1,854 research outputs found
Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats
This protocol describes the use of in vitro television microscopy to evaluate vascular function in isolated cerebral resistance arteries (and other vessels), and describes techniques for evaluating tissue perfusion using Laser Doppler Flowmetry (LDF) and microvessel density utilizing fluorescently labeled Griffonia simplicifolia (GS1) lectin. Current methods for studying isolated resistance arteries at transmural pressures encountered in vivo and in the absence of parenchymal cell influences provide a critical link between in vivo studies and information gained from molecular reductionist approaches that provide limited insight into integrative responses at the whole animal level. LDF and techniques to selectively identify arterioles and capillaries with fluorescently-labeled GS1 lectin provide practical solutions to enable investigators to extend the knowledge gained from studies of isolated resistance arteries. This paper describes the application of these techniques to gain fundamental knowledge of vascular physiology and pathology in the rat as a general experimental model, and in a variety of specialized genetically engineered designer rat strains that can provide important insight into the influence of specific genes on important vascular phenotypes. Utilizing these valuable experimental approaches in rat strains developed by selective breeding strategies and new technologies for producing gene knockout models in the rat, will expand the rigor of scientific premises developed in knockout mouse models and extend that knowledge to a more relevant animal model, with a well understood physiological background and suitability for physiological studies because of its larger size
Type II Quasars from the Sloan Digital Sky Survey: V. Imaging host galaxies with the Hubble Space Telescope
Type II quasars are luminous Active Galactic Nuclei whose centers are
obscured by large amounts of gas and dust. In this paper we present 3-band HST
images of nine type II quasars with redshifts 0.2 < z < 0.4 selected from the
Sloan Digital Sky Survey based on their emission line properties. The intrinsic
luminosities of these AGN are estimated to be -24 > M_B > -26, but optical
obscuration allows their host galaxies to be studied unencumbered by bright
nuclei. Each object has been imaged in three continuum filters (`UV', `blue'
and `yellow') placed between the strong emission lines. The spectacular, high
quality images reveal a wealth of details about the structure of the host
galaxies and their environments. Six of the nine galaxies in the sample are
ellipticals with de Vaucouleurs light profiles, one object has a well-defined
disk component and the remaining two have marginal disks. Stellar populations
of type II quasar hosts are more luminous (by a median of 0.3-0.7 mag,
depending on the wavelength) and bluer (by about 0.4 mag) than are M* galaxies
at the same redshift. When smooth fits to stellar light are subtracted from the
images, we find both positive and negative residuals that become more prominent
toward shorter wavelengths. We argue that the negative residuals are due to
kpc-scale dust obscuration, while most positive residuals are due to the light
from the nucleus scattered off interstellar material in the host galaxy.
Scattered light makes a significant contribution to the broad band continuum
emission and can be the dominant component of the extended emission in the UV
in extreme cases.Comment: 51 pages, including 12 grey scale figures, 4 color figures, 5 tables.
In press in AJ. Version with higher-resolution images available at
http://www.astro.princeton.edu/~nadia/qso2.html. (Minor changes in response
to the referee report
Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer
SummaryChromosomal instability in human breast cancer is known to take place before mammary neoplasias display morphological signs of invasion. We describe here the unexpected finding of a tumor cell population with normal karyotypes isolated from bone marrow of breast cancer patients. By analyzing the same single cells for chromosomal aberrations, subchromosomal allelic losses, and gene amplifications, we confirmed their malignant origin and delineated the sequence of genomic events during breast cancer progression. On this trajectory of genomic progression, we identified a subpopulation of patients with very early HER2 amplification. Because early changes have the highest probability of being shared by genetically unstable tumor cells, the genetic characterization of disseminated tumor cells provides a novel rationale for selecting patients for targeted therapies
Radial Mixing in Galactic Disks: The Effects of Disk Structure and Satellite Bombardment
We use a suite of numerical simulations to investigate the mechanisms and
effects of radial migration of stars in disk galaxies like the Milky Way (MW).
An isolated, collisionless stellar disk with a MW-like scale-height shows only
the radial "blurring" expected from epicyclic orbits. Reducing the disk
thickness or adding gas to the disk substantially increases the level of radial
migration, induced by interaction with transient spiral arms and/or a central
bar. We also examine collisionless disks subjected to gravitational
perturbations from a cosmologically motivated satellite accretion history. In
the perturbed disk that best reproduces the observed properties of the MW, 20%
of stars that end up in the solar annulus 7 kpc < R < 9 kpc started at R < 6
kpc, and 7% started at R > 10 kpc. This level of migration would add
considerable dispersion to the age-metallicity relation of solar neighborhood
stars. In the isolated disk models, the probability of migration traces the
disk's radial mass profile, but in perturbed disks migration occurs
preferentially at large radii, where the disk is more weakly bound. The orbital
dynamics of migrating particles are also different in isolated and perturbed
disks: satellite perturbations drive particles to lower angular momentum for a
given change in radius. Thus, satellite perturbations appear to be a distinct
mechanism for inducing radial migration, which can operate in concert with
migration induced by bars and spiral structure. We investigate correlations
between changes in radius and changes in orbital circularity or vertical
energy, identifying signatures that might be used to test models and
distinguish radial migration mechanisms in chemo-dynamical surveys of the MW
disk.Comment: Full resolution paper available at
http://www.astronomy.ohio-state.edu/~bird/bkw11_fullres.pdf . 13 pages, 12
figures; emulate MNRAS format. Accepted for publication in MNRA
Candidate Type II Quasars from the SDSS: III. Spectropolarimetry Reveals Hidden Type I Nuclei
We have conducted spectropolarimetry of 12 type II (obscured) quasar
candidates selected from the spectroscopic database of the Sloan Digital Sky
Survey based on their emission line properties. Polarization was detected in
all objects, with nine being highly polarized (> 3%) and with polarization
reaching as high as 17% in two objects. Broad lines were detected in the
polarized spectra of five objects. These observations prove beyond a reasonable
doubt that the objects in our sample are indeed type II quasars, in that they
harbor luminous UV-excess AGNs in their centers and that the direct view to the
AGN is highly obscured. For three of the objects in this paper, we have
obtained HST images in three bands. The HST observations, combined with the
spectropolarimetry data, imply that scattering off material outside the
obscuration plane is the dominant polarization mechanism. In all three objects
the sizes of scattering regions are a few kpc. For one object, the extent of
the scattering region, coupled with the characteristics of the polarized
spectrum, argue strongly that dust scattering rather than electron scattering
dominates the polarized light. Our observations are well-described by the basic
orientation-based unification model of toroidal obscuration and off-plane
scattering, implying that the model can be extended to include at least some
high-luminosity AGNs.Comment: 31 pages including 4 b/w pictures, 1 color HST image and 2 tables.
