Reactive capture and electrochemical conversion of CO2 with ionic liquids and deep eutectic solvents.

Ionic liquids (ILs) and deep eutectic solvents (DESs) have tremendous potential for reactive capture and conversion (RCC) of CO2 due to their wide electrochemical stability window, low volatility, and high CO2 solubility. There is environmental and economic interest in the direct utilization of the captured CO2 using electrified and modular processes that forgo the thermal- or pressure-swing regeneration steps to concentrate CO2, eliminating the need to compress, transport, or store the gas. The conventional electrochemical conversion of CO2 with aqueous electrolytes presents limited CO2 solubility and high energy requirement to achieve industrially relevant products. Additionally, aqueous systems have competitive hydrogen evolution. In the past decade, there has been significant progress toward the design of ILs and DESs, and their composites to separate CO2 from dilute streams. In parallel, but not necessarily in synergy, there have been studies focused on a few select ILs and DESs for electrochemical reduction of CO2, often diluting them with aqueous or non-aqueous solvents. The resulting electrode-electrolyte interfaces present a complex speciation for RCC. In this review, we describe how the ILs and DESs are tuned for RCC and specifically address the CO2 chemisorption and electroreduction mechanisms. Critical bulk and interfacial properties of ILs and DESs are discussed in the context of RCC, and the potential of these electrolytes are presented through a techno-economic evaluation.

Active Sites and Their Individual Turnover Frequencies for Ethylene Hydrogenation on Reduced Graphene Aerogel.

Graphene aerogel (GA) was reduced at various temperatures to prepare a series of reduced graphene aerogels (rGAs) with different surface characteristics. Detailed characterization demonstrated that an increase in the thermal reduction temperature leads to an increase in surface area accompanied by an increase in surface density of defect sites formed by the removal of the oxygen-containing functional groups. rGA samples were then tested for ethylene hydrogenation under identical conditions. A comparison of catalytic performances of each catalyst demonstrated that the rGA sample prepared by reduction in Ar at 900 °C (rGA-900) provides the highest performance compared with others prepared at lower temperatures. Next, we analyzed the per-gram activity of each catalyst as a sum of individual contributions from different defect sites quantified by Raman spectroscopy and CHNS-O analysis to determine the individual turnover frequencies (TOFs) of each active site. This analysis identified polyene-like structures and interstitial defects associated with amorphous sp2 bonded carbon atoms as the dominant active sites responsible for hydrogenation. A comparison of their TOFs further indicated that the polyene-like structures provide approximately ten times higher TOF compared to those associated with the amorphous carbon defects. These results, identifying the dominant active centers and quantifying their corresponding TOFs, provide opportunities toward the rational design of GA-based carbocatalysts.

MMR Deficiency Defines Distinct Molecular Subtype of Breast Cancer with Histone Proteomic Networks.

Mismatch repair (MMR) alterations are important prognostic and predictive biomarkers in a variety of cancer subtypes, including colorectal and endometrial. However, in breast cancer (BC), the distinction and clinical significance of MMR are largely unknown. This may be due in part to the fact that genetic alterations in MMR genes are rare and only seen to occur in around 3% of BCs. In the present study, we analyzed TCGA data using a multi-sample protein-protein interaction (PPI) analysis tool, Proteinarium, and showed a distinct separation between specific MMR-deficient and -intact networks in a cohort of 994 BC patients. In the PPI networks specific to MMR deficiency, highly connected clusters of histone genes were identified. We also found the distribution of MMR-deficient BC to be more prevalent in HER2-enriched and triple-negative (TN) BC subtypes compared to luminal BCs. We recommend defining MMR-deficient BC by next-generation sequencing (NGS) when any somatic mutation is detected in one of the seven MMR genes.

Influence of ionic liquids on the electronic environment of atomically dispersed Ir on (MgO)(100).

