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Search Results: 1 - 10 of 45108 matches for " Michael Forman "
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A new approach to multi-modal diffusions with applications to protein folding
Julie Forman,Michael S?rensen
Statistics , 2013,
Abstract: This article demonstrates that flexible and statistically tractable multi-modal diffusion models can be attained by transformation of simple well-known diffusion models such as the Ornstein-Uhlenbeck model, or more generally a Pearson diffusion. The transformed diffusion inherits many properties of the underlying simple diffusion including its mixing rates and distributions of first passage times. Likelihood inference and martingale estimating functions are considered in the case of a discretely observed bimodal diffusion. It is further demonstrated that model parameters can be identified and estimated when the diffusion is observed with additional measurement error. The new approach is applied to molecular dynamics data in form of a reaction coordinate of the small Trp-zipper protein, for which the folding and unfolding rates are estimated. The new models provide a better fit to this type of protein folding data than previous models because the diffusion coefficient is state-dependent.
Substructure: Clues to the Formation of Clusters of Galaxies
Michael J. West,Christine Jones,William Forman
Physics , 1995, DOI: 10.1086/309673
Abstract: We have examined the spatial distribution of substructure in clusters of galaxies using Einstein X-ray observations. Subclusters are found to have a markedly anisotropic distribution that reflects the surrounding matter distribution on supercluster scales. Our results suggest a picture in which cluster formation proceeds by mergers of subclusters along large-scale filaments. The implications of such an anisotropic formation process for the shapes, orientations and kinematics of clusters are discussed briefly.
Activation of Nucleotide Oligomerization Domain 2 (NOD2) by Human Cytomegalovirus Initiates Innate Immune Responses and Restricts Virus Replication
Arun Kapoor, Michael Forman, Ravit Arav-Boger
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092704
Abstract: Nucleotide-binding oligomerization domain 2 (NOD2) is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV) results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs) and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β) and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.
Intracluster Globular Clusters
Michael J. West,Patrick Cote,Christine Jones,William Forman,Ronald O. Marzke
Physics , 1995, DOI: 10.1086/309748
Abstract: Globular cluster populations of supergiant elliptical galaxies are known to vary widely, from extremely populous systems like that of UGC 9799, the centrally dominant galaxy in Abell 2052, to globular-cluster-poor galaxies such as NGC 5629 in Abell 2666. Here we propose that these variations point strongly to the existence of a population of globular clusters that are not bound to individual galaxies, but rather move freely throughout the cores of clusters of galaxies. Such intracluster globular clusters may have originated as tidally stripped debris from galaxy interactions and mergers, or alternatively they may have formed in situ in some scenarios of globular cluster formation.
Phonetics for Phonics
Ross Forman
Literacy and Numeracy Studies , 2012,
Conscious Hip-Hop, Change, and the Obama Era
Murray Forman
American Studies Journal , 2010,
Abstract: This article identifies a particular aspect of hip-hop’s range of cultural production—conscious rap—in order to isolate one of the more politicized discursive options available to youth in America and a site where critical perspectives on post-Civil Rights America have emerged most forcefully. It further suggests that Obama’s political rise corresponds with a new phase in hip-hop and has impacted the ways in which its creative artists frame and articulate issues of race, class, and identity.
Instant Video Revisiting: The Video Camera as a "Tool of the Mind" for Young Children
George Forman
Early Childhood Research & Practice , 1999,
Abstract: Once used only to record special events in the classroom, video cameras are now small enough and affordable enough to be used to document everyday events. Video cameras with foldout screens allow children to watch their activities immediately after they happen and to discuss them with a teacher. This article coins the term instant video revisiting (IVR) to describe this process and, using classroom video clips, explores the educational value of IVR.
