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Tesi sul tema "Internal words"

Autore: Grafiati

Pubblicato: 4 giugno 2021

Ultima modifica: 18 febbraio 2022

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1

Jones, D. "Ending the debate: unconventional warfare, foreign internal defense, and why words matter /". Fort Leavenworth, KS : School of Advanced Military Studies, US Army Command and General Staff College, 2006. http://cgsc.cdmhost.com/u?/p4013coll2,554.

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2

Ayan, Duygu. "Effects Of Internal, External And Preference Of Attentional Focus Feedback On Learning Volleyball". Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12608959/index.pdf.

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The purpose of this study was to examine the effects of internal and external focus feedback and their preference on skill learning at age of 12-13 years. Internal focus feedback related with body movements, whereas external focus feedbacks related with movement effects. As a task &ldquo
tennis&rdquo
service in volleyball was used for both acquisition and retention measurements. The subjects (N=78) were randomly assigned to three groups which were internal focus feedback group (IFF), external focus feedback group (EFF) and preference groups (PF). To promote learning three practice days and to assess learning one retention day was applied. Also, during these days, both technique of the skill and targeting was tried to measure. In technique measure the IFF group performed better than EFF group in acquisition and retention phases. PF group had similar scores with IFF group in acquisition phase whereas it did not show better performance than IFF group in retention phase. PF group performed better than EFF group in both phases. In product measure, significant differences between attentional focus feedback groups in acquisition and retention phases. This study indicated that for young children with limited amount of knowledge about a skill internal focus feedback is more appropriate compared to external focus feedback in terms of retention. Being able to choose among internal and external focus of attention also seems to make a difference in retention performance of novice children indicating that active participation on the learning variables is an important concept.

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3

Gilhar, Lihie. "A comparative exploration of the internal object relations world of anorexic and bulimic patients". Diss., Pretoria : [s.n.], 2008. http://upetd.up.ac.za/thesis/available/etd-08152008-132051.

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4

Tozkar, Ozge Cansu. "Comparative Sequence Analysis Of The Internal Transcribed Spacer 2 Region Of Turkish Red Pine (pinus Brutia Ten.) And Natural Aleppo Pine (pinus Halepensis Mill.) Populations From Turkey". Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12608313/index.pdf.

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ABSTRACT COMPARATIVE SEQUENCE ANALYSIS OF THE INTERNAL TRANSCRIBED SPACER 2 REGION OF TURKISH RED PINE (Pinus brutia TEN.) AND NATURAL ALEPPO PINE (Pinus halepensis MILL.) POPULATIONS FROM TURKEY Tozkar, Ö
zge M.S., Department of Biology Supervisor: Prof. Dr. Zeki Kaya April, 2007, 107 pages Turkish red pine (Pinus brutia) is wide-spread and an important forest tree species in Turkey, occurring mainly in southern, western and north-western Turkey and as small isolated populations in the Black Sea region. Aleppo pine (Pinus halepensis) has naturally found only in Adana and Mugla provinces as small population in mixture with Turkish red pine. Although Turkish red pine and Aleppo pine are morphologically different, Turkish red pine has been regarded as subspecies of Aleppo pine by some taxonomists due to occurrence of natural hybridization between these two species. However, the phylogenic relationship between these species needs to be explored further. In the present study, by sampling overlapped populations of both species from Mugla and Adana provinces (4 populations of Turkish red pine and 3 populations of Aleppo pine), internal transcribed spacer (ITS) region of ribosomal DNA were comparatively studied with sequence analysis. Although ITS1, 5.8s and ITS2 regions of ribosomal DNA were studied with ITS primers, only ITS2 region was successfully amplified with polymerase chain reaction (PCR). The complete data set for this region was analysed using MEGA3.1 and Arlequin softwares. Analysis of molecular variance (AMOVA) demonstrated the highest genetic differentiation between Turkish red pine and Aleppo pine in Mugla with 100 percentage of variation. AMOVA analysis also indicated the possibility of low-level migration of genes between Turkish red pine and Aleppo pine populations in Adana with 50.65 percent of molecular variance. Haplotype comparison revealed that two major haplotypes were represented Based on the results of ITS2 region sequence analysis, Turkish populations of Aleppo pine and Turkish red pine populations could not be fully differentiated. In Mugla province Turkish red pine and Aleppo pine revealed more differentiation due to reproductive isolation. But in Adana province, two species shared more common genetic background due to possible hybridization. Since ITS2 region of nuclear ribosomal DNA revealed a few variable and parsimony informative sites for both species, thus, only ITS2 region of ribosomal DNA does not appear to be sufficient for fully resolving genetic relationships between Turkish red pine and Aleppo pine populations. Further studies including ITS1 and 5.8s regions of ribosomal DNA and populations included from major Aleppo pine distribution areas will be useful to understand the evolutionary relationship between Aleppo pine and Turkish red pine populations in Turkey.

