101,249 research outputs found
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Effects of Cloisite nanoparticles on interlaminar fracture toughness and resistance curve of S-glass fiber reinforced polymer composite
No full textThe effect of particular nanoclay, Cloisite 20B, addition on the interlaminar fracture toughness of a plain-woven type glass fiber reinforced plastic (GFRP) composite was experimentally investigated. The mode-I tests were conducted based on a double cantilever beam (DCB) test. Results showed that the inclusion of nanoclays improved the interlaminar fracture toughness of the GFRP composite in the range of 12.65% and 54.07% as compared with the pristine one, with a progressive increment of the nanoclays weight content (from 0.5 to 2%). A better understanding of Cloisite 20B filler's contribution to improving the delamination resistance can lead to a design of better melt flow rate and good elongation at break structural composites
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Studies of hepatitis C virus envelope proteins : interaction with host cells and as targets for the humoral response
No full textHepatitis C virus (HCV) is a major cause of chronic hepatitis infection worldwide. It leads to chronic infection in over 80% in infected patients and may result in liver cirrhosis, hepatocellular carcinoma and autoimmune disorders.The aim of this thesis was to study the functional role of human antibodies to different HCV envelope protein E2 (E2) epitopes, to characterize the interaction of die E2 protein with cell surface molecules, and to study the role of glycosylation of El, the other envelope protein of HCV, in pseudotype virus infectivity. The antibody response to hyper variable region 1 (HVR1) of the E2 protein was studied in five patients infected with the same HCV strain. The patients had different clinical outcomes: three developed chronic infection and two resolved the infection. In this study, an early antibody response to HVR1 correlated with the resolution of the infection but not the E2 antibody response. This suggests that early anti-HVR1 antibodies may play an important role in the clearance of the HCV infection.To further study the nature of protective antibodies to HCV, human monoclonal antibodies against E2 were isolated from a combinatorial Fab library displayed on phages. The library was established from the bone marrow of a chronically HCV infected patient. This patient was infected by HCV of genotype 2b and the recombinant E2 used to select the monoclonal antibodies was of genotype la. Seven distinct antibody clones were further studied. Three clones had high affinity for E2 of genotype lb. All seven clones recognized conformation dependent epitopes, which seem conserved between different genotypes. Four clones expressed as IgG that bound to two or three different E2 epitopes, were NOB-positive for blocking the CD81-E2 interaction in vitro. This suggests the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2-CD81 interaction. An assay for determination of serum antibodies to two of these epitopes was established. No correlation was found between levels of such serum antibodies and the clinical outcome of acute HCV infection.Since there is not an efficient in vitro system for the propagation of HCV, a pseudotype virus using Vesicular Stomatitis Virus (VSV) bearing HCV glycoproteins was developed. The HCV glycoproteins, El and E2, contain ER retention signals in their transmembrane (TM) domain. We generated chimeric El and E2 glycoprotein constructs (E1-G and E2-G, respectively) by replacing their native TM with sequences encoding TM of the G protein of VSV and its cytoplasmic tail, allowing translocation of E1-G or E2-G to the cell surface.Subsequently, a deletion of the HVR1 sequence from E2-G was performed, creating the recombinant protein E2(delta)HVR1-G. Pseudotype virus generated using E2(delta)HVR1-G had a reduced plaquing efficiency (50%) as compared to the E2-G pseudotype virus (with intact HVR1). Cells treated with pronase were not permissive for infection with E2(delta)HVR1-G or E2-G pseudotypes. However, heparinase I treatment of cells reduced only E2-G infectivity (by 40%). but not the infectivity of E2(delta)HVR1. Similarly, plaquing efficiency of E2-G pseudotype viruses could be greatly reduced by addition of heparin, while E2(delta)HVR1 could not.. Our results suggest that the HVR1 of E2 glycoprotein binds to cell surface proteoglycans, and may facilitate virushost interaction. The role of glycosylation of chimeric E1-G for intracellular transport, and infectivity of pseudotype virus was investigated. Surface expressed E1-G exhibited sensitivity to Endo-H treatment similar to full length El, suggesting that additional complex oligosaccarides were not added while E1-G was in transit from ER to cell surface. E1-G's four N-glycosylation sites were mutated separately (aspargine ---- glutamine), or in certain combinations. FACS analysis and confocal microscopy revealed a gradual decrease in cell surface expression of E1-G protein with an increasing number of mutations to the glycosylation sites. VSV pseudotype virus generated from E1-G mutants with only two of the four-glycosylation sites still intact displayed infectivity. Nglycosidase F treatment of pseudotype viruses generated from E1-G or its mutants decreased virus titer by - 35%, and the neutralization activity of patient sera did not significantly alter with N-glycosidase F treated pseudotype virus. Our results suggest that glycosylation may not play a key role for interaction of E1-G ectodomain with the host cell surface for pseudotype entry.In conclusion, several aspects studied in this thesis may provide critical insights into HCV vaccine design and new therapeutic strategies, if any.List of scientific papersI. Allander T, Beyene A, Jacobson SH, Grillner L, Persson MA (1997). "Patients infected with the same hepatitis C virus strain display different kinetics of the isolate-specific antibody response." J Infect Dis 175(1): 26-31 https://pubmed.ncbi.nlm.nih.gov/8985192II. Allander T, Drakenberg K, Beyene A, Rosa D, Abrignani S, Houghton M, Widell A, Grillner L, Persson MA (2000). "Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81. " J Gen Virol 81(Pt 10): 2451-9 https://pubmed.ncbi.nlm.nih.gov/10993933III. Beyene A, Drakenberg K, Grillner L, Allander T, Persson MAA (2004). "The occurence of antibodies against two conserved E2-epitopes in hepatitis C infections with different clinical outcome." (Manuscript)IV. Basu A, Beyene A, Meyer K, Ray R (2004). "The hypervariable region 1 of the E2 glycoprotein of hepatitis C virus binds to glycosaminoglycans, but this binding does not lead to infection in a pseudotype system. " J Virol 78(9): 4478-86 https://pubmed.ncbi.nlm.nih.gov/15078928V. Beyene A, Basu A, Meyer K, Ray R (2004). "Influence of N-linked glycans on intracellular transport of hepatitis C virus E1 chimeric glycoprotein and its role in pseudotype virus infectivity." Virology 324(2): 273-85 https://pubmed.ncbi.nlm.nih.gov/15207615</p
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
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
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