In-process rheometry as a PAT tool for hot melt extrusion

YesReal time measurement of melt rheology has been investigated as a Process Analytical Technology (PAT) to monitor hot melt extrusion of an Active Pharmaceutical Ingredient (API) in a polymer matrix. A developmental API was melt mixed with a commercial copolymer using a heated twin screw extruder at different API loadings and set temperatures. The extruder was equipped with an instrumented rheological slit die which incorporated three pressure transducers flush mounted to the die surface. Pressure drop measurements within the die at a range of extrusion throughputs were used to calculate rheological parameters such as shear viscosity and exit pressure, related to shear and elastic melt flow properties respectively. Results showed that the melt exhibited shear thinning behavior whereby viscosity decreased with increasing flow rate. Increase in drug loading and set extrusion temperature resulted in a reduction in melt viscosity. Shear viscosity and exit pressure measurements were found to be sensitive to API loading. These findings suggest that this technique could be used as a simple tool to measure material attributes in-line, to build better overall process understanding for hot melt extrusion

Neuronal MicroRNA Deregulation in Response to Alzheimer's Disease Amyloid-β

Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-β (Aβ) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Aβ peptides. Time-course assays of neuronal Aβ treatments show that Aβ is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Aβ42-depositing APP23 mice, at the onset of Aβ plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Aβ may be an important factor contributing to the cascade of events leading to AD

Combustion 2000

This report is a presentation of work carried out on Phase II of the HIPPS program under DOE contract DE-AC22-95PC95144 from June 1995 to March 2001. The objective of this report is to emphasize the results and achievements of the program and not to archive every detail of the past six years of effort. These details are already available in the twenty-two quarterly reports previously submitted to DOE and in the final report from Phase I. The report is divided into three major foci, indicative of the three operational groupings of the program as it evolved, was restructured, or overtaken by events. In each of these areas, the results exceeded DOE goals and expectations. HIPPS Systems and Cycles (including thermodynamic cycles, power cycle alternatives, baseline plant costs and new opportunities) HITAF Components and Designs (including design of heat exchangers, materials, ash management and combustor design) Testing Program for Radiative and Convective Air Heaters (including the design and construction of the test furnace and the results of the tests) There are several topics that were part of the original program but whose importance was diminished when the contract was significantly modified. The elimination of the subsystem testing and the Phase III demonstration lessened the relevance of subtasks related to these efforts. For example, the cross flow mixing study, the CFD modeling of the convective air heater and the power island analysis are important to a commercial plant design but not to the R&D product contained in this report. These topics are of course, discussed in the quarterly reports under this contract. The DOE goal for the High Performance Power Plant System ( HIPPS ) is high thermodynamic efficiency and significantly reduced emissions. Specifically, the goal is a 300 MWe plant with > 47% (HHV) overall efficiency and {le} 0.1 NSPS emissions. This plant must fire at least 65% coal with the balance being made up by a premium fuel such as natural gas. To achieve these objectives requires a change from complete reliance of coal-fired systems on steam turbines (Rankine cycles) and moving forward to a combined cycle utilizing gas turbines (Brayton cycles) which offer the possibility of significantly greater efficiency. This is because gas turbine cycles operate at temperatures well beyond current steam cycles, allowing the working fluid (air) temperature to more closely approach that of the major energy source, the combustion of coal. In fact, a good figure of merit for a HIPPS design is just how much of the enthalpy from coal combustion is used by the gas turbine. The efficiency of a power cycle varies directly with the temperature of the working fluid and for contemporary gas turbines the optimal turbine inlet temperature is in the range of 2300-2500 F (1260-1371 C). These temperatures are beyond the working range of currently available alloys and are also in the range of the ash fusion temperature of most coals. These two sets of physical properties combine to produce the major engineering challenges for a HIPPS design. The UTRC team developed a design hierarchy to impose more rigor in our approach. Once the size of the plant had been determined by the choice of gas turbine and the matching steam turbine, the design process of the High Temperature Advanced Furnace (HITAF) moved ineluctably to a down-fired, slagging configuration. This design was based on two air heaters: one a high temperature slagging Radiative Air Heater (RAH) and a lower temperature, dry ash Convective Air Heater (CAH). The specific details of the air heaters are arrived at by an iterative sequence in the following order:-Starting from the overall Cycle requirements which set the limits for the combustion and heat transfer analysis-The available enthalpy determined the range of materials, ceramics or alloys, which could tolerate the temperatures-Structural Analysis of the designs proved to be the major limitation-Finally the commercialization issues of fabrication and reliability, availability and maintenance. The program that has sought to develop and implement these HIPPS designs is outlined below