Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies

Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, approximately 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM-1 s-1 (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM-1 s-1 (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.     

Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows

Selective serotonin reuptake inhibitors (SSRIs) represent a class of pharmaceuticals previously reported in aquatic ecosystems. SSRIs are designed to treat depression and other disorders in humans, but are recognized to elicit a variety of effects on aquatic organisms, ranging from neuroendocrine disruption to behavioral perturbations. However, an understanding of the relationships among mechanistic responses associated with SSRI targets and ecologically important behavioral responses of fish remains elusive. Herein, linking Adverse Outcomes Pathways (AOP) models with internal dosimetry represent potential approaches for developing an understanding of pharmaceutical risks to aquatic life. We selected sertraline as a model SSRI for a 28-d study with adult male fathead minnows. Binding activity of the serotonin reuptake transporter (SERT), previously demonstrated in mammals and fish models to respond to sertraline exposure, was selected as an endpoint associated with therapeutic activity. Shelter-seeking behavior was monitored using digital tracking software to diagnose behavioral abnormalities. Fish plasma levels of sertraline exceeding human therapeutic doses were accurately modeled from external exposure concentrations when pH influences on ionization and log D were considered. We observed statistically significant decreases in binding at the therapeutic target (SERT) and shelter-seeking behavior when fish plasma levels exceeded human therapeutic thresholds. Such observations highlights the strengths of coupling physiologically based pharmacokinetic modeling and AOP approaches and suggest that internal dosimetry should be monitored to advance an understanding of the ecological consequences of SSRI exposure to aquatic vertebrates.     

Improvements on "fast space-variant elliptical filtering using box splines"

It is well-known that box filters can be efficiently computed using pre-integration and local finite-differences. By generalizing this idea and by combining it with a nonstandard variant of the central limit theorem, we had earlier proposed a constant-time or O(1) algorithm that allowed one to perform space-variant filtering using Gaussian-like kernels. The algorithm was based on the observation that both isotropic and anisotropic Gaussians could be approximated using certain bivariate splines called box splines. The attractive feature of the algorithm was that it allowed one to continuously control the shape and size (covariance) of the filter, and that it had a fixed computational cost per pixel, irrespective of the size of the filter. The algorithm, however, offered a limited control on the covariance and accuracy of the Gaussian approximation. In this paper, we propose some improvements of our previous algorithm.     

Fabrication of nano-scale Cu bond pads with seal design in 3D integration applications

A method to fabricate nano-scale Cu bond pads for improving bonding quality in 3D integration applications is reported. The effect of Cu bonding quality on inter-level via structural reliability for 3D integration applications is investigated. We developed a Cu nano-scale-height bond pad structure and fabrication process for improved bonding quality by recessing oxides using a combination of SiO2 CMP process and dilute HF wet etching. In addition, in order to achieve improved wafer-level bonding, we introduced a seal design concept that prevents corrosion and provides extra mechanical support. Demonstrations of these concepts and processes provide the feasibility of reliable nano-scale 3D integration applications.     

Envelope pulsed ultrasonic distance measurement system based upon amplitude modulation and phase modulation

A novel microcomputer-based ultrasonic distance measurement system is presented. This study proposes an efficient algorithm which combines both the amplitude modulation (AM) and the phase modulation (PM) of the pulse-echo technique. The proposed system can reduce error caused by inertia delay and amplitude attenuation effect when using the AM and PM envelope square wave form (APESW). The APESW ultrasonic driving wave form causes a phase inversion phenomenon in the relative wave form of the receiver. The phase inversion phenomenon sufficiently identifies the "measurement pulse" in the received wave forms, which can be used for accurate time-of-flight (TOF) measurement. In addition, combining a countertechnique to compute the phase shifts of the last cycle for TOF, the presented system can obtain distance resolution of 0.1% of the wavelength corresponding to the 40 kHz frequency of the ultrasonic wave. The standard uncertainty of the proposed distance measurement system is found to be 0.2 mm at a range of 50-500 mm. The APESW signal generator and phase detector of this measuring system are designed on a complex programmable logic device, which is used to govern the TOF measurement and send the data to a personal computer for distance calibration and examination. The main advantages of this APESW system are high resolution, low cost, narrow bandwidth requirement, and ease of implementation.     