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5

Disque, J. Graham. "Introduction to Internal Family Systems". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/2809.

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6

Echeverri, Mondragón Paula. "Internal tide generation by tall ocean ridges". Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/55255.

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Abstract (sommario):

Thesis (Ph. D.)--Joint Program in Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and the Woods Hole Oceanographic Institution), 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 169-174).
Internal tides are internal waves of tidal period generated by tidal currents flowing over submarine topography. Tall ridges that are nominally two-dimensional (2-D) are sites of particularly strong generation. The subsequent dissipation of internal tides contributes to ocean mixing, thereby playing an important role in the circulation of the ocean. Strong internal tides can also evolve into internal wave solitons, which affect acoustic communication, offshore structures and submarine navigation. This thesis addresses the generation of internal tides by tall submarine ridges using a combined analytical and experimental approach. The first part of the thesis is an experimental investigation of a pre-existing Green function formulation for internal tide generation by a tall symmetric ridge in a uniform density stratification. A modal decomposition technique was developed to characterize the structure of the experimental wave fields generated by 2D model topographies in a specially configured wave tank. The theory accurately predicts the low mode structure of internal tides, and reasonably predicts the conversion rate of internal tides in finite tidal excursion regimes, for which the emergence of non-linearities was notable in the laboratory. In the second part of the thesis, the Green function method is advanced for asymmetric and multiple ridges in weakly non-uniform stratifications akin to realistic ocean situations.
(cont.) A preliminary investigation in uniform stratification with canonical asymmetric and double ridges reveals asymmetry in the internal tide that can be very sensitive to the geometric configuration. This approach is then used with realistic topography and stratification data to predict the internal tide generated by the ridges at Hawaii and at the Luzon Strait. Despite the assumption of two-dimensionality, there is remarkably good agreement between field data, simulations and the new theory for the magnitude, asymmetry and modal content of the internal tide at these sites. The final part of the thesis investigates the possibility of internal wave attractors in the valley of double-ridge configurations. A one-dimensional map is developed to identify the existence and stability of attractors as a function of the ridge geometry. The Green function method is further advanced to include a viscous correction to balance energy focusing and dissipation along an attracting orbit of internal wave rays, and very good agreement is obtained between experiment and theory, even in the presence of an attractor.
by Paula Echeverri Mondragón.
Ph.D.

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7

Clamon, Travis. "Real-time Insight : Developing a Internal Library Data Dashboard". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/3957.

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Library systems are becoming increasingly open, providing API’s that can deliver data in real-time. ETSU Library staff wanted a way to collect metrics from various systems and present it in one centralized dashboard. This presentation will cover our experiences with the project, including successes, challenges, and future goals.

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8

Cooper, Katie. "Anorexia, self harm and depression : exploring internal worlds and underlying deficits". Thesis, City University London, 2011. http://openaccess.city.ac.uk/8731/.

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This thesis explores the meaning of food for individuals with anorexia. 9 female inpatients aged over 18 with a diagnosis of anorexia nervosa were interviewed. The participant interviews were analyzed qualitatively using Interpretative Phenomenological Analysis and four master themes were identified: Food as a container, food as a concrete representation of internal states and relationships, food as a separator and food as a control mechanism. Within this research these master themes were expounded upon and explained in relation to current theories and also in relation to two core concepts that also emerged from the research's findings: Loss of and broken sense of self and misattuned caregiving. In conclusion this study offers its readers a potential conceptual and theoretical model based around its findings of the meaning of food, for the explanation and development of anorexia. It is hoped that these findings will be useful in informing and developing clinical understandings of anorexia and new treatment approaches.

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9

Blumenthal, Martin Benno. "Interpretation of equatorial current meter data as internal waves". Thesis, Massachusetts Institute of Technology, 1987. http://hdl.handle.net/1721.1/51460.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric and Planetary Sciences, and Woods Hole Oceanographic Institution, 1987.
Bibliography: v. 2, leaves 376-381.
by Martin Benno Blumenthal.
Ph.D.

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10

Disque, J. Graham. "How to Use Internal Family Systems with In-Home Therapy". Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/2810.

