Structure-property relationships of permeability-enhancing functional groups in polysulfones for application in membrane gas separation

( Michael D. Gyjver ),( Ying Dai ),( Gilles P. Robertson ),( Yong Soo Kang ),( Kwi Jong Lee ),( Jae Young Jho ),( Jongok Won ) 한국공업화학회 2002 한국공업화학회 연구논문 초록집 Vol.2002 No.1

Concomitant Proton Pump Inhibitor Use Does Not Reduce the Efficacy of Elbasvir/Grazoprevir

( Nancy Reau ),( Michael Robertson ),( Hwa-ping Feng ),( Luzelena Caro ),( Wendy W. Yeh ),( Bach-yen T. Nguyen ),( Janice Wahl ),( Eliav Barr ),( Peggy Hwang ),( Stephanie O. Klopfer ),( Youngmi Eun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: It is estimated that up to one-third of hepatitis-C virus (HCV)-infected patients use proton pump inhibitors (PPIs) and other acid reducing agents. Concomitant PPI use with some NS5A inhibitors impacts the pharmacokinetics (PK) of direct-acting antiviral agents (DAAs), potentially reducing efficacy. Phase I study results demonstrated no effect of PPI use on the PK of the fixed-dose combination of elbasvir/grazoprevir (EBR/GZR) in healthy volunteers. This post hoc analysis of studies in the Phase 3 clinical program of EBR/GZR assessed the 12-week sustained viral response (SVR12) in subjects with self-reported PPI use and the PK of EBR/GZR in these patients. Methods: Data were derived from six Phase 3 EBR/GZR trials with treatment-naïve or treatment experienced GT1/4-infected subjects, with or without cirrhosis. Analyses were done in the modified Full Analysis Set population (excludes administrative discontinuations). Self-reported baseline PPI use was defined as ≥7 consecutive days of use between Day -7 and Day 7. Bivariate analyses assessed PPI use and other factors associated with SVR, with gender, age (continuous and dichotomous), cirrhosis status, prior treatment status, baseline HCV RNA (continuous and dichotomous), HCV genotype, and baseline resistance associated variants as variables in the models. Results: Overall, 12% (162/1322) of EBR/GZR-treated subjects reported baseline use of PPIs. Of those, 155/162 (96%) achieved SVR12. In patients without PPI use, 1129/1160 (97%) achieved SVR12. PPI use was not a predictive factor in achieving SVR12 based on a univariate analysis (p = 0.188). In the bivariate models, none of the interaction terms was statistically significant, indicating that any potential effects of PPI were consistent across the factors considered. In addition, PPI usage was not a statistically significant effect, regardless of adjustment for the factors considered. From 3 of the 6 studies for which population PK data were available, the estimated AUC and Cmax values for EBR were comparable among patients with and without reported PPI use (table). Conclusions: These results demonstrate that PPIs use with EBR/GZR has no clinically significant effect on SVR12 rates in GT1/4-infected patients with and without cirrhosis.

Decarboxylation-Induced Cross-Linking of Polymers of Intrinsic Microporosity (PIMs) for Membrane Gas Separation†

Du, Naiying,Dal-Cin, Mauro M.,Robertson, Gilles P.,Guiver, Michael D. American Chemical Society 2012 Macromolecules Vol.45 No.12

<P>Cross-linked membranes for gas separation have been prepared by thermal treatment of carboxylated polymers of intrinsic microporosity (C-PIMs). The optimal cross-linking temperature was investigated and possible cross-linking pathways involving aryl radical-induced thermal decarboxylation are provided, while several other possible mechanisms are ruled out. Carboxylated PIMs are accessible by controlled hydrolysis of the nitrile-containing parent polymer. The resulting cross-linked PIMs were insoluble in typical solvents and were characterized by Fourier transform infrared spectroscopy (FTIR), TGA-MS, TGA-FTIR, and gel content analysis. The decarboxylated PIM (DC-PIM) membranes showed higher selectivities for the O<SUB>2</SUB>/N<SUB>2</SUB>, CO<SUB>2</SUB>/N<SUB>2</SUB>, and CO<SUB>2</SUB>/CH<SUB>4</SUB> gas pairs, with evidence of suppression of swelling-induced densification under high CO<SUB>2</SUB> pressure.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mamobx/2012/mamobx.2012.45.issue-12/ma300751s/production/images/medium/ma-2012-00751s_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ma300751s'>ACS Electronic Supporting Info</A></P>

Polymer nanosieve membranes for CO₂-capture?applications

Du, Naiying,Park, Ho Bum,Robertson, Gilles P.,Dal-Cin, Mauro M.,Visser, Tymen,Scoles, Ludmila,Guiver, Michael D. Nature Publishing Group 2011 Nature materials Vol.10 No.5

Microporous organic polymers (MOPs) are of potential significance for gas storage, gas separation and low-dielectric applications. Among many approaches for obtaining such materials, solution-processable MOPs derived from rigid and contorted macromolecular structures are promising because of their excellent mass transport and mass exchange capability. Here we show a class of amorphous MOP, prepared by [2+3] cycloaddition modification of a polymer containing an aromatic nitrile group with an azide compound, showing super-permeable characteristics and outstanding CO<SUB>2</SUB> separation performance, even under polymer plasticization conditions such as CO<SUB>2</SUB>/light gas mixtures. This unprecedented result arises from the introduction of tetrazole groups into highly microporous polymeric frameworks, leading to more favourable CO<SUB>2</SUB> sorption with superior affinity in gas mixtures, and selective CO<SUB>2</SUB> transport by presorbed CO<SUB>2</SUB> molecules that limit access by other light gas molecules. This strategy provides a direction in the design of MOP membrane materials for economic CO<SUB>2</SUB> capture processes.

