196,072 research outputs found
The cell biology of mitochondrial membrane dynamics
No full textOwing to their ability to efficiently generate ATP required to sustain normal cell function, mitochondria are often considered the ‘powerhouses of the cell’. However, our understanding of the role of mitochondria in cell biology recently expanded when we recognized that they are key platforms for a plethora of cell signalling cascades. This functional versatility is tightly coupled to constant reshaping of the cellular mitochondrial network in a series of processes, collectively referred to as mitochondrial membrane dynamics and involving organelle fusion and fission (division) as well as ultrastructural remodelling of the membrane. Accordingly, mitochondrial dynamics influence and often orchestrate not only metabolism but also complex cell signalling events, such as those involved in regulating cell pluripotency, division, differentiation, senescence and death. Reciprocally, mitochondrial membrane dynamics are extensively regulated by post-translational modifications of its machinery and by the formation of membrane contact sites between mitochondria and other organelles, both of which have the capacity to integrate inputs from various pathways. Here, we discuss mitochondrial membrane dynamics and their regulation and describe how bioenergetics and cellular signalling are linked to these dynamic changes of mitochondrial morphology
Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity
No full textAlthough expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma
Dr. 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
AIDS and endemic Kaposi's sarcoma development : comparison by histopathology, virology (HHV8/KSHV) and cytogenetics
No full textKaposi’s sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion with spindle cells (SC) affecting the skin, lymphnodes and viscera which is found in four different clinico-epidemiological forms as Classic KS (CKS), Iatrogenic KS (IKS), Endemic KS (EKS) and AIDS-associated KS (AKS). All KS forms develop from early stages of patch/plaque to late, nodular tumors and are associated with Kaposi's sarcomaassociated herpesvirus or human herpesvirus-8 (KSHV/ HHV-8). HHV-8 is also associated with primary effusion lymphoma (PEL) and multicentric castleman's disease (MCD). Various studies favour an endothelial origin (CD34+) of the KS SC but whether of vascular (VEC) or lymphatic endothelial cell (LEC) origin has not been settled. The HHV-8 latency-associated nuclear antigen type 1 (LANA-1) protein is the most frequently expressed viral antigen in infected cells. KS is promoted by HIV infection mainly by the angiogenic and proinflammatory effects of HIV-Tat. Whether KS represents a predominantly monoclonal neoplastic cell proliferation or a hyperplastic, reactive polyclonal process is still controversial. Reports on cytogenetic and molecular genetic changes in KS are few indicating that initially KS may develop as a reactive polyclonal cell proliferation associated with chromosome instability, followed by clonal chromosome changes in later stages.In the present KS histopathological studies (paper I & V) by triple antibody immunofluorescence we observed that: (a) the frequency of LANA+/CD34+ cells increased from early patch to late KS nodular lesions; (b) 30- 40% of the CD34+ SC were LANA- in both early and late KS, suggesting a continuous recruitment of noninfected endothelial cell into the KS lesion; (c) LANA+/CD34- cells were more frequent in early as compared to late KS and most of them expressed LEC markers such as LYVE-1 and D2-40, suggesting that the resident LECs represent an early target of primary HHV-8 infection; (d) LANA+/CD34-/LYVE-1+ cells decreased from early (25%) to late (4%) KS suggesting a phenotype switch from LEC to VEC; (e) the frequency of proliferating cells (Ki67+) was higher in early as compared to late KS stages and no significant difference in cell proliferation was observed between nodular AKS and EKS, suggesting that the growth of the usually more aggressive AKS tumors may reflect a higher rate of SC progenitor recruitment as compared to the slower growing EKS lesions, consistent with the observed increase in non-proliferative SC during KS (AKS) evolution to nodular stage; (f) infiltrating lymphocytes were LANA negative, whereas some