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>

Bone Morphogenetic Protein-2 and -6 Heterodimer Illustrates the Nature of Ligand-Receptor Assembly

Isaacs, Michael J.,Kawakami, Yasuhiko,Allendorph, George P.,Yoon, Byung-Hak,Belmonte, Juan Carlos Izpisua,Choe, Senyon The Endocrine Society 2010 Molecular endocrinology Vol.24 No.7

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>

BUILDING EFFECTIVE SHARED SERVICE PARTNERSHIPS

MARCHOLZER,HEDYL.ISAACS 한국행정학회 2002 International Review of Public Administration Vol.7 No.1

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.

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.

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

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

Jang, Je-Ho,Beron, Reinaldo Isaacs,Ahn, Hye-Seong,Kong, Seong-Ho,Lee, Hyuk-Joon,Kim, Woo-Ho,Lee, Kuhn-Uk,Yang, Han-Kwang The Korean Gastric Cancer Association 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.

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>

Psoas Morphology Differs between Supine and Sitting Magnetic Resonance Imaging Lumbar Spine: Implications for Lateral Lumbar Interbody Fusion

Aaron J. Buckland,Bryan M. Beaubrun,Evan Isaacs,John Moon,Peter Zhou,Sam Horn,Gregory Poorman,Jared C. Tishelman,Louis M. Day,Thomas J. Errico,Peter G. Passias,Themistocles Protopsaltis 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.1

Study Design: Retrospective radiological review. Purpose: To quantify the effect of sitting vs supine lumbar spine magnetic resonance imaging (MRI) and change in anterior displacement of the psoas muscle from L1–L2 to L4–L5 discs. Overview of Literature: Controversy exists in determining patient suitability for lateral lumbar interbody fusion (LLIF) based on psoas morphology. The effect of posture on psoas morphology has not previously been studied; however, lumbar MRI may be performed in sitting or supine positions. Methods: A retrospective review of a single-spine practice over 6 months was performed, identifying patients aged between 18–90 years with degenerative spinal pathologies and lumbar MRIs were evaluated. Previous lumbar fusion, scoliosis, neuromuscular disease, skeletal immaturity, or intrinsic abnormalities of the psoas muscle were excluded. The anteroposterior (AP) dimension of the psoas muscle and intervertebral disc were measured at each intervertebral disc from L1–L2 to L4–L5, and the AP psoas:disc ratio calculated. The morphology was compared between patients undergoing sitting and/or supine MRI. Results: Two hundred and nine patients were identified with supine-, and 60 patients with sitting-MRIs, of which 13 patients had undergone both sitting and supine MRIs (BOTH group). A propensity score match (PSM) was performed for patients undergoing either supine or sitting MRI to match for age, BMI, and gender to produce two groups of 43 patients. In the BOTH and PSM group, sitting MRI displayed significantly higher AP psoas:disc ratio compared with supine MRI at all intervertebral levels except L1–L2. The largest difference observed was a mean 32%–37% increase in sitting AP psoas:disc ratio at the L4–L5 disc in sitting compared to supine in the BOTH group (range, 0%–137%). Conclusions: The psoas muscle and the lumbar plexus become anteriorly displaced in sitting MRIs, with a greater effect noted at caudal intervertebral discs. This may have implications in selecting suitability for LLIF, and intra-operative patient positioning.