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11

Köster, Dirk. "Morphology and spoken word comprehension : electrophysiological investigations of internal compound structure /". Leipzig ; München : MPI for Human Cognitive and Brain Sciences, 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=013183589&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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12

Tat, Deniz. "Word Syntax of Nominal Compounds: Internal and Aphasiological Evidence from Turkish". Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/311666.

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This dissertation is an analysis of two types of nominal compounds in Turkish, primary compounds and synthetic compounds within the framework of Distributed Morphology. A nominal primary compound is formed by two nouns, and its meaning is largely determined by world knowledge. A synthetic compound, on the other hand, is formed by a noun and a derverbal noun, such that the former is a true argument of the latter. The meaning of such compounds is always compositional. In many languages, the structural difference between these two types of compounds is not immediately observable. However, in Turkish, a primary compound would be obligatorily marked with the compound marker, -(s)I(n) while a synthetic compound would never be marked as such. In this dissertation, I claim that primary compounds in Turkish are underlyingly possessive phrases, a claim that has been previously made by several others. My analysis differs from those previous analyses in that it maintains that -(s)I(n) figures in a morphological component that follows syntax but precedes PF. Such a post-syntactic analysis has a number of advantages as it can account for a wide range of descriptive observations about the behavior of -(s)I(n). I claim that -(s)I(n) and an agreement marker never form a sequence at any stage in the grammar. I test this claim in an experiment conducted with Turkish-speaking individuals with aphasia, and show that only a vanishingly rare number of -(s)I(n)-agreement sequences are attested in aphasic speech. My analysis of synthetic compounds in Turkish is based on three types of nominalizers and the types of categories they can select. I show that only event-denoting nominals can form true synthetic compounds. I also show that nominals that are derived directly from roots can never form true synthetic compounds, which casts doubts on roots as projecting categories. I also consider a third group of seemingly synthetic compounds, which have an overt complex verbal stem, and yet, fail to derive true synthetic compounds. Following Marantz (2013), I claim that such pseudo-synthetic compounds, in fact, have semantically null verbalizing morphemes, and therefore, the root and the nominalizing head are semantically adjacent at LF.

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13

Wang, Ling, e Shunbin Ning. "Viral and Cellular MicroRNAs in Regulation of EBV Latency and Oncogenesis". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6543.

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Epstein-Barr virus (EBV), an oncogenic virus that ubiquitously establishes life-long persistence in humans, encodes viral miRNAs in two clusters, BHRF1 and BART. EBV also regulates expression of a large pool of cellular miRNAs, including miR-155, miR-146a, miR-21, miR-29, and miR-34a. These miRNAs targets both viral and cellular genes involved in the entire viral lifetime from lytic infection to oncogenesis, including viral replication, immune responses, cell cycle regulation, apoptosis, and cell proliferation, and are indispensable for persistent infection, latency establishment and maintenance, and cancer development. Among them, circulating miRNAs and unique miRNA profiles are promising diagnosis and prognosis biomarkers alone or with other traditional biomarkers. Elucidation of the precise mechanisms of action of these miRNAs in EBV latent infection will improve our knowlege of EBV persistence and oncogenesis, and may foster new strategies to target these miRNAs for treatments of EBV-associated cancers.

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14

Pringle, James M. "Cooling and internal waves on the Continental Shelf". Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/58861.

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Thesis (Ph. D.)--Joint Program in Physical Oceanography (Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences; and the Woods Hole Oceanographic Institution), 1998.
Includes bibliographical references.
by James Maxwell Pringle.
Ph.D.

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15

Ogden, Kelly Anne. "Internal hydraulic jumps with upstream shear". Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/109055.

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Thesis: Ph. D., Joint Program in Physical Oceanography (Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences; and the Woods Hole Oceanographic Institution), 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 233-237).
Internal hydraulic jumps in flows with upstream shear are investigated numerically and theoretically. The role of upstream shear has not previously been thoroughly investigated, although it is important in many oceanographic flows such as exchange flows and stratified flow over topography. Several two-layer shock joining theories, characterized by their distribution of dissipation in the jump, are considered and extended to include upstream shear, entrainment, and topography. Theoretical results are also compared to 2D and some 3D numerical simulations of the full Navier-Stokes equations, which allow continuous velocity and density distributions. The solution space of idealized jumps with small upstream shear is identified using two-layer theories, which shows that upstream shear allows larger jumps to form and allows jumps for a larger range of parameters. Numerical simulations reveal several jump structures that can occur in these flows, including an undular bore, a fully turbulent jump, and a smooth front turbulent jump. At low shear, the 2D mixing efficiency is constant across simulations. As shear increases, the basic two-layer theories no longer provide solutions. Numerical simulations show that entrainment becomes significant as the shear increases, and adding entrainment and shape parameters to describe the continuous velocity profiles is required to accurately describe the simulations using two-layered theory. The entrainment depends on the upstream shear and can be predicted with a modified theory. However, use of the theory is limited due to its sensitivity to the value of the shape parameters. The 2D mixing efficiency also decreases significantly as shear increases. Finally, more realistic 2D and some 3D simulations including topography bridge the gap between the highly idealized simulations and the very realistic work of others. Simulations with topography show additional jump types, including a higher mode jump with a wedge of homogeneous, stagnant fluid similar to a structure seen in Knight Inlet. In all cases, numerical simulations are used to identify trends in the mixing and jumps structures that can occur in internal hydraulic jumps.
by Kelly Anne Ogden.
Ph. D.

