Search

The observation of a spontaneous electron enrichment at the apexes of bismuth vanadate (BiVO4) nanopyramidal arrays is achieved by performing synchrotron-based angular dependent X-ray absorption spectroscopy. In accordance with density function theory calculations, the formation of (112) facets enriched apexes is proposed. Such intrinsically electron-enriched (112) facets at the apexes produce a potential facilitating the diffusion of photoexcited holes, which not only mitigates the recombination with the photoexcited electrons, but also provide an active reaction site for the photoassisted selective growth of cobalt phosphate (CoPi), a well known and highly active co-catalyst for water oxidation at the apex of BiVO4 nanopyramids. Benefiting from the element-resolved properties of synchrotron-based X-ray spectroscopy, 3d electrons on the vanadium site are directly resolved by resonant inelastic X-ray scattering measurements. Due to this unique morphology, the charge at the apex is expected to induce a strong interaction with CoPi, as a result of the metal-to-ligand charge transfer spectroscopy feature observed from the cobalt site. Substantial evidences are collected by means of comprehensive soft X-ray spectroscopy techniques with high spectral resolution revealing the atomic-scale origin and the nature of the synergy as well as the strong correlation between its unique structural properties and the electronic structure of this novel highly-ordered hybrid photocatalyst and its significantly improved photoelectrochemical performance.

Activin receptor-like kinase 2 (ALK2) has been implicated as a key target in multiple rare diseases. Herein, we describe the design of a novel bicyclic lactam series of potent and selective ALK2 inhibitors. This manuscript details an improvement in potency of two orders of magnitude from the initial bicyclic structure as well as a two-fold improvement in cellular potency from the original monocyclic inhibitor. Furthermore, we provide a detailed strategy for progressing this project in the future.

BackgroundBlocking the PD-L1 immune checkpoint axis with therapeutic antibodies against either the ligand or PD-1 has proven to be an effective treatment modality for multiple cancer histologies. Small molecules targeting the PD-L1/PD-1 axis represent an alternate modality of blocking this pathway. INCB090244 is a small molecule that blocks the PD-L1/PD-1 interaction and restores T cell function similar to the clinical stage PD-L1 inhibitor INCB086550.MethodsMDA-MB-231 or CHO cells overexpressing PD-L1 were used to investigate effects of INCB090244 on PD-L1 dimerization, and intracellular trafficking. In vivo, CD34+ humanized mice harboring MDA-MB-231 tumors or C57Bl/6 mice bearing GL261 subcutaneous or orthotopic tumors were used to investigate the efficacy, biodistribution, and pharmacodynamic effects of INCB090244. Human specific gene expression changes in tumors from MDA-MB-231 bearing humanized mice were analyzed by RNA sequencing.ResultsIn vitro, INCB090244 potently disrupted the PD-L1:PD-1 interaction, induced PD-L1 dimerization, and inhibited PD-1-mediated negative signaling, resulting in enhanced IFN gamma and IL-2 production in primary human immune cells. Following dimerization, INCB090244 induced internalization of PD-L1 resulting in co-localization with the Golgi apparatus and partial localization in the nucleus. After cell treatment and washing, full restoration of PD-L1 at the cell surface was observed after 5 days of culture in vitro. In vivo, INCB090244 reduced tumor growth in CD34+ humanized mice bearing MDA-MB-231 tumors, to similar levels as atezolizumab. Antitumor activity was completely abrogated in immunodeficient mice, confirming the pharmacologic dependency on a competent immune system. RNA sequencing analysis on tumors from these mice demonstrated similar T cell activation gene signatures as clinical checkpoint blockade antibodies. Biodistribution studies in mice bearing both subcutaneous and orthotopically implanted GL261 glioma tumors demonstrated higher accumulation of INCB090244 in tumor tissue compared to PD-L1 antibodies.ConclusionsINCB090244 effectively disrupted the PD-L1/PD-1 interaction, induced dimerization and internalization of PD-L1, restored immunity in in vitro and in vivo tumor models, and is a suitable surrogate for the clinical candidate INCB086550. RNA sequencing demonstrated T cell activation signatures similar to those observed in patients receiving checkpoint blockade antibodies. Biodistribution studies demonstrated higher subcutaneous and brain tumor penetration by INCB090244 compared to PD-L1 antibodies, suggesting a potential advantage of small molecule PD-L1 inhibitors in accessing intratumoral regions. These data further support the clinical evaluation of small molecule PD-L1 inhibitors as an alternative approach to immune therapy.