Recently, ionic liquids (ILs) have been used as ligands for single-site Ir(CO)2 complexes bound to metal-oxide supports because of their electron-donor/acceptor capacities. The combined effects of supports and ILs as ligands may pave the way to the tuning of the surrounding electronic properties to increase electron-donor/acceptor efficiency in metal-oxide supported Ir(CO)2 complexes. Herein, we have used Density Functional Theory to model Ir(CO)2 complexes bound to MgO supports with and without the presence of an IL to explain the role of ILs in modifying the electronic structure of the supported complex. Comparison of the ν(CO) band stretching frequencies with experimental results has led to the rationalization of the factors driving the interactions between the IL, the support, and the catalyst as well as the justification of the methodology for further studies.

Proteinarium: Multi-sample protein-protein interaction analysis and visualization tool.

We posit the likely architecture of complex diseases is that subgroups of patients share variants in genes in specific networks which are sufficient to give rise to a shared phenotype. We developed Proteinarium, a multi-sample protein-protein interaction (PPI) tool, to identify clusters of patients with shared gene networks. Proteinarium converts user defined seed genes to protein symbols and maps them onto the STRING interactome. A PPI network is built for each sample using Dijkstra's algorithm. Pairwise similarity scores are calculated to compare the networks and cluster the samples. A layered graph of PPI networks for the samples in any cluster can be visualized. To test this newly developed analysis pipeline, we reanalyzed publicly available data sets, from which modest outcomes had previously been achieved. We found significant clusters of patients with unique genes which enhanced the findings in the original study.

Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells.

The underlying mechanism of normal lung organogenesis is not well understood. An increasing number of studies are demonstrating that extracellular vesicles (EVs) play critical roles in organ development by delivering microRNAs (miRNA) to neighboring and distant cells. miRNAs are important for fetal lung growth; however, the role of miRNA-EVs (miRNAs packaged inside the EVs) during fetal lung development is unexplored. The aim of this study was to examine the expression of miRNA-EVs in MLE-12, a murine lung epithelial cell line subjected to mechanical stretch in vitro with the long-term goal to investigate their potential role in the fetal lung development. Both cyclic and continuous mechanical stretch regulate miRNA differentially in EVs released from MLE-12 and intracellularly, demonstrating that mechanical signals regulate the expression of miRNA-EVs in lung epithelial cells. These results provide a proof-of-concept for the potential role that miRNA-EVs could play in the development of fetal lung.

Effect of prematurity on genome wide methylation in the placenta.

BACKGROUND: Preterm birth is a significant clinical problem and an enormous burden on society, affecting one in eight pregnant women and their newborns. Despite decades of research, the molecular mechanism underlying its pathogenesis remains unclear. Many studies have shown that preterm birth is associated with health risks across the later life course. The "fetal origins" hypothesis postulates that adverse intrauterine exposures are associated with later disease susceptibility. Our recent studies have focused on the placental epigenome at term. We extended these studies to genome-wide placental DNA methylation across a wide range of gestational ages. We applied methylation dependent immunoprecipitation/DNA sequencing (MeDIP-seq) to 9 placentas with gestational age from 25 weeks to term to identify differentially methylated regions (DMRs). RESULTS: Enrichment analysis revealed 427 DMRs with nominally significant differences in methylation between preterm and term placentas (p < 0.01) and 21 statistically significant DMRs after multiple comparison correction (FDR p < 0.05), of which 62% were hypo-methylated in preterm placentas vs term placentas. The majority of DMRs were in distal intergenic regions and introns. Significantly enriched pathways identified by Ingenuity Pathway Analysis (IPA) included Citrulline-Nitric Oxide Cycle and Fcy Receptor Mediated Phagocytosis in macrophages. The DMR gene set overlapped placental gene expression data, genes and pathways associated evolutionarily with preterm birth. CONCLUSION: These studies form the basis for future studies on the epigenetics of preterm birth, "fetal programming" and the impact of environment exposures on this important clinical challenge.

Core-Shell Type Ionic Liquid/Metal Organic Framework Composite: An Exceptionally High CO2/CH4 Selectivity.

