101,136 research outputs found
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Translational genomics of HIV-1 subtype C in India : molecular phylogeny and drug resistance
No full textThis thesis describes the translational genomics of HIV-1subtype C in India from its origin to therapeutic response with the aim to improve our knowledge for better therapeutic and preventive strategies to combat HIV/AIDS. In a systemic approach, we identified the molecular phylogeny of HIV-1 subtypes circulating in India and the time to most recent common ancestors (tMRCA) of predominant HIV-1 subtype C strains. Additionally, this thesis also studied drug resistance mutations in children, adolescents and adults, the role of host factors in evolution of drug resistance, and population dynamics of viremia and viral co-receptor tropism in perinatal transmission. Finally, the long term therapeutic responses on Indian national first-line antiretroviral therapy were also studied.In Paper I, we reported an increase in the HIV-1 recombinant forms in the HIV-1 epidemiology using a robust subtyping methodology. While the study confirmed HIV-1 subtype C as a dominant subtype, its origin was dated back to the early 1970s from a single or few genetically related strains from South Africa, whereafter, it has evolved independently.In Paper II, the lethal hypermutations due to the activity of human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (hA3G) was significantly associated with antiretroviral therapy (ART) failure in Indian HIV-1 subtype C patients. The presence of M184I and M230I mutations were observed due to the editing of hA3G in the proviral compartment but stop codons were also found in the open reading frames and the same drug resistance mutations were absent in plasma virus. Therefore, it is unlikely that the viral variants which exhibit hypermutated sequences and M184I and/or M230I will mature and expand in vivo and hence are unlikely to have any clinical significance. The high concordance of drug resistance genotyping in the plasma and proviral compartments in therapy-naïve patients, gives weight to the idea of using whole blood for surveillance of drug resistance mutations which precludes logistic challenges of cold chain transport.In Papers III and IV, we identified a substantial proportion of HIV-1 subtype C perinatally-infected older children who had a high burden of plasma viremia but also had high CD4+ T-cell counts. In addition, older children with HIV-1 subtype C infection presented a high prevalence of predicted X4 and R5/X4 tropic strains which indicates that HIV-1 subtype C strains required longer duration of infection and greater disease progression to co-receptor transition from R5- to X4-tropic strains (IV). Our studies also indicate that transmitted drug resistance is low among Indian HIV-1 infected children, adolescents (III) and adults (II).In Paper V, in a longitudinal cohort study, a good long-term response to the Indian national first-line therapy for a median of nearly four years with 2.8% viral failure, indicating the overall success of the Indian ART program. Our study also showed that three immunologically well patients with virological rebound and major viral drug resistance mutations (M184V, K103N and Y181C) during one study visit had undetectable viral load at their next visit. These findings suggest that use of multiple parameters like patients’ immunological (CD4+ T-cell count), virological (viral load) and drug resistance data should all be used to optimize the treatment switch to second line therapy.In conclusion, this translational genomics study enhances our knowledge about the HIV-1 subtype C strains circulating in India which are genetically distinct from prototype African subtype C strains. Considerably more research using appropriate models need to be performed to understand the phenotypic and biological characteristics of these strains to guide efficient disease intervention and management strategies.List of scientific papersI. Neogi U, Bontell I, Shet A, De Costa A, Gupta S, Diwan V, Laishram RS, Wanchu A, Ranga U, Banerjea AC, Sönnerborg A. (2012) Molecular epidemiology of HIV-1 subtypes in India: Origin and evolutionary history of the predominant subtype C. PLoS ONE. 7(6):e39819. https://doi.org/10.1371/journal.pone.0039819 II. Neogi U, Shet A, Sahoo PN, Bontell I, Ekstrand ML, Banerjea AC, Sönnerborg A. (2013) Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals. J Int AIDS Soc. 16:18472. https://doi.org/10.7448/IAS.16.1.18472 III. Neogi U, Sahoo PN, De Costa A, Shet A. (2012) High viremia and low level of transmitted drug resistance in anti-retroviral therapy-naïve perinatally-infected children and adolescents with HIV-1 subtype C infection. BMC Infec Dis. Nov 22; 12(1): 317. https://doi.org/10.1186/1471-2334-12-317 IV. Neogi U, Sahoo PN, Arumugam K, Sönnerborg A, De Costa A, Shet A. (2012) Higher prevalence of predicted X4-tropic strains in perinatally- infected older children with HIV-1 subtype C in India. J Acquir Immune Defic Syndr. 59(4): 347-53. https://doi.org/10.1097/QAI.0b013e3182405c7b V. Neogi U, Heylen E, Shet A, Chandy S, Shamsunder R, Sönnerborg A, Ekstrand ML. (2013) Long-term efficacy of first line antiretroviral therapy in Indian HIV-1 infected patients: A longitudinal cohort study. PLoS ONE. 8(1):e55421. https://doi.org/10.1371/journal.pone.0055421 </p
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
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
Global Financial and Economic Crisis: Implications for Trade and Industrial Restructuring in South Asia
No full textThis study investigates the impact of global crisis shocks on India's trade and industry. The authors use panel data modeling and vector autoregression techniques to understand the dynamic effects of global crisis shocks on Indian industry and trade. Changes in trade composition are positively associated with changes in manufacturing composition in India, controlling for other variables. However, there is no strong indication that Indian industry has been severely harmed by the fall in demand in crisis-affected advanced economies such as the United States, the European Union, and Japan, holding other things constant.india trade industry; indian industry; india manufacturing sector; india external trade; global economic crisis
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;
Stable Drop Shapes under Disjoining Pressure: II. Multiplicity and Stability
No full textThe stability of the contact line region as affected by the disjoining pressure has been analyzed by solving the augmented Young-Laplace equation. Because of the results in Part I (Zhang, X., Neogi, P., and Ybarra, R. M., J. Colloid Interface Sci.), we have concentrated on obtaining multiple solutions for the same set of conditions. as many as five solutions were obtained: drops that end in a thin film with uniform thickness and where the film shape oscillates, drops that end with microscopic contact angles, as well as uniform thin films of two different thicknesses. the results of linear stability analysis were used to show that most cases were unstable to infinitesimal disturbances. Only two stable drop shapes for the particular disjoining pressure investigated are stable, a thin film of constant thickness and a thin drop that ends in a film of same thickness. Both multiplicity and stability have been discussed here for the first time and shed considerable light on the role of the attractive and repulsive forces. © 2002 Elsevier Science (USA)
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