bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEPLOYMENT OF MEMBRANE FUSION PROTEIN DOMAINS DURING FUSION
Authors: Bentz Joe , Mittal Aditya 
Published: September 2002

AbstractIt is clear that both viral and intracellular membrane fusion proteins contain a minimal set of domains which must be deployed at the appropriate time during the fusion process. An account of these domains and their functions is given here for the four best‐described fusion systems: influenza HA, sendai virus F1, HIV gp120/41 and the neuronal SNARE core composed of synaptobrevin (syn), syntaxin (stx) and the N‐ and C‐termini of SNAP25 (sn25), together with the Ca2+binding protein synaptotagmin (syt). Membrane fusion begins with the binding of the virion or vesicle to the target membrane via receptors. The committed step in influenza HA‐ mediated fusion begins with an aggregate of HAs (at least eight) with some of their HA2 N‐termini, a.k.a. fusion peptides, embedded into the viral bilayer (Bentz, 2000 a). The hypothesis presented in Bentz (2000 b) is that the conformational change of HA to the extended coiled coil extracts the fusion peptides from the viral bilayer. When this extraction occurs from the center of the site of restricted lipid flow, it exposes acyl chains and parts of the HA transmembrane domains to the aqueous media, i.e. a hydrophobic defect is formed. This is the ‘transition state’ of the committed step of fusion. It is stabilized by a ‘dam’ of HAs, which are inhibited from diffusing away by the rest of the HAs in the aggregate and because that would initially expose more acyl chains to water. Recruitment of lipids from the apposed target membrane can heal this hydrophobic defect, initiating lipid mixing and fusion. The HA transmembrane domains are required to be part of the hydrophobic defect, because the HA aggregate must be closely packed enough to restrict lipid flow. This hypothesis provides a simple and direct coupling between the energy released by the formation of the coiled coil to the energy needed to create and stabilize the high energy intermediates of fusion. Several of these essential domains have been described for the viral fusion proteins SV5 F1 and HIV gp120/41, and for the intracellular SNARE fusion system. By comparing these domains, we have constructed a minimal set which appears to be adequate to explain how the conformational changes can produce a successful fusion event, i.e. communication of aqueous compartments.
MYCOBACTERIAL GROWTH IN HUMAN MACROPHAGES: VARIATION ACCORDING TO DONOR, INOCULUM AND BACTERIAL STRAIN
Authors: Hoal‐van Helden E. G. , Hon D. , Lewis L.‐A. , Beyers N. , van Helden P. D. 
Published: September 2002

AbstractThe microbicidal capacity of the macrophage is frequently evaded by mycobacteria, leading to tuberculosis (TB). We investigated a number of parameters affecting the rate of growth of mycobacteria in human monocyte‐derived macrophages (MDM). The results show a great deal of variation in the growth of both Mycobacterium bovis BCG and M. tuberculosis H37Rv, using a large number of human macrophage donors, (132 and 40, respectively), but no correlation was seen with the TB status of the MDM donor. Clumping of the mycobacteria resulted in more vigorous growth in MDM, suggesting that inoculum size could affect disease progression. The growth rates of 17 clinical isolates of M. tuberculosis were measured in macrophages derived from three donors and no consistent or marked differences between isolates were observed over the 5‐day period of growth measurement. However, all 17 clinical strains grew consistently faster than H37Rv in the same experiments.
DIVERSITY OF IN VITRO CYTOKINE RESPONSES BY HUMAN MACROPHAGES TO INFECTION BY MYCOBACTERIUM TUBERCULOSIS STRAINS
Authors: Hoal‐van Helden E. G. , Stanton L.‐A. , Warren R. , Richardson M. , van Helden P. D. 
Published: September 2002

