Statistical modelling of neuron degeneration

SUMMARY: Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease are all examples of neurodegenerative disorders that result from the premature death of nerve cells or neurons. In order to understand the mechanisms through which these diseases advance, a number of models have been put forward to describe the decline in the numbers of surviving neurons. Such work has been hampered by the poor quality of estimates of the numbers of surviving neurons and also by questionable model selection techniques. Recent work has favoured the adoption of the exponential model to explain neurodegenerative decline. We present in this paper a methodology for challenging this model, using data from patients with ALS. We use a two stage procedure to study motor unit numbers. The first stage involves determining the number of motor units in a muscle on several occasions over a period of time. The method of Ridall et al. (2007) is used which makes use of reversible jump Markov chain Monte Carlo (RJMCMC). The second stage involves the analysis of the RJMCMC output by using a hiddenMarkov process of decline. Two such processes of decline are compared. The first is the exponential where the rate parameter is constant. This is compared to a more general semi-parametric process where the rate parameter is allowed to vary over time. The rate is set to be piecewise constant between recordings where the magnitudes of the change in rate are weakly constrained by the length of the interval between recording occasions. Between model comparisons are based on electrophysiological data collected from a group of ALS patients where motor units (MUs) are gradually lost leading to progressive muscle weakness. By calculating marginal likelihoods, we find the Bayes factor in support of the exponential decline model against the more general alternative. This approach is illustrated with four ALS patients. Prediction of MU numbers lost, which incorporates both models, can also be made. Our methods, we therefore believe, have a role in formulating and evaluating biological models for neural degeneration of the motor system in ALS patients

Effects of Sparking from Various Classes of Tool Steel in Explosive Mixtures of Firedamp and Air with Special Reference to Sparking from Coal Cutter Picks

For nearly two centuries the Ignition of Firedamp in Coal Mines has given grave concern to the Mining Industry. The causes of these Ignitions are not always obvious, and in many cases Frictional Sparks have been considered the only probable cause, after careful study of the other possible sources of Ignition. The earliest recorded Ignitions attributed to Frictional Sparking were believed to be produced by sparks either from the blow of a hand pick on hard rock or from the sparks given off by the steel mill and flint used at that time for underground illumination. The application of machinery to coal cutting has been progressively increasing during the past 50 years or so, and probably no branch of Mining Engineering is receiving more attention at the present time. The possibility of encountering the harder rocks adjacent to, and disseminated through the coal seams, and the greater amount of energy expended in cutting, accentuates the danger, if any, of sparking effects due to contact with the coal cutter picks. In recent years such sparks have been assigned as a cause of Ignition of Firedamp underground. Different opinions have been advanced by eminent Mining Engineers, but whether sparks produced from coal cutting picks are capable of igniting inflammable mixtures of Firedamp and Air seems still to be controversial. The following report gives first, an historical review of the subject and secondly, describes a series of experiments conducted with a view to deciding whether or not Firedamp-Air mixtures can be ignited by sparks from coal cutting picks on hard rock, and any conditions which may influence the incendivity of the sparks

