423 research outputs found
The Peculiar SN 2005hk: Do Some Type Ia Supernovae Explode as Deflagrations?
We present extensive u'g'r'i'BVRIYJHKs photometry and optical spectroscopy of
SN 2005hk. These data reveal that SN 2005hk was nearly identical in its
observed properties to SN 2002cx, which has been called ``the most peculiar
known type Ia supernova.'' Both supernovae exhibited high ionization SN
1991T-like pre-maximum spectra, yet low peak luminosities like SN 1991bg. The
spectra reveal that SN 2005hk, like SN 2002cx, exhibited expansion velocities
that were roughly half those of typical type Ia supernovae. The R and I light
curves of both supernovae were also peculiar in not displaying the secondary
maximum observed for normal type Ia supernovae. Our YJH photometry of SN 2005hk
reveals the same peculiarity in the near-infrared. By combining our optical and
near-infrared photometry of SN 2005hk with published ultraviolet light curves
obtained with the Swift satellite, we are able to construct a bolometric light
curve from ~10 days before to ~60 days after B maximum. The shape and unusually
low peak luminosity of this light curve, plus the low expansion velocities and
absence of a secondary maximum at red and near-infrared wavelengths, are all in
reasonable agreement with model calculations of a 3D deflagration which
produces ~0.25 M_sun of 56Ni.Comment: Accepted by PASP, to appear in April 2007 issue, 63 pages, 16
figures, 11 table
The WiggleZ Dark Energy Survey: measuring the cosmic expansion history using the Alcock-Paczynski test and distant supernovae
Astronomical observations suggest that today's Universe is dominated by a
dark energy of unknown physical origin. One of the most notable consequences in
many models is that dark energy should cause the expansion of the Universe to
accelerate: but the expansion rate as a function of time has proven very
difficult to measure directly. We present a new determination of the cosmic
expansion history by combining distant supernovae observations with a
geometrical analysis of large-scale galaxy clustering within the WiggleZ Dark
Energy Survey, using the Alcock-Paczynski test to measure the distortion of
standard spheres. Our result constitutes a robust and non-parametric
measurement of the Hubble expansion rate as a function of time, which we
measure with 10-15% precision in four bins within the redshift range 0.1 < z <
0.9. We demonstrate that the cosmic expansion is accelerating, in a manner
independent of the parameterization of the cosmological model (although
assuming cosmic homogeneity in our data analysis). Furthermore, we find that
this expansion history is consistent with a cosmological-constant dark energy.Comment: 13 pages, 7 figures, accepted for publication by MNRA
The Sloan Digital Sky Survey-II Supernova Survey: Search Algorithm and Follow-up Observations
The Sloan Digital Sky Survey-II Supernova Survey has identified a large
number of new transient sources in a 300 sq. deg. region along the celestial
equator during its first two seasons of a three-season campaign. Multi-band
(ugriz) light curves were measured for most of the sources, which include solar
system objects, Galactic variable stars, active galactic nuclei, supernovae
(SNe), and other astronomical transients. The imaging survey is augmented by an
extensive spectroscopic follow-up program to identify SNe, measure their
redshifts, and study the physical conditions of the explosions and their
environment through spectroscopic diagnostics. During the survey, light curves
are rapidly evaluated to provide an initial photometric type of the SNe, and a
selected sample of sources are targeted for spectroscopic observations. In the
first two seasons, 476 sources were selected for spectroscopic observations, of
which 403 were identified as SNe. For the Type Ia SNe, the main driver for the
Survey, our photometric typing and targeting efficiency is 90%. Only 6% of the
photometric SN Ia candidates were spectroscopically classified as non-SN Ia
instead, and the remaining 4% resulted in low signal-to-noise, unclassified
spectra. This paper describes the search algorithm and the software, and the
real-time processing of the SDSS imaging data. We also present the details of
the supernova candidate selection procedures and strategies for follow-up
spectroscopic and imaging observations of the discovered sources.Comment: Accepted for publication in The Astronomical Journal (66 pages, 13
figures); typos correcte
Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC
The uncertainty on the calorimeter energy response to jets of particles is
derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the