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16

Ning, Shunbin, e Ling Wang. "Identification of PP1 as the First Phosphatase for IRF7". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6527.

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17

Sole, C. J., Caleb D. Bazyler, Ashley A. Kavanaugh, Satoshi Mizuguchi e Michael H. Stone. "Relationship between Internal and External Estimates of Training Load Using Wearable Inertial Sensors". Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/3837.

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PURPOSE: The purpose of the study was to examine the relationship between an external estimate of training load obtained from a wearable accelerometer device and perceived training load in women’s volleyball. METHODS: Participants of this study were thirteen NCAA Division I women’s volleyball players (Age: 20.3±1.2 y, height: 174.9±7.9cm, body mass: 68.1±12.7 kg). A wearable accelerometer device (Catapult Sports, MiniMaxX S4) was used to estimate external training load during volleyball practice sessions. In addition, following each session a rating of perceived exertion was obtained from each player using a 0-10 scale. Based on previously established methods, ratings of perceived exertion were then multiplied by the duration of practice in minutes to provide an estimate of internal training load. A Pearson product-moment zero order correlation coefficient was used to assess the relationship between external and internal training load estimates for each individual over eight practices. RESULTS: On average a positive relationship (r = 0.75±0.15) was found between training load estimates. Individual r values ranged from 0.39 to 0.92, with eight of the thirteen achieving statistical significance (p<0.05). CONCLUSIONS: Based on the relationships found between internal and external estimates of training load, both methods may be considered as an option for quantifying on-court training loads in NCAA women’s volleyball. However, the degree to which these estimates relate may vary by individual.

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18

Ning, Shunbin. "Interferon Regulatory Factors and Autoimmune Diseases". Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/6542.

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19

Merriman, Carolyn S., K. Frith e M. J. Hamilton. "Use of Computerized Testing for External and Internal Curriculum Evaluation in Undergraduate Nursing Programs". Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/8445.

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20

Wang, Ling, e Shunbin Ning. ""Toll-Free" Pathways for Production of Type I Interferons". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6540.

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Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by different cellular pathogen recognition receptors (PRRs), which are expressed on cell membrane or in the cytoplasm of cells of the innate immune system. Nucleic acids derived from pathogens or from certain cellular conditions represent a large category of PAMPs/DAMPs that trigger production of type I interferons (IFN-I) in addition to pro-inflammatory cytokines, by specifically binding to intracellular Toll-like receptors or cytosolic receptors. These cytosolic receptors, which are not related to TLRs and we call them "Toll-free" receptors, include the RNA-sensing RIG-I like receptors (RLRs), the DNA-sensing HIN200 family, and cGAS, amongst others. Viruses have evolved myriad strategies to evoke both host cellular and viral factors to evade IFN-I-mediated innate immune responses, to facilitate their infection, replication, and establishment of latency. This review outlines these "Toll-free" innate immune pathways and recent updates on their regulation, with focus on cellular and viral factors with enzyme activities.

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21

Panchal, Hemang B., Kalpit Devani, Shimin Zheng, Eunice Mogusu, Sukhdeep Bhogal, Abdul Ahad Khan, Syed Imran Zaidi, Thomas Helton, Nirat Beohar e Timir K. Paul. "Impact of Chronic Kidney Disease on Guideline Directed Interventions Among Patients Admitted With Acute ST-Elevation Myocardial Infarction: A Nationwide Inpatient Sample 2012-2014". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6305.

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22

Nedelman, Cassandra B., e L. Lee Glenn. "Effect of Tissue Plasminogen Activator Dose and Interval on Stroke Severity". Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/7480.

