Kinetics of hydrodeoxygenation of octanol over supported nickel catalysts: a mechanistic study

The hydrodeoxygenation (HDO) of 1-octanol as a model aliphatic alcohol of bio-oil was investigated in a continuous down-flow fixed-bed reactor over γ-Al2O3, SiO2, and HZSM-5 supported nickel catalysts in the temperature range of 488–533 K. The supported nickel catalysts were prepared by incipient wetness impregnation method and characterized by BET, XRD, TPR, TPD, H2 pulse chemisorption, and UV-vis spectroscopy. Characterization of supported nickel (or nickel oxide) catalysts revealed existence of dispersed as well as bulk nickel (or nickel oxide) depending on the extent of nickel loading and the nature of the support. The acidity of γ-Al2O3 supported nickel catalysts decreased with increasing the nickel loading on γ-Al2O3. n-Heptane, n-octane, di-n-octyl ether, 1-octanal, isomers of heptene and octene, tetradecane, and hexadecane were identified as products of HDO of 1-octanol. The C7 hydrocarbons were observed as primary products for catalysts with active metal sites such as γ-Al2O3 and SiO2 supported nickel catalysts. However, C8 hydrocarbons were primarily formed over acidic catalysts such as pure HZSM-5 and HZSM-5 supported nickel catalyst. The 1-octanol conversion increased with increasing nickel loading on γ-Al2O3, and temperature and decreasing pressure and WHSV. The selectivity to products was strongly influenced by temperature, nickel loading on γ-Al2O3, pressure, and types of carrier gases (nitrogen and hydrogen). The selectivity to C7 hydrocarbons was favoured over catalysts with increased nickel loading on γ-Al2O3 at elevated temperature and lower pressure. A comprehensive reaction mechanism of HDO of 1-octanol was delineated based on product distribution under various process conditions over different catalysts

Polyoxometalates for Nonvolatile Memory Applications

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Synthesis And Characterization Of Graphene Oxide –Polyoxometalate Composite Material For Device Applications

Polyoxometalates (POMs) consisting of clusters of d-block transition metals and oxygen atoms represent an important class of water soluble polynuclear nanomaterial. The tuneable size, structure and elemental composition of POM draws considerable attention for the development of functional composite materials of desired chemical and electronic properties.[1] Graphene can be the promising support for POMs due to its low band gap energy and fast electron transport properties. These properties of grapheme facilitates transport of electrons of POMs rapidly and effectively.[2] In the present investigation, graphene oxide (GO) and reduced graphene oxide (rGO) have been used as a support for POM-graphene composites for semiconductor, hydrogen production applications.[2] The deposition of POM on graphene oxide sheets were carried out through electron transfer interaction and electrostatic interaction between POM and GO sheets. ...

Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury

Problems with attention and short-term learning and memory are commonly reported after mild traumatic brain injury (mTBI). Due to the known relationships between α-synuclein (SNCA), dopaminergic transmission, and neurologic deficits, we hypothesized that SNCA polymorphisms might be associated with cognitive outcome after mTBI. A cohort of 91 mTBI patients one month after injury and 86 healthy controls completed a series of cognitive tests assessing baseline intellectual function, attentional function, and memory, and was genotyped at 13 common single nucleotide polymorphisms (SNPs) in the SNCA gene. Significant differences in two memory measures (p = 0.001 and 0.002), but not baseline intellectual function or attentional function tasks, were found between the mTBI group and controls. A highly significant protective association between memory performance and SNCA promoter SNP rs1372525 was observed in the mTBI patients (p = 0.006 and 0.029 for the long and short delay conditions of the California Verbal Learning Tests, respectively), where the presence of at least one copy of the A (minor) allele was protective after mTBI. These results may help elucidate the pathophysiology of cognitive alterations after mTBI, and thus warrant further investigation

Preparation and characterization of tin oxide, SnO2 nanoparticles decorated graphene

SnO2 nanoparticles/graphene (SnO2/GP) nanocomposite was synthesized by a facile microwave method. The X-ray diffraction (XRD) pattern of the nanocomposite corresponded to the diffraction peak typical of graphene and the rutile phase of SnO2 with tetragonal structure. The field emission scanning electron microscope (FESEM) images revealed that the graphene sheets were dotted with SnO2 nanoparticles with an average size of 10 nm. The X-ray photoelectron spectroscopy (XPS) analysis indicated that the development of SnO2/GP resulted from the removal of the oxygenous groups on graphene oxide (GO) by Sn2+ ions. The nanocomposite modified glassy carbon electrode (GCE) showed excellent enhancement of electrochemical performance when interacting with mercury(II) ions in potassium chloride supporting electrolyte. The current was increased by more than tenfold, suggesting its potential to be used as a mercury(II) sensor

Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II

Extent: 9p.Background: Insulin-like growth factor-II (IGF-II) promotes cell proliferation and survival and plays an important role in normal fetal development and placental function. IGF-II binds both the insulin-like growth factor receptor (IGF-1R) and insulin receptor isoform A (IR-A) with high affinity. Interestingly both IGF-II and the IR-A are often upregulated in cancer and IGF-II acts via both receptors to promote cancer proliferation. There is relatively little known about the mechanism of ligand induced activation of the insulin (IR) and IGF-1R. The recently solved IR structure reveals a folded over dimer with two potential ligand binding pockets arising from residues on each receptor half. Site-directed mutagenesis has mapped receptor residues important for ligand binding to two separate sites within the ligand binding pocket and we have recently shown that the IGFs have two separate binding surfaces which interact with the receptor sites 1 and 2. Methodology/Principal Findings: In this study we describe a series of partial IGF-1R and IR agonists generated by mutating Glu12 of IGF-II. By comparing receptor binding affinities, abilities to induce negative cooperativity and potencies in receptor activation, we provide evidence that residue Glu12 bridges the two receptor halves leading to receptor activation. Conclusions/Significance: This study provides novel insight into the mechanism of receptor binding and activation by IGFII,which may be important for the future development of inhibitors of its action for the treatment of cancer.Clair L. Alvino, Shee Chee Ong, Kerrie A. McNeil, Carlie Delaine, Grant W. Booker, John C. Wallace and Briony E. Forbe

Afatinib versus gefitinib or erlotinib in first-line setting for Malaysia patients with EGFR mutant advanced lung adenocarcinoma

Abstract Background Afatinib is an irreversible second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) while gefitinib or erlotinib are reversible first-generation EGFR-TKIs. Methods A retrospective analysis of patients with EGFR mutant advanced lung adenocarcinoma receiving first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 113 patients, 24 (21.2%) received afatinib, 63 (55.8%) received gefitinib and 26 (23.0%) received erlotinib in first-line setting. Their demographic and clinical characteristics are shown in the table. Afatinib was used significantly more frequently in patients with rare or complex EGFR mutations (p = 0.005), and more often in patients with symptomatic brain metastases. The median progression-free survival (mPFS) of patients treated with afatinib (13.1 months) was longer than that of patients treated with gefitinib (10.9 months) or erlotinib (7.8 months) (p = 0.479). Patients receiving afatinib had consistently longer PFS than patients receiving gefitinib for the first 17 months and erlotinib for the first 20 months. The overall response rate was higher in patients on afatinib (75.0%) than those on gefitinib (63.5%) or erlotinib (53.8%). There was no difference in the disease control rate. Three patients (2.7%) had severe side-effects while on EGFR-TKI. Of two patients on afatinib, one had grade-3 diarrhea while another had grade 3 stomatitis, rash and paronychia. One patient had grade 3 rash on gefitinib. Conclusions Patients receiving first-line afatinib demonstrated longer mPFS than those on first-line gefitinib or erlotinib. The lack of statistical significance in this study is because of the small number of patients treated with afatinib, more frequent rare or complex EGFR mutations and more symptomatic brain metastases among afatinib treated patients

Insulin in motion: The A6-A11 disulfide bond allosterically modulates structural transitions required for insulin activity

The structural transitions required for insulin to activate its receptor and initiate regulation of glucose homeostasis are only partly understood. Here, using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers (cis and trans). Remarkably, only the cis isomer displays full insulin potency, rapidly lowering blood glucose in mice (even under insulin-resistant conditions). It also posseses reduced mitogenic activity in vitro. Further biophysical, crystallographic and molecular-dynamics analyses reveal that the A6-A11 bond configuration directly affects the conformational flexibility of insulin A-chain N-terminal helix, dictating insulin's ability to engage its receptor. We reveal that in native insulin, contraction of the Cα-Cα distance of the flexible A6-A11 cystine allows the A-chain N-terminal helix to unwind to a conformation that allows receptor engagement. This motion is also permitted in the cis isomer, with its shorter Cα-Cα distance, but prevented in the extended trans analogue. These findings thus illuminate for the first time the allosteric role of the A6-A11 bond in mediating the transition of the hormone to an active conformation, significantly advancing our understanding of insulin action and opening up new avenues for the design of improved therapeutic analogues.A.J.R., B.E.F. and M.C.L. acknowledge funding from National Health and Medical Research Council (Project Grant APP1069328 and Project Grant APP1058233) and Australian Research Council. Te Walter and Eliza Hall Institute of Medical Research acknowledges Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

p53 is an important tumor-suppressor protein that is mutated in more than 50% of cancers. Strategies for restoring normal p53 function are complicated by the oncogenic properties of mutant p53 and have not met with clinical success. To counteract mutant p53 activity, a variety of drugs with the potential to reconvert mutant p53 to an active wildtype form have been developed. However, these drugs are associated with various negative effects such as cellular toxicity, nonspecific binding to other proteins, and inability to induce a wildtype p53 response in cancer tissue. Here, we report on the effects of a curcumin analog, HO-3867, on p53 activity in cancer cells from different origins. We found that HO-3867 covalently binds to mutant p53, initiates a wildtype p53-like anticancer genetic response, is exclusively cytotoxic toward cancer cells, and exhibits high anticancer efficacy in tumor models. In conclusion, HO-3867 is a p53 mutant-reactivating drug with high clinical anticancer potential