1,986 research outputs found
The role of genetics and epigenetics in the pathogenesis of systemic sclerosis
No full textSystemic sclerosis (SSc) is a complex autoimmune disease of unclear aetiology. A multitude of genetic studies, ranging from candidate-gene studies to genome-wide association studies, have identified a large number of genetic susceptibility factors for SSc and its clinical phenotypes, but the contribution of these factors to disease susceptibility is only modest. However, in an endeavour to explore how the environment might affect genetic susceptibility, epigenetic research into SSc is rapidly expanding. Orchestrated by environmental factors, epigenetic modifications can drive genetically predisposed individuals to develop autoimmunity, and are thought to represent the crossroads between the environment and genetics in SSc. Therefore, in addition to providing a comprehensive description of the current understanding of genetic susceptibility underlying SSc, this Review describes the involvement of epigenetic phenomena, including DNA methylation patterns, histone modifications and microRNAs, in SSc
Earliest Phase of Systemic Sclerosis Typified by Increased Levels of Inflammatory Proteins in the Serum
No full textOBJECTIVE: Patients with definite systemic sclerosis (SSc) who lack fibrotic features can be stratified into an intermediate stage of disease severity between preclinical/early SSc (EaSSc) and fibrotic subsets (limited cutaneous SSc [lcSSc] and diffuse cutaneous SSc [dcSSc]). The aim of the present study was to molecularly characterize nonfibrotic SSc and EaSSc on the basis of a broad panel of serum markers of inflammation and tissue damage, in order to increase the knowledge of the pathophysiologic mechanisms underlying SSc progression before the development of fibrosis. METHODS: An 88-plex immunoassay was performed in serum samples from a discovery cohort composed of 21 patients with EaSSc (meeting the LeRoy and Medsger criteria), 15 with nonfibrotic SSc (meeting the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria, without skin or lung fibrosis), and 11 healthy controls. Analyte concentrations that were consistently significantly different at the exploratory P value threshold of 0.1 were selected for replication analysis in a larger group composed of 47 patients with EaSSc, 48 with nonfibrotic SSc, and 43 healthy controls, as well as 51 patients with lcSSc and 35 with dcSSc. The value of the replicated molecules in predicting SSc progression (at a family-wise error rate of 0.05) was tested. RESULTS: Based on the results of the explorative analysis, 16 molecules were selected for testing in the replication set. The results showed that CXCL10, CXCL11, tumor necrosis factor receptor type II (TNFRII), and chitinase 3-like protein 1 levels were significantly increased in patients with EaSSc and those with nonfibrotic SSc as compared to healthy controls. The disease in patients with high concentrations of CXCL10 and TNFRII was also characterized by a faster rate of progression from EaSSc and from nonfibrotic SSc to worse disease stages. CONCLUSION: SSc patients with preclinical/early SSc and those with established, yet nonfibrotic, disease exhibit clear molecular alterations that are associated with faster rates of disease evolution. These data open novel avenues for disease interception in SSc
Our Savior and King: Theology proper in 1 Timothy
No full textIn this dissertation the author seeks to present a holistic theology proper (hereafter, simply "theology") for the first epistle to Timothy, with special regard to the letter's doxologies (King) and divine title, Savior. Chapter 1 identifies the problem, includes a history of research, and describes the method and procedure of the dissertation. The method of inquiry consists of determining the meaning and function of the letter's theology. Thus, the author seeks to understand the background and character of 1 Timothy's theology, while also wishing to discern why the author of 1 Timothy chose to emphasize these peculiar theological themes.
Chapter 2 explores the meaning and function of the theological descriptions found in the doxologies of 1 Timothy 1:17 and 6:15-16. By thorough comparison to Greco-Roman, early Jewish, and OT literature, the author suggests a basically OT-informed view of God. The doxologies depict God as the only Sovereign who rules over all. The writer then determines that the doxologies function as a support and encouragement for Timothy to heed Paul's charge. This conclusion is largely based on the positioning of the doxologies and the macrostructure of the letter.
Chapter 3 examines the meaning and function of the divine epithet Savior. After comparing this term to its occurrences in Greco-Roman, early Jewish, and OT literature, the author again favors an OT background for Savior. This term depicts God as one who mercifully and indiscriminately reconciles sinners who trust in Christ. While also recognizing other functions, the author suggests that God as Savior may have been aimed at the primary implied reader, Timothy, as well. Accordingly, the idea of Savior informs and strengthens Timothy, so that he might continue to labor in presenting the life-giving gospel of God.