AbstractMacrophages are an important component in the first line of defence of the innate immune system. They are capable of producing cytokines in response to bacterial challenge, as well as in response to cytokine stimuli from other cells in the immune system. The microbicidal response of human monocyte‐derived macrophages in vitro, induced by exogenously added cytokines, is highly variable. We found that tumour necrosis factor‐α (TNF‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) could have either stimulatory or inhibitory effects on intracellular BCG killing, depending on the macrophage donor. Macrophages infected in vitro by various clinical isolates of Mycobacterium tuberculosis or the laboratory strain H37Rv, produced varying levels of both TNF‐α and IFN‐γ. Certain M. tuberculosis strains tended to be associated with high cytokine production in each of three independent experiments, indicating that strains may differ in the host response elicited to infection.
BRIEF OCCLUSION OF THE MAIN PANCREATIC DUCT RAPIDLY INITIATES SIGNALS WHICH LEAD TO INCREASED DUCT CELL PROLIFERATION IN THE RAT
Authors: Ferris W. F. , Woodroof C. W. , Louw J. , Wolfe‐Coote S. A. 
Published: September 2002

AbstractIn the course of investigating the signals associated with pancreas regeneration, we have developed a method to initiate pancreatic duct cell proliferation by brief occlusion of the main pancreatic duct. The resulting duct cell proliferation, induced by temporary partial main duct occlusion, was compared to that induced by firmly tying a cellophane strip around the head of the pancreas for longer periods of time. Both methods stimulated a biphasic increase in duct cell proliferation, with proliferation maxima at 3 and 14 days post operation. The short duration of temporary main duct occlusion (60s) that was needed to stimulate duct cell proliferation, and the similar duct cell proliferation profiles that were observed after both the temporary and the longer term main duct occlusion, led us to conclude that the signals which initiate proliferation occur rapidly at the beginning of each procedure.
Finding Pulsars at Parkes
Authors: Manchester R. N. 
Published: September 2002

AbstractThere are many reasons why it is important to increase the number of known pulsars. Not only do pulsar searches continue to improve statistical estimates of, for example, pulsar birthrates, lifetimes and the Galactic distribution, but they continue to turn up interesting and, in some cases, unique individual pulsars. In the early days of pulsar astronomy, the Molonglo radio telescope led the world as a pulsar detection instrument. However, the Parkes radio telescope, with its frequency versatility and greater tracking ablility, combined with sensitive receivers and powerful computer detection algorithms, is now the world’s most successful telescope at finding pulsars. The Parkes multibeam survey, begun in 1997, by itself will come close to doubling the number of known pulsars. Parkes has also been very successful at finding millisecond pulsars (MSPs), especially in globular clusters. One third of the known MSPs have been found in just one cluster, 47 Tucanae.
Mid-Infrared Imaging of the Einstein Cross QSO
Authors: Agol Eric , Wyithe Stuart , Jones Barbara , Fluke Chris 
Published: September 2002

AbstractObservations of the Einstein Cross QSO reveal that the mid-infrared region is unaffected by microlensing. Thus, the infrared emission region must be extended on a scale >1017 cm, ruling out synchrotron models, but consistent with dust emission models. Other constraints rule out starburst models. The flux ratios greatly constrain the lens model.
Gravitational Microlensing of Giant Luminous Arcs: a Test for Compact Dark Matter in Clusters of Galaxies
Authors: Lewis Geraint F. 
Published: September 2002

AbstractThe true nature of dark matter in the universe still eludes us. This paper discusses a new test for the detection of stellar mass compact dark matter in galaxy clusters by observing its gravitational lensing influence on the surface brightness of giant luminous arcs. If dark matter is in the form of stellar mass compact objects, then the extremes of such variability are accessible to a monitoring campaign with the Hubble Space Telescope. With the advent of the Next Generation Space Telescope, cluster dark matter in the form of compact objects will induce a ubiquitous ‘shimmering’ of the giant arcs.
The Spectra of Red Quasars
Authors: Francis Paul J. , Drake Catherine L. , Whiting Matthew T. , Drinkwater Michael J. , Webster Rachel L. 
Published: September 2002

