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Search Results: 1 - 10 of 365256 matches for " Michael S. 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.
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
A First Look at the Nuclear Region of M31 with Chandra
Michael R. Garcia,Stephen S. Murray,Francis A. Primini,William R. Forman,Jeffrey E. McClintock,Christine Jones
Physics , 2000, DOI: 10.1086/312751
Abstract: We report on the first observation of the nuclear region of M31 with the Chandra X-ray Observatory. The nuclear source seen with the Einstein and ROSAT HRIs is resolved into five point sources. One of these sources is within 1'' of the M31 central super-massive black hole. As compared to the other point sources in M31, this nuclear source has an unusual x-ray spectrum. Based on the spatial coincidence we identify this source with the central black hole, and note that the unusual spectrum is a challenge to current theories. A bright transient is detected ~26'' to the west of the nucleus, which may be associated with a stellar mass black hole.
Detection of a Single Identical Cytomegalovirus (CMV) Strain in Recently Seroconverted Young Women
Suchetha Murthy,Gary S. Hayward,Sarah Wheelan,Michael S. Forman,Jin-Hyun Ahn,Robert F. Pass,Ravit Arav-Boger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015949
Abstract: Infection with multiple CMV strains is common in immunocompromised hosts, but its occurrence in normal hosts has not been well-studied.
The Murmur of The Hidden Monster: Chandra's Decadal View of The Super-massive Black Hole in M31
Zhiyuan Li,Michael R. Garcia,William R. Forman,Christine Jones,Ralph P. Kraft,Dharam V. Lal,Stephen S. Murray,Q. Daniel Wang
Physics , 2010, DOI: 10.1088/2041-8205/728/1/L10
Abstract: The Andromeda galaxy (M31) hosts a central super-massive black hole (SMBH), known as M31$^\ast$, which is remarkable for its mass ($\sim$$10^8{\rm~M_\odot}$) and extreme radiative quiescence. Over the past decade, the Chandra X-ray observatory has pointed to the center of M31 $\sim$100 times and accumulated a total exposure of $\sim$900 ks. Based on these observations, we present an X-ray study of a highly variable source that we associate with M31$^\ast$ based on positional coincidence. We find that M31$^\ast$ remained in a quiescent state from late 1999 to 2005, exhibiting an average 0.5-8 keV luminosity $\lesssim$$10^{36}{\rm~ergs~s^{-1}}$, or only $\sim$$10^{-10}$ of its Eddington luminosity. We report the discovery of an outburst that occurred on January 6, 2006, during which M31$^\ast$ radiated at $\sim$$4.3\times10^{37}{\rm~ergs~s^{-1}}$. After the outburst, M31$^\ast$ entered a more active state that apparently lasts to the present, which is characterized by frequent flux variability around an average luminosity of $\sim$$4.8\times10^{36}{\rm~ergs~s^{-1}}$. These flux variations are similar to the X-ray flares found in the SMBH of our Galaxy (Sgr A$^\ast$), making M31$^\ast$ the second SMBH known to exhibit recurrent flares. Future coordinated X-ray/radio observations will provide useful constraints on the physical origin of the flaring emission and help rule out a possible stellar origin of the X-ray source.
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.
The Galaxy Optical Luminosity Function from the AGN and Galaxy Evolution Survey (AGES)
Richard J. Cool,Daniel J. Eisenstein,Christopher S. Kochanek,Michael J. I. Brown,Nelson Caldwell,Arjun Dey,William R. Forman,Ryan C. Hickox,Buell T. Jannuzi,Christine Jones,John Moustakas,Stephen S. Murray
Physics , 2012, DOI: 10.1088/0004-637X/748/1/10
Abstract: We present the galaxy optical luminosity function for the redshift range 0.05
Tracing the evolution of Active Galactic Nuclei host galaxies over the last 9 Gyrs of Cosmic time
Andy D. Goulding,William R. Forman,Ryan C. Hickox,Christine Jones,Stephen S. Murray,Alessandro Paggi,Matthew L. N. Ashby,Alison L. Coil,Michael C. Cooper,Jiasheng Huang,Ralph Kraft,Jeffrey A. Newman,Benjamin J. Weiner,Steven P. Willner
Physics , 2013, DOI: 10.1088/0004-637X/783/1/40
Abstract: We present the results of a combined galaxy population analysis for the host galaxies of active galactic nuclei (AGN) identified at 0 < z < 1.4 within the SDSS, Bootes and DEEP2 surveys. We identified AGN in a uniform and unbiased manner at X-ray, infrared and radio wavelengths. Supermassive black holes undergoing radiatively-efficient accretion (detected as X-ray and/or infrared AGN) appear to be hosted in a separate and distinct galaxy population than AGN undergoing powerful mechanically dominated accretion (radio AGN). Consistent with some previous studies, radiatively efficient AGN appear to be preferentially hosted in modest star-forming galaxies, with little dependence on AGN or galaxy luminosity. AGN exhibiting radio-emitting jets due to mechanically-dominated accretion are almost exclusively observed in massive, passive galaxies. Crucially, we now provide strong evidence that the observed host-galaxy trends are independent of redshift. In particular, these different accretion-mode AGN have remained as separate galaxy populations throughout the last 9 Gyr. Furthermore, it appears that galaxies hosting AGN have evolved along the same path as galaxies that are not hosting AGN with little evidence for distinctly separate evolution.
Hypotheses of Spatial Stock Structure in Orange Roughy Hoplostethus atlanticus Inferred from Diet, Feeding, Condition, and Reproductive Activity
Matthew R. Dunn, Jeffrey S. Forman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026704
Abstract: We evaluate hypotheses for meso-scale spatial structure in an orange roughy (Hoplostethus atlanticus) stock using samples collected during research trawl surveys off the east coast of New Zealand. Distance-based linear models and generalised additive models were used to identify the most significant biological, environmental, and temporal predictors of variability in diet, proportion of stomachs containing prey, standardised weight of prey, fish somatic weight, fish total weight, and reproductive activity. The diet was similar to that observed elsewhere, and varied with ontogeny, depth, and surface water temperature. Smaller sized and female orange roughy in warmer bottom water were most likely to contain food. Fish condition and reproductive activity were highest at distances more than 20 km from the summit of the hills. Trawl survey catches indicated greater orange roughy densities in hill strata, suggesting hill habitat was favoured. However, analyses of feeding, condition, and reproductive activity indicated hill fish were not superior, despite fish densities on hills being reduced by fishing which, in principle, should have reduced intra-specific competition for food and other resources. Hypotheses for this result include: (1) fish in relatively poor condition visit hills to feed and regain condition and then leave, or (2) commercial fishing has disturbed feeding aggregations and/or caused habitat damage, making fished hills less productive. Mature orange roughy were observed on both flat and hill habitat during periods outside of spawning, and if this spatial structure was persistent then a proportion of the total spawning stock biomass would remain unavailable to fisheries targeting hills. Orange roughy stock assessments informed only by data from hills may well be misleading.
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