Cary collection web presentation & digital image database

The Melbert Cary, Jr. Graphic Arts Collection in the Wallace Memorial Library is one of the treasures the RIT community has had available for years. For this thesis project, selected materials from the collection were scanned and made available on the Internet so people at any location can experience the rare and invaluable items the facility houses. Not only has the result of this project created an educational tool for others to use, but it also challenged the author to master web publishing while developments rapidly occur on the most powerful mass communications media to arise in decades. While the primary purpose of this thesis project was to create an aesthetically pleasing and information rich web presentation for the Melbert Cary, Jr. Graphic Arts Collection, many secondary goals had to first be achieved. Those secondary goals are outlined in this list: 1. To acquire high quality color electronic images for others to access remotely. 2. To design a searchable database of 300 records. 3. To learn the ins-and-outs of web publishing by: Creating cohesive and consistent documents in the HyperText Markup Language (HTML). Developing an aesthetically pleasing interface for users to explore documents. This included keeping up-to-date with developments in HTML and using techniques created by web publishing experts to make the text as typographically pleasing as possible. Placing the necessary documents and images on a web server. Advertising the address of the presentation, or URL, to the appropriate audience. 4. Developing clear and concise instructions on how to maintain the presentation, including procedures for adding categories and images. After a substantial amount of work on this project was completed, it was linked to the Wallace Memorial Library\u27s home page. A home page is the first site a person reaches upon typing in an Internet address on the World Wide Web. Home pages can be created by individuals or organizations and serve as points of departure for exploring textual and graphical information available at these sites. The Cary presentation has a section explaining the history and growth of the collection. A user can continue by taking a virtual tour of the facilities or by reading about recent acquisitions. The main feature of the presentation is a subject library and digital image data base which contains an initial collection of approximately 300 searchable records ranging from medieval manuscripts to portraits of printers. Instructions on how to perform various types of searches, as well as what type of searches are feasible, are also integrated into this project. Finally, information about image acquisition, graphics presentation, and database installation and setup are integrated into this project. In addition, a secondary home page for the American Printing History Association has been created, and sample articles from its journal Printing History will be available in a digital format on an ongoing basis. All images were prepared to be as faithful to the originals as possible, keeping in mind the drawbacks inherent in viewing images and text on today\u27s monitors. Retaining accurate colors and details while paying heed to practical speed requirements of transmission was of great importance. A feedback form has also been made available for individuals who wish to communicate any comments, problems, requests or suggestions via e-mail. The documentation that follows is the methodology used in creating the Cary Collection\u27s web presentation

Cordarone

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which provides the chemical makeup, dosage, and the body\u27s response to Cordarone, or amiodarone hydrochloride, a medication used for the treatment of ventricular arrhythmias and supraventricular arrhythmias

Cyclosporin A Treatment Modulates Cytokine mRNA Expression by Inflammatory Cells Extracted from the Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis Induced by Inoculation with Myelin Basic Protein

In Lewis rats, treatment with high doses of cyclosporin A (CsA) suppresses clinical signs of experimental autoimmune encephalomyelitis (EAE), although disease occurs when treatment is ceased. Treatment with low doses of CsA causes EAE to take a chronic relapsing course. We have previously shown that CsA treatment causes a decline in the number of T cells and increased inflammatory cell apoptosis in the spinal cord. The present study was undertaken to assess whether CsA therapy also modulates cytokine mRNA expression by inflammatory cells in the spinal cord of rats with EAE, looking for changes that might contribute to the observed effects of CsA on the course of EAE. EAE was induced in Lewis rats by inoculation with myelin basic protein and adjuvants. At the peak of neurological signs, on day 14 after inoculation, rats were given a single intraperitoneal injection of saline, or CsA at a dose of 8, 16, 32 or 64 mg/kg. The next day, rats were sacrificed, the spinal cords removed, inflammatory cells were extracted from the cords, and mRNA isolated from these cells. Expression of cytokine mRNA was assessed by semi-quantitative reverse transcription polymerase chain reaction (PCR) and by quantitative real-time PCR. With both techniques, we found that CsA suppressed the expression of interferon-gamma mRNA and interleukin-2 (IL-2) mRNA. With real-time PCR, we found that CsA caused significantly increased expression of transforming growth factor-beta mRNA. With the different techniques, we observed no consistent pattern of alteration of expression of interleukin-10 or interleukin-4 mRNA. It is possible that these changes in cytokine mRNA expression contribute to the modulation of the clinical course of EAE that is produced by CsA treatment

The Role of Immune and Inflammatory Mechanisms in ALS

Amyotrophic lateral sclerosis (ALS) is a severe progressive neurodegenerative disease. The cause is unknown, but genetic abnormalities have been identified in subjects with familial ALS and also in subjects with sporadic ALS. Environmental factors such as occupational exposure have been shown to be risk factors for the development of ALS. Patients differ in their clinical features and differ in the clinical course of disease. Immune abnormalities have been found in the central nervous system by pathological studies and also in the blood and CSF of subjects with ALS. Inflammation and immune abnormalities are also found in animals with a model of ALS due to mutations in the SOD1 gene. Previously it has been considered that immune abnormalities might contribute to the pathogenesis of disease. However more recently it has become apparent that an immune response can occur as a response to damage to the nervous system and this can be protective