117,408 research outputs found
SNP based strategies to study candidate genes for Alzheimer’s disease
No full textAlzheimer’s disease (AD) is the most common form of dementia in the elderly. It is a genetically heterogeneous disease characterized by progressive cognitive decline and memory impairment. The rare familial form of AD is caused by three different genes called APP, PSEN1 and PSEN2. However, the predominant form of AD is a genetically complex disorder involving a combination of genetic factors. To date, the only risk factor identified for the complex form of AD is the APOE-epsilon 4 allele, but several susceptibility genes remain to be found.This thesis outlines different strategies to use common genetic variation, in the form of single nucleotide polymorphisms (SNPs), to examine candidate genes and candidate regions for AD. Large-scale genotyping is a prerequisite for performing complex disease studies using SNPs. The validity and accuracy of a newly developed genotyping assay called Dynamic allele specific hybridization (DASH) was therefore investigated. DASH was shown to be a robust genotyping method, and was proven to work as well or better than several other available methods. 'the method was first implemented for a candidate gene association study of a promoter polymorphism in the TNFRSF6 gene. Significant association was found between this variant and early onset AD, indicating its possible role in disease etiology.A large candidate pathway association study effort was then started testing for association between AD and 60 different SNPs. Genes were picked from four different pathways related to AD; oxidation, inflammation/apoptosis, amyloid interacting genes and a group of candidate genes previously showing significant association with AD. None of the markers showed significant disease association after correction for multiple testing. Although largely negative, these results high-lighted several methodological and study design issues related to association studies in general.The most successful approach yet in dissecting complex disease using genetic variation has been to perform high resolution linkage disequilibrium (LD) mapping of regions indicated by linkage. Several independent research groups recently reported linkage peaks for AD on chromosome 10q We choose two regions under the 10q linkage peak for LD mapping studies. The first region contained the previously associated TNFRSF6 gene, and the other region included the insulin-degrading enzyme (IDE) gene, which has been shown to be involved in clearance of amyloid-beta. LD maps were created for all pair-wise markers in the two regions to determine the genetic LD structure. Haplotypes were estimated and haplotype tagging markers were chosen for further analysis.Association analyses were performed for both single markers and haplotypes for case/control status as well as for quantitative traits related to the AD phenotype. Only weak significant signals were found for the TNFRSF6 gene. However, several significant associations were found for a large LD block including the IDE gene. The same haplotypes were always over-represented in cases compared to controls, or with more severe AD within the patient groups. These results indicate a role in AD for one of the three genes situated within the 276kb LD block including the IDE, KNSLI and HHEX genes. Further studies will now be required to identify the underlying risk alleles within the region.List of scientific papersI. Feuk L, Prince JA, Breen G, Emahazion T, Carothers A, St Clair D, Brookes AJ (2000). Apolipoprotein-E dependent role for the FAS receptor in early onset Alzheimers disease: finding of a positive association for a polymorphism in the TNFRSF6 gene. Hum Genet. 107(4): 391-6. https://pubmed.ncbi.nlm.nih.gov/11129341II. Prince JA, Feuk L, Howell WM, Jobs M, Emahazion T, Blennow K, Brookes AJ (2001). Robust and accurate single nucleotide polymorphism genotyping by dynamic allele-specific hybridization (DASH): design criteria and assay validation. Genome Res. 11(1): 152-62. https://pubmed.ncbi.nlm.nih.gov/11156624III. Emahazion T, Feuk L, Jobs M, Sawyer SL, Fredman D, St Clair D, Prince JA, Brookes AJ (2001). SNP association studies in Alzheimers disease highlight problems for complex disease analysis. Trends Genet. 17(7): 407-13. https://pubmed.ncbi.nlm.nih.gov/11418222IV. Feuk L, Prince JA, Blennow K, Brookes AJ (2002). Further evidence for role of a promoter variant in the TNFRSF6 gene in Alzheimers disease. Hum Mut.V. Prince JA, Feuk L, Gu HF, Gatz M, Blennow K, Brookes AJ (2002). Genetic variation in a haplotype block spanning IDE, KNSL1 and HHEX influences Alzheimers disease. [Manuscript]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
No full textIn this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Letter from unknown writer to Jesse L. Boyce
No full textLetter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County
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
Sarah L. Blum Author Visit - Warrior Nurse: PTSD and Healing
No full textHear Sarah L. Blum, author of Women Under Fire: Abuse in the Military, discuss her newest book, Warrior Nurse: PTSD and Healing followed by a Q&A and book signing.
Sarah L. Blum is a decorated Vietnam veteran who served as an operating room nurse during the intense fighting of 1967. In recognition of her service, she was awarded the Army Commendation Medal.
Sponsored by CWU Veterans Center and CWU Libraries.https://digitalcommons.cwu.edu/libraryevents/1252/thumbnail.jp
Lillian L. Lambert, Author, Speaker, and Entrepreneur
No full textLillian L. Lambert, Author, Speaker, and Entrepreneu
Letter to Alfred L. Shoemaker, February 10, 1948
No full textA handwritten letter from an unknown author addressed to Alfred L. Shoemaker, dated February 10, 1948. Within, the author discusses the Pennsylvania Dutch word for Ash Wednesday, along with traditions associated with this day.https://digitalcommons.ursinus.edu/shoemaker_documents/1118/thumbnail.jp
Array-based approaches in prenatal diagnosis
No full textThe diagnostic benefits of array comparative genomic hybridisation (CGH) have been demonstrated, with this technique now being applied as the first-line test for patients with intellectual disabilities and/or multiple congenital anomalies in numerous laboratories. There are no technical barriers preventing the introduction of array CGH to prenatal diagnosis. The question is rather how this is best implemented, and for whom. The challenges lie in the interpretation of copy number variations, particularly those which exhibit reduced penetrance or variable expression, and how to deal with incidental findings, which are not related to the observed foetal anomalies, or unclassified variants which are currently of uncertain clinical significance. Recently, applications of array technologies to the field of pre-implantation genetic diagnosis have also been demonstrated. It is important to address the ethical questions raised concerning the genome-wide analysis of prenatal samples to ensure the maximum benefit for patients. We provide an overview of the recent developments on the use of array CGH in the prenatal setting, and address the challenges posed.status: Publishe
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