Functional Nanovalves on Protein‐Coated Nanoparticles for In vitro and In vivo Controlled Drug Delivery

A multifunctional mesoporous drug delivery system that contains fluorescent imaging molecules, targeting proteins, and pH‐sensitive nanovalves is developed and tested. Three nanovalve‐mesoporous silica nanoparticle (NV‐MSN) systems with varied quantities of nanovalves on the surface are synthesized. These systems are characterized and tested to optimize the trade‐off between the coverage of nanovalves on the MSNs to effectively trap and deliver cargo, and the remaining underivatized silanol groups that can be used for protein attachments. The NV‐MSN system that has satisfactory coverage for high loading and spare silanols is chosen, and transferrin (Tf) is integrated into the system. Abiotic studies are performed to test the operation of the nanovalve in the presence of the protein. In vitro studies are carried out to demonstrate the autonomous activation and function of the nanovalves in the system under biological conditions. Enhanced cellular uptake of the Tf‐modified MSNs is seen using fluorescence microscopy and flow cytometry in MiaPaCa‐2 cells. The MSNs are then tested using SCID mice, which show that both targeted and untargeted NV‐MSN systems are fully functional to effectively deliver cargo. These new multifunctional nanoparticles serve proof of concept of nanovalve functionality in the presence of large proteins and demonstrate another dimension of MSN‐based theranostic platforms.     

Propagation of a penny-shaped hydraulic fracture parallel to the free-surface of an elastic half-space

In this paper we analyze the problem of a penny-shaped hydraulic fracture propagating parallel to the free-surface of an elastic half-space. The fracture is driven by an incompressible Newtonian fluid injected at a constant rate at the center of the fracture. The flow of viscous fluid in the fracture is governed by the lubrication equation, while the crack opening and the fluid pressure are related by singular integral equations. We construct two asymptotic solutions based on the assumption that either the solid has no toughness or that the fluid has no viscosity. These asymptotic solutions must be understood as corresponding to limiting cases when the energy expended in the creation of new fracture surfaces is either small or large compared to the energy dissipated in viscous flow. It is shown that the asymptotic solutions, when properly scaled, depend only on the dimensionless parameter cal R cal, the ratio of the fracture radius over the distance from the fracture to the free-surface. The scaled solutions can thus be tabulated once and for all and the dependence of the solution on time can be retrieved for specific parameters, through simple scaling and by solving an implicit equation.     

Nanocarriers as an emerging platform for cancer therapy

Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.     

John M. Eisenberg Patient Safety Awards. System innovation: Veterans Health Administration National Center for Patient Safety

BACKGROUND: In 1998 the Veterans Health Administration (VHA) created the National Center for Patient Safety (NCPS) to lead the effort to reduce adverse events and close calls systemwide. NCPS's aim is to foster a culture of safety in the Department of Veterans Affairs (VA) by developing and providing patient safety programs and delivering standardized tools, methods, and initiatives to the 163 VA facilities. A NOVEL APPROACH: To create a system-oriented approach to patient safety, NCPS looked for models in fields such as aviation, nuclear power, human factors, and safety engineering. Core concepts included a non-punitive approach to patient safety activities that emphasizes systems-based learning, the active seeking out of close calls, which are viewed as opportunities for learning and investigation, and the use of interdisciplinary teams to investigate close calls and adverse events through a root cause analysis (RCA) process. Participation by VA facilities and networks was voluntary. NCPS has always aimed to develop a program that would be applicable both within the VA and beyond. KEY ACTION ITEMS AND RESULTS RELATED TO RCA: NCPS's full patient safety program was tested and implemented throughout the VA system from November 1999 to August 2000. Program components included an RCA system for use by caregivers at the front line, a system for the aggregate review of RCA results, information systems software, alerts and advisories, and cognitive acids. Following program implementation, NCPS saw a 900-fold increase in reporting of close calls of high-priority events, reflecting the level of commitment to the program by VHA leaders and staff.     

Evaluation of automobile service performance using laboratory testing

A methodology is presented to evaluate martensitic advanced high-strength steels in auto service. There was essentially no influence of hydrogen for (i) linearly increasing stress tests of specimens with hydrogen contents much greater than for automobile service, and (ii) for tensile tests with simultaneous hydrogen charging and with a substantial hydrogen content. These results allow evaluation of the hydrogen influence for the tested steels for auto service. In contrast, electrochemically hydrogen charged martensitic advanced high-strength steels showed an influence of hydrogen on mechanical properties, manifest as (i) a decrease in yield strength, by hydrogen enhanced macroscopic ductility, and (ii) a change of the micro-fracture mode, by hydrogen-assisted micro-fracture.     

The design of a multi‐speed PSK modem

Abstract

Charge‐temperature, modified from bias‐temperature, technique is presented for the investigation of the interface properties of Al‐SiO₂‐Si (P) MOS capacitors. By using this technique, the change of interface trap states was found to be related to the treatment of charge‐temperature agin gand consequently the distribution of the mobile charges inside the oxide. An equivalent equation is expressed for the evaluation of interface trap states from the measured C‐V data. In addition, a two‐region model describing the distributions of the mobile charges of the capacitor after various charge‐temperature agings is proposed for the experimental observations. And the fitting results indicate that the effective Debye length due to interface trap states is about 20 Å.