Transition state stabilization is essential for rate acceleration of enzymatic reactions. Despite extensive studies on various transition state structures of enzymes, an intriguing puzzle is whether an enzyme can accommodate multiple transition states (TS) to catalyze a chemical reaction. It is experimentally challenging to interrogate this proposition in terms of the choices of suitable enzymes and the feasibility to distinguish multiple TS. As a paradigm with the protein lysine methyltransferase (PKMT) SET7/9 paired with its physiological substrates H3 and p53, their TS were solved with experimental kinetic isotope effects as computational constraints. Remarkably, SET7/9 adopts two structurally distinct TS---a nearly symmetric S(N)2 and an extremely early S(N)2---for H3K4 and p53K372 methylation, respectively. The two TS are also different from those previously revealed for other PKMTs. The setting of multiple TS is expected to be essential for SET7/9 and likely other PKMTs to act on broad substrates with high efficiency.

The electronic structures of carbon nanocages (CNCs) and nitrogen/phosphorus doped carbon nanocages (N-CNCs/P-CNCs) have been studied by X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), X-ray emission spectroscopy (XES) and resonant X-ray emission spectroscopy (RXES). The doping configurations for N/P dopants are identified from the experiments. The results have shown that there are three major doping configurations for nitrogen but only one doping configuration for phosphorus. The nitrogen doping reveals the complex coexistence of graphite-like, pyridine-like and pyrrole-like configurations that are proved by density functional theory (DFT) simulations, while the phosphorus doping presents only the “graphite-like” configuration. The different configuration profiles result in less atomic structure ordering of N-CNCs than that of P-CNCs. XAS spectra obtained from both surface and bulk sensitive detection suggest different chemical environments between the interior and shell for all types of nanocages. The electronic structure modifications show significant difference between nitrogen and phosphorus doping from the DOS calculations.

Unique experiments were designed to study the surface phenomena in steelmaking reactions. The concept of surface sulfide capacities and an understanding of the surface accumulation of surface-active species, based on experimental results, are presented. In order to understand the flow phenomenon at slag/metal interface, experiments were designed to measure the interfacial velocity of S on the surface of an iron drop immersed in an aluminosilicate slag using the X-ray sessile drop method. The oscillation of the iron drop in the slag due to the change in the surface concentration of sulfur at the slag–metal interface was monitored by X-ray imaging. From the observations, the interfacial velocity of sulfur was evaluated. Similar experiments were performed to measure the interfacial velocity of oxygen at the interface as well as the impact of oxygen potential on the interfacial velocity of sulfur. The interfacial shear viscosity and the dilatational modulus were also evaluated. In a study of the wetting of alumina base by iron drop at constant oxygen pressure under isothermal condition, the contact angle was found to be decreased with the progress of the reaction leading to the formation of hercynite as an intermediate layer creating non-wetting conditions. In the case of silica substrate, an intermediate liquid fayalite layer was formed.

Protein lysine methyltransferases (PKMTs) catalyze the methylation of protein substrates, and their dysregulation has been linked to many diseases, including cancer. Accumulated evidence suggests that the reaction path of PKMT-catalyzed methylation consists of the formation of a cofactor(cosubstrate)–PKMT–substrate complex, lysine deprotonation through dynamic water channels, and a nucleophilic substitution (SN2) transition state for transmethylation. However, the molecular characters of the proposed process remain to be elucidated experimentally. Here we developed a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method and corresponding mathematic matrix to determine precisely the ratios of isotopically methylated peptides. This approach may be generally applicable for examining the kinetic isotope effects (KIEs) of posttranslational modifying enzymes. Protein lysine methyltransferase SET8 is the sole PKMT to monomethylate histone 4 lysine 20 (H4K20) and its function has been implicated in normal cell cycle progression and cancer metastasis. We therefore implemented the MS-based method to measure KIEs and binding isotope effects (BIEs) of the cofactor S-adenosyl-l-methionine (SAM) for SET8-catalyzed H4K20 monomethylation. A primary intrinsic 13C KIE of 1.04, an inverse intrinsic α-secondary CD3 KIE of 0.90, and a small but statistically significant inverse CD3 BIE of 0.96, in combination with computational modeling, revealed that SET8-catalyzed methylation proceeds through an early, asymmetrical SN2 transition state with the C-N and C-S distances of 2.35–2.40 A and 2.00–2.05 A, respectively. This transition state is further supported by the KIEs, BIEs, and steady-state kinetics with the SAM analog Se-adenosyl-l-selenomethionine (SeAM) as a cofactor surrogate. The distinct transition states between protein methyltransferases present the opportunity to design selective transition-state analog inhibitors.

