402 research outputs found
Down-regulation of myeloid cell leukemia 1 by epigallocatechin-3-gallate sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor Α–induced apoptosis
Objective Overexpression of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of their resistance to tumor necrosis factor Α (TNFΑ)–induced apoptosis. This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial fibroblast sensitization to TNFΑ-induced apoptosis. Methods EGCG effects on cultured RA synovial fibroblast cell morphology, proliferation, and viability over 72 hours were determined by microscopy and a fluorescent cell enumeration assay. Caspase 3 activity was determined by a colorimetric assay. Western blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-ΚB. Results In RA synovial fibroblasts, EGCG (5–50 Μ M ) inhibited constitutive and TNFΑ-induced Mcl-1 protein expression in a concentration- and time-dependent manner ( P < 0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA synovial fibroblasts and affected Mcl-1 expression to a lesser extent in osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the TNFΑ-induced Akt and NF-ΚB pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast growth, and this effect was mimicked by Akt and NF-ΚB inhibitors. Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to TNFΑ-induced PARP cleavage and apoptotic cell death. Conclusion Our findings indicate that EGCG itself induces apoptosis and further sensitizes RA synovial fibroblasts to TNFΑ-induced apoptosis by specifically blocking Mcl-1 expression and, hence, may be of promising adjunct therapeutic value in regulating the invasive growth of synovial fibroblasts in RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62991/1/24488_ftp.pd
The Centaurus A Ultrahigh-Energy Cosmic Ray Excess and the Local Extragalactic Magnetic Field
The ultrahigh-energy cosmic-ray anisotropies discovered by the Pierre Auger
Observatory give the potential to finally address both the particles' origins
and properties of the nearby extragalactic magnetic field (EGMF). We examine
the implications of the excess of ~ 10^20 eV events around the nearby radio
galaxy Centaurus A. We find that, if Cen A is the source of these cosmic rays,
the angular distribution of events constrains the EGMF strength within several
Mpc of the Milky Way to > 20 nG for an assumed primary proton composition. Our
conclusions suggest that either the observed excess is a statistical anomaly or
the local EGMF is stronger then conventionally thought. We discuss the
implications of this field, including UHECR scattering from more distant
sources, time delays from transient sources, and the possibility of using
magnetic lensing signatures to attain tighter constraints.Comment: 8 pages, 8 figures; Matches published version in AP
Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer
The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad-Line Region
We present models of the H-emitting broad-line region (BLR) in seven
Seyfert 1 galaxies from the Lick AGN (Active Galactic Nucleus) Monitoring
Project 2011 sample, drawing inferences on the BLR structure and dynamics as
well as the mass of the central supermassive black hole. We find that the BLR
is generally a thick disk, viewed close to face-on, with preferential emission
back toward the ionizing source. The dynamics in our sample range from
near-circular elliptical orbits to inflowing or outflowing trajectories. We
measure black hole masses of for PG 1310108, for Mrk 50,
for Mrk 141, for Mrk 279,
for Mrk 1511, for NGC 4593, and
for Zw 229015. We use these black hole mass
measurements along with cross-correlation time lags and line widths to recover
the scale factor used in traditional reverberation mapping measurements.
Combining our results with other studies that use this modeling technique,
bringing our sample size to 16, we calculate a scale factor that can be used
for measuring black hole masses in other reverberation mapping campaigns. When
using the root-mean-square (rms) spectrum and using the line dispersion to
measure the line width, we find . Finally, we search for correlations between and other AGN
and BLR parameters and find marginal evidence that is correlated with
and the BLR inclination angle, but no significant evidence of a
correlation with the AGN luminosity or Eddington ratio.Comment: 26 pages, 14 figures. Accepted for publication in Ap
The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines
We have recently completed a 64-night spectroscopic monitoring campaign at
the Lick Observatory 3-m Shane telescope with the aim of measuring the masses
of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected
masses in the range ~10^6-10^7M_sun and also the well-studied nearby active
galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including
NGC 5548) showed optical variability of sufficient strength during the
monitoring campaign to allow for a time lag to be measured between the
continuum fluctuations and the response to these fluctuations in the broad
Hbeta emission, which we have previously reported. We present here the light
curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the
time lags for the emission-line responses relative to changes in the continuum
flux. Combining each emission-line time lag with the measured width of the line
in the variable part of the spectrum, we determine a virial mass of the central
supermassive black hole from several independent emission lines. We find that
the masses are generally consistent within the uncertainties. The time-lag
response as a function of velocity across the Balmer line profiles is examined
for six of the AGNs. Finally we compare several trends seen in the dataset
against the predictions from photoionization calculations as presented by
Korista & Goad. We confirm several of their predictions, including an increase
in responsivity and a decrease in the mean time lag as the excitation and
ionization level for the species increases. Further confirmation of
photoionization predictions for broad-line gas behavior will require additional
monitoring programs for these AGNs while they are in different luminosity
states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the
Astrophysical Journa
A panchromatic study of BLAST counterparts: total star-formation rate, morphology, AGN fraction and stellar mass
We carry out a multi-wavelength study of individual galaxies detected by the
Balloon-borne Large Aperture Submillimeter Telescope (BLAST) and identified at
other wavelengths, using data spanning the radio to the ultraviolet (UV). We
develop a Monte Carlo method to account for flux boosting, source blending, and
correlations among bands, which we use to derive deboosted far-infrared (FIR)
luminosities for our sample. We estimate total star-formation rates for BLAST
counterparts with z < 0.9 by combining their FIR and UV luminosities. Star
formation is heavily obscured at L_FIR > 10^11 L_sun, z > 0.5, but the
contribution from unobscured starlight cannot be neglected at L_FIR < 10^11
L_sun, z < 0.25. We assess that about 20% of the galaxies in our sample show
indication of a type-1 active galactic nucleus (AGN), but their submillimeter
emission is mainly due to star formation in the host galaxy. We compute stellar
masses for a subset of 92 BLAST counterparts; these are relatively massive
objects, with a median mass of ~10^11 M_sun, which seem to link the 24um and
SCUBA populations, in terms of both stellar mass and star-formation activity.
