\u3cem\u3eIn vivo\u3c/em\u3e Brainstem Imaging in Alzheimer’s Disease: Potential for Biomarker Development

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. One potential area of research that might prove fruitful in this regard is the in vivo detection of brainstem pathology. The brainstem is known to undergo pathological changes very early and progressively in AD. With an updated and harmonized AD research framework, and emerging advances in neuroimaging technology, the potential to leverage knowledge of brainstem pathology into biomarkers for AD will be discussed

Model-based Development for Event-driven Applications using MATLAB: Audio Playback Case Study

Audio playbacks are mechanisms which read data from a storage medium and produce commands and signals which an audio system turns into music. Playbacks are constantly changed to meet market demands, requiring that the control software be updated quickly and efficiently

Presentations of Wess-Zumino-Witten Fusion Rings

The fusion rings of Wess-Zumino-Witten models are re-examined. Attention is drawn to the difference between fusion rings over Z (which are often of greater importance in applications) and fusion algebras over C. Complete proofs are given characterising the fusion algebras (over C) of the SU(r+1) and Sp(2r) models in terms of the fusion potentials, and it is shown that the analagous potentials cannot describe the fusion algebras of the other models. This explains why no other representation-theoretic fusion potentials have been found. Instead, explicit generators are then constructed for general WZW fusion rings (over Z). The Jacobi-Trudy identity and its Sp(2r) analogue are used to derive the known fusion potentials. This formalism is then extended to the WZW models over the spin groups of odd rank, and explicit presentations of the corresponding fusion rings are given. The analogues of the Jacobi-Trudy identity for the spinor representations (for all ranks) are derived for this purpose, and may be of independent interest.Comment: 32 pages, 3 figures, added references, minor additions to text. To be published in Rev. Math. Phy

Indiana High Accuracy Reference Network (HARN) Final Report

This report has three main areas of interest. First, a brief discussion on the need for the Indiana HARN and why this was an important task. Second, a summary of the details surrounding the Indiana HARN survey. Finally, the station description of the HARN point in your county is attached with a map of the general area surrounding this point. We have also included a discussion on monument preservation with tips on how keep the high accuracies associated with your point(s). Also, a section is included on how the HARN is being used in Indiana with a few success stories

Energy and Charged Particle Flow in 10.8 A GeV/c Au+Au Collisions

Experimental results and a detailed analysis are presented of the transverse energy and charged particle azimuthal distributions measured by the E877 collaboration for different centralities of Au+Au collisions at a beam momentum of 10.8 A GeV/c. The anisotropy of these distributions is studied with respect to the reaction plane reconstructed on an event-by-event basis using the transverse energy distribution measured by calorimeters. Results are corrected for the reaction plane resolution. For semicentral events we observe directed flow signals of up to ten percent. We observe a stronger anisotropy for slow charged particles. For both the charged particle and transverse energy distributions we observe a small but non zero elliptic anisotropy with the major axis pointing into the reaction plane. Combining the information on transverse energy and charged particle flow we obtain information on the flow of nucleons and pions. The data are compared to event generators and the need to introduce a mean field or nucleon-nucleon potential is discussed.Comment: RevTex, 25 pages, 13 figures included as one Postscript file, submitted to Phys. Rev.

Microglial-Associated Responses to Comorbid Amyloid Pathology and Hyperhomocysteinemia in an Aged Knock-in Mouse Model of Alzheimer\u27s Disease

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer\u27s disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies. METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of B-vitamin deficiency-induced HHcy to better understand how microglia are affected in this comorbidity context. RESULTS: We found that HHcy-inducing diet increased amyloid plaque burden, altered the neuroinflammatory milieu, and upregulated the expression of multiple damage-associated and homeostatic microglial genes. CONCLUSIONS: Taken together, these data indicate complex effects of comorbid pathologies on microglial function that are not driven solely by increased amyloid burden. Given the highly dynamic nature of microglia, their central role in AD pathology, and the frequent occurrence of various comorbidities in AD patients, it is increasingly important to understand how microglia respond to mixed pathological processes

Therapeutic Treatment with the Anti-Inflammatory Drug Candidate MW151 May Partially Reduce Memory Impairment and Normalizes Hippocampal Metabolic Markers in a Mouse Model of Comorbid Amyloid and Vascular Pathology

Alzheimer\u27s disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop small molecule, anti-inflammatory therapeutics for neurological injury and disease, we have recently been exploring potentially promising treatments in preclinical multi-morbidity contexts. In the present study, we generated a mouse model of mixed amyloid and hyperhomocysteinemia (HHcy) pathology in which to test the efficacy of one of our anti-inflammatory compounds, MW151. HHcy can cause cerebrovascular damage and is an independent risk factor for both AD dementia and vascular contributions to cognitive impairment and dementia. We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context, and further, that the benefit is associated with a normalization of hippocampal metabolites detectable via magnetic resonance spectroscopy. These findings provide evidence that MW151 in particular, and potentially anti-inflammatory treatment more generally, may be beneficial in AD patients with comorbid vascular pathology

HIIphot: Automated Photometry of HII Regions Applied to M51

We have developed a robust, automated method, hereafter designated HIIphot, which enables accurate photometric characterization of HII regions while permitting genuine adaptivity to irregular source morphology. HIIphot utilizes object-recognition techniques to make a first guess at the shapes of all sources then allows for departure from such idealized ``seeds'' through an iterative growing procedure. Photometric corrections for spatially coincident diffuse emission are derived from a low-order surface fit to the background after exclusion of all detected sources. We present results for the well-studied, nearby spiral M51 in which 1229 HII regions are detected above the 5-sigma level. A simple, weighted power-law fit to the measured H-alpha luminosity function (HII LF) above log L_H-alpha = 37.6 gives alpha = -1.75+/-0.06, despite a conspicuous break in the HII LF observed near L_H-alpha = 10^38.9. Our best- fit slope is marginally steeper than measured by Rand (1992), perhaps reflecting our increased sensitivity at low luminosities and to notably diffuse objects. HII regions located in interarm gaps are preferentially less luminous than counterparts which constitute M51's grand-design spiral arms and are best fit with a power-law slope of alpha = -1.96+/-0.15. We assign arm/interarm status for HII regions based upon the varying surface brightness of diffuse emission as a function of position throughout the image. Using our measurement of the integrated flux contributed by resolved HII regions in M51, we estimate the diffuse fraction to be approximately 0.45 -- in agreement with the determination of Greenawalt et al. (1998). Automated processing of degraded datasets is undertaken to gauge systematic effects associated with limiting spatial resolution and sensitivity.Comment: 41 pages, 14 figures, Postscript version with high-resolution figures at ftp://ftp.aoc.nrao.edu/staff/dthilker/preprint