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  • 1
    Publication Date: 2014-03-29
    Description: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Chromosomes, Fungal/genetics/metabolism ; DNA, Fungal/genetics ; Genes, Fungal ; Genetic Fitness ; Genome, Fungal ; Genomic Instability ; Introns ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; RNA, Fungal/genetics ; RNA, Transfer/genetics ; Saccharomyces cerevisiae/cytology/*genetics/physiology ; Sequence Analysis, DNA ; Sequence Deletion ; Synthetic Biology/*methods ; Transformation, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-09-16
    Description: Recent advances in DNA synthesis technology have enabled the construction of novel genetic pathways and genomic elements, furthering our understanding of system-level phenomena. The ability to synthesize large segments of DNA allows the engineering of pathways and genomes according to arbitrary sets of design principles. Here we describe a synthetic yeast genome project, Sc2.0, and the first partially synthetic eukaryotic chromosomes, Saccharomyces cerevisiae chromosome synIXR, and semi-synVIL. We defined three design principles for a synthetic genome as follows: first, it should result in a (near) wild-type phenotype and fitness; second, it should lack destabilizing elements such as tRNA genes or transposons; and third, it should have genetic flexibility to facilitate future studies. The synthetic genome features several systemic modifications complying with the design principles, including an inducible evolution system, SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution). We show the utility of SCRaMbLE as a novel method of combinatorial mutagenesis, capable of generating complex genotypes and a broad variety of phenotypes. When complete, the fully synthetic genome will allow massive restructuring of the yeast genome, and may open the door to a new type of combinatorial genetics based entirely on variations in gene content and copy number.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774833/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dymond, Jessica S -- Richardson, Sarah M -- Coombes, Candice E -- Babatz, Timothy -- Muller, Heloise -- Annaluru, Narayana -- Blake, William J -- Schwerzmann, Joy W -- Dai, Junbiao -- Lindstrom, Derek L -- Boeke, Annabel C -- Gottschling, Daniel E -- Chandrasegaran, Srinivasan -- Bader, Joel S -- Boeke, Jef D -- AG023779/AG/NIA NIH HHS/ -- R01 AG023779/AG/NIA NIH HHS/ -- R37 AG023779/AG/NIA NIH HHS/ -- England -- Nature. 2011 Sep 14;477(7365):471-6. doi: 10.1038/nature10403.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉High Throughput Biology Center, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21918511" target="_blank"〉PubMed〈/a〉
    Keywords: Attachment Sites, Microbiological/genetics ; Chromosomes, Artificial, Yeast/*genetics ; Directed Molecular Evolution/methods ; Gene Dosage/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Genetic Engineering/*methods ; Genetic Fitness/genetics ; Genome, Fungal/genetics ; Genotype ; Haploidy ; Molecular Sequence Data ; Mutagenesis/genetics ; Phenotype ; RNA, Fungal/analysis/genetics ; Saccharomyces cerevisiae/classification/*genetics ; Synthetic Biology/*methods
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Keywords: THERAPY ; PATIENT ; TRIALS ; AGE ; REPRODUCIBILITY ; POSTMENOPAUSAL WOMEN ; REQUIRING PROLONGED OBSERVATION ; RECALL ; COLLABORATIVE REANALYSIS ; SEX-HORMONES
    Abstract: BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p〈0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p〈0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p〈0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p〈0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p〈0.01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.
    Type of Publication: Journal article published
    PubMed ID: 23084519
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  • 4
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 26 (1986), S. 1264-1275 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: This paper deals with computer simulation of the filling stage of the Reaction Injection Molding (RIM) process for cavities of rectangular, cylindrical, and disc shapes. The computer model is in two parts: the main flow and the flow by the moving front. In the main flow part, the transient equations of axial momentum, energy and species conservation and also the continuity equation are solved numerically by finite-difference methods using a moving, changing mesh. In the flow front part, which is quite novel, the transient (parabolic) vorticity, energy and species conservation equations and the elliptic streamfunction equation are again solved by finite-difference methods. An important feature of both parts is that convection along and across the flow is included in all the transient equations. Results are presented for all three cavity shapes and those for rectangular cavities are compared with the experimental results of previous investigators.
    Additional Material: 22 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1572-9567
    Keywords: densimeter ; density ; high pressure ; n-heptane ; vibrating wire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Measurements are reported that confirm the applicability of the theory of a vibrating-rod densimeter to a practical instrument. It is demonstrated that with such a device, liquid density measurements evaluated on an absolute basis can be made with an accuracy of ±0.2% at pressures up to 100 MPa. When the density of the liquid is evaluated on a relative basis, a precision of ±0.1% can be achieved over the same range of pressure. Future developments of the instrument that would greatly enhance its sensitivity and that rely upon the availability of a proven theory are therefore now possible.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1572-9567
    Keywords: dilute gas ; thermal conductivity ; thermal diffusivity ; transient hot wire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A new treatment of the effect of the work of compression upon thermal conductivity measurements by the transient hot-wire technique is presented. The new analysis improves upon those given earlier and leads to quite a different result. The result makes it clear that the dilute gaseous state need not be excluded from the range of thermodynamic states in which accurate measurements are made owing to this effect, in contrast to the conclusions of earlier work.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1572-9567
    Keywords: high pressure ; n-hexane ; vibrating wire ; viscosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The design and operation of a new vibrating-wire viscometer for the measurement of the viscosity of liquids at pressures up to 100 MPa are described. The design of the instrument is based on a complete theory so that it is possible to make absolute measurements with an associated error of only a few parts in one thousand. Absolute measurements of the viscosity of n-hexane are reported at 298.15 K at pressures up to 80 MPa. The overall uncertainty in the reported viscosity data is estimated to be ±0.5%, an estimate confirmed by the comparison of values of viscosity of slightly inferior accuracy.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Rheologica acta 26 (1987), S. 102-105 
    ISSN: 1435-1528
    Keywords: Injection moulding ; thermoplastic ; freezing-off ; mould cavity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Abstract A semi-quantitative analysis is presented of freezing-off in a disc cavity during the injection moulding of thermoplastics. A criterion is obtained which enables the occurrence of freezing-off to be predicted, at least crudely. The form of the criterion is found to depend on the direction of flow (radially outward or inward) in the disc.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Rheologica acta 25 (1986), S. 180-190 
    ISSN: 1435-1528
    Keywords: Injection moulding ; thermoplastic ; freezing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Abstract The injection moulding of thermoplastics involves, during mould filling, flows of hot polymer melts into mould networks, the walls of which are so cold that frozen layers form on them. An analytical study of such flows is presented here for the case when the Graetz and Nahme numbers are large and the Pearson number is small. Thus the flows are developing and temperature differences due to heat generation by viscous dissipation are sufficiently large to cause significant variations in viscosity (but the difference between the entry temperature of the polymer to a specific part of the mould network and the melting temperature of the polymer is not).
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Rheologica acta 25 (1986), S. 308-318 
    ISSN: 1435-1528
    Keywords: Injection moulding ; thermoplastic ; freezing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Abstract The injection moulding of thermoplastics involves, during mould filling, flows of hot polymer melts into mould networks, the walls of which are so cold that frozen layers form on them. An analytical study of such flows is presented here for the case when the Graetz and Pearson numbers are large and the Nahme number is small. Thus the flows are developing and the difference between the entry temperature of the polymer to a specific part of the mould network and the melting temperature of the polymer is sufficiently large to cause significant variations in viscosity (but temperature differences due to heat generation by viscous dissipation are not).
    Type of Medium: Electronic Resource
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