This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are ...presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg2 area along the celestial equator. This data release is comprised of all transient sources brighter than r 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN Ia sample and assuming a flat ΛCDM cosmology, we determine M = 0.315 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 .
Summary Objectives To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). Methods OPC treated with ...RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(−) cohorts. Results Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p = 0.25) between the HPV(+) ( n = 457) vs. the HPV(−) ( n = 167) cases. While almost all (24/25) HPV(−) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(−). Post-DM survival rates were 11% vs. 4% at 2-years ( p = 0.02) for the HPV(+) vs. HPV(−) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Conclusions Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(−) patients: it may occur after a longer interval, often with a “disseminating” phenotype, and a small number may have prolonged survival after salvage for DM.
Radiation-associated kidney injury Dawson, Laura A; Kavanagh, Brian D; Paulino, Arnold C ...
International journal of radiation oncology, biology, physics,
03/2010, Letnik:
76, Številka:
3 Suppl
Journal Article
Recenzirano
The kidneys are the dose-limiting organs for radiotherapy to upper abdominal cancers and during total body irradiation. The incidence of radiotherapy-associated kidney injury is likely underreported ...owing to its long latency and because the toxicity is often attributed to more common causes of kidney injury. The pathophysiology of radiation injury is poorly understood. Its presentation can be acute and irreversible or subtle, with a gradual progressive dysfunction over years. A variety of dose and volume parameters have been associated with renal toxicity and are reviewed to provide treatment guidelines. The available predictive models are suboptimal and require validation. Mitigation of radiation nephropathy with angiotensin-converting enzyme inhibitors and other compounds has been shown in animal models and, more recently, in patients.
We present constraints on the physical properties (including stellar mass, age, and star formation rate) of 207 \(6\lesssim z \lesssim8\) galaxy candidates from the Reionization Lensing Cluster ...Survey (RELICS) and companion Spitzer-RELICS surveys. We measure photometry using T-PHOT and perform spectral energy distribution fitting using EA\(z\)Y and BAGPIPES. Of the 207 candidates for which we could successfully measure Spitzer fluxes, 23 were demoted to likely low redshift (\(z<4\)). Among the remaining high redshift candidates, we find intrinsic stellar masses between \(1\times10^6\rm{M_{\odot}}\) and \(4\times10^9\rm{M_\odot}\), and rest-frame UV absolute magnitudes between \(-22.6\) and \(-14.5\) mag. While our sample is mostly comprised of \(L_{UV}/L^*_{UV}<1\) galaxies, there are a number of brighter objects in the sample, extending to \(L_{UV}/L^*_{UV}\sim2\). The galaxies in our sample span approximately four orders of magnitude in stellar mass and star-formation rates, and exhibit ages ranging from maximally young to maximally old. We highlight 11 galaxies which have detections in Spitzer/IRAC imaging and redshift estimates \(z\geq6.5\), several of which show evidence for some combination of evolved stellar populations, large contributions of nebular emission lines, and/or dust. Among these is PLCKG287+32-2013, one of the brightest \(z\sim7\) candidates known (AB mag 24.9) with a Spitzer 3.6\(\mu\)m flux excess suggesting strong OIII + H-\(\beta\) emission (\(\sim\)1000\AA\ rest-frame equivalent width). We discuss the possible uses and limits of our sample and present a public catalog of Hubble 0.4--1.6\(\mu\)m + Spitzer 3.6\(\mu\)m and 4.5\(\mu\)m photometry along with physical property estimates for all 207 objects in the sample. Because of their apparent brightnesses, high redshifts, and variety of stellar populations, these objects are excellent targets for follow-up with James Webb Space Telescope.
Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we ...demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent.
Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. However, a drug that directly couples targeting of a metabolic dependency with the induction of ...cell death in cancer cells has largely remained elusive. Here we report that the drug-like small-molecule ironomycin reduces the mitochondrial iron load, resulting in the potent disruption of mitochondrial metabolism. Ironomycin promotes the recruitment and activation of BAX/BAK, but the resulting mitochondrial outer membrane permeabilization (MOMP) does not lead to potent activation of the apoptotic caspases, nor is the ensuing cell death prevented by inhibiting the previously established pathways of programmed cell death. Consistent with the fact that ironomycin and BH3 mimetics induce MOMP through independent nonredundant pathways, we find that ironomycin exhibits marked in vitro and in vivo synergy with venetoclax and overcomes venetoclax resistance in primary patient samples.
Ironomycin couples targeting of cellular metabolism with cell death by reducing mitochondrial iron, resulting in the alteration of mitochondrial metabolism and the activation of BAX/BAK. Ironomycin induces MOMP through a different mechanism to BH3 mimetics, and consequently combination therapy has marked synergy in cancers such as acute myeloid leukemia. This article is highlighted in the In This Issue feature, p. 587.