Selected IMPHOS heats, have been used to make observations on decarburising and dephosphorising performance, scrap melting and slag foaming characteristics during BOS refining. If it is assumed that decarburisation takes place solely in the slag/metal emulsion then maximum metal residence time in the emulsion is just under 9 seconds and at peak decarburisation time, the maximum amount of metal in the emulsion is ∼50% of the total metal content in the converter. To evaluate the effects of changes in slag component chemistry on phosphorus refining it is necessary to account for changes in slag weight, which can change substantially throughout a heat and be significantly different heat-to-heat. Dephosphorising performance depends on the thermodynamic stability of slag phases that are able to take up phosphorus and the distribution of phosphorus between these thermodynamically stable phases. The application of proprietary thermodynamic models such as MTDATA and FACTSage has helped to clarify such even...

Selected IMPHOS (IMproving PHOSphorus refining) heats ([1], [2]: Millman et al. in Proc. Scanmet 3, 2008; and Millman et al. in Ironmak Steelmak 38:499, 2011), have been used to make observations on decarburizing and dephosphorising performance characteristics during BOS refining. If it is assumed that decarburization takes place solely in the slag/metal emulsion then maximum metal residence time in the emulsion is just under 9 sec and at peak decarburisation time, the maximum amount of metal in the emulsion is ~ 50 % of the total metal content in the converter. To evaluate the effects of changes in slag component chemistry on phosphorus refining it is necessary to account for changes in slag weight, which can change substantially throughout a heat and be significantly different heat-to-heat. Dephosphorising performance depends on the thermodynamic stability of slag phases that are able to take-up phosphorus and the distribution of phosphorus between these thermodynamically stable phases. The application of proprietary thermodynamic models such as MTDATA and FACTSage has helped to clarify such events. The stability of the foamy slag/metal emulsion changes over the period of the blow. Slag height increases with an increase in FeO (tot) wt% and decreases with a decrease in decarburisation rate and the collapse of the foamy slag.

Thiolactomycin (TLM) is a natural product inhibitor of KasA, the β-ketoacyl synthase A from Mycobacterium tuberculosis. To improve the affinity of TLM for KasA, a series of TLM analogs have been synthesized based on interligand NOEs between TLM and a pantetheine analog when both are bound simultaneously to the enzyme. Kinetic binding data reveal that position 3 of the thiolactone ring is a suitable position for elaboration of the TLM scaffold, and the structure-activity relationship studies provide information on the molecular features that govern time-dependent inhibition in this enzyme system. These experiments also exemplify the utility of transient one-dimensional NOE spectroscopy for obtaining interligand NOEs compared with traditional steady state two-dimensional NOESY spectroscopy.

β-Ketoacyl-ACP synthases (KAS) are key enzymes involved in the type II bacterial fatty acid biosynthesis (FASII) pathway and are putative targets for antibacterial discovery. Several natural product KAS inhibitors have previously been reported, including thiolactomycin (TLM), which is produced by Nocardia spp. Here we describe the synthesis and characterization of optically pure 5R-thiolactomycin (TLM) analogues that show improved whole cell activity against bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and priority pathogens such as Francisella tularensis and Burkholderia pseudomallei. In addition, we identify TLM analogues with in vivo efficacy against MRSA and Klebsiella pneumoniae in animal models of infection.

