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      • SCISCIESCOPUS
      • SCISCIESCOPUS

        Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement

        Isaacs, Farren J.,Carr, Peter A.,Wang, Harris H.,Lajoie, Marc J.,Sterling, Bram,Kraal, Laurens,Tolonen, Andrew C.,Gianoulis, Tara A.,Goodman, Daniel B.,Reppas, Nikos B.,Emig, Christopher J.,Bang, Duhe American Association for the Advancement of Scienc 2011 Science Vol.333 No.6040

        <P>We present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale. We used multiplex automated genome engineering (MAGE) to site-specifically replace all 314 TAG stop codons with synonymous TAA codons in parallel across 32 Escherichia coli strains. This approach allowed us to measure individual recombination frequencies, confirm viability for each modification, and identify associated phenotypes. We developed hierarchical conjugative assembly genome engineering (CAGE) to merge these sets of codon modifications into genomes with 80 precise changes, which demonstrate that these synonymous codon substitutions can be combined into higher-order strains without synthetic lethal effects. Our methods treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes.</P>

      • Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination

        Andre, E.,Isaacs, C.,Affolabi, D. IUATLD 2016 The international journal of tuberculosis and lung Vol.20 No.8

        <P>In regard to tuberculosis (TB) and other major global epidemics, the use of new diagnostic tests is increasing dramatically, including in resource-limited countries. Although there has never been as much digital information generated, this data source has not been exploited to its full potential. In this opinion paper, we discuss lessons learned from the global scale-up of these laboratory devices and the pathway to tapping the potential of laboratory-generated information in the field of TB by using connectivity. Responding to the demand for connectivity, innovative third-party players have proposed solutions that have been widely adopted by field users of the Xpert MTB/RIF assay. The experience associated with the utilisation of these systems, which facilitate the monitoring of wide laboratory networks, stressed the need for a more global and comprehensive approach to diagnostic connectivity. In addition to SUMMARY facilitating the reporting of test results, the mobility of digital information allows the sharing of information generated in programme settings. When they become easily accessible, these data can be used to improve patient care, disease surveillance and drug discovery. They should therefore be considered as a public health good. We list several examples of concrete initiatives that should allow data sources to be combined to improve the understanding of the epidemic, support the operational response and, finally, accelerate TB elimination. With the many opportunities that the pooling of data associated with the TB epidemic can provide, pooling of this information at an international level has become an absolute priority.</P>

      • KCI등재후보
      • KCI등재

        Inhibition Effects of Chromate, Phosphate, Sulfate, and Borate on Chloride Pitting Corrosion of Al

        Lee, Ho-Chun,Isaacs, Hugh S. The Korean Electrochemical Society 2008 한국전기화학회지 Vol.11 No.3

        Inhibitive effects of chromate, phosphate, sulfate, and borate on chloride pitting corrosion of Al have been investigated using cyclic voltammetry. During the anodic oxide growth, the critical concentration of chloride for pit initiation decreased in the order: chromate > phosphate > sulfate > borate, and the maximum pitting current density increases in the reverse order: chromate < phosphate < sulfate < borate. The decreasing pitting current density was observed in the successive polarization cycles, which was attributed to the aging of Al oxides and field relaxation at oxide/solution interface.

      • KCI등재후보

        Clinicopathological Features of Upper Third Gastric Cancer during a 21-Year Period (Single Center Analysis)

        Je-Ho Jang,Reinaldo Isaacs Beron,안혜성,공성호,Hyuk-Joon Lee,Woo-Ho Kim,Kuhn Uk Lee,Han-Kwang Yang 대한위암학회 2010 Journal of gastric cancer Vol.10 No.4

