The interface region in squeeze-infiltrated composites containing δ-alumina fibre in an aluminium matrix

This paper examines the nature of the interfaces formed between fine,-alumina fibres and aluminium-based matrices. Alloys containing magnesium and silicon have been employed, as well as high-purity aluminium. The fabrication process involved high-pressure melt infiltration of a fibrous preform. It has been found that no detectable interfacial reaction product is formed in these systems, although there is in some cases evidence of a limited exchange of magnesium between melt and fibre surface. It is concluded, both from measurements and from process analysis, that any distinct chemical reaction product formed at the interface between fibre and matrix must be limited in extent to the atomic monolayer level.     

Surface Segregation Mechanisms in Ferroelectric Thin Films

Reliability issues have hampered the adoption of ferroelectric thin films by the microelectronics industry. One of these is imprint, an important problem affecting the performance of ferroelectric non-volatile memories. This paper presents the effects of the low temperature pyrolysis step on the chemical and physical properties of SrBi₂Ta₂O₉ films. A comparison of the hysteretic properties and composition profiles shows that control of the oxidising conditions during pyrolysis is critical to the dielectric properties. Data from this work and from the literature have been used to construct a model that explains the origin of surface depletion and segregation, self poling and as-grown imprint in ferroelectric films.     

Current Therapies and Technological Advances in Aqueous Aerosol Drug Delivery

Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat®), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.     

Recent Developments in Drug Delivery to Prolong Allograft Survival in Lung Transplant Patients

Since the discovery of cyclosporine in 1971, calcineurin inhibitors have played a critical role in the therapeutic suppression of the immune response. Patients receiving solid organ transplants rely heavily on these medications to prevent the acute and chronic rejection of allografted tissue. These therapies can prove difficult because of potential toxicity, heightened risk of invasive infection, and erratic oral bioavailability, requiring frequent blood samples for monitoring of systemic levels. Added challenges are presented in immunosuppression of lung transplant patients owing to the increased susceptibility to invasive infection and extensive immune mechanisms inherent in lung tissue. With the introduction of tacrolimus, a more potent calcineurin inhibitor, clinical outcomes of transplants have continued to improve; however, little improvement has been noted in lung transplantation. While very effective upon arrival at the site of action, tacrolimus and cyclosporine present a variety of formulation challenges such as poor solubility, potential systemic toxicity, and extensive first pass metabolism. Initial attempts to improve solubility in both oral and intravenous formulations have resulted in variable drug absorption and increased systemic toxicity, respectfully, creating a need for formulation improvement. Through alternative routes of delivery and novel formulation techniques, researchers have addressed these issues and, in some cases, demonstrated improved clinical outcomes. Through enhanced solubilization, reduction in absorption variability, and more effective drug targeting with reduced systemic levels, improvements in outcomes and overall patient survival in lung and other solid organ transplantation can be expected.     

Multiresponse Estimation With Special Application to Linear Systems of Differential Equations

We present a multiresponse estimation procedure for parameters of systems described by ? = As. The procedure features a generalized Gauss–Newton algorithm for optimizing the determinant criterion, efficient evaluation of the expectation function and its derivatives directly from the reaction network or compartment diagram, automatic determination of starting values, and eficient computational procedures for handling linear constraints on the responses.     

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.     

Fabrication of Photonic/Microfluidic Integrated Devices Using an Epoxy Photoresist

Using a single layer of SU‐8 photoresist to fabricate optical waveguide cores and microfluidic channels on Pyrex glass is an ideal way to achieve photonic/microfluidic integration on a single chip. To address the problem of poor bonding, a thin nanoscale intermediate polymer layer was applied to reduce the stress generated from the material processing while maintaining strong adhesion between the patterning polymer layer and Pyrex. It was found that a 186–600 nm thick intermediate layer of a specialty epoxy photoresist effectively served the purpose without deteriorating the optical performance of the involved waveguides. Quality photonic/microfluidic integrated devices with satisfied optical performance were fabricated.