calorimeter response to single isolated charged hadrons is measured and
compared to the Monte Carlo simulation using proton-proton collisions at
centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009
and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter
response to specific types of particles (positively and negatively charged
pions, protons, and anti-protons) is measured and compared to the Monte Carlo
predictions. Finally, the jet energy scale uncertainty is determined by
propagating the response uncertainty for single charged and neutral particles
to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3%
for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table,
submitted to European Physical Journal
A multi-targeted approach to suppress tumor-promoting inflammation
Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes
The WiggleZ Dark Energy Survey: Joint measurements of the expansion and growth history at z < 1
We perform a joint determination of the distance-redshift relation and cosmic
expansion rate at redshifts z = 0.44, 0.6 and 0.73 by combining measurements of
the baryon acoustic peak and Alcock-Paczynski distortion from galaxy clustering
in the WiggleZ Dark Energy Survey, using a large ensemble of mock catalogues to
calculate the covariance between the measurements. We find that D_A(z) = (1205
+/- 114, 1380 +/- 95, 1534 +/- 107) Mpc and H(z) = (82.6 +/- 7.8, 87.9 +/- 6.1,
97.3 +/- 7.0) km/s/Mpc at these three redshifts. Further combining our results
with other baryon acoustic oscillation and distant supernovae datasets, we use
a Monte Carlo Markov Chain technique to determine the evolution of the Hubble
parameter H(z) as a stepwise function in 9 redshift bins of width dz = 0.1,
also marginalizing over the spatial curvature. Our measurements of H(z), which
have precision better than 7% in most redshift bins, are consistent with the
expansion history predicted by a cosmological-constant dark-energy model, in
which the expansion rate accelerates at redshift z < 0.7.Comment: 11 pages, 11 figures, accepted for publication in MNRA
Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer
Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866
Plexin-B2 Negatively Regulates Macrophage Motility, Rac, and Cdc42 Activation
Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2−/− macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2−/− macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing
Enzymatic capacities of metabolic fuel use in cuttlefish (Sepia officinalis) and responses to food deprivation: insight into the metabolic organization and starvation survival strategy of cephalopods
Food limitation is a common challenge for animals. Cephalopods are sensitive to starvation because of high metabolic rates and growth rates related to their "live fast, die young" life history. We investigated how enzymatic capacities of key metabolic pathways are modulated during starvation in the common cuttlefish (Sepia officinalis) to gain insight into the metabolic organization of cephalopods and their strategies for coping with food limitation. In particular, lipids have traditionally been considered unimportant fuels in cephalopods, yet, puzzlingly, many species (including cuttlefish) mobilize the lipid stores in their digestive gland during starvation. Using a comprehensive multi-tissue assay of enzymatic capacities for energy metabolism, we show that, during long-term starvation (12 days), glycolytic capacity for glucose use is decreased in cuttlefish tissues, while capacities for use of lipid-based fuels (fatty acids and ketone bodies) and amino acid fuels are retained or increased. Specifically, the capacity to use the ketone body acetoacetate as fuel is widespread across tissues and gill has a previously unrecognized capacity for fatty acid catabolism, albeit at low rates. The capacity for de novo glucose synthesis (gluconeogenesis), important for glucose homeostasis, likely is restricted to the digestive gland, contrary to previous reports of widespread gluconeogenesis among cephalopod tissues. Short-term starvation (3-5 days) had few effects on enzymatic capacities. Similar to vertebrates, lipid-based fuels, putatively mobilized from fat stores in the digestive gland, appear to be important energy sources for cephalopods, especially during starvation when glycolytic capacity is decreased perhaps to conserve available glucose
Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes. An Individual-Participant Data Meta-Analysis
IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). CONCLUSIONS AND RELEVANCE: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations
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