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Excerpt: The recent study by Sahlas et al1 in the Journal of Stroke and Cerebrovascular Diseases concluded that “the estimation of a patient's weight in the acute setting can lead to overcalculation of the tissue plasminogen activator dose, which is associated with poorer functional outcomes.” However, this conclusion is not well supported by their study1 because the most severe ischemic stroke cases were the ones that were most likely not weighed, and this severity could have led to the increased mortality that was found2 and the majority of unweighed patients were actually given an underdose that was associated with better discharge outcomes, as explained below.

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23

Panchal, Hemang B., Kalpit Devani, Shimin Zheng, Sellasi Denutsui, Sukhdeep Bhogal, Abdul Ahad Khan, Syed Imran Zaidi, Thomas Helton, Nirat Beohar e Timir K. Paul. "Impact of Chronic Kidney Disease on Length of Hospital Stay and Cost among Patients Admitted with Acute ST Elevation Myocardial Infarction: A Nationwide Inpatient Sample 2012-2014". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6303.

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24

Panchal, Hemang B., Kalpit Devani, Shimin Zheng, Sukhdeep Bhogal, Abdul Ahd Khan, Syed Imran Zaidi, Thomas Helton, Nirat Beohar e Timir K. Paul. "Impact of Chronic Kidney Disease on Clinical Outcomes Among Patients Admitted With Acute ST-Elevation Myocardial Infarction: A Nationwide Inpatient Sample 2012-2014". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6304.

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25

Nguyen, Lam Nhat, Juan Zhao, Dechao Cao, Xindi Dang, Ling Wang, Jianqi Lian, Ying Zhang et al. "Inhibition of TRF2 Accelerates Telomere Attrition and DNA Damage in Naïve CD4 T Cells During HCV Infection". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6523.

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T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was significantly inhibited posttranscriptionally via the p53-dependent Siah-1a ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the best of our knowledge, this is the first report revealing that inhibition of TRF2 promotes T-cell telomere attrition and telomeric DNA damage that accelerates T-cell senescent and apoptotic programs, which contribute to naïve T-cell loss during viral infection. Thus, restoring the impaired T-cell telomeric shelterin machinery may offer a new strategy to improve immunotherapy and vaccine response against human viral diseases.

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26

Wang, Ling, Zhi Q. Yao, Jonathan P. Moorman, Yanji Xu e Shunbin Ning. "Gene Expression Profiling Identifies IRF4-associated Molecular Signatures in Hematological Malignancies". Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/6538.

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The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is implicated in certain types of lymphoid and myeloid malignancies. However, the molecular mechanisms underlying its interactions with these malignancies are largely unknown. In this study, we have first profiled molecular signatures associated with IRF4 expression in associated cancers, by analyzing existing gene expression profiling datasets. Our results show that IRF4 is overexpressed in melanoma, in addition to previously reported contexts including leukemia, myeloma, and lymphoma, and that IRF4 is associated with a unique gene expression pattern in each context. A pool of important genes involved in B-cell development, oncogenesis, cell cycle regulation, and cell death including BATF, LIMD1, CFLAR, PIM2, and CCND2 are common signatures associated with IRF4 in non-Hodgkin B cell lymphomas. We confirmed the correlation of IRF4 with LIMD1 and CFLAR in a panel of cell lines derived from lymphomas. Moreover, we profiled the IRF4 transcriptome in the context of EBV latent infection, and confirmed several genes including IFI27, IFI44, GBP1, and ARHGAP18, as well as CFLAR as novel targets for IRF4. These results provide valuable information for understanding the IRF4 regulatory network, and improve our knowledge of the unique roles of IRF4 in different hematological malignancies.

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27

Wang, Ling, e Shunbin Ning. "LMP1 Signaling Pathway Activates IRF4 through the PI3K-Src Axis". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6544.

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28

Wang, Ling, Mary E. A. Howell, Aryianna Sparks Wallace, Caroline Hawkins, Camri A. Nicksic, Carissa Kohne, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao e Shunbin Ning. "p62-mediated Selective Autophagy Endows Virus-Transformed Cells With Insusceptibility to DNA Damage Under Oxidative Stress". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6521.

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Abstract (sommario):

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.

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29

Wang, Ling, Mary E. A. Howell, Brooke McPeak, Katrina Riggs, Carissa Kohne, Jether Uel Yohanon, Daniel E. Foxler et al. "LIMD1 Is Induced by and Required for LMP1 Signaling, and Protects EBV-transformed Cells From DNA Damage-Induced Cell Death". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6525.

