253 research outputs found

    LSST: from Science Drivers to Reference Design and Anticipated Data Products

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    (Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2^2 field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5σ\sigma point-source depth in a single visit in rr will be 24.5\sim 24.5 (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg2^2 with δ<+34.5\delta<+34.5^\circ, and will be imaged multiple times in six bands, ugrizyugrizy, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg2^2 region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to r27.5r\sim27.5. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

    The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

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    BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

    Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

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    Background: Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90 + liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90 + cells sorted from tumor (CD90 +CSCs) with parallel non-tumorous liver tissues (CD90 +NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings: CD90 + cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90 + cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90 +CSCs and CD90 +NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90 +CSCs and CD90 +NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90 +CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90 +CSCs compared to CD90 +NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90 +CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90 +CSCs in liver tumor tissues. Conclusions/Significance: The identified genes, such as GPC3 that are distinctly expressed in liver CD90 +CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells. © 2012 Ho et al.published_or_final_versio

    Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

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    Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

    Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

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    The realtime follow-up of neutrino events is a promising approach to searchfor astrophysical neutrino sources. It has so far provided compelling evidencefor a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observedin coincidence with the high-energy neutrino IceCube-170922A detected byIceCube. The detection of very-high-energy gamma rays (VHE, E>100GeV\mathrm{E} >100\,\mathrm{GeV}) from this source helped establish the coincidence andconstrained the modeling of the blazar emission at the time of the IceCubeevent. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) -FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program oftarget-of-opportunity observations of neutrino alerts sent by IceCube. Thisprogram has two main components. One are the observations of known gamma-raysources around which a cluster of candidate neutrino events has been identifiedby IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of singlehigh-energy neutrino candidate events of potential astrophysical origin such asIceCube-170922A. GFU has been recently upgraded by IceCube in collaborationwith the IACT groups. We present here recent results from the IACT follow-upprograms of IceCube neutrino alerts and a description of the upgraded IceCubeGFU system.<br

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

    Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

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    Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

    Measurement of associated W plus charm production in pp collisions at √s=7 TeV

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