Here, we present a new concept of a core-shell type ionic liquid/metal organic framework (IL/MOF) composite. A hydrophilic IL, 1-(2-hydroxyethyl)-3-methylimidazolium dicyanamide, [HEMIM][DCA], was deposited on a hydrophobic zeolitic imidazolate framework, ZIF-8. The composite exhibited approximately 5.7 times higher CO2 uptake and 45 times higher CO2/CH4 selectivity at 1 mbar and 25 °C compared to the parent MOF. Characterization showed that IL molecules deposited on the external surface of the MOF, forming a core (MOF)-shell (IL) type material, in which IL acts as a smart gate for the guest molecules.

Effect of methylation of ionic liquids on the gas separation performance of ionic liquid/metal-organic framework composites.

1-N-Butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], and its methylated form, 1-N-butyl-2,3-dimethylimidazolium hexafluorophosphate, [BMMIM][PF6], were incorporated into CuBTC to examine the effect of methylation of ionic liquids (ILs) on the gas separation performance of the corresponding IL/metal-organic framework (MOF) composites. Spectroscopic analysis revealed that the interactions of the methylated ILs with CuBTC were weaker compared to those of its non-methylated counterpart. Gas uptake measurements illustrated that this difference in the interactions influences the gas separation performance of the composites. Accordingly, the CO2/N2: 15/85 and CH4/N2: 50/50 selectivities increased by 37% and 60% for [BMMIM][PF6]/CuBTC and 34% and 50% for [BMIM][PF6]/CuBTC, respectively, compared to the corresponding selectivities of pristine CuBTC at 1000 mbar. The results revealed another structural parameter controlling the performance of the IL/MOF composites, a novel type of material with rapidly expanding application areas.

A novel, de novo mutation in the PRKAG2 gene: infantile-onset phenotype and the signaling pathway involved.

PRKAG2 encodes the γ2-subunit isoform of 5'-AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in the regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation, and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved, and therapeutic options for K475E mutation using cells stably expressing human wild-type (WT) or the K475E mutant. In human embryonic kidney-293 cells, the K475E mutation induced a marked increase in the basal phosphorylation of T172 and AMPK activity, reduced sensitivity to AMP in allosteric activation, and a loss of response to phenformin. In H9c2 cardiomyocytes, the K475E mutation induced inhibition of AMPK and reduced the response to phenformin and increases in the phosphorylation of p70S6 kinase (p70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Primary fibroblasts from the patient with the K475E mutation also showed marked increases in the phosphorylation of p70S6K and 4E-BP1 compared with those from age-matched, nondiseased controls. Moreover, overexpression of K475E induced hypertrophy in H9c2 cells, which was effectively reversed by treatment with rapamycin. Taken together, we have identified a novel, de novo infantile-onset PRKAG2 mutation causing HCM. Our study suggests the K475E mutation induces alteration in basal AMPK activity and results in a hypertrophy phenotype involving the mechanistic target of rapamycin signaling pathway, which can be reversed with rapamycin.NEW & NOTEWORTHY We identified a novel, de novo PRKAG2 mutation (K475E) in the cystathionine ß-synthase 3 repeat, a region critical for AMP binding but with no previous reported mutation. Our data suggest the mutation affects AMP-activated protein kinase activity, activates cell growth pathways, and results in cardiac hypertrophy, which can be reversed with rapamycin.

Medical morbidities and DNA methylation of NR3C1 in preterm infants.

BACKGROUND: Although there are no accepted "normal" levels of circulating cortisol in preterm infants, critically ill preterm infants show lower cortisol levels than healthy preterm infants. The regulation of cortisol reactivity by epigenetic changes in glucocorticoid receptor gene (NR3C1) expression has been demonstrated. This study aims to examine the relationship between medical morbidities in preterm infants and DNA methylation of NR3C1. METHODS: Pyrosequencing was used to determine DNA methylation in CpG sites 1-4 of promoter region 1F of NR3C1. Cluster analysis placed 67 preterm infants born <1,500 g into groups based on medical morbidities. The DNA methylation pattern was compared across groups. RESULTS: Cluster analysis identified a high medical risk cluster and a low medical risk cluster. A Mann-Whitney U-test showed lower methylation at CpG1 for infants in the high-risk group (M = 0.336, SE = 0.084) than infants in the low-risk group (M = 0.617, SE = 0.109, P = 0.032). The false discovery rate was low (q = 0.025). Cohen's D effect size was moderate (0.525). CONCLUSION: Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels.

