon-specific primer to amplify 2.4kbp rDNA fragments directly from soil. Our results also expand the known range of this group from North America to Europe and Australia. The ancient origin of SCGI implies that it may represent an important transitional form among the basal Ascomycota groups. SCGI is unusual because it currently represents the only major fungal lineage known only from sequence data. This is an important contribution towards building a more complete fungal phylogeny and highlights the need for further work to determine the function and biology of SCGI taxa.

Urinary excretion of renin in the dog: effect of changes in plasma renin.

By using standard clearance and stop flow techniques, studies were carried out in anesthetized dogs to clarify further the mechanism(s) of excretion of renin in urine. The clearance of renin was 0.61 +/- 0.19 ml/min in control experiments and increased significantly to 1.26 +/- 0.38 ml/min after furosemide. The fractional excretion of renin increased from 1.51 +/- 0.45% during control to 3.90 +/- 0.98% after furosemide. The rate of excretion of renin was increased 10-fold during furosemide diuresis associated with a 10-fold increase in plasma renin concentration. Extracellular fluid volume expansion also produced a diuresis but no increase in plasma renin or renin excretion. Hemorrhage produced a 3.5-fold increase in plasma renin concentration and a 200-fold increase in urinary excretion of renin. When renal artery perfusion pressure was reduced to one kidney, the excretion of renin in the urine from that kidney increased, whereas there was no significant change in the excretion from the contralateral kidney. Reduction in renal artery perfusion pressure was associated with a 3-fold increase in the concentration of renin in the renal vein from the experimental kidney but an insignificant 2-fold increase in the arterial plasma renin concentration. Stop-flow studies demonstrated that renin enters the urine with the glomerular filtrate. The decreased concentration of renin in samples from the proximal tubule suggests that renin is being metabolized and/or reabsorbed in this nephron segment. In the distal nephron, there appears to be a site in which renin may be added to the tubular fluid. The results of these studies suggest that renin excretion in the urine is a complicated process. Excretion of renin in the urine is related in part to plasma renin activity but probably more importantly to the rate of production of renin in the kidney.