Epigenetic regulation requires site-specific modification of the genome and is involved in multiple physiological processes and disease etiology. Methyltransferases, which catalyze the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to various substrates, are critical components of the epigenetic machinery. This group of enzymes can methylate diverse substrates including DNA, RNA, proteins, and small-molecule metabolites. Their dysregulation has also been implicated in multiple disease states such as cancer, neurological, and cardiovascular disorders. Developing potent and selective small-molecule inhibitors of methyltransferases is valuable not only for therapeutic intervention but also for investigating the roles of these enzymes in disease progression. In this chapter, we will discuss the strategies of designing and synthesizing methyltransferases inhibitors based on the SAM scaffold. Following the section of inhibitor design, we will briefly review representative assays that are available to evaluate the potency of these inhibitors along with a detailed description of the most commonly used radiometric assay.

A thermodynamic (equilibrium) model is developed for the BOF process. The predictions of this model show the trend of reactions when the process is considered to be at thermodynamic equilibrium. In the case of a real process, however, some tuning and adaptation becomes necessary to make more accurate predictions. A dynamic model is developed in which the kinetics of scrap dissolution is also incorporated. A comparison of the results of the equilibrium and dynamic models (made with some tuning parameters) reveals that mixing is the prime factor whichcanalter thecourseof reactionatanyparticularinstant.Mixingis greatlyaffectedbyoxygenflowrate, lanceheightandthenatureof scrap. The understanding of the secrets of process dynamics becomes clearer with this approach, providing a good insight into the process.

We report a systematic study of the thickness dependency of room temperature ferromagnetism in pristine MgO (~100-500 nm) and ZnO (~100-1000 nm) thin films deposited by reactive magnetron sputtering technique under the respective identical controlled optimum oxygen ambience. As far as we know this is the first such report on ferromagnetic pure MgO thin films, a result which should be of significance in understanding the functional aspects of magnetic tunnelling characteristics in devices using MgO dielectrics. From the magnetic characterization we observe a distinct variation in the saturation magnetization (MS) with increasing film thickness. In the case of MgO thin films MS values vary in the range 0.04-1.58 emu/g (i.e. 0.0012-0.046 ?B/unit cell) with increasing film thickness showing the highest MS value for the 170 nm thick film. Above this thickness MS is found to decrease and eventually above 420 nm the films show a paramagnetic behaviour followed by the well known diamagnetic property for the bulk (>500 nm). It is obvious that since initially the MS values increase with thickness, there has to be a maximum before the films become diamagnetic at some finite thickness. We also note that the MS values observed for MgO are the highest (more than twice the value observed for ZnO) to be reported for such a defect induced ferromagnetism in a pristine oxide. The origin of ferromagnetic order in both the oxides appears to arise from the respective cat-ion vacancies. The discovery of film thickness dependent ferromagnetic order should be very useful in developing multifunctional devices based on the technologically important materials MgO and ZnO.

A sessile drop investigation on the kinetics of carbon dissolution from an alumina-carbon composite (75% C, 25% alumina) and a commercial refractory (28.3% C, 66.67% alumina, 5% binder) into liquid ...

Resveratrol is a natural polyphenol with plethora of biological activities. Resveratrol has previously shown to decrease DNA methyltransferase (DNMT) enzymes expression and to reactivate silenced tumor suppressor genes. Currently, it seems that no resveratrol analogues have been developed as DNMT inhibitors. Recently, we reported the synthesis of resveratrol-salicylate derivatives and by examining the chemical structure of these analogues, we proposed that these compounds could exhibit DNMT inhibition especially that they resembled NSC 14778, a compound we previously identified as DNMT inhibitor by virtual screening. Indeed, using in vitro DNMT inhibition assay, some of the resveratrol-salicylate analogues we screened in this work showed selective inhibition against DNMT3 enzymes which was greater than resveratrol. A molecular docking study revealed key binding interactions with DNMT3A and DNMT3B enzymes. Additionally, the most active analogues, 10 showed considerable cytotoxicity against three human cancer cells; HT-29, HepG2 and SK-BR-3 which was greater than resveratrol. Further studies are needed to understand the anticancer mechanisms of these derivatives.

The electronic structure of a material plays an important role in its functionality for different applications which can be probed using synchrotron-based spectroscopy techniques. Here, various cobalt-based compounds, differing in crystal structure, ligands surrounding the central metal ion and morphology, have been studied by soft X-ray absorption spectroscopy (XAS) at the CoL-edge in order to measure the effect of these parameters on the electronic structure. A careful qualitative analysis of the spectral branching ratio and relative intensities of theL3andL2peaks provide useful insight into the electronic properties of compounds such as CoO/Co(OH)2, CoCl2.6H2O/CoF2.4H2O, CoCl2/CoF2, Co3O4(bulk/nano/micro). For further detailed analysis of the XAS spectra, quantitative analysis has been performed by fitting the spectral profile with simulated spectra for a number of cobalt compounds using crystal field atomic multiplet calculations.