AbstractWe measure the spectral properties of a representative sub-sample of 187 quasars, drawn from the Parkes Half-Jansky, Flat-radio-spectrum Sample (PHFS). Quasars with a wide range of rest-frame optical/UV continuum slopes are included in the analysis: their colours range over 2 < B–K < 7. We present composite spectra of red and blue sub-samples of the PHFS quasars, and tabulate their emission line properties.The median Hβ and [O III] emission line equivalent widths of the red quasar sub-sample are a factor of ten weaker than those of the blue quasar sub-sample. No significant differences are seen between the equivalent width distributions of the C IV, C III] and Mg II lines. Both the colours and the emission line equivalent widths of the red quasars can be explained by the addition of a featureless red synchrotron continuum component to an otherwise normal blue quasar spectrum. The red synchrotron component must have a spectrum at least as red as a power-law of the form Fυ α υ−2.8. The relative strengths of the blue and red components span two orders of magnitude at rest-frame 500 nm. The blue component is weaker relative to the red component in low optical luminosity sources. This suggests that the fraction of accretion energy going into optical emission from the jet is greater in lowluminosity quasars. This correlation between colour and luminosity may be of use in cosmological distance scale work.This synchrotron model does not, however, fit ˜10% of the quasars, which have both red colours and high equivalent width emission lines.We hypothesise that these red, strong-lined quasars have intrinsically weak Big Blue Bumps.There is no discontinuity in spectral properties between the BL Lac objects in our sample and the other quasars. BL Lac objects appear to be the red, low equivalent width tail of a continuous distribution. The synchrotron emission component only dominates the spectrum at longer wavelengths, so existing BL Lac surveys will be biased against high redshift objects. This will affect measurements of BL Lac evolution.The blue PHFS quasars have significantly higher equivalent width C IV, Hβ and [O III] emission than a matched sample of optically selected QSOs.
Investigation of Coronal Mass Ejections. I. Loop-type with Arcade Flare between the Fixed Legs, and Bubble-type Due to Flare Blast Waves
Authors: Uchida Y. , Tanaka T. , Hata M. , Cameron R. 
Published: September 2002

AbstractIn this paper, we give arguments that there are two types of coronal mass ejection (CME).The first type of CME discussed here is the ‘loop-type’, whose occurrence is related to an arcade flare somewhere between the footpoints. It was found that there were pre-event magnetic connections between the flare location and the locations of the footpoints of a CME of this type, and that these connections disappeared after the event. This suggests that the footpoints of loop-type CMEs are special prescribed points, and this was verified by the observation that the footpoints do not move in this type of CME.The other type of CME is the ‘bubble-type’, which is associated with the flare blast from explosive flares. We confirmed the association of this type of CME with the so-called EIT (Extreme Ultra-violet Imaging Telescope) waves, but the velocity of expansion of the bubble is twice or more greater than that of the EIT waves depending on events. Although EIT waves were widely considered to be Moreton waves viewed by SoHO/EIT in the solar activity minimum period, recent simultaneous observations of both have revealed that the EIT wave is something different from the Moreton wave, and propagates separately with a velocity less than half that of a Moreton wave.We therefore propose a new overall picture: the bubble-type CMEs are the flare-produced MHD blast waves themselves, whose skirt is identified as a Moreton wave. EIT waves may be interpreted as follows: the slow-mode gas motions from the source cause secondary longwavelength fast-mode waves which are trapped in the “waveguide” in the low corona. The secondary long-wavelength wave in the fast-mode, which is trapped in the low corona, has a slower propagation velocity due to the nature of the waves trapped in a “waveguide”. This trapped wave induces slow-mode motions of the gas through a mode-coupling process in the high chromosphere, where the propagation velocities of the fastand slow-mode waves match.Three-dimensional MHD simulations for these two types of CME are in progress, and are previewed in this paper.
A Test to Confirm the Source of Energy for Solar Flares
Authors: Wheatland M. S. 
Published: September 2002

AbstractA test of the hypothesis that flares derive their energy from large scale current systems inferred from active region vector magnetograms is proposed. The test involves a statistical comparison of the flarerelated change in coronal magnetic energy (based on the magnetohydrodynamic virial theorem) and an independent measure of the energy of the flare. A simulation suggests that — assuming the hypothesis is correct—the test requires around 50 flares with energy greater than 5×1023 J to return a significant result. Existing archives of vector magnetograms should provide sufficient data for such a study.
X-ray Variability of Blazars
Authors: Pian Elena 
Published: September 2002