Submitted to AJ on Sept 26, accepted for March 2005. Minor modifications to
match the accepted versio
Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation
Hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis, is a progressive disease, for which liver transplantation (LT) has been a long-standing treatment. However, disease progression continues post-LT. This Phase 3b, open-label trial evaluated efficacy and safety of patisiran in patients with ATTRv amyloidosis with polyneuropathy progression post-LT. Primary endpoint was median transthyretin (TTR) reduction from baseline. Twenty-three patients received patisiran for 12 months alongside immunosuppression regimens. Patisiran elicited a rapid, sustained TTR reduction (median reduction [Months 6 and 12 average], 91.0%; 95% CI: 86.1%-92.3%); improved neuropathy, quality of life, and autonomic symptoms from baseline to Month 12 (mean change [SEM], Neuropathy Impairment Score, -3.7 [2.7]; Norfolk Quality of Life-Diabetic Neuropathy questionnaire, -6.5 [4.9]; least-squares mean [SEM], Composite Autonomic Symptom Score-31, -5.0 [2.6]); and stabilized disability (Rasch-built Overall Disability Scale) and nutritional status (modified body mass index). Adverse events were mild or moderate; five patients experienced ≥1 serious adverse event. Most patients had normal liver function tests. One patient experienced transplant rejection consistent with inadequate immunosuppression, remained on patisiran, and completed the study. In conclusion, patisiran reduced serum TTR, was well tolerated, and improved or stabilized key disease impairment measures in patients with ATTRv amyloidosis with polyneuropathy progression post-LT (www.clinicaltrials.gov NCT03862807)
Teaching Mathematics with Technology: TPACK and Effective Teaching Practices
This paper examines how 17 secondary mathematics teacher candidates (TCs) in four university teacher preparation programs implemented technology in their classrooms to teach for conceptual understanding in online, hybrid, and face to face classes during COVID-19. Using the Professional Development: Research, Implementation, and Evaluation (PrimeD) framework, TCs, classroom mentor teachers, field experience supervisors, and university faculty formed a Networked Improvement Community (NIC) to discuss a commonly agreed upon problem of practice and a change idea to implement in the classroom. Through Plan-Do-Study-Act cycles, participants documented their improvement efforts and refinements to the change idea and then reported back to the NIC at the subsequent monthly meeting. The Technology Pedagogical Content Knowledge framework (TPACK) and the TPACK levels rubric were used to examine how teacher candidates implemented technology for Mathematics conceptual understanding. The Mathematics Classroom Observation Protocol for Practices (MCOP2) was used to further examine how effective mathematics teaching practices (e.g., student engagement) were implemented by TCs. MCOP2 results indicated that TCs increased their use of effective mathematics teaching practices. However, growth in TPACK was not significant. A relationship between TPACK and MCOP2 was not evident, indicating a potential need for explicit focus on using technology for mathematics conceptual understanding
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
This study explores how researchers’ analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers’ expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team’s workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers’ results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings
Frequency and evolution of sleep-wake disturbances after ischemic stroke: A 2-year prospective study of 437 patients.
OBJECTIVE
In the absence of systematic and longitudinal data, this study prospectively assessed both frequency and evolution of sleep-wake disturbances (SWD) after stroke.
METHODS
In 437 consecutively recruited patients with ischemic stroke or transient ischemic attack (TIA), stroke characteristics and outcome were assessed within the 1st week and 3.2 ± 0.3 years (M±SD) after the acute event. SWD were assessed by interview and questionnaires at 1 and 3 months as well as 1 and 2 years after the acute event. Sleep disordered breathing (SDB) was assessed by respirography in the acute phase and repeated in one fifth of the participants 3 months and 1 year later.
RESULTS
Patients (63.8% male, 87% ischemic stroke and mean age 65.1 ± 13.0 years) presented with mean NIHSS-score of 3.5 ± 4.5 at admission. In the acute phase, respiratory event index was >15/h in 34% and >30/h in 15% of patients. Over the entire observation period, the frequencies of excessive daytime sleepiness (EDS), fatigue and insomnia varied between 10-14%, 22-28% and 20-28%, respectively. Mean insomnia and EDS scores decreased from acute to chronic stroke, whereas restless legs syndrome (RLS) percentages (6-9%) and mean fatigue scores remained similar. Mean self-reported sleep duration was enhanced at acute stroke (month 1: 07:54 ± 01:27h) and decreased at chronic stage (year 2: 07:43 ± 01:20h).
CONCLUSIONS
This study documents a high frequency of SDB, insomnia, fatigue and a prolonged sleep duration after stroke/TIA, which can persist for years. Considering the negative effects of SWD on physical, brain and mental health these data suggest the need for a systematic assessment and management of post-stroke SWD
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