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LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor, being deregulated in many cancers to include hematological malignancies; however, very little is known about the underlying mechanisms of its deregulation and its roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of malignancies of lymphocytic and epithelial origin. Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies. In this study, we have identified potential conserved IRF4- and NFκB-binding motifs in the LIMD1 gene promoter, and both are demonstrated functional by promoter-reporter assays. We further show that LIMD1 is partially upregulated by EBV latent membrane protein 1 (LMP1) via IRF4 and NFκB in EBV latency. As to its role in the setting of EBV latent infection, we show that LIMD1 interacts with TRAF6, a crucial mediator of LMP1 signal transduction. Importantly, LIMD1 depletion impairs LMP1 signaling and functions, potentiates ionomycin-induced DNA damage and apoptosis, and inhibits p62-mediated selective autophagy. Taken together, these results show that LIMD1 is upregulated in EBV latency and plays an oncogenic role rather than that of a tumor suppressor. Our findings have identified LIMD1 as a novel player in EBV latency and oncogenesis, and open a novel research avenue, in which LIMD1 and p62 play crucial roles in linking DNA damage response (DDR), apoptosis, and autophagy and their potential interplay during viral oncogenesis

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30

Zhou, Jeff Xiwu, Xiaoyan Yang, Shunbin Ning, Ling Wang, Kesheng Wang, Yanbin Zhang, Fenghua Yuan et al. "Identification of KANSARL as the First Cancer Predisposition Fusion Gene Specific to the Population of European Ancestry Origin". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6528.

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Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model. Five of these six KANSARL fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa. In contrast, they exist in 30 - 52% of the tumors from North Americans cancer patients. Analysis of CEPH/Utah Pedigree 1463 has revealed that KANSARL is a familially-inherited fusion gene. Further analysis of RNA-seq datasets of the 1000 Genome Project has indicated that KANSARL fusion gene is specific to 28.9% of the population of European ancestry origin. In summary, we demonstrated that KANSARL is the first cancer predisposition fusion gene associated with genetic backgrounds of European ancestry origin.

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31

Wang, Ling, Junping Ren, Guang Li, Jonathan P. Moorman, Zhi Q. Yao e Shunbin Ning. "LMP1 Signaling Pathway Activates IRF4 in Latent EBV Infection and a Positive Circuit Between PI3K and Src Is Required". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6530.

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Abstract (sommario):

Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4. As to more precise mechanism, we show that LMP1 physically interacts with c-Src, and the phosphatidylinositol 3 kinase (PI3K) subunit P85 mediates their interaction. Depletion of P85 by P85-specific short hairpin RNAs disrupts their interaction and diminishes IRF4 phosphorylation in EBV-transformed cells. Furthermore, we show that Src is upstream of PI3K for activation of both IRF4 and Akt. In turn, inhibition of PI3K kinase activity by the PI3K-speicfic inhibitor LY294002 impairs Src activity. Our results show that LMP1 signaling is responsible for IRF4 activation, and further characterize the IRF4 regulatory network that is a promising therapeutic target for specific hematological malignancies.

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Ning, Shunbin, e Ling Wang. "Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/6533.

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Abstract (sommario):

Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet the underlying mechanism of this paradoxical phenomenon remains unclear. It is well known that tyrosine phosphorylation of most components of the IFN-I Jak-STAT pathway is essential for its signaling transduction. Thus, we have performed phosphotyrosine proteomics. We have found that the IFN-I Jak-STAT pathway is inactive due to the attenuated STAT2 activity, whereas the IFN-II Jak-STAT pathway is constitutively active, in EBV latency. We further confirmed these results by immunoblotting. This pilot study provides valuable information for the critical question regarding how the IRF7-mediated IFN-I response is evaded by EBV in its latency, and will prompt us to elucidate the underlying mechanisms.

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33

Yuan, Fenghua, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez et al. "Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-stranded RNA". Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/6537.

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Abstract (sommario):

3′ repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent Km of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native tRNA substrates. Previously reported TREX1 crystal structures have revealed that the substrate binding sites are open enough to accommodate the extra hydroxyl group in RNA, further supporting our conclusion that TREX1 acts on RNA. These findings indicate that its RNase activity needs to be taken into account when evaluating the physiological role of TREX1.

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34

Ren, Junping, Rue S. Ying, Yong Q. Cheng, Ling Wang, Gazzar Mohamed A. El, Guang Y. Li, Shun B. Ning, Jonathon P. Moorman e Zhi Q. Yao. "HCV-induced miR146a Controls SOCS1/STAT3 and Cytokine Expression in Monocytes to Promote Regulatory T-cell Development". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/6535.