Slag foaming is an important phenomenon in steelmaking processes with both beneficial as well as negative effects. The present work is part of the wider project on the modelling of slag foaming, with special reference to dynamic conditions. Since bubble formation is the first step to foam formation, the present work was carried out in an attempt to simulate the bubble formation in slag/metal reactions in steel making processes by water-modelling experiments. The bubble formation due to the gas produced through chemical reaction at the interface between oleic acid and sodium bicarbonate solution was systematically monitored. The chemical reaction rate was varied by varying the concentration of sodium bicarbonate. The bubbles were observed to be generated in the heavier aqueous phase just below the water-oil interface. The bubbles penetrated the interface and escaped through the oil phase. The rate of the reaction was estimated from the volume of the gas that passed the water/oil interface. It was observed that the bubble formation and bubble growth mechanism were influenced by the reaction rate while the bubble size seemed to be unaffected by the reaction rate.

As part of refractory erosion studies, the wetting behaviour of molten iron containing varying amounts of oxygen on refractory oxides was investigated by the sessile drop method. The oxides investigated in the present work were alumina, silica and mullite. The reactions were followed in static as well as dynamic modes, under isothermal conditions, through contact angle measurements. Other parameters investigated in the present study were temperature and oxygen partial pressure.

Refractory-metal interactions and associated reactions are important during casting as they can lead to the formation of inclusions. High temperature interactions between aluminosilicate refractori ...

In the present work, reactions occurring between molten iron containing varying amounts of oxygen and mullite substrate were investigated through optical Sessile drop experiments. The reactions were followed in static as well as dynamic modes through contact angle measurements. Further, the reactions were followed as functions of time, temperature and oxygen partial pressure. The latter was changed by means of imposing a gas mixture of Ar-CO-CO 2 into the furnace. The results showed that the contact angle between the substrate and the iron in purified argon gas was lower than the contact angles reported in literature for alumina and silica. Formation of a ternary slag during the reaction was observed and was subjected to SEM and EDS analysis. The thermodynamic criteria for slag formation and possible mechanisms of the reaction are discussed in the light of the experiments. The results are of relevance in understanding the mechanism of corrosion of aluminosilicate refractories by molten iron.

The X-ray sessile-drop method was employed in the present investigation to measure the contact angle between liquid iron and a silica substrate under argon as well as CO-CO2-Ar atmospheres in the temperature range of 1823 to 1833 K. In the latter case, the measurements were carried out in the dynamic mode, and the contact-angle changes were followed as a function of time as oxygen in the gas dissolved in the metal. The static measurements in argon showed that the contact angles in the experimental temperature range are of the order of 135 deg, similar to those observed in the case of the alumina substrate. In the dynamic mode, oxygen partial pressures varying between 9.9.10(-4) and 1.5.10(-2) Pa were imposed on the system. In these experiments, the contact angle decreased in two stages, with an intermediate steady-state region. Fayalite slag, formed due to the reaction between the metallic phase and the substrate, was found to accumulate around the drop. The results are of relevance in understanding the mechanism of corrosion of silica-containing refractories by molten iron.

We report on the interfacial behaviour of a series of nonionic diblock copolymers at solid hydrophobic and hydrophilic surfaces/water and silicone oil/water interfaces, studied by ellipsometry. The polymers consist of a hydrophobic C-18 chain linked to a hydrophilic poly(ethylene oxide) (PEO), block varying from 50 to 250 U. The adsorption of these copolymers at low bulk concentrations was found to be dominated by the PEO block at all interfaces. At higher concentration the copolymer forms surface aggregates at the silica surface whereas we observe a gradual increase in the adsorbed layer thickness with increased surface excess at the solid hydrophobic surface, indicating a transition from a flat conformation to brush-like layer structure. The results indicate a similar evolution in adsorbed amount with concentration at the silicone oil/water interface as at the hydrophobic silica surface. The influence of the rheological proper ies of the interface on the adsorption of the diblock copolymer was investigated by comparing results from two silicon oils with different viscosities. The copolymers were found to have stronger affinity to a low viscosity (990 mPa s) silicone oil than to a higher viscosity (12 800 mPa s) silicone oil and the hydrophobised silica surface. At the silicone oil/water interface the adsorption of a commercial nonionic triblock copolymer was furthermore investigated and compared with the diblock copolymers. (C) 2003 Elsevier B.V. All rights reserved. (Less)