Gangliosides Block Aggregatibacter Actinomycetemcomitans Leukotoxin (LtxA)-Mediated Hemolysis
Michael S. Forman,Jason B. Nishikubo,Rebecca K. Han,Amy Le,Nataliya V. Balashova,Scott C. Kachlany
Toxins , 2010, DOI: 10.3390/toxins2122824
Abstract: Aggregatibacter actinomycetemcomitans is an oral pathogen and etiologic agent of localized aggressive periodontitis. The bacterium is also a cardiovascular pathogen causing infective endocarditis. A. actinomycetemcomitans produces leukotoxin (LtxA), an important virulence factor that targets white blood cells (WBCs) and plays a role in immune evasion during disease. The functional receptor for LtxA on WBCs is leukocyte function antigen-1 (LFA-1), a b-2 integrin that is modified with N-linked carbohydrates. Interaction between toxin and receptor leads to cell death. We recently discovered that LtxA can also lyse red blood cells (RBCs) and hemolysis may be important for pathogenesis of A. actinomycetemcomitans. In this study, we further investigated how LtxA might recognize and lyse RBCs. We found that, in contrast to a related toxin, E. coli a-hemolysin, LtxA does not recognize glycophorin on RBCs. However, gangliosides were able to completely block LtxA-mediated hemolysis. Furthermore, LtxA did not show a preference for any individual ganglioside. LtxA also bound to ganglioside-rich C6 rat glioma cells, but did not kill them. Interaction between LtxA and C6 cells could be blocked by gangliosides with no apparent specificity. Gangliosides were only partially effective at preventing LtxA-mediated cytotoxicity of WBCs, and the effect was only observed when a high ratio of ganglioside:LtxA was used over a short incubation period. Based on the results presented here, we suggest that because of the similarity between N-linked sugars on LFA-1 and the structures of gangliosides, LtxA may have acquired the ability to lyse RBCs.
Recombinant luciferase-expressing human cytomegalovirus (CMV) for evaluation of CMV inhibitors
Ran He, Gordon Sandford, Gary S Hayward, William H Burns, Gary H Posner, Michael Forman, Ravit Arav-Boger
Virology Journal , 2011, DOI: 10.1186/1743-422x-8-40
Abstract: Infection with Cytomegalovirus (CMV) continues to be a major threat in organ transplant recipients and congenitally-infected children [1,2]. Although existing systemic therapies are effective in suppressing virus replication, serious side effects and the emergence of resistant viral strains pose significant treatment dilemmas [3]. The need to identify and develop new anti-CMV compounds coincides with the advancement of rapid, sensitive, and high-throughput methods for screening of lead compounds. While the plaque reduction assay remains the gold-standard for screening of anti-viral compounds, new techniques based on recombinant DNA technology and highly sensitive molecular assays have recently been suggested as alternatives [4-6]. Real-time PCR, the standard of care in the management of CMV disease in high- risk patient populations, may also provide a sensitive tool for drug screening [7-12]In earlier studies, a series of chloramphenicol acetyl transferase (CAT) recombinants expressing CAT under the control of UL54 (DNA polymerase, POL) or UL99 (pp28) promoters were constructed. The expression of CAT in infected cells highly mimicked the expression pattern of the endogenous UL54 and UL99 [4,13]. Thus, these two gene promoters were selected to construct luciferase-recombinant CMV for quatification of CMV replication in a rapid and reproducuble way. We report on the evaluation of two luciferase recombinant viruses (pp28 and POL) and the correlation of the pp28-luciferase system with plaque reduction and real-time PCR in evaluation of CMV inhibition by anti-CMV compounds.Recombinant CMV based on the laboratory-adapted strain, Towne, was constructed by homologous recombination in transfected-infected cells. A β- galactosidase (β -gal)-expressing Towne virus was first constructed using an intergenic insertion site between US9 and US10. Prior studies in which a β-glucuronidase expression cassette was inserted in this intergenic region of the laboratory-adapted AD169 virus
Engineering Human T Cells for Resistance to Methotrexate and Mycophenolate Mofetil as an In Vivo Cell Selection Strategy
Mahesh Jonnalagadda, Christine E. Brown, Wen-Chung Chang, Julie R. Ostberg, Stephen J. Forman, Michael C. Jensen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065519
Abstract: Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX) and mycophenolate mofetil (MMF) in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFRFS; L22F, F31S) and inosine monophosphate dehydrogenase II (IMPDH2IY; T333I, S351Y) conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 μM MTX and 1.0 μM MPA). Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt+DHFRFS+IMPDH2IY+ T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold), MMF alone (2.9-fold), or combined MTX and MMF (4.9-fold). These findings demonstrate the utility of both DHFRFS/MTX and IMPDH2IY/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.
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