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Abstract (sommario):

Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up‐regulated in monocytes from hepatitis C virus (HCV )‐infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll‐like receptor (TLR ) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co‐cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV ‐infected patients led to a decrease in IL ‐23, IL ‐10 and TGF ‐β expressions through the induction of suppressor of cytokine signalling 1 (SOCS 1) and the inhibition of signal transducer and activator transcription 3 (STAT 3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS 1/STAT 3 and cytokine signalling in monocytes, directing T‐cell differentiation and balancing immune clearance and immune injury during chronic viral infection.

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35

Tian, Ye. "A STUDY OF CHARRING BEHAVIOR OF WOODS BASED ON INTERNAL TEMPERATURE AND CT-SCAN MEASUREMENTS". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554473937988922.

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36

Dodd, Will. "Morning Report Case Presentation". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/8936.

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37

Dodd, Will. "Failure to Thrive: When to Watch and When to Test". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/8943.

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38

Xu, Jinshan. "Effects of internal waves on low frequency, long range, acoustic propagation in the deep ocean". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/42295.

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Abstract (sommario):

Thesis (Ph. D.)--Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and the Woods Hole Oceanographic Institution), 2007.
Includes bibliographical references (p. 183-191).
This thesis covers a comprehensive analysis of long-range, deep-ocean, low-frequency, sound propagation experimental results obtained from the North Pacific Ocean. The statistics of acoustic fields after propagation through internal-wave-induced sound-speed fluctuations are explored experimentally and theoretically. The thesis starts with the investigation of the North Pacific Acoustic Laboratory 98-99 data by exploring the space-time scales of ocean sound speed variability and the contributions from different frequency bands. The validity of the Garret & Munk internal-wave model is checked in the upper ocean of the eastern North Pacific. All these results impose hard bounds on the strength and characteristic scales of sound speed fluctuations one might expect in this region of the North Pacific for both internal-wave band fluctuations and mesoscale band fluctuations. The thesis then presents a detailed analysis of the low frequency, broadband sound arrivals obtained in the North Pacific Ocean. The observed acoustic variability is compared with acoustic predictions based on the weak fluctuation theory of Rytov, and direct parabolic equation Monte Carlo simulations. The comparisons show that a resonance condition exists between the local acoustic ray and the internal wave field such that only the internal-waves whose crests are parallel to the local ray path will contribute to acoustic scattering: This effect leads to an important filtering of the acoustic spectra relative to the internal-wave spectra. We believe that this is the first observational evidence for the acoustic ray and internal wave resonance. Finally, the thesis examined the evolution with distance, of the acoustic arrival pattern of the off-axis sound source transmissions in the Long-range Ocean Acoustic Propagation EXperiment.
(cont.) The observations of mean intensity time-fronts are compared to the deterministic ray, parabolic equation (with/without internal waves) and (one-way coupled) normal mode calculations. It is found the diffraction effect is dominant in the shorter-range transmission. In the longer range, the (internal wave) scattering effect smears the energy in both the spatial and temporal scales and thus has a dominant role in the finale region.
by Jinshan Xu.
Ph.D.

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39

Zhou, Yun, Guang Y. Li, Jun P. Ren, Ling Wang, Juan Zhao, Shun B. Ning, Ying Zhang et al. "Protection of CD4+ T Cells From Hepatitis C Virus Infection-Associated Senescence via ΔNp63-miR-181a-Sirt1 Pathway". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/6534.

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Abstract (sommario):

T cell dysfunction has a crucial role in establishing and maintaining viral persistence. We have previously shown a decline in miR‐181a, which regulates CD4+ T cell responses via DUSP6 overexpression, in individuals with hepatitis C virus (HCV) infection. Here, we describe accelerated T cell senescence in HCV‐infected individuals compared with age‐ and sex‐matched healthy subjects. Mechanistic studies revealed that up‐regulation of transcription factor ΔNp63 led to the decline of miR‐181a expression, resulting in an overexpression of the antiaging protein Sirt1, in CD4+ T cells from HCV‐infected individuals. Either reconstituting miR‐181a or silencing ΔNp63 or Sirt1 expression in CD4+ T cells led to accelerated T cell senescence, as evidenced by an increased senescence‐associated β‐galactosidase (SA‐β‐gal) expression, shortened telomere length, and decreased EdU incorporation; this suggests that HCV‐induced T cell senescence is counterregulated by the ΔNp63–miR‐181a–Sirt1 pathway. An increase of IL‐2 production was observed in these senescent CD4+ T cells and was driven by a markedly reduced frequency of Foxp3+ regulatory T (Treg) cells and increased number of Foxp3− effector T (Teff) cells upon manipulating the ΔNp63–miR‐181a–Sirt1 pathway. In conclusion, these findings provide novel mechanistic insights into how HCV uses cellular senescent pathways to regulate T cell functions, revealing new targets for rejuvenating impaired T cell responses during chronic viral infection.