The developmental expression of the CDK inhibitor p57(kip2) (Cdkn1c) in the early mouse placenta.

p57(kip2) (encoded by the Cdkn1c gene) is a member of the cip/kip family of cyclin-dependent kinase inhibitors that mediates cell cycle arrest in G1, allowing cells to differentiate. In the placenta, p57(kip2) is involved in endoreduplication, formation of trophoblast giant cells, trophoblast invasion, and expansion of placental cell layers. Here, we quantitatively and qualitatively define the cell- and region-specific expression of mouse placental p57(kip2) using laser-capture microdissection, in situ hybridization, and immunohistochemistry. Cdkn1c RNA was quantified by real-time quantitative PCR. Co-expression of Pl1 was used to identify trophoblast giant cells while Tbpba was used to identify spongiotrophoblast cells. Timed sacrifices were also carried out at embryonic days E7.5, E8.5, E9.5, and E12.5 to profile the expression in embryos and their placentas. At E8.5, intense expression of Cdkn1c was seen in invasive TGCs and the ectoplacental cone. Cdkn1c expression was more diffuse and more abundant in the labyrinth that in the junctional zone at both E9.5 and E12.5. Immunohistochemistry revealed robust p57(kip2) staining in trophoblast giant cells and in the ectoplacental cone at E8.5. p57(kip2) protein was seen in giant cells and throughout the labyrinth, although its abundance was reduced in the junctional zone at E9.5, and became more diffuse by E12.5. The early and intense expression in trophoblast giant cells is consistent with a role for p57(kip2) in the invasive phenotype of these cells. Mol. Reprod. Dev. 83: 405-412, 2016. © 2016 Wiley Periodicals, Inc.

Tuning the Gas Separation Performance of CuBTC by Ionic Liquid Incorporation.

The efficient separation of gases has industrial, economic, and environmental importance. Here, the gas separation performance of a metal organic framework (MOF) is enhanced by ionic liquid (IL) incorporation. One of the most commonly used ILs, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), was incorporated into a commercially available MOF, CuBTC. Detailed characterization by combining spectroscopy with diffraction, electron microscopy, and thermal analysis confirmed that the structures were intact after incorporation. Adsorption isotherms of CH4, H2, N2, and CO2 in IL-incorporated CuBTC were experimentally measured and compared with those of pristine CuBTC. Consequently, ideal selectivities for CO2/CH4, CO2/N2, CO2/H2, CH4/N2, CH4/H2, and N2/H2 separations were calculated. The results showed that the CH4 selectivity of CuBTC over CO2, H2, and N2 gases becomes at least 1.5 times higher than that of pristine CuBTC upon the incorporation of IL. For example, the CH4/H2 selectivity of CuBTC increased from 26 to 56 at 0.2 bar when the IL loading was 30 wt %. These results show that the incorporation of ILs into MOFs can lead to unprecedented improvements in the gas separation performance of MOFs. The tunable physicochemical properties of ILs combined with a large number of possible MOF structures open up opportunities for the rational design of novel materials for meeting future energy challenges.

Structural and genomic variation in preterm birth.