In the present work, the reaction between a molten iron drop and dense alumina was studied using the X-ray sessile-drop method under different oxygen partial pressures in the gas atmosphere. The changes in contact angles between the iron drop and the alumina substrate were followed as functions of temperature and varying partial pressures of oxygen in the temperature range 1823 to 1873 K both in static and dynamic modes. The results of the contact angle measurements with pure iron in contact with dense alumina in extremely well-purified argon as well as under different oxygen partial pressures in the gas atmosphere showed good agreement with earlier measurements reported in the literature. In the dynamic mode, when argon was replaced by a CO-CO2-Ar mixture with a well-defined PO, in the gas, the contact angle showed an initial decrease followed by a period of nearly constant contact angle. At the end of this period, the length of which was a function of the P-O2 imposed, a further steep decrease in the contact angle was noticed. An intermediate layer of FeAl2O4 was detected in the scanning electron microscope (SEM) analysis of the reacted substrates. An interesting observation in the present experiments is that the iron drop moved away from the site of the reaction once the product layer covered the interface. The results are analyzed on the basis of the various forces acting on the drop.

Probing the Optical Property and Electronic Structure of TiO2 Nanomaterials for Renewable Energy Applications

The X-ray absorption spectra (XAS) of lithium polysulfides (Li2Sx) of various chain lengths (x) dissolved in a model solvent are obtained from first-principles calculations. The spectra exhibit two main absorption features near the sulfur K-edge, which are unambiguously interpreted as a pre-edge near 2471 eV due to the terminal sulfur atoms at either end of the linear polysulfide dianions and a main-edge near 2473 eV due to the (x -2) internal atoms in the chain, except in the case of Li2S2, which only has a low-energy feature. We find an almost linear dependence between the ratio of the peaks and chain length, although the linear dependence is modified by the delocalized, molecular nature of the core-excited states that can span up to six neighboring sulfur atoms. Thus, our results indicate that the ratio of the peak area, and not the peak intensities, should be used when attempting to differentiate the polysulfides from XAS. © 2014 American Chemical Society.

The isothermal reduction of synthetic CoTiO3 and NiTiO3 in hydrogen (1 atm) was investigated using thermogravimetric analysis technique in the temperature range, 928–1287 K (CoTiO3) and 884–1387 K (NiTiO3). Shallow beds of fine titanate powders were reduced by hydrogen at a high flow rate. Quenched samples were analyzed by scanning electron microscopy. The rates of the reaction of the titanates with H2 were very fast during the reduction of Co2+, Ni2+, or Fe2+ ions into metals. The reduction of the remaining titanium oxide was very slow. The activation energy for the reduction of CoTiO3 by hydrogen to Co and TiO2 was evaluated to be 151 ± 1 kJ/mol, and the activation energy for the reduction of NiTiO3 by hydrogen to Ni and TiO2 was evaluated to be 153 ± 1 kJ/mol. The study was complemented by hydrogen reduction of synthetic TiO2 (rutile). The results were also compared with the hydrogen reduction of FeTiO3.

The survival of Mycobacterium tuberculosis depends on mycolic acids, very long α-alkyl-β-hydroxy fatty acids comprising 60–90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38–42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction and support an induced fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several α-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors.

In the present study, the reduction kinetics of synthetic ilmenite by H 2 has been carried out using thermogravimetric technique. This has been complemented by X-ray diffraction and scanning electron microscopic (SEM) analyses. The morphology of the reduced product shows that iron metal is distributed around the titanium oxide particles, which has important implications for the separation of iron and titanium dioxide in the recovery of the same from ilmenite. The reduction proceeds very fast in the initial period and a high degree of reduction is obtained in the case of all reductions. A decrease in the reaction rate is observed at later stages of the reduction due to the slow diffusion process. An activation energy for the reduction of FeTiO 3 to iron and titanium dioxide was estimate to be of 108 kJ.mole -1 .