        Purpose: The aim of this study was to determine proportions of upper third gastric cancer (UTG) among all gastric cancers and analyze clinicopathological features of the disease. Materials and Methods: The medical records of 12,300 patients who underwent gastric surgery between 1986 and 2006 at Seoul National University Hospital (SNUH) were retrospectively reviewed. Clinicopathological features of 1,260 patients with UTG and 9,929 patients with middle or lower third gastric cancer (MLG) were compared, and annual proportions of UTG were evaluated. Results: The proportion of patients with UTG rapidly increased from 2.6% in 1986 to 12.5% in 1992. However, linear regression analysis showed that the rate of increase was reduced (0.21%/year) after 1992 (12.5% to 14.2% from 1992 to 2006). Compared with the MLG group, the UTG group had a lower proportion of (22.3% vs. 39.7%, P<0.001) and a greater proportion of stage III/IV disease (39.4% vs. 31.7%, P<0.001). The UTG group also had larger tumors than the MLG group in stages I/II and III (3.5 cm/5.3 cm/6.5 cm vs. 3.2 cm/5.0 cm/5.8 cm, P=0.020/0.028 /<0.001), a higher proportion of undifferentiated cancer (63.1% vs. 53.7%, P<0.001), and less intestinal Lauren's type (38.8% vs. 47.4%, P<0.001). The 5-year survival rate of the UTG group was significantly lower than that of the MLG group in stages I/II and III (85.6%/63.1%/34.2% vs. 91.6%/ 69.2%/44.7%, P<0.001/0.028/0.006). Conclusions: The proportion of UTGs has increased over the last two decades at SNUH, but the rate of increase has been greatly reduced since 1992. The UTG group showed a poorer prognosis compared with the MLG group in stages I/II and III.

      • KCI등재

        Inhibition effects of chromate, phosphate, sulfate, and borate on chloride pitting corrosion of Al

        이호춘,Hugh S. Isaacs 한국전기화학회 2008 한국전기화학회지 Vol.11 No.3

        Inhibitive effects of chromate, phosphate, sulfate, and borate on chloride pitting corrosion of Al have been investigated using cyclic voltammetry. During the anodic oxide growth, the critical concentration of chloride for pit initiation decreased in the order: chromate > phosphate > sulfate > borate, and the maximum pitting current density increases in the reverse order: chromate < phosphate < sulfate < borate. The decreasing pitting current density was observed in the successive polarization cycles, which was attributed to the aging of Al oxides and field relaxation at oxide/solution interface

      • A porous activated carbon supported Pt catalyst for the oxidative degradation of poly[(naphthaleneformaldehyde)sulfonate]

        Karthikeyan, S.,Jo, Wan-Kuen,Dhanalakshmi, R.,Isaacs, Mark A.,Wilson, Karen,Sekaran, G.,Lee, Adam F. Elsevier 2018 JOURNAL- TAIWAN INSTITUTE OF CHEMICAL ENGINEERS Vol.93 No.-

        <P><B>Abstract</B></P> <P>Wet catalytic oxidation of sodium poly[(naphthaleneformaldehyde)sulfonate], a hazardous contaminant of wastewater streams from the textiles industry, by hydrogen peroxide under ambient conditions was explored over platinum supported on a porous activated carbon (PAC). Bulk and surface properties of the Pt/PAC catalyst were investigated by XRD, XPS, SEM, TEM, FTIR, EPR and thermogravimetric analysis. The parent PAC, derived from pyrolysis and subsequent activation of rice husks, exhibited significant micro- and mesoporosity, and a high degree of surface oxidation. Incorporation of 1.7 wt% Pt resulted in mesopore blockage, and a corresponding drop in surface area, associated with the formation of large ∼8 nm metallic nanoparticles. Poly[(naphthaleneformaldehyde)sulfonate] oxidative degradation was studied as a function of reactant concentration and solution pH, revealing first order decomposition kinetics and good activity over pH 3–9 at ambient temperature. Electron Paramagnetic Resonance (EPR)-DMPO spin trapping experiments confirm that oxidation of the organic pollutant proceeded via hydroxyl radical generation. The 1.7 wt% Pt/PAC catalyst showed excellent catalyst stability for five consecutive runs over 25 h in a fluidised bed reactor, delivering > 85% removal of 100 mg/L sulfonate with negligible Pt leaching or activity loss, and comparable performance for treatment of a real tannery effluent stream with a COD equivalent of 1860 mg/L.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A facile route to Pt functionalized biogenically sourced porous activated carbon. </LI> <LI> First heterogeneous catalyst for poly[(naphthaleneformaldehyde)sulfonate] oxidation. </LI> <LI> Excellent activity and stability over a broad concentration and pH range. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        Amyloid Burden in Alzheimer's Disease Patients Is Associated with Alterations in Circadian Rhythm