The bulk of the BLAST counterparts at z<1 appear to be run-of-the-mill
star-forming galaxies, typically spiral in shape, with intermediate stellar
masses and practically constant specific star-formation rates. On the other
hand, the high-z tail of the BLAST counterparts significantly overlaps with the
SCUBA population, in terms of both star-formation rates and stellar masses,
with observed trends of specific star-formation rate that support strong
evolution and downsizing.Comment: Accepted for publication in the Astrophysical Journal. 44 pages, 11
figures. The SED template for the derivation of L_FIR has changed (added new
figure) and the discussion on the stellar masses has been improved. The
complete set of full-color postage-stamps can be found at
http://blastexperiment.info/results_images/moncelsi
Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City
This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed
The Effect of Lattice Vibrations on Substitutional Alloy Thermodynamics
A longstanding limitation of first-principles calculations of substitutional
alloy phase diagrams is the difficulty to account for lattice vibrations. A
survey of the theoretical and experimental literature seeking to quantify the
impact of lattice vibrations on phase stability indicates that this effect can
be substantial. Typical vibrational entropy differences between phases are of
the order of 0.1 to 0.2 k_B/atom, which is comparable to the typical values of
configurational entropy differences in binary alloys (at most 0.693 k_B/atom).
This paper describes the basic formalism underlying ab initio phase diagram
calculations, along with the generalization required to account for lattice
vibrations. We overview the various techniques allowing the theoretical
calculation and the experimental determination of phonon dispersion curves and
related thermodynamic quantities, such as vibrational entropy or free energy. A
clear picture of the origin of vibrational entropy differences between phases
in an alloy system is presented that goes beyond the traditional bond counting
and volume change arguments. Vibrational entropy change can be attributed to
the changes in chemical bond stiffness associated with the changes in bond
length that take place during a phase transformation. This so-called ``bond
stiffness vs. bond length'' interpretation both summarizes the key phenomenon
driving vibrational entropy changes and provides a practical tool to model
them.Comment: Submitted to Reviews of Modern Physics 44 pages, 6 figure
Reverberation Mapping of the Kepler-Field AGN KA1858+4850
KA1858+4850 is a narrow-line Seyfert 1 galaxy at redshift 0.078 and is among
the brightest active galaxies monitored by the Kepler mission. We have carried
out a reverberation mapping campaign designed to measure the broad-line region
size and estimate the mass of the black hole in this galaxy. We obtained 74
epochs of spectroscopic data using the Kast Spectrograph at the Lick 3-m
telescope from February to November of 2012, and obtained complementary V-band
images from five other ground-based telescopes. We measured the H-beta light
curve lag with respect to the V-band continuum light curve using both
cross-correlation techniques (CCF) and continuum light curve variability
modeling with the JAVELIN method, and found rest-frame lags of lag_CCF = 13.53
(+2.03, -2.32) days and lag_JAVELIN = 13.15 (+1.08, -1.00) days. The H-beta
root-mean-square line profile has a width of sigma_line = 770 +/- 49 km/s.
Combining these two results and assuming a virial scale factor of f = 5.13, we
obtained a virial estimate of M_BH = 8.06 (+1.59, -1.72) x 10^6 M_sun for the
mass of the central black hole and an Eddington ratio of L/L_Edd ~ 0.2. We also
obtained consistent but slightly shorter emission-line lags with respect to the
Kepler light curve. Thanks to the Kepler mission, the light curve of
KA1858+4850 has among the highest cadences and signal-to-noise ratios ever
measured for an active galactic nucleus; thus, our black hole mass measurement
will serve as a reference point for relations between black hole mass and
continuum variability characteristics in active galactic nuclei
Berkeley Supernova Ia Program I: Observations, Data Reduction, and Spectroscopic Sample of 582 Low-Redshift Type Ia Supernovae
In this first paper in a series we present 1298 low-redshift (z\leq0.2)
optical spectra of 582 Type Ia supernovae (SNe Ia) observed from 1989 through
2008 as part of the Berkeley SN Ia Program (BSNIP). 584 spectra of 199 SNe Ia
have well-calibrated light curves with measured distance moduli, and many of
the spectra have been corrected for host-galaxy contamination. Most of the data
were obtained using the Kast double spectrograph mounted on the Shane 3 m
telescope at Lick Observatory and have a typical wavelength range of
3300-10,400 Ang., roughly twice as wide as spectra from most previously
published datasets. We present our observing and reduction procedures, and we
describe the resulting SN Database (SNDB), which will be an online, public,
searchable database containing all of our fully reduced spectra and companion
photometry. In addition, we discuss our spectral classification scheme (using
the SuperNova IDentification code, SNID; Blondin & Tonry 2007), utilising our
newly constructed set of SNID spectral templates. These templates allow us to
accurately classify our entire dataset, and by doing so we are able to
reclassify a handful of objects as bona fide SNe Ia and a few other objects as
members of some of the peculiar SN Ia subtypes. In fact, our dataset includes
spectra of nearly 90 spectroscopically peculiar SNe Ia. We also present
spectroscopic host-galaxy redshifts of some SNe Ia where these values were
previously unknown. [Abridged]Comment: 34 pages, 11 figures, 11 tables, revised version, re-submitted to
MNRAS. Spectra will be released in January 2013. The SN Database homepage
(http://hercules.berkeley.edu/database/index_public.html) contains the full
tables, plots of all spectra, and our new SNID template
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