Thermal effects of the electron beam and implications of surface damage in the analysis of bone tissue

Electron beam interactions with specimens in the scanning electron microscope (SEM) can lead to increased surface temperatures and damage. These changes may have significant consequences in the analysis of bone tissue. An investigation was performed to measure the surface temperature changes associated with the electron beam on a thermocouple with systematic variations in operating conditions. Probe currents, magnifications, and accelerating voltages were incrementally adjusted to measure the temperature changes and to make assessments for determining optimal operating conditions for the SEM in future analyses of bone tissue. Results from this study suggest that thermal effects were minimal at lower accelerating voltages (< 20 kV), lower probe currents (< 10 nA), and lower magnifications, but surface damage may still occur during the analysis of bone tissue.     

Effects of simulated deposition of acid mist and iron ore particulate matter on photosynthesis and the generation of oxidative stress in Schinus terebinthifolius Radii and Sophora tomentosa L

Particulate matter is a natural occurrence in the environment, but some industries, such as the iron ore sector, can raise the total amount of particles in the atmosphere. This industry is primarily a source of iron and sulfur dioxide particulates. The effects of the pollutants from the iron ore industries on representatives of restinga vegetation in a Brazilian coastal ecosystem were investigated using physiological and biochemical measures. Two species, Schinus terebinthifolius and Sophora tomentosa, were exposed to simulated deposition of acid mist and iron ore particulate matter in acrylic chambers in a greenhouse. Parameters such as gas exchange, fluorescence emission, chlorophyll content, total iron content, antioxidant enzyme activity and malondialdehyde content were assessed in order to evaluate the responses of the two species. Neither treatment was capable of inducing oxidative stress in S. terebinthifolius. Nevertheless, the deposition of iron ore particulates on this species increased chlorophyll content, the maximum quantum efficiency of photosystem II and the electron transport rate, while iron content was unaltered. On the other hand, S. tomentosa showed a greater sensitivity to the treatments. Plants of S. tomentosa that were exposed to acid mist had a decrease in photosynthesis, while the deposition of iron particulate matter led to an increase in iron content and membrane permeability of the leaves. The activities of antioxidant enzymes, such as catalases and superoxide dismutase, were enhanced by both treatments. The results suggested that the two restinga species use different strategies to overcome the stressful conditions created by the deposition of particulate matter, either solid or wet. It seems that while S. terebinthifolius avoided stress, S. tomentosa used antioxidant enzyme systems to partially neutralize oxidative stress. The findings also point to the potential use of S. tomentosa as a biomarker species under field conditions.     

Inability to start hemodialysis after a smooth temporary hemodialysis catheter insertion procedure

Cannulation of the central vein for placement of the temporary dual-lumen catheter for hemodialysis can usually be safely and reliably performed under ultrasonographic guidance. Here, we report a case of aberrant catheter entry into the internal thoracic vein during an apparently smooth procedure. The value of sonographic guidance, together with fluoroscopy with or without venography, will be discussed.     

The influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate–PMMA composite cement

The objective of this study is to assess the influence of lithium fluoride on in vitro biocompatibility and bioactivity of calcium aluminate (CA)-polymethylmethacrylate (PMMA) composite cement exhibiting quick setting time ( < 15 min), low exothermic temperature (< 47 degrees C), and high compressive strength (> 100 MPa). The biocompatibility was measured by examining cytotoxicity tests such as the agar diffusion test with L929 cell line and the hemolysis test with fresh rabbit blood. To estimate the bioactivity of CA-PMMA composite cement, we determined hydroxyapatite (HAp) formation on the surface of composite cement in the simulated body (SBF) solution by using thin-film XRD, XPS, SEM, EPMA and ICP-AES. The results of biocompatibility tests indicated that all experimental compositions of this study had no cytotoxicity and no hemolysis so that there was no cytotoxicity with regard to non-reacted monomers (MMA and TEGDMA) and lithium fluoride. The results of bioactivity tests revealed that CA-PMMA composite cement without lithium fluoride did not form HAp on its surface after 60 days of soaking in the SBF. On the other hand, LiAl2(OH)7 . 2H2O and HAp were formed on the surface of CA-PMMA composite cement including 1.0% by weight of lithium fluoride after 7 and 15 days of soaking in the SBF, respectively. The 5 microm of LiAl2(OH)7 . 2H2O and HAp mixed layers were formed on the surface of specimen after 60 days of soaking in the SBF.