BACKGROUND: Runs of homozygosity (ROH) are consecutive homozygous genotypes, which may result from population inbreeding or consanguineous marriages. ROH enhance the expression of recessive traits. METHODS: We mapped ROH in a case control study of women delivering at term compared with women delivering at or before 34 wk gestation. Gene sets known to be important in risk of preterm birth were examined for their overlap with identified ROH segments. RESULTS: While we found no evidence of increased burden of ROH or copy number variations in mothers delivering at or before 34 wk compared with term, we identified 424 genome-wide 50 kb segments with significant difference in abundance of overlapping ROH segments in cases vs. controls, P < 0.05. These regions overlap 199 known genes. We found preterm birth associated genes (CXCR4, MYLK, PAK1) and genes shown to have an evolutionary link to preterm (CXCR4, PPP3CB, C6orf57, DUSP13, and SLC25A45) with significant differences in abundance of overlapping ROH blocks in cases vs. controls, P < 0.001. CONCLUSION: We conclude, while we found no significant burden of ROH, we did identify genomic regions with significantly greater abundance of ROH blocks in women delivering preterm that overlapped genes known to be involved in preterm birth.

Comparison of cutaneous nerve injury and vessel disruption complications following saphenous vein stripping using big or small olive heads.

OBJECTIVE: To compare the nerve injury and vessel disruption complicaitons in patients undergoing saphenous vein stripping using olive heads of different sizes. METHODS: Big olive heads were used in group A (n=50) and small olive heads were used in group B (n=50) from the ankle to the groin; in group C (n=50), the vein was stripped in two sections; in an upward fashion by stripping the distal portion from the ankle to the level of the knee using small olive heads and by stripping the proximal portion from the knee to the level of the groin using big olive heads. RESULTS: Six months after the operation, nerve injury symptoms were identified in 26%, 4%, 6% of patients in groups A, B, and C respectively. Vessel disruption occurred 2% in group A, 32% in group B, and 4% in group C. Both vessel disruption and nerve injury complications of group C were significantly lower than group A and B (p<0.001). CONCLUSION: Saphenous stripping using big olive heads for the proximal portion from the groin down to the level of the knee and using small olive heads for the distal portion from the knee to the level of the ankle is the alternative method which results in minimal nerve injury and vessel disruption.

Thermal Stability Limits of Imidazolium Ionic Liquids Immobilized on Metal-Oxides.

Thermal stability limits of 33 imidazolium ionic liquids (ILs) immobilized on three of the most commonly used high surface area metal-oxides, SiO2, γ-Al2O3, and MgO, were investigated. ILs were chosen from a family of 13 cations and 18 anions. Results show that the acidity of C2H of an imidazolium ring is one of the key factors controlling the thermal stability. An increase in C2H bonding strength of ILs leads to an increase in their stability limits accompanied by a decrease in interionic energy. Systematic changes in IL structure, such as changes in electronic structure and size of anion/cation, methylation on C2 site, and substitution of alkyl groups on the imidazolium ring with functional groups have significant effects on thermal stability limits. Furthermore, thermal stability limits of ILs are influenced strongly by acidic character of the metal-oxide surface. Generally, as the point of zero charge (PZC) of the metal-oxide increases from SiO2 to MgO, the interactions of IL and metal-oxide dominate over interionic interactions, and metal-oxide becomes the significant factor controlling the stability limits. However, thermal stability limits of some ILs show the opposite trend, as the chemical activities of the cation functional group or the electron donating properties of the anion alter IL/metal-oxide interactions. Results presented here can help in choosing the most suitable ILs for materials involving ILs supported on metal-oxides, such as for supported ionic liquid membranes (SILM) in separation applications or for solid catalyst with ionic liquid layer (SCILL) and supported ionic liquid phase (SILP) catalysts in catalysis.

Pathway-based genetic analysis of preterm birth.

Preterm birth in the United States is now 12%. Multiple genes, gene networks, and variants have been associated with this disease. Using a custom database for preterm birth (dbPTB) with a refined set of genes extensively curated from literature and biological databases, we analyzed GWAS of preterm birth for complete genotype data on nearly 2000 preterm and term mothers. We used both the curated genes and a genome-wide approach to carry out a pathway-based analysis. There were 19 significant pathways, which withstood FDR correction for multiple testing that were identified using both the curated genes and the genome-wide approach. The analysis based on the curated genes was more significant than genome-wide in 15 out of 19 pathways. This approach demonstrates the use of a validated set of genes, in the analysis of otherwise unsuccessful GWAS data, to identify gene-gene interactions in a way that enhances statistical power and discovery.

