546 research outputs found
Climate Change, Markets, and Technology
Environmental Economics and Policy, Resource /Energy Economics and Policy, Q15, Q25, Q38,
Author Response: A Meta-Analysis of Glaucoma Risk in Hyperlipidemic Individuals: A Critical Problem in Design
VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory
VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l.
in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design,
construction techniques and data acquisition system of the HAWC observatory.
HAWC is an air-shower array currently under construction at the same site of
VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water
Cherenkov detectors and two different data acquisition systems. It was in
operation between October 2011 and May 2012 with an average live time of 30%.
Besides the scientific verification purposes, the eight months of data were
used to obtain the results presented in this paper: the detector response to
the Forbush decrease of March 2012, and the analysis of possible emission, at
energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages,
10 figures). Corresponding authors: A.Marinelli and D.Zaboro
Modeling Stem Cell Induction Processes
Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols.Fundação para a Ciência e a Tecnologia (BD 42942)MIT-Portugal ProgramNational Institutes of Health (U.S.) (CA112967)Singapore–MIT Alliance for Research and TechnologyIntel Corporatio
GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells
Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.Burroughs Wellcome FundCharles E. Culpeper FoundationMassachusetts General HospitalBroad Institute of MIT and Harvar
A common variant near TGFBR3 is associated with primary open angle glaucoma
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/
licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic
contribution.We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most
significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart
from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we
observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This
particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are
regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease
pathogenesis
Why a successful task substitution in glaucoma care could not be transferred from a hospital setting to a primary care setting: A qualitative study
Background: Healthcare systems are challenged by a demand that exceeds available resources. One policy to meet this challenge is task substitution-transferring tasks to other professions and settings. Our study aimed to explore stakeholders' perceived feasibility of transferring hospital-based monitoring of stable glaucoma patients to primary care optometrists.Methods: A case study was undertaken in the Rotterdam Eye Hospital (REH) using semi-structured interviews and document reviews. They were inductively analysed using three implementation related theoretical perspectives: sociological theories on professionalism, management theories, and applied political analysis.Results: Currently it is not feasible to use primary care optometrists as substitutes for optometrists and ophthalmic technicians working in a hospital-based gl
H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation
The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.Z[superscript AP3]) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.Z[superscript AP3] interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.Z[superscript AP3] was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.Z[superscript AP3] ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.Z[superscript AP3] ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.Z[superscript AP3] displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.Z[superscript AP3] mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment.Massachusetts Life Sciences Center (David H. Koch Institute for Integrative Cancer Research at MIT Core Grant P30-CA14051)National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511)MIT Faculty Start-up FundMassachusetts Institute of Technology. Computational and Systems Biology Initiative (Merck & Co. Postdoctoral Fellowship
Study on the effects of using a carbon dioxide atmosphere on the properties of vine shoots-derived biochar
This study analyzes the effects of using a different atmosphere (pure N2 or pure CO2) at two levels of absolute pressure (0.1 and 1.1 MPa) on the pyrolysis of vine shoots at a constant peak temperature of 600 °C. Recycling CO2 from residual flue gases into the pyrolysis process may be economically beneficial, since CO2 can replace the use of an expensive N2 environment. In addition, the use of a moderate pressure (e.g., 1.1 MPa) can result in higher carbonization efficiencies and an improvement in the pyrolysis gas (in terms of yield and composition). Results from our study suggest that the use of CO2 instead of N2 as pyrolysis environment led to similar carbonization efficiencies (i.e., fixed-carbon yields) and mass yields of biochar. The chemical properties related to the potential stability of biochar (i.e., fixed-carbon content and molar H:C and O:C ratios) were very similar for both pyrolysis atmospheres. Under an atmosphere of CO2, the yield of produced CO2 was drastically decreased at the expense of an increase in the yield of CO, probably as a consequence of the promotion of the reverse Boudouard reaction, especially at high pressure. The enhanced reverse Boudouard reaction can also explain the relatively high BET specific surface area and the macro-porosity development observed for the biochar produced under a CO2 environment at 1.1 MPa. In summary, the pressurized pyrolysis of biomass under an atmosphere of CO2 appears as a very interesting route to produce highly stable and porous biochars and simultaneously improving the yield of CO
Economic Analysis of the 2016 California Drought on Agriculture: A report for the California Department of Food and Agriculture
UC Davis researchers forecast the socio-economic effects of the drought on California agriculture for 2014 and beyond. Economists use computer models and the latest estimates of water deliveries, well-pumping capacities and acres fallowed. The researchers exploit new satellite remote-sensing technologies to estimate fallowed acreage as the drought unfolds.UC Davis researchers forecast the socio-economic effects of the drought on California agriculture for 2014 and beyond. Economists use computer models and the latest estimates of water deliveries, well-pumping capacities and acres fallowed. The researchers exploit new satellite remote-sensing technologies to estimate fallowed acreage as the drought unfolds
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