General amyloid inhibitors? A critical examination of the inhibition of IAPP amyloid formation by inositol stereoisomers.

Islet amyloid polypeptide (IAPP or amylin) forms amyloid deposits in the islets of Langerhans; a process that is believed to contribute to the progression of type 2 diabetes and to the failure of islet transplants. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation by different polypeptides share common features and exert their effects by common mechanisms. If correct, this suggests that inhibitors of amyloid formation by one polypeptide might be effective against other amyloidogenic sequences. IAPP and Aβ, the peptide responsible for amyloid formation in Alzheimers disease, are particularly interesting in this regard as they are both natively unfolded in their monomeric states and share some common characteristics. Comparatively little effort has been expended on the design of IAPP amyloid inhibitors, thus it is natural to inquire if Aβ inhibitors are effective against IAPP, especially since no IAPP inhibitors have been clinically approved. A range of compounds inhibit Aβ amyloid formation, including various stereoisomers of inositol. Myo-, scyllo-, and epi-inositol have been shown to induce conformational changes in Aβ and prevent Aβ amyloid fibril formation by stabilizing non-fibrillar β-sheet structures. We investigate the ability of inositol stereoisomers to inhibit amyloid formation by IAPP. The compounds do not induce a conformational change in IAPP and are ineffective inhibitors of IAPP amyloid formation, although some do lead to modest apparent changes in IAPP amyloid fibril morphology. Thus not all classes of Aβ inhibitors are effective against IAPP. This work provides a basis of comparison to work on polyphenol based inhibitors of IAPP amyloid formation and helps provide clues as to the features which render them effective. The study also helps provide information for further efforts in rational inhibitor design

Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.

Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures

ACE Inhibitor-Induced Angioedema of the Bowel

Angiotensin converting enzyme inhibitor ACEI-induced angioedema of the intestine is a rare occurrence and often unrecognized complication of ACEI. We present a case of a 45-year-old Hispanic female with angioedema of the small bowel progressing to facial and oral pharyngeal angioedema. Patients are typically middle-aged females on ACEI therapy who present to the emergency department with abdominal pain, nausea, vomiting, and diarrhea. This is a diagnosis of exclusion, and physicians must have a high index of suspicion to make the diagnosis. Symptoms typically resolve within 24–48 hours after ACE inhibitor withdrawal. Recognizing these signs and symptoms, and discontinuing the medication, can save a patient from unnecessary, costly, and invasive procedures

HAPs-Rx: Precombustion Removal of Hazardous Air Pollutant Precursors

CQ Inc. and its project team members--Howard University, PrepTech Inc., Fossil Fuel Sciences, the United States Geological Survey (USGS), and industry advisors--are applying mature coal cleaning and scientific principles to the new purpose of removing potentially hazardous air pollutants from coal. The team uniquely combines mineral processing, chemical engineering, and geochemical expertise. This project meets more than 11 goals of the U.S. Department of Energy (DOE), the National Energy Strategy, and the 1993 Climate Change Action Plan. During this project: (1) Equations were developed to predict the concentration of trace elements in as-mined and cleaned coals. These equations, which address both conventional and advanced cleaning processes, can be used to increase the removal of hazardous air pollutant precursors (HAPs) by existing cleaning plants and to improve the design of new cleaning plants. (2) A promising chemical method of removing mercury and other HAPs was developed. At bench-scale, mercury reductions of over 50 percent were achieved on coal that had already been cleaned by froth flotation. The processing cost of this technology is projected to be less than $3.00 per ton ($3.30 per tonne). (3) Projections were made of the average trace element concentration in cleaning plant solid waste streams from individual states. Average concentrations were found to be highly variable. (4) A significantly improved understanding of how trace elements occur in coal was gained, primarily through work at the USGS during the first systematic development of semiquantitative data for mode of occurrence. In addition, significant improvement was made in the laboratory protocol for mode of occurrence determination. (5) Team members developed a high-quality trace element washability database. For example, the poorest mass balance closure for the uncrushed size and washability data for mercury on all four coals is 8.44 percent and the best is 0.46 percent. This indicates an extremely high level of reproducibility of the data. In addition, a series of ''round-robin'' tests involving various laboratories was performed to assure analytical accuracy. (6) A comparison of the cost of lowering mercury emissions through the use of coal cleaning technologies versus the use of post-combustion control methods such as activated carbon injection indicates that, in many cases, coal cleaning may prove to be the lower-cost option. The most significant disadvantage for using coal cleaning for control of mercury emissions is that a reduction of 90 percent or greater from as-fired coal has not yet been demonstrated, even at laboratory-scale

Overview of the Aeroelastic Prediction Workshop

The Aeroelastic Prediction Workshop brought together an international community of computational fluid dynamicists as a step in defining the state of the art in computational aeroelasticity. This workshop's technical focus was prediction of unsteady pressure distributions resulting from forced motion, benchmarking the results first using unforced system data. The most challenging aspects of the physics were identified as capturing oscillatory shock behavior, dynamic shock-induced separated flow and tunnel wall boundary layer influences. The majority of the participants used unsteady Reynolds-averaged Navier Stokes codes. These codes were exercised at transonic Mach numbers for three configurations and comparisons were made with existing experimental data. Substantial variations were observed among the computational solutions as well as differences relative to the experimental data. Contributing issues to these differences include wall effects and wall modeling, non-standardized convergence criteria, inclusion of static aeroelastic deflection, methodology for oscillatory solutions, post-processing methods. Contributing issues pertaining principally to the experimental data sets include the position of the model relative to the tunnel wall, splitter plate size, wind tunnel expansion slot configuration, spacing and location of pressure instrumentation, and data processing methods

Methods for Planning the Great Lakes MegaRegion

http://deepblue.lib.umich.edu/bitstream/2027.42/110967/1/glmegaregion_methodsmanual_finalcorrect2006.pd

Through a Wider Lens: Re-envisioning the Great Lakes Mega Region

http://deepblue.lib.umich.edu/bitstream/2027.42/110966/1/throughwiderlens2006.pd

Report of the special session of "Chesapeake Bay Ecological Forecasting: Moving Ecosystem Modeling from Research to Operation" of the 2010 Chesapeake Modeling Symposium

Moving ecosystem modeling from research to applications and operations has direct management relevance and will be integral to achieving the water quality and living resource goals of the 2010 Chesapeake Bay Executive Order. Yet despite decades of ecosystem modeling efforts of linking climate to water quality, plankton and fish, ecological models are rarely taken to the operational phase. In an effort to promote operational ecosystem modeling and ecological forecasting in Chesapeake Bay, a meeting was convened on this topic at the 2010 Chesapeake Modeling Symposium (May, 10-11). These presentations show that tremendous progress has been made over the last five years toward the development of operational ecological forecasting models, and that efforts in Chesapeake Bay are leading the way nationally. Ecological forecasts predict the impacts of chemical, biological, and physical changes on ecosystems, ecosystem components, and people. They have great potential to educate and inform not only ecosystem management, but also the outlook and opinion of the general public, for whom we manage coastal ecosystems. In the context of the Chesapeake Bay Executive Order, ecological forecasting can be used to identify favorable restoration sites, predict which sites and species will be viable under various climate scenarios, and predict the impact of a restoration project on water quality