Enabling the clinical application of artificial intelligence in genomics: a perspective of the AMIA Genomics and Translational Bioinformatics Workgroup.

OBJECTIVE: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space. PROCESS: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members. CONCLUSIONS: Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of larger datasets is crucial to emulating the success AI is achieving in other domains. It is important that AI methods do not exacerbate existing socio-economic, racial, and ethnic disparities. Genomic data standards are critical to effectively scale such technologies across institutions. With so much uncertainty, complexity and novelty in genomics and medicine, and with an evolving regulatory environment, the current focus should be on using these technologies in an interface with clinicians that emphasizes the value each brings to clinical decision-making.

Evaluation of positive inotropic drug effects on thyroid hormone levels after open heart surgery.

OBJECTIVE: The aim of this study was to examine the effects of positive inotropic drugs, including adrenaline, dopamine, and dobutamine on thyroid hormone levels following open heart surgery. METHODS: We analyzed free thyroid hormones (FT3 and FT4) and thyroid-stimulating hormones (TSH) in 200 consecutive patients undergoing open heart surgery. Patients were divided into 5 groups according to the inotropic drug administration as follows: Group A (n = 46) received dopamine alone; Group B (n = 40), dopamine and dobutamine; Group C (n = 36), dopamine, dobutamine, and adrenaline; Group D (n = 32), adrenaline alone; and Group E (n = 46), placebo. Procedural factors affecting thyroid hormones were recorded and included cardiopulmonary bypass (CPB) time, cross-clamping time, degree of hypothermia, and the duration and doses of positive inotropic drugs. Blood samples for hormone assays were collected before initiation of inotropic drug therapy (baseline) and postoperatively at 24, 72, and 120 hours after drug therapy. RESULTS: FT3, FT4, and TSH levels at baseline were similar in all groups. Although there was a trend showing very slight increases in thyroid hormone levels from baseline to the 24th, 72nd, and 120th postoperative hours after drug therapy, these changes were not significant, and there were also no significant differences between the groups. There was also no significant statistical difference in CPB time, cross-clamping time, degree of hypothermia, and duration and doses of positive inotropic drugs between groups. CONCLUSION: Although thyroid hormone levels were affected by positive inotropic drug usage after open heart surgery, this effect was not significant and thyroid hormone levels remained within normal ranges.

Evaluating CH4/N2 Separation Performances of Hundreds of Thousands of Real and Hypothetical MOFs by Harnessing Molecular Modeling and Machine Learning.

Considering the large abundance and diversity of metal-organic frameworks (MOFs), evaluating the gas adsorption and separation performance of the entire MOF material space using solely experimental techniques or brute-force computer simulations is impractical. In this study, we integrated high-throughput molecular simulations with machine learning (ML) to explore the potential of both synthesized, the real MOFs, and computer-generated, the hypothetical MOFs (hypoMOFs), for adsorption-based CH4/N2 separation. CH4/N2 mixture adsorption data obtained from molecular simulations were used to train the ML models that could accurately predict gas uptakes of 4612 real MOFs. These models were then transferred to two distinct databases consisting of 98 601 hypoMOFs and 587 anion-pillared hypoMOFs to examine their CH4/N2 mixture separation performances using various adsorbent evaluation metrics. The top adsorbents were identified for vacuum swing adsorption (VSA) and pressure swing adsorption (PSA) conditions and examined in detail to gain molecular insights into their structural and chemical properties. Results revealed that the hypoMOFs offered high CH4 selectivities, up to 14.8 and 13.6, and high working capacities, up to 3.1 and 5.8 mol/kg, at VSA and PSA conditions, respectively, and many of the hypoMOFs could outperform the real MOFs. Our approach offers a rapid and accurate assessment of the mixture adsorption and separation properties of MOFs without the need for computationally demanding simulations. Our results for the best adsorbents will be useful in accelerating the experimental efforts for the design of novel MOFs that can achieve high-performance CH4/N2 separation.