Automatic quantification of changes in bone in serial MR images of joints

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.     

Energy Quantization in Solution‐Processed Layers of Indium Oxide and Their Application in Resonant Tunneling Diodes

The formation of quantized energy states in ultrathin layers of indium oxide (In₂O₃) grown via spin coating and thermally annealed at 200 °C in air is studied. Optical absorption measurements reveal a characteristic widening of the optical band gap with reducing In₂O₃ layer thickness from ≈43 to ≈3 nm in agreement with theoretical predictions for an infinite quantum well. Through sequential deposition of In₂O₃ and gallium oxide (Ga­₂O₃) layers, superlattice‐like structures with controlled dimensionality and spatially varying conduction band characteristics are demonstrated. This simple method is then explored for the fabrication of functional double‐barrier resonant tunneling diodes. Nanoscale current mapping analysis using conductive atomic force microscopy reveals that resonant tunneling is not uniform but localized in specific regions of the apparent device area. The latter observation is attributed to variation in the layer(s) thickness of the In₂O₃ quantum well and/or the Ga₂O₃ barrier layers. Despite the nonidealities, the tremendous potential of solution‐processable oxide semiconductors for the development of quantum effect devices that have so far been demonstrated only via sophisticated growth techniques is demonstrated.     

Sustained‐Release Synthetic Biomarkers for Monitoring Thrombosis and Inflammation Using Point‐of‐Care Compatible Readouts

Postoperative infection and thromboembolism represent significant sources of morbidity and mortality but cannot be easily tracked after hospital discharge. Therefore, a molecular test that could be performed at home would significantly impact disease management. The laboratory has previously developed intravenously delivered “synthetic biomarkers” that respond to dysregulated proteases to produce a urinary signal. These assays, however, have been limited to chronic diseases or acute diseases initiated at the time of diagnostic administration. Here, a subcutaneously administered sustained‐release system, using small poly(ethylene glycol) scaffolds (<10 nm) to promote diffusion into the bloodstream over a day, is formulated. The utility of a thrombin sensor to identify thrombosis and an Matrix metalloproteinase (MMP) sensor to measure inflammation is demonstrated. Finally, a companion paper ELISA (Enzyme‐linked immunosorbent sssay), using printed wax barriers, with nanomolar sensitivity for urinary reporters for point‐of‐care detection is developed. The approach for subcutaneous delivery of nanosensors combined with urinary paper analysis may enable facile monitoring of at‐risk patients.     

Codelivery of NOD2 and TLR9 Ligands via Nanoengineered Protein Antigen Particles for Improving and Tuning Immune Responses

Vaccine adjuvants that can induce robust protective immunity are highly sought after for the development of safer and more effective vaccines. Vaccine formulation parameters that govern efficacy are still far from clear, such as the diverse impacts of codelivering agonist molecules for innate cell receptors (e.g., pattern recognition receptors). In this study, a mesoporous silica‐templating approach is used to fabricate protein antigen (ovalbumin) particles covalently functionalized with agonists for NOD‐like receptor 2 (NOD2) and Toll‐like receptor 9 (TLR9). Particle‐induced combinatorial NOD2/TLR9 signaling results in synergistic inflammatory cytokine secretion by mouse macrophages (RAW 264.7). Administration of NOD2/TLR9 particles in mice results in adaptive immune responses that are both quantitatively and qualitatively different than those resulting from administration of particles conjugated with either NOD2 or TLR9 agonists alone. While delivery of NOD2 agonists alone activates T helper 2 (Th2)‐type responses (and no CD8+ T cell activation) and delivery of TLR9 agonists alone activates CD8+ T cell and T helper 1 (Th1)‐type responses, codelivery of NOD2 and TLR9 agonists enhances Th1‐type responses and abrogates CD8+ T cell activation. The results illustrate that in the particle‐based system, NOD2 activation plays different roles in polarizing adaptive immune responses depending on coactivation of TLR9.     