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40

Ning, Shunbin, e Ling Wang. "The Multifunctional Protein p62 and Its Mechanistic Roles in Cancers". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6539.

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Abstract (sommario):

The multifunctional signaling hub p62 is well recognized as a ubiquitin sensor and a selective autophagy receptor. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 sorts ubiquitinated substrates including p62 itself for lysosome-mediated degradation. p62 plays crucial roles in myriad cellular processes including DNA damage response, aging/senescence, infection and immunity, chronic inflammation, and cancerogenesis, dependent on or independent of autophagy. Targeting p62-mediated autophagy may represent a promising strategy for clinical interventions of different cancers. In this review, we summarize the transcriptional and post-translational regulation of p62, and its mechanistic roles in cancers, with the emphasis on its roles in regulation of DNA damage response and its connection to the cGAS-STING-mediated antitumor immune response, which is promising for cancer vaccine design.

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41

Wang, Ling, Juan Zhao, Junping Ren, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao e Shunbin Ning. "Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/6519.

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Abstract (sommario):

Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN‐α in response to viral infection, and phosphorylation at IRF7 C‐terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)‐binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε‐stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7‐mediated IFN‐α production in response to Newcastle disease virus (NDV) infection or Toll‐like receptor 7 (TLR7) challenge, leading to impaired viral replication. In addition, IFN treatment, TLR challenges and viral infection induce PP1 expression. Our findings disclose for the first time a pivotal role for PP1 in impeding IRF7‐mediated IFN‐α production in host immune responses.

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42

Zhao, Juan, Xindi Dang, Peixin Zhang, Lam Nhat Nguyen, Dechao Cao, Lin Wang, Xiaoyuan Wu et al. "Insufficiency of DNA Repair Enzyme ATM Promotes Naive CD4 T-cell Loss in Chronic Hepatitis C Virus Infection". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6526.

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Abstract (sommario):

T cells have a crucial role in viral clearance and vaccine response; however, the mechanisms regulating their responses to viral infections or vaccinations remain elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA damage, and repair machineries in a large cohort of subjects with hepatitis C virus (HCV) infection. We found that naive CD4 T cells in chronically HCV-infected individuals (HCV T cells) were significantly reduced compared with age-matched healthy subjects. In addition, HCV T cells were prone to apoptosis and DNA damage, as evidenced by increased 8-oxoguanine expression and γH2AX/53BP1-formed DNA damage foci—hallmarks of DNA damage responses. Mechanistically, the activation of DNA repair enzyme ataxia telangiectasia mutated (ATM) was dampened in HCV T cells. ATM activation was also diminished in healthy T cells exposed to ATM inhibitor or to HCV (core protein) that inhibits the phosphoinositide 3 kinase pathway, mimicking the biological effects in HCV T cells. Importantly, ectopic expression of ATM was sufficient to repair the DNA damage, survival deficit, and cell dysfunctions in HCV T cells. Our results demonstrate that insufficient DNA repair enzyme ATM leads to increased DNA damage and renders HCV T cells prone to apoptotic death, which contribute to the loss of naive T cells in HCV infection. Our study reveals a novel mechanism for T-cell dysregulation and viral persistence, providing a new strategy to improve immunotherapy and vaccine responses against human viral diseases.

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43

Wang, Ling, e Shunbin Ning. "Protein Phosphatase 1 Abrogates IRF7-Mediated type I IFN Response in Antiviral Immunity". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6545.

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44

Dodd, Will. "Immunizations". Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/etsu-works/8919.

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45

Dodd, Will. "Immunizations". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/8928.

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46

Dodd, Will. "IPASS Training". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/8935.

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47

Dodd, Will. "Anemias". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/8939.

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48

Dodd, Will. "PDSA Cycle and Development of Aim Statements". Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/8942.

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49

Cho, Chang-hoan. "How advertising works on the WWW : copytesting and audience processing /". Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/fullcit?p9947200.

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50

Cao, Dechao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank et al. "Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6520.

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Abstract (sommario):

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity by inhibiting telomeric repeat binding factor 2 (TRF2), telomerase, topoisomerase I and II alpha (Top1/2a), and ataxia telangiectasia mutated (ATM) kinase activities. Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult.

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