AbstractCritical progress in our understanding of high energy emission from AGN has been determined in the last 10 years by X-ray monitoring campaigns with many space missions, notably ROSAT, ASCA, RXTE, BeppoSAX, and XMM, often in conjunction with observations at other frequencies. The emphasis of the present review is on recent findings about X-ray variability of blazars. Among AGN, these exhibit the largest amplitude variations of the X-ray emission, often well correlated with variations at higher energies (GeV and TeV radiation). The accurate sampling of the X-ray spectra over more than three decades in energy, made possible by the wide energy range of BeppoSAX, has also shown strong spectral variability in blazar active states, suggesting extreme electron energies and leading to the identification of a class of ‘extreme synchrotron’ sources.
Very High Energy Gamma-ray Observations of AGN with CANGAROO
Authors: Nishijima Kyoshi 
Published: September 2002

AbstractWe have observed eight AGN since 1993 in the energy region above several hundred GeV using the CANGAROO telescopes. We observed Mrk 421 for ten nights with the CANGAROO-II 10 m telescope during its active state in early 2001 using the very large zenith angle technique. Our preliminary result implies the detection of gamma-ray emission from Mrk 421 in the energy range above 9.3 TeV. The high energy peaked BL Lacs (HBLs) PKS 2005–489 and PKS 2155–304 have been also observed. No statistically significant signals are found for both HBLs and flux upper limits are obtained. A summary of results of observations of AGN is presented in this paper.
High Energy Radiation Generated at Boundary Shear Layers of Relativistic Jets
Authors: Stawarz Ł. , Ostrowski M. 
Published: September 2002

AbstractA simple model of cosmic ray electron acceleration at the jet boundary yields a power law particle energy distribution of ultra-relativistic electrons with an energy cut-off growing with time, and, finally, a growing particle bump at the energy where energy gains equal radiation losses. For such electron distribution, in tens-of-kpc scale jets, we derived the observed time-varying spectra of synchrotron and inverse Compton radiation, including Comptonisation of synchrotron and cosmic microwave background photons. Slowly varying spectral index along the jet in the ‘low frequency’ spectral range is a natural consequence of boundary layer acceleration. Variations of the high energy bump of the electron distribution can give rise to anomalous behaviour in the X-ray band in comparison to the lower frequencies.
Multifrequency Monitoring of the Blazar PKS 2005-489
Authors: Rector Travis , Perlman Eric , Sambruna Rita , Madejski Greg , Rantakyro Frederik ,   CANGAROO collaboration
Published: September 2002

AbstractWe present a multifrequency monitoring campaign of PKS 2005–489, a bright and highly variable blazar. Simultaneous observations were completed over a 13 day period in the X-ray with RXTE, in the optical at the CTIO 0.9 m telescope, at TeV energies with CANGAROO-II, and at submillimetre wavelengths with SEST. Previous multiwavelength monitoring campaigns of PKS 2005–489 and other blazars have found complex flux and spectral variability behaviour, with different modes and timescales from days to hours and shorter.PKS 2005–489 was observed in transition from a quiescent state into the early stages of a flare. A gradual increase in flux density was observed at optical and X-ray wavelengths during 19–27 August 2000, and a dramatic increase in X-ray emission was observed starting on 2 September 2000. Intraday and spectral variability were not detected during the campaign.
Millimetre Continuum Variations, VLBI Structure and Gamma-rays: Investigating Shocked Jet Physics
Authors: Valtaoja E. , Savolainen T. , Wiik K. , Lähteenmäki A. 
Published: September 2002

AbstractWe compare the total flux density variations and the VLBI structural variations in a sample of 27 gamma-ray blazars. We find that all the radio variations are due to shocks; the flux of the underlying jet remains constant. A large fraction of the shocks grow and fade within the innermost 0.1 mas, appearing only as ‘core flares’. Comparisons with the EGRET data show that gamma-ray flares must come from the shocks, not from the jet. At the time of an EGRET flare, the shock is typically already over a parsec downstream from the radio core, beyond the accretion disk and/or the broad line region (BLR) photon fields. Thus, present models for gamma-ray production are inadequate, since they typically model the gamma-ray inverse Compton flux as coming from the jet, with significant disk or BLR external Compton components.
Australian fur seals, Arctocephalus pusillus doriferus: pup numbers at Lady Julia Percy Island, Victoria, and a synthesis of the species' population status
Authors: Shaughnessy P. D. , Kirkwood R. J. , Warneke R. M. 
Published: September 2002