Planar InP/InGaAs avalanche photodetector with integrated dielectric wavelength filter

Patterned bandpass dielectric interference filters with centre wavelengths around 1.3 mu m have been applied to top-entry photodiodes to produce high-speed, high-responsivity, photodetectors for wavelength division multiplexing. The measured responsivity exceeded 25 A/W with a full width half maximum of 19 nm and peak rejection of over 25 dB.<>     

High-gain free electron lasers using induction linear accelerators

High-power free electron lasers (FEL's) can be realized using induction linear accelerators as the source of the electron beam. These accelerators are currently capable of producing intense currents (10²-10⁴A) at moderately high energy (1-50 MeV). Experiments using a 500 A, 3.3 MeV beam have produced 80 MW of radiation at 34.6 GHz and are in good agreement with theoretical analysis. Future experiments include a high-gain, high-efficiency FEL operating at 10.6 μm using a 50 MeV beam.     

Genetic counseling. An evaluation of public health genetic clinics

The geographic distribution of County Health Department clinic facilities in the state of California has made it readily possible to establish a regionalized program for genetic counseling services, using public health nurses as a major source of case-finding. From both consumer and health professional standpoints, regionalized satellite genetic counseling clinics have been successful, and in particular, the effectiveness of public health nurses in identifying clinical genetic problems is readily apparent.Long-term follow-up reinforcement of genetic counseling appears to be an important conclusion from these studies. It is our suggestion that reinforcement of counseling would best be accomplished through the health team member (physician, nurse and so forth) following the patient or family rather than through the consulting geneticist.     

Hydride habit planes in titanium-aluminum alloys

The habit plane of hydride precipitates in pure Ti has been previously reported as being predominantly the &#x007B;10-10&#x007D; prism plane, with precipitation also taking place on &#x007B;10-11&#x007D; planes, while habit planes in a Ti-3 pet Al alloy were &#x007B;10-11&#x007D; &#x007B;11-21&#x007D; and &#x007B;10-12&#x007D;. No habit planes near the basal plane have been reported in Ti alloys, although the &#x007B;10-17&#x007D; plane (14 deg from the basal plane) has been observed in certain zirconium alloys. In this work, Ti single crystals containing up to 6.6 wt pet Al were charged with hydrogen and the ef-fect of Al on hydride habit plane observed with both transmission and optical microscopy. Hydrides with a basal and near-basal habit plane were found in the higher Al content al-loys and it is suggested that the increased propensity for basal slip in these alloys is the reason for the change in habit plane. The implications of these observations in under-standing hydrogen induced fracture in Ti alloys are discussed, and possible modifica-tions to the conclusions of other investigators in this field suggested.     

Fate of endogenous steroid hormones in steer feedlots under simulated rainfall-induced runoff

Steroid hormones pose potential risks to fish and other aquatic organisms at extremely low concentrations. To assess the factors affecting the release of endogenous estrogenic and androgenic steroids from feedlots during rainfall, runoff, and soil samples were collected after simulated rainfall on a 14-steer feedlot under different rainfall rates and aging periods and analyzed for six steroid hormones. While only 17α-estradiol, testosterone, and progesterone were detected in fresh manure, 17β-estradiol, estrone, and androstenedione were present in the surficial soil after two weeks. In the feedlot surficial soil, concentrations of 17α-estradiol decreased by approximately 25% accompanied by an equivalent increase in estrone and 17β-estradiol. Aging of the feedlot soils for an additional 7 days had no effect on estrogen and testosterone concentrations, but androstenedione concentrations decreased substantially, and progesterone concentrations increased. Androstenedione and progesterone concentrations in the surficial soil were much higher than could be accounted for by excretion or conversion from testosterone, suggesting that other potential precursors, such as sterols, were converted after excretion. The concentration of androgens and progesterone in the soil were approximately 85% lower after simulated rainfall, but the estrogen concentrations remained approximately constant. The decreased masses could not be accounted for by runoff, suggesting the possibility of rapid microbial transformation upon wetting. All six steroids in the runoff, with the exception of 17β-estradiol, were detected in both the filtered and particle-associated phases at concentrations well above thresholds for biological responses. Runoff from the aged plots contained less 17α-estradiol and testosterone, but more estrone, androstenedione, and progesterone relative to the runoff from the unaged plots, and most of the steroids had a lower particle-associated fraction.