CD68+ monocyte-macrophase appeared to be LANA+.To validate our results from LANA immunostaining, we established and optimized a semi-quantitative PCR assay for HHV-8 detection in formalin-fixed paraffin-embedded KS biopsies (paper III) and two different protocols for DNA extraction were compared namely the Chelex 100 and Qia-gene kit method. Our result indicate a better performance for Chelex-extracted DNA in paraffin embedded archival biopsies. In late, nodular stage of both AKS and EKS the virus load per unit tissue actin (HHV-8/actin) is higher than in early stages (patch/plaque), which corroborates our findings from double immunostaining for LANA and CD34 of the same cases. Thus these PCR results by serial dilutions of HHV-8 DNA show a correlation between virus load and progressive stages of KS development i.e. the increase in LANA+ SC and does not indicate an increase in viral content of individual tumor cells.With quantitative real time PCR on sera (paper II), we found higher HHV8 DNA load in AKS compared to EKS, patch compared to nodular KS and males compared to females as well as a significantly higher serum viral DNA load in KS compared to non-KS patients’ sera.AKS patient sera studied by ELISA for HIV-Tat antibodies showed that patients with high HHV8-DNA level had no or low levels of anti-Tat antibodies while patients with very low HHV8-DNA levels had several fold higher anti-Tat IgG titers. Analysis of these KS sera for epitope specificity showed reactivity to various Tat epitopes but not to the transcriptional (functional) epitopes 46-60 (TAR-binding region). To determine cytogenetic changes during the development of KS as well as possible differences between AKS and EKS we studied 27 KS (10 nodular AKS, 8 patch AKS, 8 nodular EKS and 1 patch EKS) cases by laser microdissection, global amplification of DNA and comparative genomic hybridization (paper IV). Deletion of Chromosome Y was detected in 20 of 23 male KS and was the only chromosomal deletion observed in early (patch) KS biopsies. Late AKS and EKS apart from random aberrations also showed recurrent chromosomal deletions of chromosome 16, 17, Y and a gain of chromosome 21. The deletion of chromosome 16 and Y was confirmed by interphase FISH on paraffin embedded sections. EKS had higher number of chromosomal abnormalities than AKS.In summary KS SC apparently represents a mixed pool endothelial cells including cells from both VEC and LEC the later being a possible early target for HHV-8 infection. Non-infected CD34+ progenitor cells appears to be continuously recruited to the developing KS lesion and locally infected during the development of KS. Serum HHV-8 DNA load is higher in AKS compared to EKS and HIV-Tat titers were inversely correlated to HHV-8 DNA load in AKS patients. Increased number of recurrent and sporadic chromosomal abnormalities found mostly in a subset of late nodular KS cases may indicate the onset of a clonal cell population (sarcoma).List of scientific papersI. Pyakurel P, Massambu C, Castanos-Velez E, Ericsson S, Kaaya E, Biberfeld P, Heiden T (2004). Human herpesvirus 8/Kaposi sarcoma herpesvirus cell association during evolution of Kaposi sarcoma. J Acquir Immune Defic Syndr. 36(2): 678-83. https://doi.org/10.1097/00126334-200406010-00004 II. Massambu C, Pyakurel P, Kaaya E, Enbom M, Urassa W, Demirhan I, Loewer J, Linde A, Chandra A, Heiden T, Doerr HW, Chandra P, Biberfeld P (2003). Serum HHV8 DNA and Tat antibodies in Kaposis sarcoma patients with and without HIV-1 infection. Anticancer Res. 23(3B): 2389-95. https://pubmed.ncbi.nlm.nih.gov/12894519 III. Pak F, Pyakural P, Kokhaei P, Kaaya E, Akbar Pourfathollah A, Selinova G, Biberfeld P (2005). HHV-8/KSHV during development of Kaposis sarcoma: evaluation by PCR and immunohistochemistry. J Cutan Pathol. 32(1): 21-7. https://doi.org/10.1111/j.0303-6987.2005.00256.x IV. Pyakurel P, Montag U, Castanos-Velez E, Kaaya E, Christensson B, Biberfeld P, Schrock E, Heiden T (2005). Kaposis sarcoma: CGH ctogenetic analysis of microdissected early and late stage biopsies. [Manuscript]V. Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Heiden T, Biberfeld P (2005). Recruitment of Kaposis sarcoma spindle cells during tumor development. [Manuscript]</p
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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