The abundance of Australian fur seal pups was determined at Lady Julia Percy Island in early January 2000 when the average age of pups was 5 weeks. A mark-recapture procedure with repeated recapture sessions was used to estimate abundance of pups in six accessible breeding areas. Pups (n = 1836) were marked by clipping guard hair on the head. Recaptures were conducted visually on 2-4 occasions, when a mean of 41% of sighted pups had been marked. Pup numbers were calculated using a modified Petersen estimate and combined by taking their arithmetic mean. The combined estimate in the accessible breeding areas was 4487 380 pups were counted at two inaccessible sites and 347 dead pups were recorded. Overall, the estimate of abundance for Lady Julia Percy Island was 5214 pups. This exceeds three previous estimates of doubtful veracity for pupping seasons in 1935-36, 1975-76 and 1986-87, and is the greatest number of pups recorded at any Australian fur seal colony. Summation of the most recent estimates of abundance of Australian fur seal pups in all colonies indicates pup production of 16 900 per annum in the 1990s. New Zealand fur seals were also breeding on the island (a mating and four new-born pups were recorded) and two adult male Australian sea lions were observed.
Endogenous Reactive Oxygen Species Is an Important Mediator of Miconazole Antifungal Effect
Authors: Kobayashi Daisuke , Kondo Kei , Uehara Nobuyuki , Otokozawa Seiko , Tsuji Naoki , Yagihashi Atsuhito , Watanabe Naoki 
Published: September 2002

ABSTRACTWe investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production inCandida albicanswas measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 μg/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 μg/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 μM. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates ofCandidaspecies was inversely correlated with the miconazole MIC (r= −0.8818;P< 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.
Discovery of a Novel and Potent Class of FabI-Directed Antibacterial Agents
Authors: Payne David J. , Miller William H. , Berry Valerie , Brosky John , Burgess Walter J. , Chen Emile , DeWolf Walter E. , Fosberry Andrew P. , Greenwood Rebecca , Head Martha S. , Heerding Dirk A. , Janson Cheryl A. , Jaworski Deborah D. , Keller Paul M. , Manley Peter J. , Moore Terrance D. , Newlander Kenneth A. , Pearson Stewart , Polizzi Brian J. , Qiu Xiayang , Rittenhouse Stephen F. , Slater-Radosti Courtney , Salyers Kevin L. , Seefeld Mark A. , Smyth Martin G. , Takata Dennis T. , Uzinskas Irene N. , Vaidya Kalindi , Wallis Nicola G. , Winram Scott B. , Yuan Catherine C. K. , Huffman William F. 
Published: September 2002

ABSTRACT

Bacterial enoyl-acyl carrier protein (ACP) reductase (FabI) catalyzes the final step in each elongation cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. High-throughput screening of the
Staphylococcus aureus
FabI enzyme identified a novel, weak inhibitor with no detectable antibacterial activity against
S. aureus
. Iterative medicinal chemistry and X-ray crystal structure-based design led to the identification of compound 4 [(
E
)-
N
-methyl-
N
-(2-methyl-1
H
-indol-3-ylmethyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide], which is 350-fold more potent than the original lead compound obtained by high-throughput screening in the FabI inhibition assay. Compound 4 has exquisite antistaphylococci activity, achieving MICs at which 90% of isolates are inhibited more than 500 times lower than those of nine currently available antibiotics against a panel of multidrug-resistant strains of
S. aureus
and
Staphylococcus epidermidis
. Furthermore, compound 4 exhibits excellent in vivo efficacy in an
S. aureus
infection model in rats. Biochemical and genetic approaches have confirmed that the mode of antibacterial action of compound 4 and related compounds is via inhibition of FabI. Compound 4 also exhibits weak FabK inhibitory activity, which may explain its antibacterial activity against
Streptococcus pneumoniae
and
Enterococcus faecalis
, which depend on FabK and both FabK and FabI, respectively, for their enoyl-ACP reductase function. These results show that compound 4 is representative of a new, totally synthetic series of antibacterial agents that has the potential to provide novel alternatives for the treatment of
S. aureus
infections that are resistant to our present armory of antibiotics.