Searching for Transit Timing Variations and Fitting a New Ephemeris to Transits of TrES-1 b

Paige Yeung,Quinn Perian,Peyton Robertson,Michael Fitzgerald,Martin Fowler,Frank Sienkiewicz,Kalee Tock 한국천문학회 2022 Journal of The Korean Astronomical Society Vol.55 No.4

Based on the light an exoplanet blocks from its host star as it passes in front of it during a transit, the mid-transit time can be determined. Periodic variations in mid-transit times can indicate another planet's gravitational influence. We investigate 83 transits of TrES-1 b as observed from 6-inch telescopes in the MicroObservatory robotic telescope network. The EXOTIC data reduction pipeline is used to process these transits, fit transit models to light curves, and calculate transit midpoints. This paper details the methodology for analyzing transit timing variations (TTVs) and using transit measurements to maintain ephemerides. The application of Lomb-Scargle period analysis for studying the plausibility of TTVs is explained. The analysis of the resultant TTVs from 46 transits from MicroObservatory and 47 transits from archival data in the Exoplanet Transit Database indicated the possible existence of other planets affecting the orbit of TrES-1 and improved the precision of the ephemeris by one order of magnitude. We now estimate the ephemeris to be 2455489.66026 BJD_{TDB} ± 0.00044 d + (3.0300689 ± 0.0000007) d × epoch. This analysis also demonstrates the role of small telescopes in making precise mid-transit time measurements, which can be used to help maintain ephemerides and perform TTV analysis. The maintenance of ephemerides allows for an increased ability to optimize telescope time on large ground-based telescopes and space telescope missions.

Genome Wide Proteomics of ERBB2 and EGFR and Other Oncogenic Pathways in Inflammatory Breast Cancer

Zhang, Emma Yue,Cristofanilli, Massimo,Robertson, Fredika,Reuben, James M.,Mu, Zhaomei,Beavis, Ronald C.,Im, Hogune,Snyder, Michael,Hofree, Matan,Ideker, Trey,Omenn, Gilbert S.,Fanayan, Susan,Jeong, S American Chemical Society 2013 Journal of proteome research Vol.12 No.6

<P>In this study we selected three breast cancer cell lines (SKBR3, SUM149 and SUM190) with different oncogene expression levels involved in ERBB2 and EGFR signaling pathways as a model system for the evaluation of selective integration of subsets of transcriptomic and proteomic data. We assessed the oncogene status with reads per kilobase per million mapped reads (RPKM) values for ERBB2 (14.4, 400, and 300 for SUM149, SUM190, and SKBR3, respectively) and for EGFR (60.1, not detected, and 1.4 for the same 3 cell lines). We then used RNA-Seq data to identify those oncogenes with significant transcript levels in these cell lines (total 31) and interrogated the corresponding proteomics data sets for proteins with significant interaction values with these oncogenes. The number of observed interactors for each oncogene showed a significant range, e.g., 4.2% (JAK1) to 27.3% (MYC). The percentage is measured as a fraction of the total protein interactions in a given data set vs total interactors for that oncogene in STRING (Search Tool for the Retrieval of Interacting Genes/Proteins, version 9.0) and I2D (Interologous Interaction Database, version 1.95). This approach allowed us to focus on 4 main oncogenes, ERBB2, EGFR, MYC, and GRB2, for pathway analysis. We used bioinformatics sites GeneGo, PathwayCommons and NCI receptor signaling networks to identify pathways that contained the four main oncogenes and had good coverage in the transcriptomic and proteomic data sets as well as a significant number of oncogene interactors. The four pathways identified were ERBB signaling, EGFR1 signaling, integrin outside-in signaling, and validated targets of C-MYC transcriptional activation. The greater dynamic range of the RNA-Seq values allowed the use of transcript ratios to correlate observed protein values with the relative levels of the ERBB2 and EGFR transcripts in each of the four pathways. This provided us with potential proteomic signatures for the SUM149 and 190 cell lines, growth factor receptor-bound protein 7 (GRB7), Crk-like protein (CRKL) and Catenin delta-1 (CTNND1) for ERBB signaling; caveolin 1 (CAV1), plectin (PLEC) for EGFR signaling; filamin A (FLNA) and actinin alpha1 (ACTN1) (associated with high levels of EGFR transcript) for integrin signalings; branched chain amino-acid transaminase 1 (BCAT1), carbamoyl-phosphate synthetase (CAD), nucleolin (NCL) (high levels of EGFR transcript); transferrin receptor (TFRC), metadherin (MTDH) (high levels of ERBB2 transcript) for MYC signaling; S100-A2 protein (S100A2), caveolin 1 (CAV1), Serpin B5 (SERPINB5), stratifin (SFN), PYD and CARD domain containing (PYCARD), and EPH receptor A2 (EPHA2) for PI3K signaling, p53 subpathway. Future studies of inflammatory breast cancer (IBC), from which the cell lines were derived, will be used to explore the significance of these observations.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2013/jprobs.2013.12.issue-6/pr4001527/production/images/medium/pr-2013-001527_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr4001527'>ACS Electronic Supporting Info</A></P>

Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines

Kochhar, Sonali,Excler, Jean-Louis,Bok, Karin,Gurwith, Marc,McNeil, Michael M.,Seligman, Stephen J.,Khuri-Bulos, Najwa,Klug, Bettina,Laderoute, Marian,Robertson, James S.,Singh, Vidisha,Chen, Robert T Elsevier Ltd. 2019 Vaccine Vol. No.

<P><B>Abstract</B></P> <P>Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely <I>potential or known</I> AEFI and establish the optimal risk window(s); and (3) conducting “near real-time“ prospective monitoring for <I>unknown</I> clustering’s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.</P>

Down the Rabbit Hole-Considerations for Ingested Foreign Bodies

Brown, Jerry,Kidder, Molly,Fabbrini, Abigail,deVries, Jonathan,Robertson, Jason,Chandler, Nicole,Wilsey, Michael The Korean Society of Pediatric Gastroenterology 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.6

We report the case of a seven-year-old boy with an ingested foreign body, which was retained within the appendix for a known duration of ten months, ultimately requiring appendectomy. The ingested foreign body was incidentally discovered by abdominal x-ray at an emergency room visit for constipation. Despite four bowel cleanouts, subsequent x-rays showed persistence of the foreign body in the right lower quadrant. While the patient did not have signs or symptoms of acute appendicitis, laparoscopic appendectomy was performed due to the risk of this foreign body causing appendicitis in the future. A small metallic object was found within the appendix upon removal. This case highlights the unique challenge presented by foreign body ingestions in non-verbal or developmentally challenged children and the importance of further diagnostic workup when concerns arise for potential retained foreign bodies.

A clustered sulfonated poly(ether sulfone) based on a new fluorene-based bisphenol monomer

Wang, Chenyi,Shin, Dong Won,Lee, So Young,Kang, Na Rae,Robertson, Gilles P.,Lee, Young Moo,Guiver, Michael D. The Royal Society of Chemistry 2012 Journal of materials chemistry Vol.22 No.48

<P>A new fluorene-based bisphenol monomer containing two pendant phenyl groups, 9,9-bis(3-phenyl-4-hydroxy)phenyl-fluorene, was readily synthesized in high yield by a one-step reaction from inexpensive starting materials. A series of poly(ether sulfone)s with clustered sulfonic acid groups was prepared for fuel cell applications by polycondensation of the new monomer with bis(4-hydroxyphenyl)sulfone and bis(4-fluorophenyl)sulfone, followed by sulfonation exclusively on the fluorene rings and pendant phenyl rings, using concentrated sulfuric acid at room temperature. The sulfonated polymers gave tough, flexible, and transparent membranes by solvent casting. The ionic exchange capacity (IEC), water-uptake, dimensional stabilities, mechanical properties, thermal and oxidative stabilities as well as proton conductivities and single fuel cell properties of the membranes were investigated. The membranes with high IEC values show high proton transport properties, and their proton conductivities exhibit lower dependence on relative humidity compared with typical aromatic ion exchange membranes. 4-SPES-38 with an IEC value of 2.23 mequiv. g<SUP>−1</SUP> displays comparable fuel cell performance with Nafion 212 under low humidity conditions.</P> <P>Graphic Abstract</P><P>A new fluorene-based bisphenol monomer with pendant phenyl substituents was prepared by a facile synthetic route, from which clustered sulfonated poly(ether sulfone)s with excellent overall membrane properties were achieved for fuel cell tests. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2jm34414a'> </P>

Down the Rabbit Hole-Considerations for Ingested Foreign Bodies

Jerry Brown,Molly Kidder,Abigail Fabbrini,Jonathan deVries,Jason Robertson,Nicole Chandler,Michael Wilsey 대한소아소화기영양학회 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.6

We report the case of a seven-year-old boy with an ingested foreign body, which was retained within the appendix for a known duration of ten months, ultimately requiring appendectomy. The ingested foreign body was incidentally discovered by abdominal x-ray at an emergency room visit for constipation. Despite four bowel cleanouts, subsequent x-rays showed persistence of the foreign body in the right lower quadrant. While the patient did not have signs or symptoms of acute appendicitis, laparoscopic appendectomy was performed due to the risk of this foreign body causing appendicitis in the future. A small metallic object was found within the appendix upon removal. This case highlights the unique challenge presented by foreign body ingestions in non-verbal or developmentally challenged children and the importance of further diagnostic workup when concerns arise for potential retained foreign bodies.