To assess the efficiency of target-enrichment next-generation sequencing (NGS) with copy number assessment in inherited neuropathy diagnosis.
A 197 polyneuropathy gene panel was designed to assess ...for mutations in 93 patients with inherited or idiopathic neuropathy without known genetic cause. We applied our novel copy number variation algorithm on NGS data, and validated the identified copy number mutations using CytoScan (Affymetrix). Cost and efficacy of this targeted NGS approach was compared to earlier evaluations.
Average coverage depth was ∼760× (median = 600, 99.4% > 100×). Among 93 patients, 18 mutations were identified in 17 cases (18%), including 3 copy number mutations: 2 PMP22 duplications and 1 MPZ duplication. The 2 patients with PMP22 duplication presented with bulbar and respiratory involvement and had absent extremity nerve conductions, leading to axonal diagnosis. Average onset age of these 17 patients was 25 years (2-61 years), vs 45 years for those without genetic discovery. Among those with onset age less than 40 years, the diagnostic yield of targeted NGS approach is high (27%) and cost savings is significant (∼20%). However, the cost savings for patients with late onset age and without family history is not demonstrated.
Incorporating copy number analysis in target-enrichment NGS approach improved the efficiency of mutation discovery for chronic, inherited, progressive length-dependent polyneuropathy diagnosis. The new technology is facilitating a simplified genetic diagnostic algorithm utilizing targeted NGS, clinical phenotypes, age at onset, and family history to improve diagnosis efficiency. Our findings prompt a need for updating the current practice parameters and payer guidelines.
Osteoarthritis (OA) is a common degenerative condition that afflicts more than 70% of the population between 55 and 77 years of age. Although its prevalence is rising globally with aging of the ...population, current therapy is limited to symptomatic relief and, in severe cases, joint replacement surgery. We report that intra-articular expression of proteoglycan 4 (Prg4) in mice protects against development of OA. Long-term Prg4 expression under the type II collagen promoter (Col2a1) does not adversely affect skeletal development but protects from developing signs of age-related OA. The protective effect is also shown in a model of posttraumatic OA created by cruciate ligament transection. Moreover, intra-articular injection of helper-dependent adenoviral vector expressing Prg4 protected against the development of posttraumatic OA when administered either before or after injury. Gene expression profiling of mouse articular cartilage and in vitro cell studies show that Prg4 expression inhibits the transcriptional programs that promote cartilage catabolism and hypertrophy through the up-regulation of hypoxia-inducible factor 3α. Analyses of available human OA data sets are consistent with the predictions of this model. Hence, our data provide insight into the mechanisms for OA development and offer a potential chondroprotective approach to its treatment.
The second most significant detection of the Planck Sunyaev Zel'dovich
survey, PLCK~G287.0+32.9 ($z=0.385$) boasts two similarly bright radio relics
and a radio halo. One radio relic is located $\sim ...400$ kpc northwest of the
X-ray peak and the other $\sim 2.8$ Mpc to the southeast. This large difference
suggests that a complex merging scenario is required. A key missing puzzle for
the merging scenario reconstruction is the underlying dark matter distribution
in high resolution. We present a joint Subaru Telescope and {\it Hubble Space
Telescope} weak-lensing analysis of the cluster. Our analysis shows that the
mass distribution features four significant substructures. Of the
substructures, a primary cluster of mass
$M_{200\text{c}}=1.59^{+0.25}_{-0.22}\times 10^{15} \ h^{-1}_{70} \
\text{M}_{\odot}$ dominates the weak-lensing signal. This cluster is likely to
be undergoing a merger with one (or more) subcluster whose mass is
approximately a factor of 10 lower. One candidate is the subcluster of mass
$M_{200\text{c}}=1.16^{+0.15}_{-0.13}\times 10^{14} \ h^{-1}_{70} \
\text{M}_{\odot}$ located $\sim 400$ kpc to the southeast. The location of this
subcluster suggests that its interaction with the primary cluster could be the
source of the NW radio relic. Another subcluster is detected $\sim 2$ Mpc to
the SE of the X-ray peak with mass $M_{200\text{c}}=1.68^{+0.22}_{-0.20}\times
10^{14} \ h^{-1}_{70} \ \text{M}_{\odot}$. This SE subcluster is in the
vicinity of the SE radio relic and may have created the SE radio relic during a
past merger with the primary cluster. The fourth subcluster,
$M_{200\text{c}}=1.87^{+0.24}_{-0.22}\times 10^{14} \ h^{-1}_{70} \
\text{M}_{\odot}$, is northwest of the X-ray peak and beyond the NW radio
relic.
PDF
