196,056 research outputs found
Alzheimer's disease mutations and cellular signalling
No full textAlzheimer's disease is the most frequent cause of dementia in elderly and is characterised neuropathologically by the extracellular deposition of amyloid plaques (containing the 39-43 amino acid Abeta peptide), as well as intracellular neurofibrillary tangles (NFTs) composed primarily of an abnormally hyperphosphorylated form of the microtubule-associated protein tau. A proportion (10- 15%) of Alzheimer's disease cases is familial, the remainder being sporadic. Familial Alzheimer's disease is genetically heterogeneous and can be caused by defects in at least three early- onset genes located on chromosomes 21 (amyloid precursor protein, APP), 14 (presenilin 1, PS 1) and 1 (presenilin 2, PS2).Increased production of Abeta is a common pathogenic phenotype in familial Alzheimer's disease due to APP and PS mutations. The major aim of this thesis was to determine whether the phenotypes of Alzheimer's disease causing APP and PSI mutations also include altered signalling. For this we used peripheral skin fibroblasts from sporadic as well as from familial Alzheimer's disease cases with the Swedish APP KM670/67 1 NI, mutation or different PSI mutations.Experiments were also performed on SH-SY5Y neuroblastoma cells transfected with wild-type and mutated forms of PSI. We studied signalling pathways known to be disrupted in sporadic Alzheimer's disease and thought to be implicated in either Abeta production, tau hyperphosphorylation, intracellular calcium homeostasis or apoptosis.The results obtained provide supportive evidence that an altered signalling occurs in Alzheimer's disease, but those groups with different disease origins (sporadic or familial) are affected in different ways. Mutations in different genes (APP vs PSI) differentially affect cellular signalling. The clearest finding was that the Swedish APP KM670/67INL mutation does not change any of the signal transduction parameters studied (beta-adrenoceptor-stimulated adenylyl cyclase, PKC activity, bradykinin-stimulated calcium release), the exception being a reduced bombesin-induced calcium release. The only abnormality previously reported in fibroblasts with this mutation is that of an increased secretion of Abeta. This effect appears to be relatively clean and is the most likely explanation for disease pathology in this family.The PSI mutations studied in primary skin fibroblasts gave alterations in a number of signalling parameters. These included an increased beta-adrenoceptor-stimulated adenylyl cyclase activity (as compared to a decrease seen in sporadic Alzheimer's disease fibroblasts), as well as a decreased PKC-mediated APPs secretion.We also conclude that the reported increased susceptibility of PSI mutation transfected SH-SY5Y neuroblastoma cells to undergo apoptosis after serum deprivation and high glucose stress, is unlikely due to a downregulation of Akt. Finally, the regulation of GSK-3 beta in response to the pro-apoptotic stimuli of either serum deprivation, P13 kinase inhibition or staurosporine treatment did not differ in PSI wild-type and mutation transfected SH-SY5Y cells.List of scientific papersI. Vestling M, Adem A, Racchi M, Gibson GE, Lannfelt L, Cowburn RF (1997). "Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimers disease cases with PS1 and APP mutations. " Neuroreport 8(8): 2031-5 https://pubmed.ncbi.nlm.nih.gov/9223097II. Gibson GE, Vestling M, Zhang H, Szolosi S, Alkon D, Lannfelt L, Gandy S, Cowburn RF (1997). "Abnormalities in Alzheimers disease fibroblasts bearing the APP670/671 mutation. " Neurobiol Aging 18(6): 573-80 https://pubmed.ncbi.nlm.nih.gov/9461055III. Vestling M, Cedazo-Minguez A, Adem A, Wiehager B, Racchi M, Lannfelt L, Cowburn RF (1999). "Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimers disease cases" Biochim Biophys Acta 1453(3): 341-50 https://pubmed.ncbi.nlm.nih.gov/10101252IV. Vestling M, Wiehager B, Tanii H, Cowburn RF (2001). "Akt activity in prsenilin 1 wild-type and mutation transfected human SHSY5Y neuroblastoma cells after serum deprivation and high glucose stress." J Neurosci Res 66: 448-456V. Vestling M, Lovestone S, Cowburn CF (2001). "Presenilin 1 regulation of glycogen synthase kinase-3beta." (Manuscript)</p
Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimer's disease cases with PS1 and APP mutations.
No full textbeta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were determined in primary skin fibroblasts established from patients with sporadic Alzheimer's disease (AD) and from individuals with familial APP KM670/671NL, PS1 M146V and PS1 H163Y mutations. Our data showed a significantly decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in fibroblasts from sporadic AD compared with age-matched controls (p < 0.001, Student's unpaired t-test). In contrast, both beta-adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were significantly increased in fibroblasts bearing PS1 M146V and PS1 H163Y mutations compared with controls (p < 0.01 and p < 0.05, respectively). No differences were seen between cell lines with and without the Swedish APP KM670/671NL double mutation. We suggest that various gene mutations associated with AD have different consequences for the regulation of adenylyl cyclase signal transduction in this disorder
Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimer's disease cases.
No full textDr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
Intern experience at CH���M Hill, Inc.: an internship report
No full textIncludes author's vita"Submitted to the College of Engineering of Texas A&M University in partial
fulfillment of the requirement for the degree of Doctor of Engineering."Includes bibliographical referencesA review of the author's internship experience with CH���M HILL, Inc.
during the period September 1975 through May 1976 is presented. During this nine month
internship the author worked as an Engineer II in the Industrial Processes discipline of this
large consulting engineering firm... The author's prime responsibility was as one of three
lead design engineers on the design of a large wastewater treatment facility for a pulp mill
in Hoquiam, Washington owned by ITT Rayonier Inc. The work generally consisted of the design
of individual treatment units and associated piping and pumping. The purpose of the project
was to provide wastewater treatment capabilities that would satisfy the effluent limitations
(standards) imposed upon the mill by the State of Washington Department of Ecology and the
U.S. Environmental Protection Agency. The author's assignment also entailed necessary
interaction with the project manager and other CH���M HILL design engineers and support staff
members, the client's representatives, and representatives of two other consulting engineering
firms working on the project. Thus, the internship position at CH���M HILL provided considerable
experience coordinating the author's work with the work of other engineers, guiding the design
and administrative efforts of a support staff, and interacting regularly with the client and
other consulting firms. This broad exposure to a variety of engineering and organizational
problems provided a valuable educational experience
Transition to turbulence in a qblique shock-wave/boundary-layer interaction at M=15
No full textDirect numerical simulations are carried out for different forcing techniques to trigger transition during the interaction between an oblique shock-wave and a laminar boundary-layer at M = 1.5. Three forcing methods are used: a) forcing of oblique unstable modes, whose shape and behaviour are determined by the local linear stability theory, b) broadband free-stream acoustic disturbances, and c) a cold plasma flow control device. While the oblique-mode breakdown is dominant for low-amplitude forcing, long streaky structures drive the transition process in a high-amplitude disturbance environment. LES are also performed on the experimental setup by the Institute of Theoretical and Applied Mechanics (ITAM) from Novosibirsk State University with cold plasma actuation. As well as the disturbance type, the effect of Reynolds number and forcing amplitude will be investigated
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