Ferromagnetic ordering at room temperature (RTFM) in MgO thin films deposited by RF magnetron sputtering under various atmospheric conditions and temperatures is reported. A saturation magnetization (M(S)) value as high as 1.58 emu g(-1) is (0.046 μB/unit cell) observed for a 170 nm film deposited at RT under an oxygen pressure of 1.3 × 10(-4) mbar. In contrast, films deposited at elevated temperature (under an identical oxygen pressure), or at higher oxygen pressures, as well as under a nitrogen atmosphere at RT show significantly suppressed magnetization. The ferromagnetic order in the MgO matrix is believed to be defect induced.

Thiolactomycin (TLM), a natural product thiolactone antibiotic produced by species of Nocardia and Streptomyces, is an inhibitor of the beta-ketoacyl-acyl carrier protein synthase (KAS) enzymes in the bacterial fatty acid synthase pathway. Using enzyme kinetics and direct binding studies, TLM has been shown to bind preferentially to the acyl-enzyme intermediates of the KASI and KASII enzymes from Mycobacterium tuberculosis and Escherichia coli. These studies, which utilized acyl-enzyme mimics in which the active site cysteine was replaced by a glutamine, also revealed that TLM is a slow onset inhibitor of the KASI enzymes KasA and ecFabB but not of the KASII enzymes KasB and ecFabF. The differential affinity of TLM for the acyl-KAS enzymes is proposed to result from structural change involving the movement of helices alpha5 and alpha6 that prepare the enzyme to bind malonyl-AcpM or TLM and that is initiated by formation of hydrogen bonds between the acyl-enzyme thioester and the oxyanion hole. The finding that TLM is a slow onset inhibitor of ecFabB supports the proposal that the long residence time of TLM on the ecFabB homologues in Serratia marcescens and Klebsiella pneumonia is an important factor for the in vivo antibacterial activity of TLM against these two organisms despite the fact that the in vitro MIC values are only 100-200 microg/ml. The mechanistic data on the interaction of TLM with KasA will provide an important foundation for the rational development of high affinity KasA inhibitors based on the thiolactone skeleton.

We report a systematic study of the film thickness dependence (0.1-1 mu m) of room-temperature ferromagnetism in pure magnetron-sputtered ZnO thin films wherein a sequential transition from ferroma ...

Room temperature ferromagnetic ordering is reported in Ni–tetracyanoethylene (TCNE) thin films fabricated on Au substrates using physical vapor deposition (PVD) under ultra high vacuum conditions. This technique enables the preparation of very clean films without having any kind of contamination from oxygen-containing species, solvents or precursor molecules. Film stoichiometry was obtained from X-ray photoelectron spectroscopy (XPS) measurements. XPS derived stoichiometry points to a ∼1 : 2 ratio between Ni and TCNE resulting in Ni(TCNE)x, x ≈ 2. No evidence of pure Ni metal in the in situ grown films was present in the XPS or the ultraviolet photoelectron spectroscopy (UPS) measurements within the detection limits of the techniques.

We present laboratory experiments employing differential scanning calorimetry as well as flow cell microscopy to study the microphysics of aqueous NaCl and sea-salt solutions and droplets at temperatures below 273 K. The freezing and melting points of ice and other precipitates were determined in NaCl and sea-salt bulk samples as well as in emulsion samples. Using flow cell microscopy, we have determined the deliquescence and efflorescence relative humidities of NaCl and sea-salt droplets at temperatures between 249 and 273 K, extending the existing room temperature data to polar conditions. Our measurements suggest that sea-salt aerosols will most likely be liquid most of the time under polar marine boundary conditions. In addition, we show that sea-salt aerosols or seawater spray deposited on the polar ice pack will remain partly liquid down to 230 K, with concentrations of Cl− and Br− increasing by more than an order of magnitude upon cooling when compared to normal seawater concentrations. This is likely to enhance the rate at which heterogeneous bromine activation reactions occur in the sea-salt deposits. Such reaction rate enhancements with decreasing temperatures are currently not implemented in chemical models, and might help explain the fast bromine activation and subsequent ozone destruction observed during ozone depletion events in the polar marine boundary layer in spring.