108 research outputs found
Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells
<p>Abstract</p> <p>Background</p> <p>uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts.</p> <p>Methods</p> <p>To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts) to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling.</p> <p>Results</p> <p>Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. <it>In vitro </it>angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells.</p> <p>Conclusion</p> <p>Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9.</p
Machi: Neighborhood and Small Town—The Foundation for Urban Transformation in Japan
The term machi, signifying both neighborhood and small town, is a key element for understanding Japanese urban form and city planning. After tracing the origins of the term, this article explores the historic and contemporary significance of the concept and its particular spatial and socioeconomic forms. The article then argues that the concept of machi influenced the ways in which Japanese planners picked up foreign concepts through the nineteenth and particularly the twentieth century, absorbing some ideas and rejecting others. Building on their perception of the city as composed of urban units that allowed for planning in patchwork patterns, leading Japanese planners carefully selected models—independently of international appreciation—making, for example, the book The New Town by the German planner Gottfried Feder a standard reference. The article concludes by arguing that foreign observers must understand the concept of machi to comprehend contemporary Japanese neighborhoods, city life, and urban forms
Response shift in patient-reported outcomes:definition, theory, and a revised model
International audiencePurpose The extant response shift definitions and theoretical response shift models, while helpful, also introduce predicaments and theoretical debates continue. To address these predicaments and stimulate empirical research, we propose a more specific formal definition of response shift and a revised theoretical model. Methods This work is an international collaborative effort and involved a critical assessment of the literature. Results Three main predicaments were identified. First, the formal definitions of response shift need further specification and clarification. Second, previous models were focused on explaining change in the construct intended to be measured rather than explaining the construct at multiple time points and neglected the importance of using at least two time points to investigate response shift. Third, extant models do not explicitly distinguish the measure from the construct. Here we define response shift as an effect occurring whenever observed change (e.g., change in patient-reported outcome measures (PROM) scores) is not fully explained by target change (i.e., change in the construct intended to be measured). The revised model distinguishes the measure (e.g., PROM) from the underlying target construct (e.g., quality of life) at two time points. The major plausible paths are delineated, and the underlying assumptions of this model are explicated. Conclusion It is our hope that this refined definition and model are useful in the further development of response shift theory. The model with its explicit list of assumptions and hypothesized relationships lends itself for critical, empirical examination. Future studies are needed to empirically test the assumptions and hypothesized relationships
All-sky search for long-duration gravitational-wave bursts in the third Advanced LIGO and Advanced Virgo run
After the detection of gravitational waves from compact binary coalescences, the search for transient gravitational-wave signals with less well-defined waveforms for which matched filtering is not well suited is one of the frontiers for gravitational-wave astronomy. Broadly classified into “short” ≲1 s and “long” ≳1 s duration signals, these signals are expected from a variety of astrophysical processes, including non-axisymmetric deformations in magnetars or eccentric binary black hole coalescences. In this work, we present a search for long-duration gravitational-wave transients from Advanced LIGO and Advanced Virgo’s third observing run from April 2019 to March 2020. For this search, we use minimal assumptions for the sky location, event time, waveform morphology, and duration of the source. The search covers the range of 2–500 s in duration and a frequency band of 24–2048 Hz. We find no significant triggers within this parameter space; we report sensitivity limits on the signal strength of gravitational waves characterized by the root-sum-square amplitude hrss as a function of waveform morphology. These hrss limits improve upon the results from the second observing run by an average factor of 1.8
Search for anisotropic gravitational-wave backgrounds using data from Advanced LIGO and Advanced Virgo's first three observing runs
We report results from searches for anisotropic stochastic gravitational-wave
backgrounds using data from the first three observing runs of the Advanced LIGO
and Advanced Virgo detectors. For the first time, we include Virgo data in our
analysis and run our search with a new efficient pipeline called {\tt PyStoch}
on data folded over one sidereal day. We use gravitational-wave radiometry
(broadband and narrow band) to produce sky maps of stochastic
gravitational-wave backgrounds and to search for gravitational waves from point
sources. A spherical harmonic decomposition method is employed to look for
gravitational-wave emission from spatially-extended sources. Neither technique
found evidence of gravitational-wave signals. Hence we derive 95\%
confidence-level upper limit sky maps on the gravitational-wave energy flux
from broadband point sources, ranging from and on the
(normalized) gravitational-wave energy density spectrum from extended sources,
ranging from , depending on direction () and spectral index
(). These limits improve upon previous limits by factors of . We also set 95\% confidence level upper limits on the frequency-dependent
strain amplitudes of quasimonochromatic gravitational waves coming from three
interesting targets, Scorpius X-1, SN 1987A and the Galactic Center, with best
upper limits range from a factor of
improvement compared to previous stochastic radiometer searches.Comment: 23 Pages, 9 Figure
Constraints on dark photon dark matter using data from LIGO's and Virgo's third observing run
We present a search for dark photon dark matter that could couple to
gravitational-wave interferometers using data from Advanced LIGO and Virgo's
third observing run. To perform this analysis, we use two methods, one based on
cross-correlation of the strain channels in the two nearly aligned LIGO
detectors, and one that looks for excess power in the strain channels of the
LIGO and Virgo detectors. The excess power method optimizes the Fourier
Transform coherence time as a function of frequency, to account for the
expected signal width due to Doppler modulations. We do not find any evidence
of dark photon dark matter with a mass between eV/, which corresponds to frequencies between 10-2000
Hz, and therefore provide upper limits on the square of the minimum coupling of
dark photons to baryons, i.e. dark matter. For the
cross-correlation method, the best median constraint on the squared coupling is
at eV/; for the
other analysis, the best constraint is at eV/. These limits improve upon those obtained
in direct dark matter detection experiments by a factor of for
eV/, and are, in absolute terms, the
most stringent constraint so far in a large mass range eV/.Comment: 20 pages, 7 figure
Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910
We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar
All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO and Advanced Virgo O3 data
We present results of an all-sky search for continuous gravitational waves which can be produced by spinning neutron stars with an asymmetry around their rotation axis, using data from the third observing run of the Advanced LIGO and Advanced Virgo detectors. Four different analysis methods are used to search in a gravitational-wave frequency band from 10 to 2048 Hz and a first frequency derivative from to Hz/s. No statistically-significant periodic gravitational-wave signal is observed by any of the four searches. As a result, upper limits on the gravitational-wave strain amplitude are calculated. The best upper limits are obtained in the frequency range of 100 to 200 Hz and they are at 95\% confidence-level. The minimum upper limit of is achieved at a frequency 111.5 Hz. We also place constraints on the rates and abundances of nearby planetary- and asteroid-mass primordial black holes that could give rise to continuous gravitational-wave signals
- …