1,792 research outputs found
Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.
Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease
Analysis of the In Vivo Transcriptome of Bordetella pertussis during Infection of Mice
Bordetella pertussis causes the disease whooping cough through coordinated control of virulence factors by the Bordetella virulence gene system. Microarrays and, more recently, RNA sequencing (RNA-seq) have been used to describe in vitro gene expression profiles of B. pertussis and other pathogens. In previous studies, we have analyzed the in vitro gene expression profiles of B. pertussis, and we hypothesize that the infection transcriptome profile in vivo is significantly different from that under laboratory growth conditions. To study the infection transcriptome of B. pertussis, we developed a simple filtration technique for isolation of bacteria from infected lungs. The work flow involves filtering the bacteria out of the lung homogenate using a 5-μm-pore-size syringe filter. The captured bacteria are then lysed to isolate RNA for Illumina library preparation and RNA-seq analysis. Upon comparing the in vitro and in vivo gene expression profiles, we identified 351 and 255 genes as activated and repressed, respectively, during murine lung infection. As expected, numerous genes associated with virulent-phase growth were activated in the murine host, including pertussis toxin (PT), the PT secretion apparatus, and the type III secretion system. A significant number of genes encoding iron acquisition and heme uptake proteins were highly expressed during infection, supporting iron acquisition as critical for B. pertussis survival in vivo. Numerous metabolic genes were repressed during infection. Overall, these data shed light on the gene expression profile of B. pertussisduring infection, and this method will facilitate efforts to understand how this pathogen causes infection
Acceleration of generalized hypergeometric functions through precise remainder asymptotics
We express the asymptotics of the remainders of the partial sums {s_n} of the
generalized hypergeometric function q+1_F_q through an inverse power series z^n
n^l \sum_k c_k/n^k, where the exponent l and the asymptotic coefficients {c_k}
may be recursively computed to any desired order from the hypergeometric
parameters and argument. From this we derive a new series acceleration
technique that can be applied to any such function, even with complex
parameters and at the branch point z=1. For moderate parameters (up to
approximately ten) a C implementation at fixed precision is very effective at
computing these functions; for larger parameters an implementation in higher
than machine precision would be needed. Even for larger parameters, however,
our C implementation is able to correctly determine whether or not it has
converged; and when it converges, its estimate of its error is accurate.Comment: 36 pages, 6 figures, LaTeX2e. Fixed sign error in Eq. (2.28), added
several references, added comparison to other methods, and added discussion
of recursion stabilit
Epitaxial Graphene Growth on SiC Wafers
An in vacuo thermal desorption process has been accomplished to form
epitaxial graphene (EG) on 4H- and 6H-SiC substrates using a commercial
chemical vapor deposition reactor. Correlation of growth conditions and the
morphology and electrical properties of EG are described. Raman spectra of EG
on Si-face samples were dominated by monolayer thickness. This approach was
used to grow EG on 50 mm SiC wafers that were subsequently fabricated into
field effect transistors with fmax of 14 GHz.Comment: 215th Meeting of the Electrochemical Society, 8 pages, 8 figure
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
Prognostic value of abdominal aortic calcification: A systematic review and meta‐analysis of observational studies
Background
The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results
We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all‐cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random‐effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older‐elderly (median, 68 years; range, 60–80 years) populations (26%) had sufficient data to meta‐analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40–2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44–2.39), and all‐cause mortality (RR, 1.98; 95% CI, 1.55–2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21–5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32–5.84), and all‐cause mortality (RR, 2.40; 95% CI, 1.95–2.97). Conclusions
Higher‐risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients\u27 cardiovascular risk better
High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo
Learning perceptually grounded word meanings from unaligned parallel data
In order for robots to effectively understand natural language commands, they must be able to acquire meaning representations that can be mapped to perceptual features in the external world. Previous approaches to learning these grounded meaning representations require detailed annotations at training time. In this paper, we present an approach to grounded language acquisition which is capable of jointly learning a policy for following natural language commands such as “Pick up the tire pallet,” as well as a mapping between specific phrases in the language and aspects of the external world; for example the mapping between the words “the tire pallet” and a specific object in the environment. Our approach assumes a parametric form for the policy that the robot uses to choose actions in response to a natural language command that factors based on the structure of the language. We use a gradient method to optimize model parameters. Our evaluation demonstrates the effectiveness of the model on a corpus of commands given to a robotic forklift by untrained users.U.S. Army Research Laboratory (Collaborative Technology Alliance Program, Cooperative Agreement W911NF-10-2-0016)United States. Office of Naval Research (MURIs N00014-07-1-0749)United States. Army Research Office (MURI N00014-11-1-0688)United States. Defense Advanced Research Projects Agency (DARPA BOLT program under contract HR0011-11-2-0008
Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample
In the epoch of precise and accurate cosmology, cross-confirmation using a
variety of cosmographic methods is paramount to circumvent systematic
uncertainties. Owing to progenitor histories and explosion physics differing
from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are
unlikely to be affected by evolution in the same way. Based on a new analysis
of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good
standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble
diagram with a dispersion of 10% in distance, using the simple correlation
between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002.
We show that the descendent method of Nugent et al. 2006 can be further
simplified and that the correction for dust extinction has low statistical
impact. We find that our SN sample favors, on average, a very steep dust law
with total to selective extinction R_V<2. Such an extinction law has been
recently inferred for many SNe Ia. Our results indicate that a distance
measurement can be obtained with a single spectrum of a SN II-P during the
plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change
Thresholds for adding degraded tropical forest to the conservation estate
Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2, 3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked
- …