        Kang Jubin,Choi Hyung Jin,Isaacs Gary D.,Sung Wonjae,김희진 대한치매학회 2021 Dementia and Neurocognitive Disorders Vol.20 No.4

        Background and Purpose: In this study we evaluated the relationship between amyloid-beta (Aβ) deposition and 3 aspects of sleep quality in a group of clinically diagnosed Alzheimer's disease (AD) patients. Methods: We used self-report questionnaires to assess the quality of sleep using 3 previously established surveys: the Glasgow Sleep Effort Scale (GSES), the Pittsburgh Sleep Quality Index (PSQI), and the Morningness-Eveningness Questionnaire (MEQ). These questionnaires focused on the sleep effort, sleep efficiency, and circadian rhythm patterns of each participant. Also, we evaluated the regional distribution of Aβ in the brain by amyloid positron emission tomography-computed tomography (PET-CT) standardized uptake value ratios (SUVRs) in healthy normal (HN), mild cognitive impairment (MCI), and AD dementia groups. The MCI and AD dementia groups were combined to form the group with cognitive impairment due to AD (CIAD). Results: GSES and MEQ scores differed significantly between the HN, MCI, and AD dementia groups (p<0.037), whereas PSQI scores were similar across the groups (p=0.129). GSES and MEQ scores also differed between the HN and CIAD groups (p<0.018). Circadian rhythm scores positively correlated with amyloid PET-CT SUVR in posterior cingulate cortices (p<0.049). Conclusions: Sleep effort and abnormal shifts in circadian rhythm were more significant in the CIAD group than in the HN group. At the same time, HN subjects had minimal sleep disturbance, irrespective of clinical status. Thus, alterations in circadian rhythm may be indicative of neurodegeneration due to Aβ deposition.

      • SCOPUSKCI등재

        Implant Anneal Process for Activating Ion Implanted Regions in SiC Epitaxial Layers

        Saddow, S.E.,Kumer, V.,Isaacs-Smith, T.,Williams, J.,Hsieh, A.J.,Graves, M.,Wolan, J.T. The Korean Institute of Electrical and Electronic 2000 Transactions on Electrical and Electronic Material Vol.1 No.4

        The mechanical strength of silicon carbide dose nor permit the use of diffusion as a means to achieve selective doping as required by most electronic devices. While epitaxial layers may be doped during growth, ion implantation is needed to define such regions as drain and source wells, junction isolation regions, and so on. Ion activation without an annealing cap results in serious crystal damage as these activation processes must be carried out at temperatures on the order of 1600$^{\circ}C$. Ion implanted silicon carbide that is annealed in either a vacuum or argon environment usually results in a surface morphology that is highly irregular due to the out diffusion of Si atoms. We have developed and report a successful process of using silicon overpressure, provided by silane in a CAD reactor during the anneal, to prevent the destruction of the silicon carbide surface, This process has proved to be robust and has resulted in ion activation at a annealing temperature of 1600$^{\circ}C$ without degradation of the crystal surface as determined by AFM and RBS. In addition XPS was used to look at the surface and near surface chemical states for annealing temperatures of up to 1700$^{\circ}C$. The surface and near surface regions to approximately 6 nm in depth was observed to contain no free silicon or other impurities thus indicating that the process developed results in an atomically clean SiC surface and near surface region within the detection limits of the instrument(${\pm}$1 at %).

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