Chapter 4 considers every remaining theological description in 1 Timothy, as well as themes that significantly relate to the letter's theology, such as Christology. The author suggests that the entire theology of 1 Timothy either coheres with or supports the predominant ideas of God as King and Savior.
Chapter 5 summarizes the dissertation's findings and concludes with suggested implications for NT studies
A web-based screening tool for near-port air quality assessments
No full textAuthor(s): Isakov, Vlad; Barzyk, Timothy M; Smith, Elizabeth R; Arunachalam, Saravanan; Naess, Brian; Venkatram, Akul
Roma, magistra mundi. Itineraria culturae medievalis. Mélanges offerts au Père L.E. Boyle à l\u27occasion de son 75e anniversaire
No full textR. James Long (with Timothy B. Noone) is a contributing author, Fishacre and Rufus on the Metaphysics of Light: Two Unedited Texts , Volume 2, pp. 517-548
Reading Barcodes from Digital Imagery
No full textThis document was prepared for Dr. John Loomis as part of the written PhD. candidacy exam by Timothy R. Tuinstra. This report provides a look at the automatic detection and decoding of barcodes found within imagery. Such techniques could conceivably be used in the retail, manufacturing, inventory and travel industries as well as others. A general description of barcodes is included as well as a review of some of the techniques used to automatically locate barcodes within larger images containing additional objects. The author will also present some results from implementing a variant of these techniques. I
Clarinet quintet in A major, K. 581 ; Horn quintet in E-flat major, K. 407 ; Divertimento in D major, K. 251
No full textMore Author/Title Info: Mozart, Wolfgang Amadeus
Physical Description: 1 audio disc : digital ; 4 3/4 in.
Performers: Stanley Drucker, clarinet (1st work) ; Joseph Robinson, oboe (3rd work) ; L. William Kuyper (2nd & 3rd works), R. Allen Spanjer (3rd work), horns ; Timothy Cobb, double bass (3rd work) ; Elysium String quartet (Jennifer Tiboris, Gary Levinson, violins ; Veronica R. Salas, viola ; Lutz Rath, violoncello).
Event Details: Recorded at the American Academy of Arts and Letters, New York City, Sept. 21, Dec. 2 and 6, 1998
AN INVESTIGATION OF DIFFERENTIAL REINFORCEMENT OF ALTERNATIVE BEHAVIOR WITHOUT EXTINCTION
No full textWe manipulated relative reinforcement for problem behavior and appropriate behavior using differential reinforcement of alternative behavior (DRA) without an extinction component. Seven children with developmental disabilities participated. We manipulated duration (Experiment 1), quality (Experiment 2), delay (Experiment 3), or a combination of each (Experiment 4), such that reinforcement favored appropriate behavior rather than problem behavior even though problem behavior still produced reinforcement. Results of Experiments 1 to 3 showed that behavior was often sensitive to manipulations of duration, quality, and delay in isolation, but the largest and most consistent behavior change was observed when several dimensions of reinforcement were combined to favor appropriate behavior (Experiment 4). Results suggest strategies for reducing problem behavior and increasing appropriate behavior without extinction.Peer reviewedFinal article publishedAttention deficit hyperactivity disorderAutismConcurrent schedulesDifferential reinforcementExtinctionProblem behavio
Evaluating Research Impact through Open Access to Scholarly Communication
No full textScientific research is a competitive business – in order to secure funding, promotion and tenure researchers must demonstrate their work has impact in their field. To maximise impact researchers undertake high priority research, aim to get results first, and publish in the highest impact journals. The Internet now presents a new opportunity to the scholarly author seeking higher impact: s/he can now make their work instantly accessible on the Web through author self-archiving. This growing body of open access literature (coupled with new publishing models that make journals available for-free to the reader) maximises research impact by maximising the number of people who can read it, and making it available sooner. Open access also provides a new opportunity for bibliometric research. This thesis describes the relatively recent phenomenon of open access to research literature, tools that were built to collect and analyse that literature, and the results of analyses of the effect of open access and its effect on author behaviour. It shows that articles self-archived by authors receive between 50-250% more citations, that rapid pre-printing on the Web has dramatically reduced the peak citation rate from over a year to virtually instant and how citation-impact – now widely used for evaluation – can be expanded to include a new web metric of download impact
Damage detection using frequency domain ARX models and extreme value statistics
No full textThe author acknowledges Tim Johnson and Seth Gregg
and the Los Alamos Dynamic Summer School for providing
the test structure as well as helping with the set-up,
instrumentation and acquisition of data from the test
structure. Funding for the summer school was provided by
the Engineering Sciences and Application Division at Los
Alamos National Laboratory and the Department of
Energy’s Education Program Office
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